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Conserved domains on  [gi|1333675876|ref|XP_023498208|]
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dedicator of cytokinesis protein 10 isoform X7 [Equus caballus]

Protein Classification

C2_Dock-D and DHR2_DOCK domain-containing protein( domain architecture ID 10351409)

protein containing domains PH-like, C2_Dock-D, and DHR2_DOCK

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DHR2_DOCK super family cl06123
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1469-1881 0e+00

Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins comprise a family of atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. They are also called the CZH (CED-5, Dock180, and MBC-zizimin homology) family, after the first family members identified. Dock180 was first isolated as a binding partner for the adaptor protein Crk. The Caenorhabditis elegans protein, Ced-5, is essential for cell migration and phagocytosis, while the Drosophila ortholog, Myoblast city (MBC), is necessary for myoblast fusion and dorsal closure. DOCKs are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1 (or Dock180), 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1, and DHR-2 (also called CZH2 or Docker). This alignment model represents the DHR-2 domain of DOCK proteins, which contains the catalytic GEF activity for Rac and/or Cdc42.


The actual alignment was detected with superfamily member cd11699:

Pssm-ID: 471388  Cd Length: 446  Bit Score: 886.31  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1469 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKG---------------------------------MFSM 1515
Cdd:cd11699      1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGywkmekictssmlpedsqvydsnlllttstggsMFSM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1516 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYD 1595
Cdd:cd11699     81 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSELYYD 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1596 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKV 1675
Cdd:cd11699    161 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKV 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1676 NPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTVLTTSHLFPYVKKR 1755
Cdd:cd11699    241 NPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHSFPYVKKR 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1756 IQVISQSSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVK 1835
Cdd:cd11699    321 IQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVK 400

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*.
gi 1333675876 1836 LLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLGEL 1881
Cdd:cd11699    401 LLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 449-638 9.70e-100

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. 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: 176079  Cd Length: 185  Bit Score: 318.11  E-value: 9.70e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  449 YKNQIYIYPKHLKFDSQKCFNKARNITVCIEFKNSDEEGAKPVKCIYGKPGGPlFTSAAYTAVLHHSQNPDFSDEVKIEL 528
Cdd:cd08697      1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  529 PTQLHEKHHILFSFYHVTCDInaKANAKKKEALETSVGYAWLPLLK-HDQIASQEYNIPVATSL---PPNYLSFQDSasg 604
Cdd:cd08697     80 PTQLHEKHHLLFTFYHVSCDI--NKKGKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLpnyPDGYLSIQPH--- 154

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1333675876  605 khaGSDIKWVDGGKPLFKVSTFVVSTVNTQDPHV 638
Cdd:cd08697    155 ---GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 1-80 6.68e-39

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13267:

Pssm-ID: 473070  Cd Length: 126  Bit Score: 141.70  E-value: 6.68e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876    1 MNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFELKMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGALQGRRS 80
Cdd:cd13267     48 LEFYKDEK-KKEAKGTIFLDSCTGVVQNSKRRKFCFELRMQDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
 
Name Accession Description Interval E-value
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1469-1881 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212572  Cd Length: 446  Bit Score: 886.31  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1469 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKG---------------------------------MFSM 1515
Cdd:cd11699      1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGywkmekictssmlpedsqvydsnlllttstggsMFSM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1516 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYD 1595
Cdd:cd11699     81 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSELYYD 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1596 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKV 1675
Cdd:cd11699    161 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKV 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1676 NPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTVLTTSHLFPYVKKR 1755
Cdd:cd11699    241 NPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHSFPYVKKR 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1756 IQVISQSSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVK 1835
Cdd:cd11699    321 IQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVK 400

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*.
gi 1333675876 1836 LLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLGEL 1881
Cdd:cd11699    401 LLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 449-638 9.70e-100

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. 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: 176079  Cd Length: 185  Bit Score: 318.11  E-value: 9.70e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  449 YKNQIYIYPKHLKFDSQKCFNKARNITVCIEFKNSDEEGAKPVKCIYGKPGGPlFTSAAYTAVLHHSQNPDFSDEVKIEL 528
Cdd:cd08697      1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  529 PTQLHEKHHILFSFYHVTCDInaKANAKKKEALETSVGYAWLPLLK-HDQIASQEYNIPVATSL---PPNYLSFQDSasg 604
Cdd:cd08697     80 PTQLHEKHHLLFTFYHVSCDI--NKKGKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLpnyPDGYLSIQPH--- 154

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1333675876  605 khaGSDIKWVDGGKPLFKVSTFVVSTVNTQDPHV 638
Cdd:cd08697    155 ---GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 449-637 2.88e-61

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 464171  Cd Length: 185  Bit Score: 207.84  E-value: 2.88e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  449 YKNQIYIYPKHLKFDSQKcFNKARNITVCIEFKNSDEEGAKpvKCIYGKPGGPlFTSAAYTAVLHHSQNPDFSDEVKIEL 528
Cdd:pfam14429    4 YRNDLYVTPKSGNFSKQK-KSSARNIEVTVEVRDSDGEPLP--NCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKIAL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  529 PTQLHEKHHILFSFYHVTCDinakanaKKKEALETSVGYAWLPLLKHDQ--IASQEYNIPVAT--SLPPNYLSFQDSASG 604
Cdd:pfam14429   80 PAELTPKHHLLFTFYHVSCD-------EKKDKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKydELPPGYLSLPWSSGG 152

                          170       180       190
                   ....*....|....*....|....*....|...
gi 1333675876  605 KHAGSDIKWVDGGKPLFKVSTFVVSTVNTQDPH 637
Cdd:pfam14429  153 EKESSALPGLKGGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1456-1605 2.82e-59

DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs), that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminus and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DHR-2 is a GEF catalytic domain organized into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe A, formed from an antiparallel array of alpha helices that adopts a tetratricopeptide repeat-like fold, which through extensive contacts with lobe B, stabilizes DHR-2 domain.


