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Conserved domains on  [gi|283837842|ref|NP_001073890.2|]
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protein unc-13 homolog A [Homo sapiens]

Protein Classification

C2A_Munc13 and C2B_Munc13 domain-containing protein (domain architecture ID 11579680)

protein containing domains C2A_Munc13, C2B_Munc13, Membr_traf_MHD, and C2C_Munc13

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
676-802 9.23e-86

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


:

Pssm-ID: 175993  Cd Length: 127  Bit Score: 278.30  E-value: 9.23e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  676 AKISITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDDDIKSRVKQ 755
Cdd:cd04027     1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWDEDDDIKSRLKQ 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 283837842  756 RFKRESDDFLGQTIIEVRTLSGEMDVWYNLDKRTDKSAVSGAIRLHI 802
Cdd:cd04027    81 KFTRESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 127
C2A_Munc13 cd08394
C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
1-127 1.19e-80

C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


:

Pssm-ID: 176040  Cd Length: 127  Bit Score: 263.93  E-value: 1.19e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842    1 MSLLCVGVKKAKFDGAQEKFNTYVTLKVQNVKSTTIAVRGSQPSWEQDFMFEINRLDLGLTVEVWNKGLIWDTMVGTVWI 80
Cdd:cd08394     1 MSLLCVLVKKAKLDGAPDKFNTYVTLKVQNVKSTTIAVRGSQPCWEQDFMFEINRLDLGLVIELWNKGLIWDTLVGTVWI 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 283837842   81 PLRTIRQSNEEGPGEWLTLDSQVIMADSEICGTKDPTFHRILLDTRF 127
Cdd:cd08394    81 PLSTIRQSNEEGPGEWLTLDSEVNMKNGQIVGTKDPTFHRILLDVRF 127
C2C_Munc13 cd08395
C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
1546-1665 7.33e-78

C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins.C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


:

Pssm-ID: 176041  Cd Length: 120  Bit Score: 255.78  E-value: 7.33e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1546 KVTVKVVAANDLKWQTSGIFRPFIEVNIIGPQLSDKKRKFATKSKNNSWAPKYNESFQFTLSADAGPECYELQVCVKDYC 1625
Cdd:cd08395     1 KVTVKVVAANDLKWQTTGMFRPFVEVNLIGPHLSDKKRKFATKSKNNNWSPKYNETFQFILGNEDDPESYELHICVKDYC 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 283837842 1626 FAREDRTVGLAVLQLRELAQRGSAACWLPLGRRIHMDDTG 1665
Cdd:cd08395    81 FARDDRLVGVTVLQLRDIAQAGSCACWLPLGRRIHMDETG 120
Membr_traf_MHD pfam10540
Munc13 (mammalian uncoordinated) homology domain; Munc13 proteins constitute a family of three ...
1346-1508 3.88e-64

Munc13 (mammalian uncoordinated) homology domain; Munc13 proteins constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3) with homology to Caenorhabditis elegans unc-13p. Munc13 proteins contain a phorbol ester-binding C1 domain and two C2 domains, which are Ca2+/phospholipid binding domains. Sequence analyses have uncovered two regions called Munc13 homology domains 1 (MHD1) and 2 (MHD2) that are arranged between two flanking C2 domains. MHD1 and MHD2 domains are present in a wide variety of proteins from Arabidopsis thaliana, C. elegans, Drosophila melanogaster, mouse, rat and human, some of which may function in a Munc13-like manner to regulate membrane trafficking. The MHD1 and MHD2 domains are predicted to be alpha-helical.


:

Pssm-ID: 313710  Cd Length: 140  Bit Score: 217.51  E-value: 3.88e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  1346 NVLQPIMDLLDSNLTLFAKICEKTVLKRVLKELWKLVMNTMEKTIVLPPLTDQTMIGNLLRKHGKGlekgrvklpshsdg 1425
Cdd:pfam10540    1 DVLRPLMDYLNSNLSILAQILEKTVLKRVLKELWKVVLTTAEKTLVLPPLSDAKVKGRRKSLWDNA-------------- 66
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  1426 tqmifNAAKELGQLSKLkdhMVREEAKSLTPKQCAVVELALDTIKQYFHAGGVGLKKTFLeKSPDLQSLRYALSLYTQAT 1505
Cdd:pfam10540   67 -----NSAKELGQLSKL---EISGYGRPLTPKQCAVLFAWLDTLKDFFHNGGNGLKKEFL-KSPEYQSLLYALSLYTQST 137

                   ...
gi 283837842  1506 DLL 1508
Cdd:pfam10540  138 DEL 140
DUF1041 pfam06292
Domain of Unknown Function (DUF1041); This family consists of several eukaryotic domains of ...
994-1102 1.81e-54

Domain of Unknown Function (DUF1041); This family consists of several eukaryotic domains of unknown function. Members of this family are often found in tandem repeats and co-occur with pfam00168, pfam00130 and pfam00169 domains.


:

Pssm-ID: 310709  Cd Length: 107  Bit Score: 188.60  E-value: 1.81e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842   994 QVVKDCVKACLNSTYEYIFNNCHELYSREYQTDPAKkgEVLPEEQGPSIKNLDFWSKLITLIVSIIEEDKNSYTPCLNQF 1073
Cdd:pfam06292    1 QVVRDCLEACALSTYQRIFENAKELYSREFQDDEAT--EDPPESLGPSLKSLEFWHRLIELCVSVLEEDKEHYAPVLNQF 78
                           90       100
                   ....*....|....*....|....*....
gi 283837842  1074 PQELNVGKISAEVMWNLFAQDMKYAMEEH 1102
Cdd:pfam06292   79 PWELNLGVESAETFWSLFAVDMDAALEEH 107
C1 cd00029
Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of ...
554-603 1.69e-17

Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second messenger, released by activation of Phospholipase D. Phorbol Esters (PE) can act as analogues of DAG and mimic its downstream effects in, for example, tumor promotion. Protein Kinases C are activated by DAG/PE, this activation is mediated by their N-terminal conserved region (C1). DAG/PE binding may be phospholipid dependent. C1 domains may also mediate DAG/PE signals in chimaerins (a family of Rac GTPase activating proteins), RasGRPs (exchange factors for Ras/Rap1), and Munc13 isoforms (scaffolding proteins involved in exocytosis).


:

Pssm-ID: 237996  Cd Length: 50  Bit Score: 80.61  E-value: 1.69e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 283837842  554 HNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADC 603
Cdd:cd00029     1 HRFVRKSFFKPTFCDVCRKSIWGLFKQGLRCSWCKVKCHKKCADKVPPSC 50
Ribosomal_S16 super family cl00368
Ribosomal protein S16;
364-427 2.16e-04

Ribosomal protein S16;


The actual alignment was detected with superfamily member PRK14520:

Pssm-ID: 320936  Cd Length: 155  Bit Score: 43.14  E-value: 2.16e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 283837842  364 VAVAEPKDFKRiSLPPAAPGKEDKAPVAPTEAPDMAKVAPKPATPDKVPAAEQIPEAEPPKDEE 427
Cdd:PRK14520   93 LKVAEPKPSKL-ELFNAALAEADGGPTAEATTPKKKKAAAEAAAAEAAAPAAEAAAAAAAEEEA 155
 
Name Accession Description Interval E-value
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
676-802 9.23e-86

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175993  Cd Length: 127  Bit Score: 278.30  E-value: 9.23e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  676 AKISITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDDDIKSRVKQ 755
Cdd:cd04027     1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWDEDDDIKSRLKQ 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 283837842  756 RFKRESDDFLGQTIIEVRTLSGEMDVWYNLDKRTDKSAVSGAIRLHI 802
Cdd:cd04027    81 KFTRESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 127
C2A_Munc13 cd08394
C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
1-127 1.19e-80

C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176040  Cd Length: 127  Bit Score: 263.93  E-value: 1.19e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842    1 MSLLCVGVKKAKFDGAQEKFNTYVTLKVQNVKSTTIAVRGSQPSWEQDFMFEINRLDLGLTVEVWNKGLIWDTMVGTVWI 80
Cdd:cd08394     1 MSLLCVLVKKAKLDGAPDKFNTYVTLKVQNVKSTTIAVRGSQPCWEQDFMFEINRLDLGLVIELWNKGLIWDTLVGTVWI 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 283837842   81 PLRTIRQSNEEGPGEWLTLDSQVIMADSEICGTKDPTFHRILLDTRF 127
Cdd:cd08394    81 PLSTIRQSNEEGPGEWLTLDSEVNMKNGQIVGTKDPTFHRILLDVRF 127
C2C_Munc13 cd08395
C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
1546-1665 7.33e-78

C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins.C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176041  Cd Length: 120  Bit Score: 255.78  E-value: 7.33e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1546 KVTVKVVAANDLKWQTSGIFRPFIEVNIIGPQLSDKKRKFATKSKNNSWAPKYNESFQFTLSADAGPECYELQVCVKDYC 1625
Cdd:cd08395     1 KVTVKVVAANDLKWQTTGMFRPFVEVNLIGPHLSDKKRKFATKSKNNNWSPKYNETFQFILGNEDDPESYELHICVKDYC 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 283837842 1626 FAREDRTVGLAVLQLRELAQRGSAACWLPLGRRIHMDDTG 1665
Cdd:cd08395    81 FARDDRLVGVTVLQLRDIAQAGSCACWLPLGRRIHMDETG 120
Membr_traf_MHD pfam10540
Munc13 (mammalian uncoordinated) homology domain; Munc13 proteins constitute a family of three ...
1346-1508 3.88e-64

Munc13 (mammalian uncoordinated) homology domain; Munc13 proteins constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3) with homology to Caenorhabditis elegans unc-13p. Munc13 proteins contain a phorbol ester-binding C1 domain and two C2 domains, which are Ca2+/phospholipid binding domains. Sequence analyses have uncovered two regions called Munc13 homology domains 1 (MHD1) and 2 (MHD2) that are arranged between two flanking C2 domains. MHD1 and MHD2 domains are present in a wide variety of proteins from Arabidopsis thaliana, C. elegans, Drosophila melanogaster, mouse, rat and human, some of which may function in a Munc13-like manner to regulate membrane trafficking. The MHD1 and MHD2 domains are predicted to be alpha-helical.


Pssm-ID: 313710  Cd Length: 140  Bit Score: 217.51  E-value: 3.88e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  1346 NVLQPIMDLLDSNLTLFAKICEKTVLKRVLKELWKLVMNTMEKTIVLPPLTDQTMIGNLLRKHGKGlekgrvklpshsdg 1425
Cdd:pfam10540    1 DVLRPLMDYLNSNLSILAQILEKTVLKRVLKELWKVVLTTAEKTLVLPPLSDAKVKGRRKSLWDNA-------------- 66
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  1426 tqmifNAAKELGQLSKLkdhMVREEAKSLTPKQCAVVELALDTIKQYFHAGGVGLKKTFLeKSPDLQSLRYALSLYTQAT 1505
Cdd:pfam10540   67 -----NSAKELGQLSKL---EISGYGRPLTPKQCAVLFAWLDTLKDFFHNGGNGLKKEFL-KSPEYQSLLYALSLYTQST 137

                   ...
gi 283837842  1506 DLL 1508
Cdd:pfam10540  138 DEL 140
DUF1041 pfam06292
Domain of Unknown Function (DUF1041); This family consists of several eukaryotic domains of ...
994-1102 1.81e-54

Domain of Unknown Function (DUF1041); This family consists of several eukaryotic domains of unknown function. Members of this family are often found in tandem repeats and co-occur with pfam00168, pfam00130 and pfam00169 domains.


Pssm-ID: 310709  Cd Length: 107  Bit Score: 188.60  E-value: 1.81e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842   994 QVVKDCVKACLNSTYEYIFNNCHELYSREYQTDPAKkgEVLPEEQGPSIKNLDFWSKLITLIVSIIEEDKNSYTPCLNQF 1073
Cdd:pfam06292    1 QVVRDCLEACALSTYQRIFENAKELYSREFQDDEAT--EDPPESLGPSLKSLEFWHRLIELCVSVLEEDKEHYAPVLNQF 78
                           90       100
                   ....*....|....*....|....*....
gi 283837842  1074 PQELNVGKISAEVMWNLFAQDMKYAMEEH 1102
Cdd:pfam06292   79 PWELNLGVESAETFWSLFAVDMDAALEEH 107
C2 pfam00168
C2 domain;
677-785 1.27e-25

C2 domain;


Pssm-ID: 306639  Cd Length: 104  Bit Score: 105.47  E-value: 1.27e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842   677 KISITVVCAQGLQAKDKTGSSDPYVTVQV--GKTKKRTKTIYGNLNPVWEENFHFECHNSSDR-IKVRVWDEDddiksrv 753
Cdd:pfam00168    2 RLRVTVIEAKNLPPKDLNGKSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAvLEIEVYDYD------- 74
                           90       100       110
                   ....*....|....*....|....*....|....
gi 283837842   754 kqRFKResDDFLGQTIIEVRTL--SGEMDVWYNL 785
Cdd:pfam00168   75 --RFGR--DDFIGEVRIPLSELdsGEVLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
677-782 1.56e-22

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577  Cd Length: 101  Bit Score: 96.40  E-value: 1.56e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842    677 KISITVVCAQGLQAKDKTGSSDPYVTVQVG---KTKKRTKTIYGNLNPVWEENFHFECHNSSDR-IKVRVWDEDddiksr 752
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVPPPELAeLEIEVYDKD------ 74
                            90       100       110
                    ....*....|....*....|....*....|..
gi 283837842    753 vkqrfKRESDDFLGQTIIEVRTL--SGEMDVW 782
Cdd:smart00239   75 -----RFGRDDFIGQVTIPLSDLllGGRHEKL 101
C1 cd00029
Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of ...
554-603 1.69e-17

Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second messenger, released by activation of Phospholipase D. Phorbol Esters (PE) can act as analogues of DAG and mimic its downstream effects in, for example, tumor promotion. Protein Kinases C are activated by DAG/PE, this activation is mediated by their N-terminal conserved region (C1). DAG/PE binding may be phospholipid dependent. C1 domains may also mediate DAG/PE signals in chimaerins (a family of Rac GTPase activating proteins), RasGRPs (exchange factors for Ras/Rap1), and Munc13 isoforms (scaffolding proteins involved in exocytosis).


Pssm-ID: 237996  Cd Length: 50  Bit Score: 80.61  E-value: 1.69e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 283837842  554 HNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADC 603
Cdd:cd00029     1 HRFVRKSFFKPTFCDVCRKSIWGLFKQGLRCSWCKVKCHKKCADKVPPSC 50
C2 pfam00168
C2 domain;
1545-1655 4.17e-17

C2 domain;


Pssm-ID: 306639  Cd Length: 104  Bit Score: 80.82  E-value: 4.17e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  1545 HKVTVKVVAANDL-KWQTSGIFRPFIEVniigpQLSDKKRKFATKSKNNSWAPKYNESFQFTLSAdagPECYELQVCVKD 1623
Cdd:pfam00168    1 GRLRVTVIEAKNLpPKDLNGKSDPYVKV-----YLLDGKQKKKTKVVKNTLNPVWNETFTFSVPD---PENAVLEIEVYD 72
                           90       100       110
                   ....*....|....*....|....*....|..
gi 283837842  1624 YCFAREDRTVGLAVLQLRELAQRGSAACWLPL 1655
Cdd:pfam00168   73 YDRFGRDDFIGEVRIPLSELDSGEVLDGWYPL 104
C1 smart00109
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ...
554-603 6.48e-17

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.


Pssm-ID: 197519  Cd Length: 50  Bit Score: 78.66  E-value: 6.48e-17
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|
gi 283837842    554 HNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADC 603
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50
C1_1 pfam00130
Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the ...
554-603 3.24e-14

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.


Pssm-ID: 278556  Cd Length: 53  Bit Score: 70.93  E-value: 3.24e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 283837842   554 HNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADC 603
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPEC 50
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
1546-1652 7.55e-13

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577  Cd Length: 101  Bit Score: 68.28  E-value: 7.55e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842   1546 KVTVKVVAANDLKW-QTSGIFRPFIEVNIIGpqlsDKKRKFATKSKNNSWAPKYNESFQFTLSAdagPECYELQVCVKDY 1624
Cdd:smart00239    1 TLTVKIISARNLPPkDKGGKSDPYVKVSLDG----DPKEKKKTKVVKNTLNPVWNETFEFEVPP---PELAELEIEVYDK 73
                            90       100
                    ....*....|....*....|....*...
gi 283837842   1625 CFAREDRTVGLAVLQLRELAQRGSAACW 1652
Cdd:smart00239   74 DRFGRDDFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
3-99 3.69e-10

C2 domain;


Pssm-ID: 306639  Cd Length: 104  Bit Score: 60.40  E-value: 3.69e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842     3 LLCVGVKKAKF---DGAQEKFNTYVTLKV---QNVKSTTIAVRGSQPSWEQDFMFEI-NRLDLGLTVEVWNKG-LIWDTM 74
Cdd:pfam00168    2 RLRVTVIEAKNlppKDLNGKSDPYVKVYLldgKQKKKTKVVKNTLNPVWNETFTFSVpDPENAVLEIEVYDYDrFGRDDF 81
                           90       100
                   ....*....|....*....|....*
gi 283837842    75 VGTVWIPLRTIRQSneEGPGEWLTL 99
Cdd:pfam00168   82 IGEVRIPLSELDSG--EVLDGWYPL 104
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
680-802 1.46e-08

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371  Cd Length: 1227  Bit Score: 59.77  E-value: 1.46e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKDKTGSSDPYVTVQV-GKTKKRTKTIYGNLNPVWEENFHFECHN-SSDRIKVRVWDEDDDiksrvkqrf 757
Cdd:COG5038  1044 IMLRSGENLPSSDENGYSDPFVKLFLnEKSVYKTKVVKKTLNPVWNEEFTIEVLNrVKDVLTINVNDWDSG--------- 1114
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 283837842  758 krESDDFLGQTIIEVRTLSGEMDVWYNLdKRTDKSAVSGAIRLHI 802
Cdd:COG5038  1115 --EKNDLLGTAEIDLSKLEPGGTTNSNI-PLDGKTFIVLDGTLHP 1156
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
3-93 1.68e-08

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577  Cd Length: 101  Bit Score: 55.57  E-value: 1.68e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842      3 LLCVGVKKAKF---DGAQEKFNTYVTLKVQN----VKSTTIAVRGSQPSWEQDFMFEINRLDLG-LTVEVWNKGLIW-DT 73
Cdd:smart00239    1 TLTVKIISARNlppKDKGGKSDPYVKVSLDGdpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAeLEIEVYDKDRFGrDD 80
                            90       100
                    ....*....|....*....|
gi 283837842     74 MVGTVWIPLRTIRQSNEEGP 93
Cdd:smart00239   81 FIGQVTIPLSDLLLGGRHEK 100
rpsP PRK14520
30S ribosomal protein S16; Provisional
364-427 2.16e-04

30S ribosomal protein S16; Provisional


Pssm-ID: 184724  Cd Length: 155  Bit Score: 43.14  E-value: 2.16e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 283837842  364 VAVAEPKDFKRiSLPPAAPGKEDKAPVAPTEAPDMAKVAPKPATPDKVPAAEQIPEAEPPKDEE 427
Cdd:PRK14520   93 LKVAEPKPSKL-ELFNAALAEADGGPTAEATTPKKKKAAAEAAAAEAAAPAAEAAAAAAAEEEA 155
 
Name Accession Description Interval E-value
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
676-802 9.23e-86

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175993  Cd Length: 127  Bit Score: 278.30  E-value: 9.23e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  676 AKISITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDDDIKSRVKQ 755
Cdd:cd04027     1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWDEDDDIKSRLKQ 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 283837842  756 RFKRESDDFLGQTIIEVRTLSGEMDVWYNLDKRTDKSAVSGAIRLHI 802
Cdd:cd04027    81 KFTRESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 127
C2A_Munc13 cd08394
C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
1-127 1.19e-80

C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176040  Cd Length: 127  Bit Score: 263.93  E-value: 1.19e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842    1 MSLLCVGVKKAKFDGAQEKFNTYVTLKVQNVKSTTIAVRGSQPSWEQDFMFEINRLDLGLTVEVWNKGLIWDTMVGTVWI 80
Cdd:cd08394     1 MSLLCVLVKKAKLDGAPDKFNTYVTLKVQNVKSTTIAVRGSQPCWEQDFMFEINRLDLGLVIELWNKGLIWDTLVGTVWI 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 283837842   81 PLRTIRQSNEEGPGEWLTLDSQVIMADSEICGTKDPTFHRILLDTRF 127
Cdd:cd08394    81 PLSTIRQSNEEGPGEWLTLDSEVNMKNGQIVGTKDPTFHRILLDVRF 127
C2C_Munc13 cd08395
C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
1546-1665 7.33e-78

C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins.C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176041  Cd Length: 120  Bit Score: 255.78  E-value: 7.33e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1546 KVTVKVVAANDLKWQTSGIFRPFIEVNIIGPQLSDKKRKFATKSKNNSWAPKYNESFQFTLSADAGPECYELQVCVKDYC 1625
Cdd:cd08395     1 KVTVKVVAANDLKWQTTGMFRPFVEVNLIGPHLSDKKRKFATKSKNNNWSPKYNETFQFILGNEDDPESYELHICVKDYC 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 283837842 1626 FAREDRTVGLAVLQLRELAQRGSAACWLPLGRRIHMDDTG 1665
Cdd:cd08395    81 FARDDRLVGVTVLQLRDIAQAGSCACWLPLGRRIHMDETG 120
Membr_traf_MHD pfam10540
Munc13 (mammalian uncoordinated) homology domain; Munc13 proteins constitute a family of three ...
1346-1508 3.88e-64

Munc13 (mammalian uncoordinated) homology domain; Munc13 proteins constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3) with homology to Caenorhabditis elegans unc-13p. Munc13 proteins contain a phorbol ester-binding C1 domain and two C2 domains, which are Ca2+/phospholipid binding domains. Sequence analyses have uncovered two regions called Munc13 homology domains 1 (MHD1) and 2 (MHD2) that are arranged between two flanking C2 domains. MHD1 and MHD2 domains are present in a wide variety of proteins from Arabidopsis thaliana, C. elegans, Drosophila melanogaster, mouse, rat and human, some of which may function in a Munc13-like manner to regulate membrane trafficking. The MHD1 and MHD2 domains are predicted to be alpha-helical.