Pssm-ID: 462040 [Multi-domain]  Cd Length: 154  Bit Score: 200.98  E-value: 2.82e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1456 DLQYSLANSYASTPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKG--MFSMGWPAFLSITPNI-KEEGA 1532
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLKGkiPNPLGASAFEKISPNIlREESA 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1333675876 1533 MKEDSGMQDTP-YNENILVEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVAE 1605
Cdd:pfam06920   81 LKDDSGVCDSPhFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIVE 154
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
 1-80 6.68e-39

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 141.70  E-value: 6.68e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876    1 MNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFELKMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGALQGRRS 80
Cdd:cd13267     48 LEFYKDEK-KKEAKGTIFLDSCTGVVQNSKRRKFCFELRMQDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1-68 5.11e-09

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 55.63  E-value: 5.11e-09
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1333675876     1 MNFYKDEK--ISKEPKGCIFLDSCT---GVVQNNRLRKYAFELKMNDLTYFVLAAETESDMDEWIHTLNRILQ 68
Cdd:smart00233   30 LLYYKSKKdkKSYKPKGSIDLSGCTvreAPDPDSSKKPHCFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1-67 5.20e-07

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 49.87  E-value: 5.20e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1333675876    1 MNFYKDEKI--SKEPKGCIFLDSCTGV---VQNNRLRKYAFELKMNDLTY---FVLAAETESDMDEWIHTLNRIL 67
Cdd:pfam00169   30 LLYYKDDKSgkSKEPKGSISLSGCEVVevvASDSPKRKFCFELRTGERTGkrtYLLQAESEEERKDWIKAIQSAI 104
 
Name Accession Description Interval E-value
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1469-1881 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212572  Cd Length: 446  Bit Score: 886.31  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1469 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKG---------------------------------MFSM 1515
Cdd:cd11699      1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGywkmekictssmlpedsqvydsnlllttstggsMFSM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1516 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYD 1595
Cdd:cd11699     81 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSELYYD 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1596 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKV 1675
Cdd:cd11699    161 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKV 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1676 NPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTVLTTSHLFPYVKKR 1755
Cdd:cd11699    241 NPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHSFPYVKKR 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1756 IQVISQSSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVK 1835
Cdd:cd11699    321 IQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVK 400

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*.
gi 1333675876 1836 LLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLGEL 1881
Cdd:cd11699    401 LLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1470-1881 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class D, also called the Zizimin subfamily, includes Dock9, 10 and 11. Class D Docks are specific GEFs for Cdc42. Dock9 plays important roles in spine formation and dendritic growth. Dock10 and Dock11 are preferentially expressed in lymphocytes. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class D DOCKs, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212567  Cd Length: 376  Bit Score: 692.93  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1470 ELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGMfsmgwpaflsitpnikeegamkedsgmqdtpyneniL 1549
Cdd:cd11694      1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKRKDL------------------------------------L 44

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1550 VEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFE 1629
Cdd:cd11694     45 LELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMESGKRLLGTYYRVAFYGQAFFE 124

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1630 EEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFE 1709
Cdd:cd11694    125 EEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEKELEDRKTEFE 204

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1710 MHHNINRFVFETPFTLSGKKHGGVEEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSKKVSELNQLCTM 1789
Cdd:cd11694    205 RNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSKVKELEELIST 284

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1790 EEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEE 1869
Cdd:cd11694    285 EPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTVKNYPDDQVEDLKDVFRDFIKACGQALELNERLIKEDQREYHEV 364

                          410
                   ....*....|..
gi 1333675876 1870 LRSHYKDMLGEL 1881
Cdd:cd11694    365 LKENYRKMVKEL 376
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1470-1884 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also called Zizimin1, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. It plays important roles in spine formation and dendritic growth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock9, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212571  Cd Length: 415  Bit Score: 675.21  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1470 ELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGMFSMGWPAFLSITPNIKEEGAMKEDSGMQDTPYNENIL 1549
Cdd:cd11698      1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLTRKGMFRQGCTAFRVITPNIDEEASMMEDVGMQDVHFNEDVL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1550 VEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFE 1629
Cdd:cd11698     81 MELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTLHRAYSKVTEVMHSGKRLLGTYFRVAFFGQGFFE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1630 EEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFE 1709
Cdd:cd11698    161 DEDGKEYIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGKVNPKDLDSKYAYIQVTHVTPYFDEKELQERKTDFE 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1710 MHHNINRFVFETPFTLSGKKHGGVEEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSKKVSELNQLCTM 1789
Cdd:cd11698    241 RSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSKKVAELRQLCSS 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1790 EEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEE 1869
Cdd:cd11698    321 AEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDDTNTKRYPDNKVKLLKEVFRQFVEACGQALAVNERLIKEDQLEYQEE 400

                          410
                   ....*....|....*
gi 1333675876 1870 LRSHYKDMLGELSTI 1884
Cdd:cd11698    401 MKANYREMAKELSEI 415
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 1469-1881 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also called Zizimin2 or activated Cdc42-associated GEF (ACG), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock11 is predominantly expressed in lymphocytes and is found in high levels in germinal center B lymphocytes after T cell dependent antigen immunization. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock11, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212573  Cd Length: 413  Bit Score: 650.91  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1469 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGMFSMGWPAFLSITPNIKEEGAMKEDSGMQDTPYNENI 1548
Cdd:cd11700      1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFLHRKKLFPSGCAAFKKITPNIDEEGAMKEDIGMMDVHYSEEV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1549 LVEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFF 1628
Cdd:cd11700     81 LVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRTLHGAYAKILEVMHTGKRLLGTFFRVAFYGQGFF 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1629 EEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDF 1708
Cdd:cd11700    161 EEEDGKEYIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSNKVNQKDLDPKYAHIQVTYVKPYFDDKEMAERKTEF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1709 EMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSKKVSELNQLCT 1788
Cdd:cd11700    241 ERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEIKDKTAELQKLCS 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1789 MEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQE 1868
Cdd:cd11700    321 NQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPNKKVKELKEMFRKFIQACSIALELNERLIKEDQVEYHE 400