Pssm-ID: 313710  Cd Length: 140  Bit Score: 217.51  E-value: 3.88e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  1346 NVLQPIMDLLDSNLTLFAKICEKTVLKRVLKELWKLVMNTMEKTIVLPPLTDQTMIGNLLRKHGKGlekgrvklpshsdg 1425
Cdd:pfam10540    1 DVLRPLMDYLNSNLSILAQILEKTVLKRVLKELWKVVLTTAEKTLVLPPLSDAKVKGRRKSLWDNA-------------- 66
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  1426 tqmifNAAKELGQLSKLkdhMVREEAKSLTPKQCAVVELALDTIKQYFHAGGVGLKKTFLeKSPDLQSLRYALSLYTQAT 1505
Cdd:pfam10540   67 -----NSAKELGQLSKL---EISGYGRPLTPKQCAVLFAWLDTLKDFFHNGGNGLKKEFL-KSPEYQSLLYALSLYTQST 137

                   ...
gi 283837842  1506 DLL 1508
Cdd:pfam10540  138 DEL 140
DUF1041 pfam06292
Domain of Unknown Function (DUF1041); This family consists of several eukaryotic domains of ...
994-1102 1.81e-54

Domain of Unknown Function (DUF1041); This family consists of several eukaryotic domains of unknown function. Members of this family are often found in tandem repeats and co-occur with pfam00168, pfam00130 and pfam00169 domains.


Pssm-ID: 310709  Cd Length: 107  Bit Score: 188.60  E-value: 1.81e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842   994 QVVKDCVKACLNSTYEYIFNNCHELYSREYQTDPAKkgEVLPEEQGPSIKNLDFWSKLITLIVSIIEEDKNSYTPCLNQF 1073
Cdd:pfam06292    1 QVVRDCLEACALSTYQRIFENAKELYSREFQDDEAT--EDPPESLGPSLKSLEFWHRLIELCVSVLEEDKEHYAPVLNQF 78
                           90       100
                   ....*....|....*....|....*....
gi 283837842  1074 PQELNVGKISAEVMWNLFAQDMKYAMEEH 1102
Cdd:pfam06292   79 PWELNLGVESAETFWSLFAVDMDAALEEH 107
C2 pfam00168
C2 domain;
677-785 1.27e-25

C2 domain;


Pssm-ID: 306639  Cd Length: 104  Bit Score: 105.47  E-value: 1.27e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842   677 KISITVVCAQGLQAKDKTGSSDPYVTVQV--GKTKKRTKTIYGNLNPVWEENFHFECHNSSDR-IKVRVWDEDddiksrv 753
Cdd:pfam00168    2 RLRVTVIEAKNLPPKDLNGKSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAvLEIEVYDYD------- 74
                           90       100       110
                   ....*....|....*....|....*....|....
gi 283837842   754 kqRFKResDDFLGQTIIEVRTL--SGEMDVWYNL 785
Cdd:pfam00168   75 --RFGR--DDFIGEVRIPLSELdsGEVLDGWYPL 104
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
678-785 2.86e-24

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973  Cd Length: 102  Bit Score: 101.76  E-value: 2.86e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKDKTGSSDPYVTVQVGKTKK-RTKTIYGNLNPVWEENFHFECHN-SSDRIKVRVWDEDddiksrvkq 755
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKfKTKVVKNTLNPVWNETFEFPVLDpESDTLTVEVWDKD--------- 71
                          90       100       110
                  ....*....|....*....|....*....|...
gi 283837842  756 rfKRESDDFLGQTIIEVRTL---SGEMDVWYNL 785
Cdd:cd00030    72 --RFSKDDFLGEVEIPLSELldsGKEGELWLPL 102
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
677-782 1.56e-22

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577  Cd Length: 101  Bit Score: 96.40  E-value: 1.56e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842    677 KISITVVCAQGLQAKDKTGSSDPYVTVQVG---KTKKRTKTIYGNLNPVWEENFHFECHNSSDR-IKVRVWDEDddiksr 752
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVPPPELAeLEIEVYDKD------ 74
                            90       100       110
                    ....*....|....*....|....*....|..
gi 283837842    753 vkqrfKRESDDFLGQTIIEVRTL--SGEMDVW 782
Cdd:smart00239   75 -----RFGRDDFIGQVTIPLSDLllGGRHEKL 101
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
680-805 1.47e-19

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.


Pssm-ID: 176037  Cd Length: 121  Bit Score: 88.50  E-value: 1.47e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKDK------TGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHF---ECHNSSdrIKVRVWDEDDDik 750
Cdd:cd08391     5 IHVIEAQDLVAKDKfvgglvKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAvvdEVPGQE--LEIELFDEDPD-- 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 283837842  751 srvkqrfkreSDDFLGQTIIEVRTL--SGEMDVWYNLDkrtdkSAVSGaiRLHISVE 805
Cdd:cd08391    81 ----------KDDFLGRLSIDLGSVekKGFIDEWLPLE-----DVKSG--RLHLKLE 120
C1 cd00029
Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of ...
554-603 1.69e-17

Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second messenger, released by activation of Phospholipase D. Phorbol Esters (PE) can act as analogues of DAG and mimic its downstream effects in, for example, tumor promotion. Protein Kinases C are activated by DAG/PE, this activation is mediated by their N-terminal conserved region (C1). DAG/PE binding may be phospholipid dependent. C1 domains may also mediate DAG/PE signals in chimaerins (a family of Rac GTPase activating proteins), RasGRPs (exchange factors for Ras/Rap1), and Munc13 isoforms (scaffolding proteins involved in exocytosis).


Pssm-ID: 237996  Cd Length: 50  Bit Score: 80.61  E-value: 1.69e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 283837842  554 HNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADC 603
Cdd:cd00029     1 HRFVRKSFFKPTFCDVCRKSIWGLFKQGLRCSWCKVKCHKKCADKVPPSC 50
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
680-804 3.66e-17

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176023  Cd Length: 119  Bit Score: 81.58  E-value: 3.66e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDddiksrvkqrfKR 759
Cdd:cd08377     5 VKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKDIHDVLEVTVYDED-----------KD 73
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 283837842  760 ESDDFLGQTIIEVRTL-SGEMDvWYNLDKRTDKSAVSGAIRLHISV 804
Cdd:cd08377    74 KKPEFLGKVAIPLLSIkNGERK-WYALKDKKLRTRAKGSILLEMDV 118
C2 pfam00168
C2 domain;
1545-1655 4.17e-17

C2 domain;


Pssm-ID: 306639  Cd Length: 104  Bit Score: 80.82  E-value: 4.17e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  1545 HKVTVKVVAANDL-KWQTSGIFRPFIEVniigpQLSDKKRKFATKSKNNSWAPKYNESFQFTLSAdagPECYELQVCVKD 1623
Cdd:pfam00168    1 GRLRVTVIEAKNLpPKDLNGKSDPYVKV-----YLLDGKQKKKTKVVKNTLNPVWNETFTFSVPD---PENAVLEIEVYD 72
                           90       100       110
                   ....*....|....*....|....*....|..
gi 283837842  1624 YCFAREDRTVGLAVLQLRELAQRGSAACWLPL 1655
Cdd:pfam00168   73 YDRFGRDDFIGEVRIPLSELDSGEVLDGWYPL 104
C1 smart00109
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ...
554-603 6.48e-17

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.


Pssm-ID: 197519  Cd Length: 50  Bit Score: 78.66  E-value: 6.48e-17
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|
gi 283837842    554 HNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADC 603
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
678-801 2.65e-15

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005  Cd Length: 115  Bit Score: 75.68  E-value: 2.65e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKDKTGSSDPYVTVQV-GKTKKRTKTIYGNLNPVWEENFHFECHNSSDR-IKVRVWDEDddiksRVkq 755
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPVPSRVRAvLKVEVYDWD-----RG-- 73
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 283837842  756 rfkrESDDFLGQTIIEVRTLSGEMDVWYNLDKRTDKSAVSGAIRLH 801
Cdd:cd04040    74 ----GKDDLLGSAYIDLSDLEPEETTELTLPLDGQGGGKLGAVFLP 115
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
677-802 1.09e-14

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989  Cd Length: 127  Bit Score: 74.30  E-value: 1.09e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECH----NSSDRIKVRVWDEDDDIKSR 752
Cdd:cd04022     1 KLVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSdpsrLSNLVLEVYVYNDRRSGRRR 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 283837842  753 vkqrfkresdDFLGQTIIEVRTLSGEMD---VWYNLDKRTDKSAVSGAIRLHI 802
Cdd:cd04022    81 ----------SFLGRVRISGTSFVPPSEavvQRYPLEKRGLFSRVRGEIGLKV 123
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
678-806 2.41e-14

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176011  Cd Length: 126  Bit Score: 73.47  E-value: 2.41e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDddiksrvkqrf 757
Cdd:cd04046     5 TQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIKIQVWNSN----------- 73
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 283837842  758 kRESDDFLGQTIIEVRTLSGEMDVWYNLDKRTDKSAvsGAIRLHISVEI 806
Cdd:cd04046    74 -LLCDEFLGQATLSADPNDSQTLRTLPLRKRGRDAA--GEVPGTISVKV 119
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
679-811 3.16e-14

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008  Cd Length: 126  Bit Score: 73.07  E-value: 3.16e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  679 SITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKR---TKTIYGNLNPVWEENFHFEC-HNSSDRIKVRVWDE----DDDI- 749
Cdd:cd04043     4 TIRIVRAENLKADSSNGLSDPYVTLVDTNGKRRiakTRTIYDTLNPRWDEEFELEVpAGEPLWISATVWDRsfvgKHDLc 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 283837842  750 -KSRVKQRFKRESDDFLGQtiievrtlsgemDVWYNLDKRtdksavsGAIRLHISVEikGEEK 811
Cdd:cd04043    84 gRASLKLDPKRFGDDGLPR------------EIWLDLDTQ-------GRLLLRVSME--GERD 125
C1_1 pfam00130
Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the ...
554-603 3.24e-14

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.


Pssm-ID: 278556  Cd Length: 53  Bit Score: 70.93  E-value: 3.24e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 283837842   554 HNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADC 603
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPEC 50
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
677-775 3.81e-14

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974  Cd Length: 128  Bit Score: 72.96  E-value: 3.81e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCAQGL--QAKDKTGSSDPYVTVQV------GKTKKRTKTIYGN-LNPVWEENFHFECHNSS-DRIKVRVWDED 746
Cdd:cd00275     3 TLTIKIISGQQLpkPKGDKGSIVDPYVEVEIhglpadDSAKFKTKVVKNNgFNPVWNETFEFDVTVPElAFLRFVVYDED 82
                          90       100
                  ....*....|....*....|....*....
gi 283837842  747 DdiksrvkqrfkrESDDFLGQTIIEVRTL 775
Cdd:cd00275    83 S------------GDDDFLGQACLPLDSL 99
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
678-787 6.91e-14

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176022  Cd Length: 116  Bit Score: 71.90  E-value: 6.91e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDRI-KVRVWDEDddiksrvkqr 756
Cdd:cd08376     2 VTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQIlEIEVWDKD---------- 71
                          90       100       110
                  ....*....|....*....|....*....|...
gi 283837842  757 fKRESDDFLGQTIIEVRTLSGEM--DVWYNLDK 787
Cdd:cd08376    72 -TGKKDEFIGRCEIDLSALPREQthSLELELED 103
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
680-804 9.12e-14

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175990  Cd Length: 128  Bit Score: 71.69  E-value: 9.12e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKD--KTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWeeNFHFECHNSSDR---IKVRVWDEDddiksrvk 754
Cdd:cd04024     5 VHVVEAKDLAAKDrsGKGKSDPYAILSVGAQRFKTQTIPNTLNPKW--NYWCEFPIFSAQnqlLKLILWDKD-------- 74
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 283837842  755 qRFKResDDFLGQTIIEVR-----TLSGEMDVWYNL-DKRTDK-SAVSGAIRLHISV 804
Cdd:cd04024    75 -RFAG--KDYLGEFDIALEevfadGKTGQSDKWITLkSTRPGKtSVVSGEIHLQFSW 128
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
677-775 1.27e-13

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176003  Cd Length: 145  Bit Score: 71.59  E-value: 1.27e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCAQGLQAKDKTgSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDddiksrvkqR 756
Cdd:cd04038     3 LLKVRVVRGTNLAVRDFT-SSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAPLKLEVFDKD---------T 72
                          90
                  ....*....|....*....
gi 283837842  757 FKreSDDFLGQTIIEVRTL 775
Cdd:cd04038    73 FS--KDDSMGEAEIDLEPL 89
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
678-780 1.36e-13

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176006  Cd Length: 111  Bit Score: 70.75  E-value: 1.36e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKD-KTGSSDPYVTVQVGKTKK---RTKTIYGNLNPVWEENfHF-----ECHNSSDRIKVRVWDEDdd 748
Cdd:cd04041     3 LVVTIHRATDLPKADfGTGSSDPYVTASFAKFGKplySTRIIRKDLNPVWEET-WFvlvtpDEVKAGERLSCRLWDSD-- 79
                          90       100       110
                  ....*....|....*....|....*....|..
gi 283837842  749 iksrvkqrfKRESDDFLGQTIIEVRTLSGEMD 780
Cdd:cd04041    80 ---------RFTADDRLGRVEIDLKELIEDRN 102
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
686-775 5.12e-13

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176007  Cd Length: 121  Bit Score: 69.23  E-value: 5.12e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  686 QGLQAKDKTGSSDPYVTVQV-GKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDddiksrvkqrfKRESDDF 764
Cdd:cd04042    10 RNLAARDRGGTSDPYVKFKYgGKTVYKSKTIYKNLNPVWDEKFTLPIEDVTQPLYIKVFDYD-----------RGLTDDF 78
                          90
                  ....*....|.
gi 283837842  765 LGQTIIEVRTL 775
Cdd:cd04042    79 MGSAFVDLSTL 89
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
679-785 6.44e-13

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997  Cd Length: 125  Bit Score: 69.20  E-value: 6.44e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  679 SITVVCAQGLQAKDKTGSSDPYVTV-----QVGKTKKRTKTIYGNLNPVWEENFHFEcHNSSDRIKVR-----VWDEDDD 748
Cdd:cd04031    19 IVTVLQARDLPPRDDGSLRNPYVKVyllpdRSEKSKRRTKTVKKTLNPEWNQTFEYS-NVRRETLKERtlevtVWDYDRD 97
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 283837842  749 iksrvkqrfkrESDDFLGQTIIEVRT--LSGEMdVWYNL 785
Cdd:cd04031    98 -----------GENDFLGEVVIDLADalLDDEP-HWYPL 124
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
1546-1652 7.55e-13

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577  Cd Length: 101  Bit Score: 68.28  E-value: 7.55e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842   1546 KVTVKVVAANDLKW-QTSGIFRPFIEVNIIGpqlsDKKRKFATKSKNNSWAPKYNESFQFTLSAdagPECYELQVCVKDY 1624
Cdd:smart00239    1 TLTVKIISARNLPPkDKGGKSDPYVKVSLDG----DPKEKKKTKVVKNTLNPVWNETFEFEVPP---PELAELEIEVYDK 73
                            90       100
                    ....*....|....*....|....*...
gi 283837842   1625 CFAREDRTVGLAVLQLRELAQRGSAACW 1652
Cdd:smart00239   74 DRFGRDDFIGQVTIPLSDLLLGGRHEKL 101
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
644-785 9.15e-13

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176058  Cd Length: 153  Bit Score: 69.32  E-value: 9.15e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  644 LIQEIFAVTKTAHTQQMKAVKQSvldgtSKWSAKISITVVCAQGLQAKDKTGSSDPY----------VTVQVGKTK---- 709
Cdd:cd08676     1 YAQQAFGVSPEEHEALLERVREA-----EPPIFVLKVTVIEAKGLLAKDVNGFSDPYcmlgivpasrERNSEKSKKrksh 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  710 ---------------KRTKTIYGNLNPVWEENFHFECHN-SSDRIKVRVWDEDddiksrvkqrfkresDDFLGQTIIEVR 773
Cdd:cd08676    76 rkkavlkdtvpaksiKVTEVKPQTLNPVWNETFRFEVEDvSNDQLHLDIWDHD---------------DDFLGCVNIPLK 140
                         170
                  ....*....|...
gi 283837842  774 TLSGE-MDVWYNL 785
Cdd:cd08676   141 DLPSCgLDSWFKL 153
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
680-804 2.44e-12

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175999  Cd Length: 133  Bit Score: 67.38  E-value: 2.44e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKDKTGSSDPYVTVQVGKTKK-------RTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDddiksr 752
Cdd:cd04033     4 VKVLAGIDLAKKDIFGASDPYVKISLYDPDGngeidsvQTKTIKKTLNPKWNEEFFFRVNPREHRLLFEVFDEN------ 77
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  753 vkqRFKResDDFLGQT--------IIEVRTLSGEMDVWYNLDKRTDKSAVSGAIRLHISV 804
Cdd:cd04033    78 ---RLTR--DDFLGQVevplnnlpTETPGNERRYTFKDYLLRPRSSKSRVKGHLRLYMAY 132
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
677-785 2.54e-12

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992  Cd Length: 131  Bit Score: 67.29  E-value: 2.54e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCAQGLQAKDKTGSSDPYVTVQV-----GKTKKRTKTIYGNLNPVWEENFHFEChNSSD---RIKVRVWDEDdd 748
Cdd:cd04026    14 KLTVEVREAKNLIPMDPNGLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETFTFDL-KPADkdrRLSIEVWDWD-- 90
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 283837842  749 iksrvkqRFKResDDFLGQTIIEVRTLSGE-MDVWYNL 785
Cdd:cd04026    91 -------RTTR--NDFMGSLSFGVSELIKMpVDGWYKL 119
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
677-770 6.74e-12

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975  Cd Length: 134  Bit Score: 66.07  E-value: 6.74e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCAQGLQAKDKTGSSDPYVTV---QVGK--TKKRTKTIYGNLNPVWEENFHFEChnSSDRIkvrvwdEDDDIKS 751
Cdd:cd00276    15 RLTVVVLKARNLPPSDGKGLSDPYVKVsllQGGKklKKKKTSVKKGTLNPVFNEAFSFDV--PAEQL------EEVSLVI 86
                          90
                  ....*....|....*....
gi 283837842  752 RVKQRFKRESDDFLGQTII 770
Cdd:cd00276    87 TVVDKDSVGRNEVIGQVVL 105
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
681-778 1.65e-11

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000  Cd Length: 123  Bit Score: 65.00  E-value: 1.65e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  681 TVVCAQGLQAKDKTGSSDPYVTVQV-----GKTKKRTKTIYGNLNPVWEENFHFECHNSSD----RIKVRVWDEDddiks 751
Cdd:cd04035    20 TIIRAKGLKAMDANGLSDPYVKLNLlpgasKATKLRTKTVHKTRNPEFNETLTYYGITEEDiqrkTLRLLVLDED----- 94
                          90       100
                  ....*....|....*....|....*..
gi 283837842  752 rvkqrfkRESDDFLGQTIIEVRTLSGE 778
Cdd:cd04035    95 -------RFGNDFLGETRIPLKKLKPN 114
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
677-785 2.22e-11

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996  Cd Length: 127  Bit Score: 64.60  E-value: 2.22e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCAQGLQAKDKTGSSDPYVTV-----QVGKTKKRTKTIYGNLNPVWEENFHFEChnSSDRIKVRVWDEddDIKS 751
Cdd:cd04030    17 KLIVTVHKCRNLPPCDSSDIPDPYVRLyllpdKSKSTRRKTSVKKDNLNPVFDETFEFPV--SLEELKRRTLDV--AVKN 92
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 283837842  752 RVKqRFKRESdDFLGQTIIEV--RTLSGEMDVWYNL 785
Cdd:cd04030    93 SKS-FLSREK-KLLGQVLIDLsdLDLSKGFTQWYDL 126
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
678-803 4.16e-11

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176064  Cd Length: 126  Bit Score: 63.63  E-value: 4.16e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRvwdedDDIKSRVKQRF 757
Cdd:cd08682     1 VQVTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSFELPGLLSGNGNR-----ATLQLTVMHRN 75
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 283837842  758 KRESDDFLGQTIIEVRTLSGEMDV----WYNLD-KRTDKSAVSGAIRLHIS 803
Cdd:cd08682    76 LLGLDKFLGQVSIPLNDLDEDKGRrrtrWFKLEsKPGKDDKERGEIEVDIQ 126
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
685-800 5.27e-11

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176063  Cd Length: 118  Bit Score: 63.42  E-value: 5.27e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  685 AQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIY-GNLNPVWEENFHFECHNSSDRI-KVRVWDEDddiksrvkqrfkRESD 762
Cdd:cd08681    10 ARNLPNKRKLDKQDPYCVLRIGGVTKKTKTDFrGGQHPEWDEELRFEITEDKKPIlKVAVFDDD------------KRKP 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 283837842  763 DFLGQTIIEVRT--LSGEMDVWYNLdkrTDKSAVSGAIRL 800
Cdd:cd08681    78 DLIGDTEVDLSPalKEGEFDDWYEL---TLKGRYAGEVYL 114
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
684-787 7.90e-11