                          410
                   ....*....|...
gi 1333675876 1869 ELRSHYKDMLGEL 1881
Cdd:cd11700    401 GLKSNFRDMVKEL 413
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 1469-1877 4.94e-120

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class C, also called the Zizimin-related (Zir) subfamily, includes Dock6, 7 and 8. Class C DOCKs have been shown to have GEF activity for both Rac and Cdc42. Dock6 regulates neurite outgrowth. Dock7 plays a critical roles in the early stages of axon formation, neuronal polarity, and myelination. Dock8 regulates T and B cell numbers and functions, and plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Class C Docks, which contains the catalytic GEF activity for Rac and Cdc42.


Pssm-ID: 212568  Cd Length: 368  Bit Score: 383.96  E-value: 4.94e-120
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1469 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALiaeylkrkgmfsmGWPAflsitpnikeegamkedsgmqdtpyneni 1548
Cdd:cd11695      2 PDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL-------------GLVG----------------------------- 39

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1549 LVEQlymCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVAEVVNsEKRLFGRYYRVAFYGqGFF 1628
Cdd:cd11695     40 LLEQ---AAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQQG-GKRMFGTYFRVGFYG-SKF 114

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1629 EEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDF 1708
Cdd:cd11695    115 GDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDEYELKERTTYF 194

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1709 EMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSKKVSELNQLCT 1788
Cdd:cd11695    195 ERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQKKTRELAAATT 274

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1789 MEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEE-TNAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQ 1867
Cdd:cd11695    275 QEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDiPLDPKELDRHQNKLRLCFKEFSKKCYDALEKNKELIGPDQKEYQ 354

                          410
                   ....*....|
gi 1333675876 1868 EELRSHYKDM 1877
Cdd:cd11695    355 KELERNYENF 364
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1467-1877 1.57e-109

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also called Zizimin-related 3 (Zir3), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. Dock8 is highly expressed in the immune system and it regulates T and B cell numbers and functions. It plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. Dock8 deficiency is a primary immune deficiency that results in extreme susceptibility to cutaneous viral infections, elevated IgE levels, and eosinophilia. It was originally described as an autosomal recessive form of hyper IgE syndrome (AR-HIES). DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock8, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212574  Cd Length: 422  Bit Score: 356.27  E-value: 1.57e-109
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1467 STPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYL---KRKGMFSMGWPAFLSITPNIKEEGAMKEDSGMQDTP 1543
Cdd:cd11701      1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLsmlEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDED 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1544 -------YNENILVEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVAEvvNSEKRLFGR 1616
Cdd:cd11701     81 gvcsgryFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIIN--KGHKRMFGT 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1617 YYRVAFYGQGFFEEEEGKeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFF 1696
Cdd:cd11701    159 YFRVGFYGSKFGDLDEQE-FIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYF 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1697 EEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEM 1776
Cdd:cd11701    238 DDYEMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDM 317

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1777 SKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLKEIFRQFADACGQALDVNE 1856
Cdd:cd11701    318 QKKTRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNK 397

                          410       420
                   ....*....|....*....|.
gi 1333675876 1857 RLIKEDQLEYQEELRSHYKDM 1877
Cdd:cd11701    398 RLITADQREYQQELKKNYNKL 418
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1470-1881 1.31e-108

Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins comprise a family of atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. They are also called the CZH (CED-5, Dock180, and MBC-zizimin homology) family, after the first family members identified. Dock180 was first isolated as a binding partner for the adaptor protein Crk. The Caenorhabditis elegans protein, Ced-5, is essential for cell migration and phagocytosis, while the Drosophila ortholog, Myoblast city (MBC), is necessary for myoblast fusion and dorsal closure. DOCKs are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1 (or Dock180), 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1, and DHR-2 (also called CZH2 or Docker). This alignment model represents the DHR-2 domain of DOCK proteins, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212566 [Multi-domain]  Cd Length: 392  Bit Score: 352.37  E-value: 1.31e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1470 ELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGmfsmgwpaflsitpnikeegAMKEDSGMQDTPYNENIL 1549
Cdd:cd11684      1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDLKALV--------------------PALAESLSFPEQTSFERK 60

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1550 VEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVAEVvnseKRLFGRYYRVAFYGQGFFE 1629
Cdd:cd11684     61 EALYKKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEK----DRLFPTYFRVGFYGKGFPE 136

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1630 EEEGKEYIYKEPKLTGLSEISQRLLKLYADKfgadnvKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRK---- 1705
Cdd:cd11684    137 SLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSEEPDDEILDSEGQYIQITSVEPYFDDEDLVSRAapgv 210

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1706 TDFEMHHNINRFVFETPFTLSGKK-HGGVEEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSKKVSELN 1784
Cdd:cd11684    211 RQFYRNNNINTFVYERPFTKGGKKsQNEITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIEDIEKKTEELR 290

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1785 QLC----TMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYP-DNQVKLLKEIFRQFADACGQALDVNERLI 1859
Cdd:cd11684    291 SLInkyrSGDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSEEYLSNYPeAEKVKKLKEAFEEFLEILKRGLALHAKLC 370

                          410       420
                   ....*....|....*....|..
gi 1333675876 1860 KEDQLEYQEELRSHYKDMLGEL 1881
Cdd:cd11684    371 PPEMAPLHEELEEGFEKLFKEL 392
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1429-1896 1.74e-103

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also called Zizimin-related 2 (Zir2), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. It plays a critical role in the initial specification of axon formation in hippocampal neurons. It affects neuronal polarity by regulating microtubule dynamics. Dock7 also plays a role in controlling myelination by Schwann cells. It may also play important roles in the function and distribution of dermal and follicular melanocytes. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock7, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212576  Cd Length: 473  Bit Score: 340.90  E-value: 1.74e-103
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1429 DLTKRIRTVLMATAQMKEHEKDPEMLVDLQYSLANSYASTPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYL- 1507
Cdd:cd11703      1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLs 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1508 --KRKGMFSMGWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENILVEQLYMCVEFLWKSERYELIAEVNKPIIA 1578
Cdd:cd11703     81 mlEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEgicsgkyFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1579 VFEKQRDFKKLSDLYYDIHRSYLKVaeVVNSEKRLFGRYYRVAFYGqGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYA 1658
Cdd:cd11703    161 IHEANRDAKKLATIHGKLQEAFSKI--VHQDGKRMFGTYFRVGFYG-TKFGDLDEQEFVYKEPAITKLAEISHRLEGFYG 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1659 DKFGADNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCK 1738
Cdd:cd11703    238 ERFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFK 317

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1739 RRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYAR 1818
Cdd:cd11703    318 RKTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQ 397

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1333675876 1819 AFLEETNAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLGELSTIMNEQLcrgPCLY 1896
Cdd:cd11703    398 VFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKI---PQLY 472
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1468-1874 1.07e-101

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also called Zizimin-related 1 (Zir1), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. It is widely expressed and shows highest expression in the dorsal root ganglion and the brain. It regulates neurite outgrowth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock6, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212575  Cd Length: 423  Bit Score: 333.90  E-value: 1.07e-101
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1468 TPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYL---KRKGMFSMGWPAFLSITPNIKEEGAMKEDSGMQDTP- 1543
Cdd:cd11702      1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLsmlEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEg 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1544 ------YNENILVEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVAEVVNSEKRLFGRY 1617
Cdd:cd11702     81 icsgkyFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSGWERMFGTY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1618 YRVAFYGqGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFE 1697
Cdd:cd11702    161 FRVGFYG-CKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFD 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1698 EKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMS 1777
Cdd:cd11702    240 TYELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQ 319

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1778 KKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETnakkyPDNQvKL------LKEIFRQFADACGQA 1851
Cdd:cd11702    320 KKTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEI-----PEDP-KLfrhhnkLRLCFKDFTKRCEDA 393

                          410       420
                   ....*....|....*....|...
gi 1333675876 1852 LDVNERLIKEDQLEYQEELRSHY 1874
Cdd:cd11702    394 LRKNKALIGPDQKEYHRELERNY 416
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 449-638 9.70e-100

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. 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: 176079  Cd Length: 185  Bit Score: 318.11  E-value: 9.70e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  449 YKNQIYIYPKHLKFDSQKCFNKARNITVCIEFKNSDEEGAKPVKCIYGKPGGPlFTSAAYTAVLHHSQNPDFSDEVKIEL 528
Cdd:cd08697      1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  529 PTQLHEKHHILFSFYHVTCDInaKANAKKKEALETSVGYAWLPLLK-HDQIASQEYNIPVATSL---PPNYLSFQDSasg 604
Cdd:cd08697     80 PTQLHEKHHLLFTFYHVSCDI--NKKGKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLpnyPDGYLSIQPH--- 154

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1333675876  605 khaGSDIKWVDGGKPLFKVSTFVVSTVNTQDPHV 638
Cdd:cd08697    155 ---GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 449-637 2.88e-61

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 464171  Cd Length: 185  Bit Score: 207.84  E-value: 2.88e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  449 YKNQIYIYPKHLKFDSQKcFNKARNITVCIEFKNSDEEGAKpvKCIYGKPGGPlFTSAAYTAVLHHSQNPDFSDEVKIEL 528
Cdd:pfam14429    4 YRNDLYVTPKSGNFSKQK-KSSARNIEVTVEVRDSDGEPLP--NCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKIAL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  529 PTQLHEKHHILFSFYHVTCDinakanaKKKEALETSVGYAWLPLLKHDQ--IASQEYNIPVAT--SLPPNYLSFQDSASG 604
Cdd:pfam14429   80 PAELTPKHHLLFTFYHVSCD-------EKKDKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKydELPPGYLSLPWSSGG 152

                          170       180       190
                   ....*....|....*....|....*....|...
gi 1333675876  605 KHAGSDIKWVDGGKPLFKVSTFVVSTVNTQDPH 637
Cdd:pfam14429  153 EKESSALPGLKGGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1456-1605 2.82e-59

DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs), that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminus and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DHR-2 is a GEF catalytic domain organized into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe A, formed from an antiparallel array of alpha helices that adopts a tetratricopeptide repeat-like fold, which through extensive contacts with lobe B, stabilizes DHR-2 domain.


Pssm-ID: 462040 [Multi-domain]  Cd Length: 154  Bit Score: 200.98  E-value: 2.82e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1456 DLQYSLANSYASTPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKG--MFSMGWPAFLSITPNI-KEEGA 1532
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLKGkiPNPLGASAFEKISPNIlREESA 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1333675876 1533 MKEDSGMQDTP-YNENILVEQLYMCVEFLWKSERYELIAEVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVAE 1605
Cdd:pfam06920   81 LKDDSGVCDSPhFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIVE 154
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 449-638 3.60e-54