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176015  Cd Length: 105  Bit Score: 62.58  E-value: 7.90e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  684 CAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHN-SSDRIKVRVWDEDDDiKSrvkqrfkresd 762
Cdd:cd04050     8 SAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNpENQELEIEVKDDKTG-KS----------- 75
                          90       100
                  ....*....|....*....|....*....
gi 283837842  763 dfLGQTIIEVRTLSGE----MDVWYNLDK 787
Cdd:cd04050    76 --LGSLTLPLSELLKEpdltLDQPFPLDN 102
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
682-770 1.12e-10

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002  Cd Length: 124  Bit Score: 62.18  E-value: 1.12e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  682 VVCAQGLQAKDKTGSSDPYVTVQVGKTK--KRTKTIYGNLNPVWEENFHFECHNSSDRI-KVRVWDEDddiksrvkqrfK 758
Cdd:cd04037     6 VVRARNLQPKDPNGKSDPYLKIKLGKKKinDRDNYIPNTLNPVFGKMFELEATLPGNSIlKISVMDYD-----------L 74
                          90
                  ....*....|..
gi 283837842  759 RESDDFLGQTII 770
Cdd:cd04037    75 LGSDDLIGETVI 86
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
680-785 2.68e-10

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032  Cd Length: 125  Bit Score: 61.19  E-value: 2.68e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKDKTGSSDPYVTV---QVGKTKKRTKTIYGNLNPVWEENFHFECHnSSDRIKVR-----VWDEDddiks 751
Cdd:cd08386    20 LKILKAVELPAKDFSGTSDPFVKIyllPDKKHKLETKVKRKNLNPHWNETFLFEGF-PYEKLQQRvlylqVLDYD----- 93
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 283837842  752 rvkqRFKResDDFLGQTIIEVRT--LSGEMDVWYNL 785
Cdd:cd08386    94 ----RFSR--NDPIGEVSLPLNKvdLTEEQTFWKDL 123
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
677-803 2.86e-10

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.


Pssm-ID: 176028  Cd Length: 123  Bit Score: 61.17  E-value: 2.86e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCAQGLQAKDKTGSSDPYVTVQV--GKTKKrTKTIYGNLNPVWEENFHFECHNSSDrIKVRVWDEdddiksrvk 754
Cdd:cd08382     1 KVRLTVLCADGLAKRDLFRLPDPFAVITVdgGQTHS-TDVAKKTLDPKWNEHFDLTVGPSSI-ITIQVFDQ--------- 69
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 283837842  755 QRFKRESDDFLGQTIIEVRTLSGEMDVWY-NLD----KRTDKSAVSGAIRLHIS 803
Cdd:cd08382    70 KKFKKKDQGFLGCVRIRANAVLPLKDTGYqRLDlrklKKSDNLSVRGKIVVSLS 123
C2 pfam00168
C2 domain;
3-99 3.69e-10

C2 domain;


Pssm-ID: 306639  Cd Length: 104  Bit Score: 60.40  E-value: 3.69e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842     3 LLCVGVKKAKF---DGAQEKFNTYVTLKV---QNVKSTTIAVRGSQPSWEQDFMFEI-NRLDLGLTVEVWNKG-LIWDTM 74
Cdd:pfam00168    2 RLRVTVIEAKNlppKDLNGKSDPYVKVYLldgKQKKKTKVVKNTLNPVWNETFTFSVpDPENAVLEIEVYDYDrFGRDDF 81
                           90       100
                   ....*....|....*....|....*
gi 283837842    75 VGTVWIPLRTIRQSneEGPGEWLTL 99
Cdd:pfam00168   82 IGEVRIPLSELDSG--EVLDGWYPL 104
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
676-747 4.32e-10

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175998  Cd Length: 127  Bit Score: 60.74  E-value: 4.32e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 283837842  676 AKISITVVCAQGLQAkDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHN--SSDRIKVRVWDEDD 747
Cdd:cd04032    28 ATLTVTVLRATGLWG-DYFTSTDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDFGSVElsPGGKLRFEVWDRDN 100
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
678-796 8.60e-10

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057  Cd Length: 137  Bit Score: 60.08  E-value: 8.60e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKdKTGSSDPYVTVQVGKTK----KRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDDDI-KSR 752
Cdd:cd08675     1 LSVRVLECRDLALK-SNGTCDPFARVTLNYSSktdtKRTKVKKKTNNPRFDEAFYFELTIGFSYEKKSFKVEEEDLeKSE 79
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 283837842  753 VKQRFKRES----DDFLGQTIIEVRTL--SGEMDVWYNLDKRTDKSAVSG 796
Cdd:cd08675    80 LRVELWHASmvsgDDFLGEVRIPLQGLqqAGSHQAWYFLQPREAPGTRSS 129
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
1547-1655 9.63e-10

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973  Cd Length: 102  Bit Score: 59.00  E-value: 9.63e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1547 VTVKVVAANDLKWQ-TSGIFRPFIEVNIigpqlsDKKRKFATKSKNNSWAPKYNESFQFTLSadaGPECYELQVCVKDYC 1625
Cdd:cd00030     1 LRVTVIEARNLPAKdLNGKSDPYVKVSL------GGKQKFKTKVVKNTLNPVWNETFEFPVL---DPESDTLTVEVWDKD 71
                          90       100       110
                  ....*....|....*....|....*....|.
gi 283837842 1626 FAREDRTVGLAVLQLRELAQRG-SAACWLPL 1655
Cdd:cd00030    72 RFSKDDFLGEVEIPLSELLDSGkEGELWLPL 102
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
678-782 1.30e-09

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050  Cd Length: 136  Bit Score: 59.35  E-value: 1.30e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKDKTGSSDPYVTVQV---GK--TKKRTKTIYGNLNPVWEENFHFEChnSSDRIK-----VRVWDEDd 747
Cdd:cd08405    17 ITVNIIKARNLKAMDINGTSDPYVKVWLmykDKrvEKKKTVIKKRTLNPVFNESFIFNI--PLERLRettliITVMDKD- 93
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 283837842  748 diksrvkqRFKResDDFLGQTIIEVRTLSGEMDVW 782
Cdd:cd08405    94 --------RLSR--NDLIGKIYLGWKSGGLELKHW 118
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
677-796 1.45e-09

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977  Cd Length: 148  Bit Score: 59.33  E-value: 1.45e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCAQGLQAKDktGSSDPYVTVQV----GKTK-KRTKTIYGNLNPVWEENFHFECHNSSDRIK--VRVWDEDDDi 749
Cdd:cd04010     1 KLSVRVIECSDLALKN--GTCDPYASVTLiysnKKQDtKRTKVKKKTNNPQFDEAFYFDVTIDSSPEKkqFEMPEEDAE- 77
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 283837842  750 KSRVKQRFKRES----DDFLGQTIIEVRTLSGEMDV---WYNLDKRTDKSAVSG 796
Cdd:cd04010    78 KLELRVDLWHASmgggDVFLGEVRIPLRGLDLQAGShqaWYFLQPREEKSTPPG 131
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
679-749 2.72e-09

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.


Pssm-ID: 176001  Cd Length: 119  Bit Score: 58.04  E-value: 2.72e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 283837842  679 SITVVCAQGLQAKDKTGSSDPYVTVQVGKT---KKRTKTIYGNLNPVWEENFHFECHNSSDRI-KVRVWDED---DDI 749
Cdd:cd04036     3 TVRVLRATNITKGDLLSTPDCYVELWLPTAsdeKKRTKTIKNSINPVWNETFEFRIQSQVKNVlELTVMDEDyvmDDH 80
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
682-804 3.53e-09

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175982  Cd Length: 158  Bit Score: 58.08  E-value: 3.53e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  682 VVCAQGLQAKDKT------GSSDPYVTVQVGKTK-KRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDedddiksrvk 754
Cdd:cd04015    37 VGCSEPTLKRPSShrhvgkITSDPYATVDLAGARvARTRVIENSENPVWNESFHIYCAHYASHVEFTVKD---------- 106
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 283837842  755 qrfkresDDFLGQTIIEV------RTLSGE-MDVWYNLDKRTDKSAVSGAiRLHISV 804
Cdd:cd04015   107 -------NDVVGAQLIGRayipveDLLSGEpVEGWLPILDSNGKPPKPGA-KIRVSL 155
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
678-744 7.77e-09

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978  Cd Length: 111  Bit Score: 56.43  E-value: 7.77e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283837842  678 ISITVVCAQGLQakdkTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDR-----IKVRVWD 744
Cdd:cd04011     6 VRVRVIEARQLV----GGNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHESPDElfdkiIKISVYD 73
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
681-803 1.16e-08

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175991  Cd Length: 123  Bit Score: 56.34  E-value: 1.16e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  681 TVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDR-IKVRVWDEddDIKSRvkqrfkr 759
Cdd:cd04025     5 HVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSpLSVEVWDW--DLVSK------- 75
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 283837842  760 esDDFLGQTIIEVRTL--SGEMDVWYNL--DKRTDKSAVS--GAIRLHIS 803
Cdd:cd04025    76 --NDFLGKVVFSIQTLqqAKQEEGWFRLlpDPRAEEESGGnlGSLRLKVR 123
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
680-802 1.46e-08

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371  Cd Length: 1227  Bit Score: 59.77  E-value: 1.46e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKDKTGSSDPYVTVQV-GKTKKRTKTIYGNLNPVWEENFHFECHN-SSDRIKVRVWDEDDDiksrvkqrf 757
Cdd:COG5038  1044 IMLRSGENLPSSDENGYSDPFVKLFLnEKSVYKTKVVKKTLNPVWNEEFTIEVLNrVKDVLTINVNDWDSG--------- 1114
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 283837842  758 krESDDFLGQTIIEVRTLSGEMDVWYNLdKRTDKSAVSGAIRLHI 802
Cdd:COG5038  1115 --EKNDLLGTAEIDLSKLEPGGTTNSNI-PLDGKTFIVLDGTLHP 1156
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
3-93 1.68e-08

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577  Cd Length: 101  Bit Score: 55.57  E-value: 1.68e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842      3 LLCVGVKKAKF---DGAQEKFNTYVTLKVQN----VKSTTIAVRGSQPSWEQDFMFEINRLDLG-LTVEVWNKGLIW-DT 73
Cdd:smart00239    1 TLTVKIISARNlppKDKGGKSDPYVKVSLDGdpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAeLEIEVYDKDRFGrDD 80
                            90       100
                    ....*....|....*....|
gi 283837842     74 MVGTVWIPLRTIRQSNEEGP 93
Cdd:smart00239   81 FIGQVTIPLSDLLLGGRHEK 100
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
1546-1647 1.77e-08