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 classes of Dock family proteins. The members here include: Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3. Dock-C members are GEFs for both Rac and Cdc42. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-C members contain a functionally uncharacterized domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). 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: 176078  Cd Length: 179  Bit Score: 187.56  E-value: 3.60e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  449 YKNQIYIYPKHLKFDSQKcfNKARNITVCIEFKNSDEEGAKPVKCIYGKpGGPLFTSAAYTAVLHHSQNPDFSDEVKIEL 528
Cdd:cd08696      1 YRNLLYVYPQSLNFSNRL--GSARNIAVKVQLMSGEDESQALPVIFKGS-SPEEFLTEAYTAVTYHNKSPDFYDEIKIKL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  529 PTQLHEKHHILFSFYHVTCdinakANAKKKEALETSVGYAWLPLLKHDQIASQEYNIPVATSLPPNYLSFqDSASGKHAG 608
Cdd:cd08696     78 PADLTDNHHLLFTFYHISC-----QKKQEGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSP-DSPEVKLPG 151

                          170       180       190
                   ....*....|....*....|....*....|
gi 1333675876  609 sdIKWVDGGKPLFKVSTFVVSTVNTQDPHV 638
Cdd:cd08696    152 --TKWVDNHKGVFSVSVEAVSSVHTQDSYL 179
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
 1-80 6.68e-39

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 141.70  E-value: 6.68e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876    1 MNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFELKMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGALQGRRS 80
Cdd:cd13267     48 LEFYKDEK-KKEAKGTIFLDSCTGVVQNSKRRKFCFELRMQDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 449-638 1.20e-38

C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was first identified as an 180kd proto-oncogene product c-Crk-interacting protein involved in actin cytoskeletal changes. It is now known that it has Rac-specific GEF activity, but lacks the conventional Dbl homology (DH) domain. There are 10 additional related proteins that can be divided into four classes based on sequence similarity and domain organization: Dock-A which includes Dock180/Dock1, Dock2, and Dock5; Dock-B which includes Dock3/MOCA (modifier of cell adhesion) and Dock4; Dock-C which includes Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3; and Dock-D, which includes Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Most of members of classes Dock-A and Dock-B are the GEFs specific for Rac. Those of Dock-D are Cdc42-specific GEFs while those of Dock-C are the GEFs for both. All Dock180-related proteins have two common homology domains: the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker). DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). 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: 176061  Cd Length: 178  Bit Score: 142.85  E-value: 1.20e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  449 YKNQIYIYPKHLKFDSQKcfNKARNITVCIEFKNSDEEGAKPVKCIYGKpgGPLFTSAaYTAVLHHSQNPDFSDEVKIEL 528
Cdd:cd08679      1 LRNDLYVYPQSGELSKAK--SKGRNIEITVEVRDDDGDIIEPCISAPGS--GSELRSE-YTSVVYYHKNPVFNDEIKIQL 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876  529 PTQLHEKHHILFSFYHVTCDinakanAKKKEALETSVGYAWLPLLKHDQ--IASQEYNIPVAT------SLPPNYLSFQD 600
Cdd:cd08679     76 PADLTPQHHLLFTFYHVSSK------KKQGDKEETPFGYAFLPLMDKDGafIKDGDHTLPVYKydkrpdVGPSGYLSLPS 149

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1333675876  601 SASGKHAGSDikwvdggkpLFKVSTFVVSTVNTQDPHV 638
Cdd:cd08679    150 TLANGKSSKD---------TFKIKTRLCSTILTQDKSL 178
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1782-1884 4.41e-38

DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe C which form an antiparallel four alpha-helical bundle and contains a loop known as the nucleotide sensor characterized by a conserved valine residue essential for catalytic activity.


Pssm-ID: 466570 [Multi-domain]  Cd Length: 103  Bit Score: 138.50  E-value: 4.41e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1782 ELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKE 1861
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPAEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80

                           90       100
                   ....*....|....*....|...
gi 1333675876 1862 DQLEYQEELRSHYKDMLGELSTI 1884
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLEPY 103
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1672-1747 3.69e-37

DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe B which adopts an unusual architecture of two antiparallel beta sheets disposed in a loosely packed orthogonal arrangement. This lobe changes its position relative to lobe C and the bound GTPase, which suggests that lobe B distinguishes between the switch 1 conformations of Rac1 and Cdc42.


Pssm-ID: 466571 [Multi-domain]  Cd Length: 77  Bit Score: 134.66  E-value: 3.69e-37
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1333675876 1672 SNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTVLTTSH 1747
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDRVTYFERNNNVNRFVFETPFTKSGKAQGEFEEQWKRRTILTTEH 76
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 1549-1877 2.28e-18

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. Class A DOCKs are specific GEFs for Rac. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock2 plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class A DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212570  Cd Length: 400  Bit Score: 89.69  E-value: 2.28e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1549 LVEQLYM-CVEFLWKSERYELIAEVNKPIIAVFEKQR-DFKKLSDLYYDIHRSYLKVAEVVNSEKRlfgrYYRVAFYGQG 1626
Cdd:cd11697     59 LKEALYYdIIDYFDKGKMWECAISLCKELAEQYENETfDYLQLSELLKRMATFYDNIMKTLRPEPE----YFRVGYYGQG 134

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1627 FFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKfgadnvkiiQDSNKVNPKDLDPKYA---YIQVTYVTPFFEE----- 1698
Cdd:cd11697    135 FPSFLRNKVFIYRGKEYERLSDFSARLLNQFPNA---------ELMNTLTPPGDEIKESpgqYLQINKVDPVMDErprfk 205

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1699 -KEIEDRKTDFEMHHNINRFVFETPFTlSGKKHGGVE--EQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDE 1775
Cdd:cd11697    206 gKPVSDQILNYYKVNEVQRFTFSRPFR-RGTKDPDNEfaNMWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIET 284

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1776 MSKKVSELNQLCTMEEVD----MIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKL--LKEIFRQFADACG 1849
Cdd:cd11697    285 MEDTNKKIRDLILQHQSDptlpINPLSMLLNGIVDAAVMGGIANYEKAFFTEEYLDEHPEDQELIerLKDLIAEQIPLLE 364

                          330       340
                   ....*....|....*....|....*...
gi 1333675876 1850 QALDVNERLIKEDQLEYQEELRSHYKDM 1877
Cdd:cd11697    365 AGLKIHKQKAPESLRPLHERMEECFAKM 392
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
 1574-1870 5.90e-15

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. Dock3 is a specific GEF for Rac and it regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class B DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212569  Cd Length: 391  Bit Score: 79.03  E-value: 5.90e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1574 KPIIAVFEKQRDFKKLSDlyydIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRL 1653
Cdd:cd11696     81 RELAELYESLYDYAKLSH----ILRMEASFYDNILTQLRPEPEYFRVGFYGKGFPLFLRNKQFVYRGLDYERIGAFTQRL 156

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1654 LKLYAdkfgadNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKE------IEDRKTDFEMHHNINRFVFETPFtlsg 1727
Cdd:cd11696    157 QSEFP------QAHILTKNTPPDDAILQADGQYIQICNVKPVPERRPvlqmvgVPDKVRSFYRVNDVRKFQYDRPI---- 226

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1728 kkHGGV---EEQCK----RRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIR---- 1796
Cdd:cd11696    227 --HKGPidkDNEFKslwiERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISQYQADPTRninp 304

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1333675876 1797 LQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDN--QVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEEL 1870
Cdd:cd11696    305 FSMRLQGVIDAAVNGGIAKYQEAFFTPEFILSHPEDaeHIARLRELILEQVQILEAGLALHGKLAPPEVRPLHKRL 380
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
 1544-1840 7.10e-14

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It functions upstream of Rac1 to regulate osteoclast function. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock5, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock5, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212581  Cd Length: 400  Bit Score: 75.75  E-value: 7.10e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1544 YNENILVEQLYM-CVEFLWKSERYELIAEVNKPIIAVFEKQR-DFKKLSDLYYDIHRSYlkvaEVVNSEKRLFGRYYRVA 1621
Cdd:cd11708     54 YTQQELKERLYQeIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFY----ENIMKAMRPQPEYFAVG 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1622 FYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDldpkyaYIQVTYVTPF------ 1695
Cdd:cd11708    130 YYGQGFPSFLRNKIFIYRGKEYERLEDFSLKLLTQFPNAEKMTSTSPPGDEIKSSTKQ------YVQCFTVKPVmnlpsh 203

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1696 FEEKEIEDRKTDFEMHHNINRFVFETPFTlSGKKHGGVEEQCK--RRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAI 1773
Cdd:cd11708    204 YKDKPVPEQILNYYRANEVQQFQYSRPFR-KGEKDPDNEFATMwiERTTFTTAYRFPGILKWFEVKQISTEEISPLENAI 282

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1333675876 1774 DEM---SKKVSEL------NQLCTMEEVDMIrlqlkLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ--VKLLKEI 1840
Cdd:cd11708    283 ETMeltNEKISNLvqqhawDRSLPVHPLSML-----LNGIVDPAVMGGFSNYEKAFFTEKYLQEHPEDQekIELLKQL 355
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1587-1881 8.99e-14

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock3 is a specific GEF for Rac. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock3, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212577  Cd Length: 392  Bit Score: 75.43  E-value: 8.99e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1587 KKLSDLYYDihrsylkvaeVVNSEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGadnv 1666
Cdd:cd11704    100 RKMEAAYYD----------NIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQRMLSEFPQAIA---- 165

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1667 kiIQDSNKVNPKDLDPKYAYIQVTYVTPF------FEEKEIEDRKTDFEMHHNINRFVFETPFTLSGK-KHGGVEEQCKR 1739
Cdd:cd11704    166 --MQHPNHPDDGILQCDAQYLQIYAVTPIpdnmdvLQMDRVPDRIKSFYRVNNVRKFRYDRPFHKGPKdKENEFKSLWIE 243

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1740 RTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIR-----LQLKLQGSVSVKVNAGPM 1814
Cdd:cd11704    244 RTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRTLISQYQHKQLHgninlLSMCLNGVIDAAVNGGIA 323

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1333675876 1815 AYARAFLEETNAKKYPDNQVKL--LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLGEL 1881
Cdd:cd11704    324 RYQEAFFDKDYISKHPGDAEKItqLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRSSL 392
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
 1529-1877 1.80e-13

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a hematopoietic cell-specific, class A DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock2, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock2, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212579  Cd Length: 421  Bit Score: 74.64  E-value: 1.80e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1529 EEGAMKEDSGMQDTPYNENILVEQLY-MCVEFLWKSERYELIAEVNKPIIAVFEKQ-RDFKKLSDLYYDIHRSYLKVAEV 1606
Cdd:cd11706     57 EQCASQVMQTGQQHPQTQRQLKETLYeTIIGYFDKGKMWEEAISLCKELAEQYEMEiFDYELLSQNLIQQAKFYESIMKI 136

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1607 VnsekRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYAdkfgadNVKIIQDSNKVNPKDLDPKYAY 1686
Cdd:cd11706    137 L----RPKPDYFAVGYYGQGFPSFLRNKVFIYRGKEYERREDFQMQLMSQFP------NAEKLNTTSAPGDDIKNSPGQY 206

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1687 IQVTYVTPFFEE------KEIEDRKTDFEMHHNINRFVFETPFtlsgkKHGGVEEQCK------RRTVLTTSHLFPYVKK 1754
Cdd:cd11706    207 IQCFTVQPVLEEhprlknKPVPDQIINFYKSNYVQRFHYSRPV-----RKGPVDPENEfasmwiERTTFVTAYKLPGILR 281

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1755 RIQVISQSSTELNPIEVAIDEMS----KKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYP 1830
Cdd:cd11706    282 WFEVTHMSQTTISPLENAIETMSttneKILMMINQYQSDESLPINPLSMLLNGIVDPAVMGGFAKYEKAFFTEEYVRDHP 361