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974  Cd Length: 128  Bit Score: 55.63  E-value: 1.77e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1546 KVTVKVVAANDL---KWQTSGIFRPFIEVNIIGPQLSDKKrKFATKS-KNNSWAPKYNESFQFTLSAdagPECYELQVCV 1621
Cdd:cd00275     3 TLTIKIISGQQLpkpKGDKGSIVDPYVEVEIHGLPADDSA-KFKTKVvKNNGFNPVWNETFEFDVTV---PELAFLRFVV 78
                          90       100
                  ....*....|....*....|....*.
gi 283837842 1622 KDYCFAReDRTVGLAVLQLRELaQRG 1647
Cdd:cd00275    79 YDEDSGD-DDFLGQACLPLDSL-RQG 102
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
678-811 2.13e-08

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371  Cd Length: 1227  Bit Score: 59.39  E-value: 2.13e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKDKT--GSSDPYVTVQV-GKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDDdiksrvk 754
Cdd:COG5038   438 VEVKIKSAEGLKKSDSTinGTVDPYITVTFsDRVIGKTRVKKNTLNPVWNETFYILLNSFTDPLNLSLYDFNS------- 510
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283837842  755 qrfkRESDDFLGQTIIEVRTL---SGEMDVWYNLdKRTDKSA--VSGAIRLHISVEIKGEEK 811
Cdd:COG5038   511 ----FKSDKVVGSTQLDLALLhqnPVKKNELYEF-LRNTKNVgrLTYDLRFFPVIEDKKELK 567
C2A_Rasal1_RasA4 cd04054
C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...
680-804 2.45e-08

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176018  Cd Length: 121  Bit Score: 55.21  E-value: 2.45e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKDKTGSSDPYVTVQV-GKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDddiksrvkqrfK 758
Cdd:cd04054     4 IRIVEGKNLPAKDITGSSDPYCIVKVdNEVIIRTATVWKTLNPFWGEEYTVHLPPGFHTVSFYVLDED-----------T 72
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 283837842  759 RESDDFLGQTIIEVRTLSGE---MDVWYNLDKRTDKSAVSGAIRLHISV 804
Cdd:cd04054    73 LSRDDVIGKVSLTREVISAHprgIDGWMNLTEVDPDEEVQGEIHLELSV 121
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
685-808 2.47e-08

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176010  Cd Length: 120  Bit Score: 55.29  E-value: 2.47e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  685 AQGLQAKDKTGSSDPYVTVQV-GKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDDDIKSRvkqrfkresdd 763
Cdd:cd04045    10 ANDLKNLEGVGKIDPYVRVLVnGIVKGRTVTISNTLNPVWDEVLYVPVTSPNQKITLEVMDYEKVGKDR----------- 78
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 283837842  764 FLGQTIIEVRTLSGEMDVWYNLDKRTDKSAVSgaiRLHISVEIKG 808
Cdd:cd04045    79 SLGSVEINVSDLIKKNEDGKYVEYDDEEERLK---RLLSLKGVKG 120
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
675-785 2.48e-08

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031  Cd Length: 124  Bit Score: 55.35  E-value: 2.48e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  675 SAKISITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKR---TKTIYGNLNPVWEENFHF-----ECHNSSdrIKVRVWDED 746
Cdd:cd08385    15 SNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKKkfeTKVHRKTLNPVFNETFTFkvpysELGNKT--LVFSVYDFD 92
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 283837842  747 ddiksrvkqRFKREsdDFLGQTIIEVRT--LSGEMDVWYNL 785
Cdd:cd08385    93 ---------RFSKH--DLIGEVRVPLLTvdLGHVTEEWRDL 122
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
677-793 2.55e-08

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176013  Cd Length: 120  Bit Score: 55.27  E-value: 2.55e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCaQGLQAKDKTGSSDPYVTV--QVGKTKK-----RTKTIYGNLNPVWEE----NFHFEChnsSDRIKVRVWDE 745
Cdd:cd04048     2 KVELSISC-RNLLDKDVLSKSDPFVVVyvKTGGSGQwveigRTEVIKNNLNPDFVTtftvDYYFEE---VQKLRFEVYDV 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 283837842  746 DDDIKsrvkqrfKRESDDFLGQTIIEVRTLSGEMDVWYNLDKRTDKSA 793
Cdd:cd04048    78 DSKSK-------DLSDHDFLGEAECTLGEIVSSPGQKLTLPLKGGKGK 118
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
675-782 2.79e-08

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047  Cd Length: 136  Bit Score: 55.10  E-value: 2.79e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  675 SAKISITVVCAQGLQAKDKTGSSDPYVTVQV---GKTKKRTKTI--YGNLNPVWEENFHFEChnSSDRIK-----VRVWD 744
Cdd:cd08402    14 AGKLTVVILEAKNLKKMDVGGLSDPYVKIHLmqnGKRLKKKKTTikKRTLNPYYNESFSFEV--PFEQIQkvhliVTVLD 91
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 283837842  745 EDddiksrvkqrfKRESDDFLGQTIIEVRTLSGEMDVW 782
Cdd:cd08402    92 YD-----------RIGKNDPIGKVVLGCNATGAELRHW 118
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
4-99 7.09e-08

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973  Cd Length: 102  Bit Score: 53.61  E-value: 7.09e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842    4 LCVGVKKAKFDGAQEKF---NTYVTLKVQNVKS--TTIAVRGSQPSWEQDFMFEINRLDLG-LTVEVWNKGLIW-DTMVG 76
Cdd:cd00030     1 LRVTVIEARNLPAKDLNgksDPYVKVSLGGKQKfkTKVVKNTLNPVWNETFEFPVLDPESDtLTVEVWDKDRFSkDDFLG 80
                          90       100
                  ....*....|....*....|...
gi 283837842   77 TVWIPLRTIRQSNEEGPgEWLTL 99
Cdd:cd00030    81 EVEIPLSELLDSGKEGE-LWLPL 102
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
679-802 1.22e-07

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176029  Cd Length: 117  Bit Score: 53.04  E-value: 1.22e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  679 SITVVCAQGLQAKdktGSSDPYVTV-----QVGKTKKRTKtiygnLNPVWEENFHFE---CHNSSDRIKVRVWDED--DD 748
Cdd:cd08383     3 RLRILEAKNLPSK---GTRDPYCTVsldqvEVARTKTVEK-----LNPFWGEEFVFDdppPDVTFFTLSFYNKDKRskDR 74
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 283837842  749 IKSRVKQRFKRESddfLGQTIievrtlsgemDVWYNLDKRTDKSAVSGAIRLHI 802
Cdd:cd08383    75 DIVIGKVALSKLD---LGQGK----------DEWFPLTPVDPDSEVQGSVRLRA 115
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
677-772 1.30e-07

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.


Pssm-ID: 176021  Cd Length: 136  Bit Score: 53.16  E-value: 1.30e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFEchnssdrikvrVWD-EDDDIKSRVKQ 755
Cdd:cd08375    16 RLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFF-----------VKDlEQDVLCITVFD 84
                          90
                  ....*....|....*..
gi 283837842  756 RFKRESDDFLGQTIIEV 772
Cdd:cd08375    85 RDFFSPDDFLGRTEIRV 101
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
678-782 4.32e-07

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176033  Cd Length: 124  Bit Score: 51.25  E-value: 4.32e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKDKTGSSDPYVTVQV---GKTKKRTKTIYGNLNPVWEENFHFECH-NSSDRIKVRVWDEDDDIKSRv 753
Cdd:cd08387    18 LNVKLIQARNLQPRDFSGTADPYCKVRLlpdRSNTKQSKIHKKTLNPEFDESFVFEVPpQELPKRTLEVLLYDFDQFSR- 96
                          90       100       110
                  ....*....|....*....|....*....|.
gi 283837842  754 kqrfkresDDFLGQTIIEVR--TLSGEMDVW 782
Cdd:cd08387    97 --------DECIGVVELPLAevDLSEKLDLW 119
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
683-772 6.25e-07

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.


Pssm-ID: 176014  Cd Length: 124  Bit Score: 50.79  E-value: 6.25e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  683 VCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYG-NLNPVWEENFHFECHNSSdrikvrvWDEDDDIKSRVKQRFKRES 761
Cdd:cd04049     8 ISAKGLQDTDFLGKIDPYVIIQCRTQERKSKVAKGdGRNPEWNEKFKFTVEYPG-------WGGDTKLILRIMDKDNFSD 80
                          90
                  ....*....|.
gi 283837842  762 DDFLGQTIIEV 772
Cdd:cd04049    81 DDFIGEATIHL 91
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
678-775 8.21e-07

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009  Cd Length: 124  Bit Score: 50.63  E-value: 8.21e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKDK-TGSSDPYVTVQVGKTKK--RTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDDDIKsrvk 754
Cdd:cd04044     4 LAVTIKSARGLKGSDIiGGTVDPYVTFSISNRRElaRTKVKKDTSNPVWNETKYILVNSLTEPLNLTVYDFNDKRK---- 79
                          90       100
                  ....*....|....*....|.
gi 283837842  755 qrfkresDDFLGQTIIEVRTL 775
Cdd:cd04044    80 -------DKLIGTAEFDLSSL 93
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
1546-1638 1.01e-06

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975  Cd Length: 134  Bit Score: 50.27  E-value: 1.01e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1546 KVTVKVVAANDLKWQT-SGIFRPFIEVNIIGPQLSDKKRKfaTKSKNNSWAPKYNESFQFTLSADAGPECyELQVCVKDY 1624
Cdd:cd00276    15 RLTVVVLKARNLPPSDgKGLSDPYVKVSLLQGGKKLKKKK--TSVKKGTLNPVFNEAFSFDVPAEQLEEV-SLVITVVDK 91
                          90
                  ....*....|....
gi 283837842 1625 CFAREDRTVGLAVL 1638
Cdd:cd00276    92 DSVGRNEVIGQVVL 105
C2D_MCTP_PRT_plant cd08379
C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
687-776 1.35e-06

C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 176025  Cd Length: 126  Bit Score: 49.71  E-value: 1.35e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  687 GLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDedddiKSRVKQRFKRESDDFLG 766
Cdd:cd08379    14 VLRAKDGRGSTDAYCVAKYGPKWVRTRTVEDSSNPRWNEQYTWPVYDPCTVLTVGVFD-----NSQSHWKEAVQPDVLIG 88
                          90
                  ....*....|
gi 283837842  767 QTIIEVRTLS 776
Cdd:cd08379    89 KVRIRLSTLE 98
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
681-803 1.95e-06

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019  Cd Length: 127  Bit Score: 49.17  E-value: 1.95e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  681 TVVCAQGLQAKdkTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEEnfHFECHNSSdrikvrVWDEDDDIKSRVKQRFKRE 760
Cdd:cd08373     1 LVVSLKNLPGL--KGKGDRIAKVTFRGVKKKTRVLENELNPVWNE--TFEWPLAG------SPDPDESLEIVVKDYEKVG 70
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 283837842  761 SDDFLGQTIIEVRTL--SGEMDVWYNLdKRTDKSAVSGAIRLHIS 803
Cdd:cd08373    71 RNRLIGSATVSLQDLvsEGLLEVTEPL-LDSNGRPTGATISLEVS 114
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
685-793 2.64e-06