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 1333675876 1831 DNQVKL--LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDM 1877
Cdd:cd11706    362 EDQDKLtrLKDLIAWQIPLLGAGIKIHGKRVTDDLRPFHERMEECFKQL 410
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1580-1881 1.15e-11

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. It may also regulate spine morphology and synapse formation. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock4, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212578  Cd Length: 391  Bit Score: 68.90  E-value: 1.15e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1580 FEKQRDFKKLSDLYYDIHRSYLKVAEvvnsEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYAD 1659
Cdd:cd11705     87 YESYYDYRNLSKMRMMEASLYDKIMD----QQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQRMLNEFPH 162

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1660 KFGadnvkiIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDR-------KTDFEMHHnINRFVFETPFTLSGK-KHG 1731
Cdd:cd11705    163 AIA------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQRdgvpdniKSFYKVNH-IWRFRYDRPFHKGTKdKEN 235

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1732 GVEEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSKKVSELNQL---CTMEEVDMIR-LQLKLQGSVSV 1807
Cdd:cd11705    236 EFKSLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLisqCQTRQMQNINpLTMCLNGVIDA 315

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1333675876 1808 KVNAGPMAYARAFLEETNAKKYPDNQVKL--LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLGEL 1881
Cdd:cd11705    316 AVNGGVSRYQEAFFVKEYILNHPEDGDKItrLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 1549-1838 1.92e-11

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also called Dock180, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. In the nervous system, it mediates attractive responses to netrin-1 and thus, plays a role in axon outgrowth and pathfinding. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock1, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock1, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212580  Cd Length: 400  Bit Score: 68.14  E-value: 1.92e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1549 LVEQLYM-CVEFLWKSERYELIAEVNKPIIAVFEKQR-DFKKLSDLYYDIHRSYLKVAEVVNSEKRlfgrYYRVAFYGQG 1626
Cdd:cd11707     59 LKDQLYQeIIHYFDKGKMWEEAIALGKELAEQYENEMfDYEQLSELLKKQAQFYENIVKVIRPKPD----YFAVGYYGQG 134

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1627 FFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADkfgADNVKiiqdsnKVNPKDLDPKYA---YIQVTYVTPF------FE 1697
Cdd:cd11707    135 FPTFLRNKMFIYRGKEYERREDFEARLLTQFPN---AEKMK------TTSPPGDDIKNSsgqYIQCFTVKPLlelppkFQ 205

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876 1698 EKEIEDRKTDFEMHHNINRFVFETPFTlSGKKHGGVE--EQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDE 1775
Cdd:cd11707    206 NKPVSEQIVSFYRVNEVQRFQYSRPVR-KGEKDPDNEfaNMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIET 284

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1333675876 1776 MSKKVSELNQLCTMEEVD----MIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLK 1838
Cdd:cd11707    285 MQLTNEKINNMVQQHLNDpnlpINPLSMLLNGIVDPAVMGGFANYEKAFFTEKYMQEHPEDHEKIEK 351
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1-68 5.11e-09

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 55.63  E-value: 5.11e-09
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1333675876     1 MNFYKDEK--ISKEPKGCIFLDSCT---GVVQNNRLRKYAFELKMNDLTYFVLAAETESDMDEWIHTLNRILQ 68
Cdd:smart00233   30 LLYYKSKKdkKSYKPKGSIDLSGCTvreAPDPDSSKKPHCFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 3-65 9.33e-08

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 52.24  E-value: 9.33e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1333675876    3 FYKDEKISKEPKGCIFLDSCTgVVQNNRLRKYAFELKMNDL---TYfVLAAETESDMDEWIHTLNR 65
Cdd:cd13288     37 FYFEKKGDREPLGVIVLEGCT-VELAEDAEPYAFAIRFDGPgarSY-VLAAENQEDMESWMKALSR 100
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1-67 5.20e-07

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 49.87  E-value: 5.20e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1333675876    1 MNFYKDEKI--SKEPKGCIFLDSCTGV---VQNNRLRKYAFELKMNDLTY---FVLAAETESDMDEWIHTLNRIL 67
Cdd:pfam00169   30 LLYYKDDKSgkSKEPKGSISLSGCEVVevvASDSPKRKFCFELRTGERTGkrtYLLQAESEEERKDWIKAIQSAI 104
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 3-66 5.11e-06

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270133  Cd Length: 112  Bit Score: 47.02  E-value: 5.11e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876    3 FYKDEKiSKEPKGCIFLDSC----TGVVQNNRLRKYA--FELKMNDLTYFvLAAETESDMDEWIHTLNRI 66
Cdd:cd13324     42 YYTDDH-CKKLKGIIDLDQCeqvdAGLTFEKKKFKNQfiFDIRTPKRTYY-LVAETEEEMNKWVRCICQV 109
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
 1-63 6.98e-06

Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. Members here include insect, nematodes, and crustacean Gab2s. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241535  Cd Length: 115  Bit Score: 47.05  E-value: 6.98e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876    1 MNFYKDEKISKEpKGCIFLDSCTGVVQ-------NNRLRKYAFELKMNDLTYFvLAAETESDMDEWIHTL 63
Cdd:cd13384     41 LEYYTDRTCRKL-KGSIDLDQCEQVDAgltfetkNKLKDQHIFDIRTPKRTYY-LVADTEDEMNKWVNCI 108
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 3-63 7.50e-06

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 46.00  E-value: 7.50e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1333675876    3 FYKDEK-ISKEPKGCIFLDSCTGVVQNNRL-RKYAFELKMNDLTYFVLAAETESDMDEWIHTL 63
Cdd:cd00821     30 YYKSKKdSSYKPKGSIPLSGILEVEEVSPKeRPHCFELVTPDGRTYYLQADSEEERQEWLKAL 92
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
 3-75 7.53e-06