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 175984  Cd Length: 135  Bit Score: 49.08  E-value: 2.64e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  685 AQGLQAKDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENF---HFECHNSSDRIK-------VRVWDEDDDIKsrvk 754
Cdd:cd04017    10 ARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLifdEVELYGSPEEIAqnpplvvVELFDQDSVGK---- 85
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 283837842  755 qrfkresDDFLGQTII--EVRtLSGEMDV-----WYNLDKRTDKSA 793
Cdd:cd04017    86 -------DEFLGRSVAkpLVK-LDLEEDFppklqWFPIYKGGQSAG 123
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
680-766 3.79e-06

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030  Cd Length: 133  Bit Score: 48.50  E-value: 3.79e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKDKTGSSDPYVTVQV-----GKTKKRTKTIYGNLNPVWEENFHFEChNSSDRIK----VRVWDEDddik 750
Cdd:cd08384    17 VGIIRCVNLAAMDANGYSDPFVKLYLkpdagKKSKHKTQVKKKTLNPEFNEEFFYDI-KHSDLAKktleITVWDKD---- 91
                          90
                  ....*....|....*.
gi 283837842  751 srvkqrfKRESDDFLG 766
Cdd:cd08384    92 -------IGKSNDYIG 100
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
677-730 4.79e-06

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976  Cd Length: 133  Bit Score: 48.00  E-value: 4.79e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 283837842  677 KISITVVCAQGLQAKDKTGSSDPYVTVQV-------GKTKKRTKTIYGNLNPVWEENFHFE 730
Cdd:cd04009    17 SLRVEILNARNLLPLDSNGSSDPFVKVELlprhlfpDVPTPKTQVKKKTLFPLFDESFEFN 77
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
678-753 1.21e-05

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070  Cd Length: 110  Bit Score: 46.92  E-value: 1.21e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQAKDKT-GSSDPYVTVQVGKTKKRTKTIYGNLNPVWE-ENFHFECHN---SSDRIKVRVWDED----DD 748
Cdd:cd08688     1 LKVRVVAARDLPVMDRSsDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNsEWFRFEVDDeelQDEPLQIRVMDHDtysaND 80

                  ....*
gi 283837842  749 IKSRV 753
Cdd:cd08688    81 AIGKV 85
C2C_MCTP_PRT_plant cd04019
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
680-817 1.38e-05

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175986  Cd Length: 150  Bit Score: 46.89  E-value: 1.38e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKDKTGSSDPYVTVQVGKTKKRTKT-IYGNLNPVWEENFHFechnssdrikvrVWDE--DDDIKSRVKQR 756
Cdd:cd04019     4 VTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPsQTRNGNPSWNEELMF------------VAAEpfEDHLILSVEDR 71
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 283837842  757 FKRESDDFLGQTIIEVRTLSGEMDV------WYNL------DKRTDKSAVSGAIRLHISVEikgeekvAPYHV 817
Cdd:cd04019    72 VGPNKDEPLGRAVIPLNDIERRVDDrpvpsrWFSLerpggaMEQKKKRKFASRIHLRLCLD-------GGYHV 137
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
680-776 1.49e-05

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176060  Cd Length: 126  Bit Score: 46.59  E-value: 1.49e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLQAKdkTGSSDPYVTVQVGK--TKKRTKTIYGNLNPVWEENFHFECHNSSDRIKVRVWDEDddiksrvkqrf 757
Cdd:cd08678     3 VKNIKANGLSEA--AGSSNPYCVLEMDEppQKYQSSTQKNTSNPFWDEHFLFELSPNSKELLFEVYDNG----------- 69
                          90
                  ....*....|....*....
gi 283837842  758 KRESDDFLGQTIIEVRTLS 776
Cdd:cd08678    70 KKSDSKFLGLAIVPFDELR 88
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
675-771 1.56e-05

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175988  Cd Length: 125  Bit Score: 46.50  E-value: 1.56e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  675 SAKISITVVCAQgLQAKDKTGSSDPYVTVQV-GKTKKRTKTIYGNLNPVWEENFHFECHNSSdRIKVRVWDedddiksrv 753
Cdd:cd04021     1 KSQLQITVESAK-LKSNSKSFKPDPYVEVTVdGQPPKKTEVSKKTSNPKWNEHFTVLVTPQS-TLEFKVWS--------- 69
                          90
                  ....*....|....*...
gi 283837842  754 KQRFKResDDFLGQTIIE 771
Cdd:cd04021    70 HHTLKA--DVLLGEASLD 85
C2_NEDL1-like cd08691
C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 ...
678-803 2.10e-05

C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1)) is a newly identified HECT-type E3 ubiquitin protein ligase highly expressed in favorable neuroblastomas. In vertebrates it is found primarily in neuronal tissues, including the spinal cord. NEDL1 is thought to normally function in the quality control of cellular proteins by eliminating misfolded proteins. This is thought to be accomplished via a mechanism analogous to that of ER-associated degradation by forming tight complexes and aggregating misfolded proteins that have escaped ubiquitin-mediated degradation. NEDL1, is composed of a C2 domain, two WW domains, and a ubiquitin ligase Hect domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176073  Cd Length: 137  Bit Score: 46.24  E-value: 2.10e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  678 ISITVVCAQGLQaKDKTGSSDPYV--TVQVGK-----------TKKRTKTIYGNLNPVWE-ENFHFECHnSSDRIKVRVW 743
Cdd:cd08691     3 FSLSGLQARNLK-KGMFFNPDPYVkiSIQPGKrhifpalphhgQECRTSIVENTINPVWHrEQFVFVGL-PTDVLEIEVK 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 283837842  744 DEDDdiKSRvkQRFKResddFLGQTIIEV-----RTLSGEMDVWYNLDKRTDKSAVSGAIRLHIS 803
Cdd:cd08691    81 DKFA--KSR--PIIRR----FLGKLSIPVqrlleRHAIGDQELSYTLGRRTPTDHVSGQLTFRFE 137
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
680-767 2.13e-05

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176024  Cd Length: 121  Bit Score: 46.15  E-value: 2.13e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  680 ITVVCAQGLqakdKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFEcHNS--SDRIKVRVWDEDDDIksrvkqrf 757
Cdd:cd08378     4 VRVVKARGL----PANSNDPVVEVKLGNYKGSTKAIERTSNPEWNQVFAFS-KDRlqGSTLEVSVWDKDKAK-------- 70
                          90
                  ....*....|
gi 283837842  758 kresDDFLGQ 767
Cdd:cd08378    71 ----DDFLGG 76
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
675-791 3.34e-05

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176056  Cd Length: 123  Bit Score: 45.32  E-value: 3.34e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  675 SAKISITVVCAQGLQAKD-KTGSSDPYVTVQV-----GKTKKRTKTIYGNLNPVWEENFHFECHNS---SDRIKVRVWDE 745
Cdd:cd08521    13 TGSLEVHIKECRNLAYADeKKKRSNPYVKVYLlpdksKQSKRKTSVKKNTTNPVFNETLKYHISKSqleTRTLQLSVWHH 92
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 283837842  746 DddiksrvkqRFKResDDFLGQTIIevrtlsgEMDVWyNLDKRTDK 791
Cdd:cd08521    93 D---------RFGR--NTFLGEVEI-------PLDSW-DLDSQQSE 119
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
685-766 3.83e-05

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987  Cd Length: 162  Bit Score: 45.78  E-value: 3.83e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  685 AQGLQAKDKTGSSDPYVTVQV-----GKTKKRTKTIYGNLNPVWEENFHFECHNSSDR----IKVRVWDEDddiksrvkq 755
Cdd:cd04020    36 AKNLPALKSGGTSDSFVKCYLlpdksKKSKQKTPVVKKSVNPVWNHTFVYDGVSPEDLsqacLELTVWDHD--------- 106
                          90
                  ....*....|.
gi 283837842  756 RFKreSDDFLG 766
Cdd:cd04020   107 KLS--SNDFLG 115
C2_PKC_epsilon cd04014
C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The ...
698-808 3.96e-05

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175981  Cd Length: 132  Bit Score: 45.34  E-value: 3.96e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  698 DPYVTVQV-----GKTKKRTKTiygnLNPVWEENFHFECHNSSDrIKVRVWdEDDDIKsrvkqrfkreSDDFLGQTIIEV 772
Cdd:cd04014    36 DPYVSIDVddthiGKTSTKPKT----NSPVWNEEFTTEVHNGRN-LELTVF-HDAAIG----------PDDFVANCTISF 99
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 283837842  773 RTL----SGEMDVWYNLDKrtdksavsgAIRLHISVEIKG 808
Cdd:cd04014   100 EDLiqrgSGSFDLWVDLEP---------QGKLHVKIELKG 130
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
691-780 4.25e-05

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985  Cd Length: 151  Bit Score: 45.32  E-value: 4.25e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  691 KDKTGSSDPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFE------ChnssDRIKVRVWDEDddiksrvkqrfKRESDDF 764
Cdd:cd04018    29 GEKKELVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPemfpplC----ERIKIQIRDWD-----------RVGNDDV 93
                          90
                  ....*....|....*.
gi 283837842  765 LGQTIIEVRTLSGEMD 780
Cdd:cd04018    94 IGTHFIDLSKISNSGD 109
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
675-730 4.62e-05

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048  Cd Length: 134  Bit Score: 45.19  E-value: 4.62e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 283837842  675 SAKISITVVCAQGLQAKDKTGSSDPYVTVQV---GK-TKKRTKTIYGN-LNPVWEENFHFE 730
Cdd:cd08403    13 AGRLTLTIIKARNLKAMDITGFSDPYVKVSLmceGRrLKKKKTSVKKNtLNPTYNEALVFD 73
C2A_Synaptotagmin-14_16 cd08389
C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
677-786 5.48e-05

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176035  Cd Length: 124  Bit Score: 44.92  E-value: 5.48e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVCAQGLQAKDKTGSSdpyvTVQV-------GKTKKRTKTIYGNlNPVWEENFHFECHNSSD----RIKVRVWde 745
Cdd:cd08389    17 KLTVTVIRAQDIPTKDRGGAS----SWQVhlvllpsKKQRAKTKVQRGP-NPVFNETFTFSRVEPEElnnmALRFRLY-- 89
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 283837842  746 dddiksrVKQRFKRESddFLGQTIIEVRTLS--GEMDVWYNLD 786
Cdd:cd08389    90 -------GVERMRKER--LIGEKVVPLSQLNleGETTVWLTLE 123
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
675-770 7.30e-05

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176055  Cd Length: 135  Bit Score: 44.50  E-value: 7.30e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  675 SAKISITVVCAQGLQAKDKTGSSDPYVTVQ------VGKTKKrTKTIYGNLNPVWEENFHF-----ECHNSSdrIKVRVW 743
Cdd:cd08410    13 AGRLNVDIIRAKQLLQTDMSQGSDPFVKIQlvhglkLIKTKK-TSCMRGTIDPFYNESFSFkvpqeELENVS--LVFTVY 89
                          90       100
                  ....*....|....*....|....*..
gi 283837842  744 DEddDIKSrvkqrfkreSDDFLGQTII 770
Cdd:cd08410    90 GH--NVKS---------SNDFIGRIVI 105
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
22-83 8.66e-05

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176024  Cd Length: 121  Bit Score: 44.23  E-value: 8.66e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 283837842   22 TYVTLKVQNVKSTTIAV-RGSQPSWEQDFMFEINRLDLG-LTVEVWNKGLIWDTMVGTVW-----IPLR 83
Cdd:cd08378    19 PVVEVKLGNYKGSTKAIeRTSNPEWNQVFAFSKDRLQGStLEVSVWDKDKAKDDFLGGVCfdlseVPTR 87
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
680-729 9.97e-05

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176034  Cd Length: 128  Bit Score: 43.88  E-value: 9.97e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 283837842  680 ITVVCAQGLQAKD-KTGSSDPYVTVQVGKTKK---RTKTIYGNLNPVWEENFHF 729
Cdd:cd08388    20 VNIIECRDLPAMDeQSGTSDPYVKLQLLPEKEhkvKTRVLRKTRNPVYDETFTF 73
rpsP PRK14520
30S ribosomal protein S16; Provisional
364-427 2.16e-04

30S ribosomal protein S16; Provisional


Pssm-ID: 184724  Cd Length: 155  Bit Score: 43.14  E-value: 2.16e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 283837842  364 VAVAEPKDFKRiSLPPAAPGKEDKAPVAPTEAPDMAKVAPKPATPDKVPAAEQIPEAEPPKDEE 427
Cdd:PRK14520   93 LKVAEPKPSKL-ELFNAALAEADGGPTAEATTPKKKKAAAEAAAAEAAAPAAEAAAAAAAEEEA 155
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
680-730 2.37e-04

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049  Cd Length: 136  Bit Score: 42.80  E-value: 2.37e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 283837842  680 ITVVC--AQGLQAKDKTGSSDPYVTVQVGK-----TKKRTKTIYGNLNPVWEENFHFE 730
Cdd:cd08404    17 LTVVVlkARHLPKMDVSGLADPYVKVNLYYgkkriSKKKTHVKKCTLNPVFNESFVFD 74
C2_Tollip cd04016
C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 ...
677-803 3.31e-04

C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 receptor (IL-1R) signaling pathway. Tollip is proposed to link serine/threonine kinase IRAK to IL-1Rs as well as inhibiting phosphorylation of IRAK. There is a single C2 domain present in Tollip. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175983  Cd Length: 121  Bit Score: 42.32  E-value: 3.31e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  677 KISITVVcaqglQAK--DKTGSS--DPYVTVQVGKTKKRTKTIY-GNLNPVWEENFHFECHNSSDRIKVRVWDEdddiks 751
Cdd:cd04016     3 RLSITVV-----QAKlvKNYGLTrmDPYCRIRVGHAVYETPTAYnGAKNPRWNKTIQCTLPEGVDSIYIEIFDE------ 71
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 283837842  752 rvkQRFKreSDDFLGQTIIEVR--TLSGE-MDVWYNLDKRT--DKsavSGAIRLHIS 803
Cdd:cd04016    72 ---RAFT--MDERIAWTHITIPesVFNGEtLDDWYSLSGKQgeDK---EGMINLVFS 120
C2A_Munc13 cd08394
C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
685-786 8.15e-04

C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176040  Cd Length: 127  Bit Score: 41.28  E-value: 8.15e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  685 AQGLQAKDKTgssdpYVTVQVGKTKKRTKTIYGNLnPVWEENFHFECHNSSDRIKVRVWDedddiKSRVKqrfkresDDF 764
Cdd:cd08394    13 LDGAPDKFNT-----YVTLKVQNVKSTTIAVRGSQ-PCWEQDFMFEINRLDLGLVIELWN-----KGLIW-------DTL 74
                          90       100
                  ....*....|....*....|....*....
gi 283837842  765 LGQTIIEVRTL-------SGEmdvWYNLD 786
Cdd:cd08394    75 VGTVWIPLSTIrqsneegPGE---WLTLD 100
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
1547-1658 1.13e-03

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057  Cd Length: 137  Bit Score: 40.82  E-value: 1.13e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1547 VTVKVVAANDLKWQTSGIFRPFIEVNIIGPQLSDKKRkfaTKSKNNSWAPKYNESFQFTLSADAGPECYELQVCVKDYCF 1626
Cdd:cd08675     1 LSVRVLECRDLALKSNGTCDPFARVTLNYSSKTDTKR---TKVKKKTNNPRFDEAFYFELTIGFSYEKKSFKVEEEDLEK 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 283837842 1627 AR------------EDRTVGLAVLQLRELAQRGSAACWLPLGRR 1658
Cdd:cd08675    78 SElrvelwhasmvsGDDFLGEVRIPLQGLQQAGSHQAWYFLQPR 121
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
677-735 2.26e-03

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176016  Cd Length: 125  Bit Score: 39.91  E-value: 2.26e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 283837842  677 KISITVVCAQGLQAKDKTGSSDPYVTVQV-GKTKKRTKTIY-GNLNPVWEENFHFECHNSS 735
Cdd:cd04051     1 TLEITIISAEDLKNVNLFGKMKVYAVVWIdPSHKQSTPVDRdGGTNPTWNETLRFPLDERL 61
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
703-800 2.37e-03

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176045  Cd Length: 126  Bit Score: 39.66  E-value: 2.37e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  703 VQVGKTKKRTktiygNLNPVWEENFHFEchnssdrikvrvwDEDDDIKS---RVKQRFKRESDDFLGQTIIEVRTLSG-- 777
Cdd:cd08400    33 VKVARTKVRE-----GPNPVWSEEFVFD-------------DLPPDVNSftiSLSNKAKRSKDSEIAEVTVQLSKLQNgq 94
                          90       100
                  ....*....|....*....|....
gi 283837842  778 EMDVWYNLDKRTDKSAVS-GAIRL 800
Cdd:cd08400    95 ETDEWYPLSSASPLKGGEwGSLRI 118
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
698-775 3.31e-03

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176004  Cd Length: 108  Bit Score: 39.16  E-value: 3.31e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842  698 DPYVTVQVGKTKKRTKTIYGNLNPVWEENFHFEC--HNSSDRIKVRVWDEDddiksrvkqrfKRESDDFLGQTIIEVRTL 775
Cdd:cd04039    27 DPFVIISFGRRVFRTSWRRHTLNPVFNERLAFEVypHEKNFDIQFKVLDKD-----------KFSFNDYVATGSLSVQEL 95
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
1546-1627 3.69e-03

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977  Cd Length: 148  Bit Score: 39.30  E-value: 3.69e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1546 KVTVKVVAANDLKwQTSGIFRPFIEVNIIGPQLSDKKRKFATKSKNNSwaPKYNESFQFTLSADAGPECYELQVCVKDYC 1625
Cdd:cd04010     1 KLSVRVIECSDLA-LKNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNN--PQFDEAFYFDVTIDSSPEKKQFEMPEEDAE 77

                  ..
gi 283837842 1626 FA 1627
Cdd:cd04010    78 KL 79
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
1584-1655 3.73e-03

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019  Cd Length: 127  Bit Score: 39.16  E-value: 3.73e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 283837842 1584 KFATKSKNNSWAPKYNESFQFTLSADAGPEcYELQVCVKDYCFAREDRTVGLAVLQLRELAQRGSAACWLPL 1655
Cdd:cd08373    27 KKKTRVLENELNPVWNETFEWPLAGSPDPD-ESLEIVVKDYEKVGRNRLIGSATVSLQDLVSEGLLEVTEPL 97
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
1547-1646 3.74e-03

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009  Cd Length: 124  Bit Score: 39.08  E-value: 3.74e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1547 VTVKVVAANDLKWQT--SGIFRPFIEVNIIGPQLSDKkrkfaTKSKNNSWAPKYNESFQFTLSADAGPecyeLQVCVKDY 1624
Cdd:cd04044     4 LAVTIKSARGLKGSDiiGGTVDPYVTFSISNRRELAR-----TKVKKDTSNPVWNETKYILVNSLTEP----LNLTVYDF 74
                          90       100
                  ....*....|....*....|..
gi 283837842 1625 CFAREDRTVGLAVLQLRELAQR 1646
Cdd:cd04044    75 NDKRKDKLIGTAEFDLSSLLQN 96
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
13-87 4.89e-03

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974  Cd Length: 128  Bit Score: 38.68  E-value: 4.89e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842   13 FDGAQEKFNTYVTLKV------QNVKSTTIAVR--GSQPSWEQDFMFEINRLDLG-LTVEVWNKGLIWDTMVGTVWIPLR 83
Cdd:cd00275    18 KGDKGSIVDPYVEVEIhglpadDSAKFKTKVVKnnGFNPVWNETFEFDVTVPELAfLRFVVYDEDSGDDDFLGQACLPLD 97

                  ....
gi 283837842   84 TIRQ 87
Cdd:cd00275    98 SLRQ 101
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
1544-1643 5.09e-03

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976  Cd Length: 133  Bit Score: 38.76  E-value: 5.09e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1544 EHKVTVKVVAANDLK-WQTSGIFRPFIEVNIIGPQL--SDKKRKFATKSKNNSwaPKYNESFQFTLSadagPECYE---- 1616
Cdd:cd04009    15 EQSLRVEILNARNLLpLDSNGSSDPFVKVELLPRHLfpDVPTPKTQVKKKTLF--PLFDESFEFNVP----PEQCSvega 88
                          90       100
                  ....*....|....*....|....*...
gi 283837842 1617 -LQVCVKDYCFAREDRTVGLAVLQLREL 1643
Cdd:cd04009    89 lLLFTVKDYDLLGSNDFEGEAFLPLNDI 116
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
1548-1604 6.68e-03

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031  Cd Length: 124  Bit Score: 38.40  E-value: 6.68e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 283837842 1548 TVKVVAANDLK-WQTSGIFRPFIEVNIigpqLSDKKRKFATKSKNNSWAPKYNESFQF 1604
Cdd:cd08385    19 TVGIIQAADLPaMDMGGTSDPYVKVYL----LPDKKKKFETKVHRKTLNPVFNETFTF 72
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
1534-1619 7.16e-03

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049  Cd Length: 136  Bit Score: 38.56  E-value: 7.16e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 283837842 1534 VELFTHPGTgeHKVTVKVVAANDL-KWQTSGIFRPFIEVNIigpqLSDKKR--KFATKSKNNSWAPKYNESFQFTLSADA 1610
Cdd:cd08404     6 LSLCYQPTT--NRLTVVVLKARHLpKMDVSGLADPYVKVNL----YYGKKRisKKKTHVKKCTLNPVFNESFVFDIPSEE 79
                          90
                  ....*....|
gi 283837842 1611 GPE-CYELQV 1619
Cdd:cd08404    80 LEDiSVEFLV 89
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.16
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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