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270094  Cd Length: 104  Bit Score: 46.56  E-value: 7.53e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1333675876    3 FYKDEKI--SKEPKGCIFLDSCTGVVQNNRLRKYAFELKMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGAL 75
Cdd:cd13275     29 YYRDPSAeeAGELDGVIDLSSCTEVTELPVSRNYGFQVKTWDGKVYVLSAMTSGIRTNWIQALRKAAGLPSPPAL 103
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
 1-74 1.26e-05

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270083  Cd Length: 114  Bit Score: 46.22  E-value: 1.26e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876    1 MNFYKDEKISKePKGCIFLDSCT-GVVQNNRLR--KYAFEL---------KMNDLTYfVLAAETESDMDEWIHTLNRILQ 68
Cdd:cd13263     31 LYYYKDEDDTK-PQGTIPLPGNKvKEVPFNPEEpgKFLFEIipggggdrmTSNHDSY-LLMANSQAEMEEWVKVIRRVIG 108


                   ....*.
gi 1333675876   69 ISPEGA 74
Cdd:cd13263    109 SPFGGG 114
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 3-64 5.16e-04

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 41.16  E-value: 5.16e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1333675876    3 FYKDEKISKEPKGCIFLDSCTGVVQNNRLRK-YAFELKMNDLTYFvLAAETESDMDEWIHTLN 64
Cdd:cd10573     32 KYFKTRGDTKPIRVLDLRECSSVQRDYSQGKvNCFCLVFPERTFY-MYANTEEEADEWVKLLK 93
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 1-80 1.09e-03

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 39.97  E-value: 1.09e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333675876    1 MNFYKDEK-ISKEPKGCIFLDSCTGVVQNNRLRkyAFELKMNDLTYFvLAAETESDMDEWIhtlnRILQispeGALQGRR 79
Cdd:cd13282     27 LFYYKSPNdVIRKPQGQIALDGSCEIARAEGAQ--TFEIVTEKRTYY-LTADSENDLDEWI----RVIQ----NVLRRQA 95


                   .
gi 1333675876   80 S 80
Cdd:cd13282     96 S 96
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
 4-68 1.36e-03

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 39.88  E-value: 1.36e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1333675876    4 YKDEKISKEPKGCIFLDSC-------TGVVQN-NRLRKYAFELKMNDLTyFVLAAETESDMDEWIHTLNRILQ 68
Cdd:cd01251     33 YFKDPLDAFPKGEIFIGSKeegysvrEGLPPGiKGHWGFGFTLVTPDRT-FLLSAETEEERREWITAIQKVLE 104
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 3-64 1.43e-03

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 39.95  E-value: 1.43e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1333675876    3 FYKDEKiSKEPKGCIFLDSCT---GVVQNNRLRKYAFELKMNDLTYFVLAAETESDMDEWIHTLN 64
Cdd:cd13248     38 YYKDPE-EEKALGSILLPSYTispAPPSDEISRKFAFKAEHANMRTYYFAADTAEEMEQWMNAMS 101
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 3-63 2.18e-03

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 39.58  E-value: 2.18e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1333675876    3 FYKDEK---ISKEPKGCIFLDSCTGVvqNNRL---RKYAFELKMNDlTYFVLAAETESDMDEWIHTL 63
Cdd:cd01257     35 YYENEKkfrRNAEPKRVIPLSSCFNI--NKRAdakHKHLIALYTKD-ECFGLVAESEEEQDEWYQAL 98
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
 3-64 2.71e-03

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269975  Cd Length: 106  Bit Score: 39.13  E-value: 2.71e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1333675876    3 FYKDEKISKEPKGC-----IFLDSCTG-VVQNNRLRKYAFELKMNDLTYFVLAAETESDMDEWIHTLN 64
Cdd:cd10571     37 FYKDQKAAKSGITYaaeppLNLYNAVCeVASDYTKKKHVFRLKLSDGAEFLFQAKDEEEMNQWVKKIS 104
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 3-70 3.24e-03

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 38.84  E-value: 3.24e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1333675876    3 FYKDEKI--SKEPKGCIFLDSCTGV--VQNNRLRKYAFELKMNDLTYFvLAAETESDMDEWIHTLNR-ILQIS 70
Cdd:cd13276     29 WFKEPDVtpYSKPRGVIDLSKCLTVksAEDATNKENAFELSTPEETFY-FIADNEKEKEEWIGAIGRaIVKHS 100
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 471-546 7.44e-03

C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 classes of Dock family proteins. The members here include: Dock3/MOCA (modifier of cell adhesion) and Dock4. Most of these members have been shown to be GEFs specific for Rac, although Dock4 has also been shown to interact indirectly with the Ras family GTPase Rap1, probably through Rap regulatory proteins. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-B members contain a SH3 domain upstream of the C2 domain and a proline-rich region downstream. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). 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: 176077  Cd Length: 189  Bit Score: 39.67  E-value: 7.44e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1333675876  471 ARNITVCIEFknSDEEGAKPVKCIYGKPGGPLfTSAAYTAVLHHSQNPDFSDEVKIELPTQLHEKHHILFSFYHVT 546
Cdd:cd08695     22 AKNIEVTMVV--LDADGQVLKDCISLGSGEPP-CSEYRSFVLYHNNSPRWNETIKLPIPIDKFRGSHLRFEFRHCS 94
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
 2-63 8.32e-03

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270099  Cd Length: 139  Bit Score: 38.46  E-value: 8.32e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1333675876    2 NFYKDEKISKEPKGCIFLDSCTGVVQNNRLRKYAFELKMNDLT-YFVLAAETESDMDEWIHTL 63
Cdd:cd13281     52 DFEKTRHFNIHPKGVIPLGGCSIEAVEDPGKPYAISISHSDFKgNIILAADSEFEQEKWLDML 114
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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