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Conserved domains on  [gi|398366535|ref|NP_010661|]
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frequenin [Saccharomyces cerevisiae S288C]

Protein Classification

EF-hand domain-containing protein (domain architecture ID 11473824)

EF-hand (EFh) domain-containing protein similar to Homo sapiens guanylyl cyclase-activating proteins (GCAP1 and GCAP2), myosin regulatory light chain proteins, (MYL2, MYL5, MYL9, MYL10, and MYL12), and Kv channel-interacting proteins (KChIP1, KChIP2 and KChIP4)

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
4-179 1.06e-46

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


:

Pssm-ID: 227455 [Multi-domain]  Cd Length: 160  Bit Score: 150.54  E-value: 1.06e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535   4 KTSKLSKddltcLKQSTYFDRREIQQWHKGFLRDCP--SGQLAREDFVKIYKqFFPFGSPEDFANHLFTVFDKdNNGFIH 81
Cdd:COG5126    1 MRSKISD-----LLTFTQLTEEQIQELKEAFQLFDRdsDGLIDRNELGKILR-SLGFNPSEAEINKLFEEIDA-GNETVD 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  82 FEEFITVLSTTS-RGTLEEKLSWAFELYDLNHDGYITFDEMLTIVASvykmmgsmvtlnEDEATPEMRVKKIFKLMDKNE 160
Cdd:COG5126   74 FPEFLTVMSVKLkRGDKEEELREAFKLFDKDHDGYISIGELRRVLKS------------LGERLSDEEVEKLLKEYDEDG 141
                        170
                 ....*....|....*....
gi 398366535 161 DGYITLDEFREGSKVDPSI 179
Cdd:COG5126  142 DGEIDYEEFKKLIKDSPTI 160
 
Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
4-179 1.06e-46

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 227455 [Multi-domain]  Cd Length: 160  Bit Score: 150.54  E-value: 1.06e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535   4 KTSKLSKddltcLKQSTYFDRREIQQWHKGFLRDCP--SGQLAREDFVKIYKqFFPFGSPEDFANHLFTVFDKdNNGFIH 81
Cdd:COG5126    1 MRSKISD-----LLTFTQLTEEQIQELKEAFQLFDRdsDGLIDRNELGKILR-SLGFNPSEAEINKLFEEIDA-GNETVD 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  82 FEEFITVLSTTS-RGTLEEKLSWAFELYDLNHDGYITFDEMLTIVASvykmmgsmvtlnEDEATPEMRVKKIFKLMDKNE 160
Cdd:COG5126   74 FPEFLTVMSVKLkRGDKEEELREAFKLFDKDHDGYISIGELRRVLKS------------LGERLSDEEVEKLLKEYDEDG 141
                        170
                 ....*....|....*....
gi 398366535 161 DGYITLDEFREGSKVDPSI 179
Cdd:COG5126  142 DGEIDYEEFKKLIKDSPTI 160
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
67-126 5.65e-15

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 66.03  E-value: 5.65e-15
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  67 HLFTVFDKDNNGFIHFEEFITVLSTTSRGTLEEKLSWAFELYDLNHDGYITFDEMLTIVA 126
Cdd:cd00051    4 EAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
98-171 8.02e-11

EF-hand domain pair;


Pssm-ID: 338778 [Multi-domain]  Cd Length: 68  Bit Score: 55.35  E-value: 8.02e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 398366535   98 EEKLSWAFELYDLNHDGYITFDEMLTIVASVYKmmgsmvtlnEDEATPEMRVKKIFKLMDKNEDGYITLDEFRE 171
Cdd:pfam13499   1 EEKLKEAFKLLDKDGDGYLDVEELKKLLRKLFE---------EGEKLSDEEVEELFKEFDLDKDGRISFEEFLE 65
PTZ00184 PTZ00184
calmodulin; Provisional
69-170 3.22e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 44.75  E-value: 3.22e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  69 FTVFDKDNNGFIHFEEFITVLSTTSRGTLEEKLSWAFELYDLNHDGYITFDEMLTIVASvyKMMGsmvTLNEDEatpemr 148
Cdd:PTZ00184  17 FSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMAR--KMKD---TDSEEE------ 85
                         90       100
                 ....*....|....*....|..
gi 398366535 149 VKKIFKLMDKNEDGYITLDEFR 170
Cdd:PTZ00184  86 IKEAFKVFDRDGNGFISAAELR 107
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
100-128 2.71e-04

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 36.59  E-value: 2.71e-04
                           10        20
                   ....*....|....*....|....*....
gi 398366535   100 KLSWAFELYDLNHDGYITFDEMLTIVASV 128
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
 
Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
4-179 1.06e-46

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 227455 [Multi-domain]  Cd Length: 160  Bit Score: 150.54  E-value: 1.06e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535   4 KTSKLSKddltcLKQSTYFDRREIQQWHKGFLRDCP--SGQLAREDFVKIYKqFFPFGSPEDFANHLFTVFDKdNNGFIH 81
Cdd:COG5126    1 MRSKISD-----LLTFTQLTEEQIQELKEAFQLFDRdsDGLIDRNELGKILR-SLGFNPSEAEINKLFEEIDA-GNETVD 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  82 FEEFITVLSTTS-RGTLEEKLSWAFELYDLNHDGYITFDEMLTIVASvykmmgsmvtlnEDEATPEMRVKKIFKLMDKNE 160
Cdd:COG5126   74 FPEFLTVMSVKLkRGDKEEELREAFKLFDKDHDGYISIGELRRVLKS------------LGERLSDEEVEKLLKEYDEDG 141
                        170
                 ....*....|....*....
gi 398366535 161 DGYITLDEFREGSKVDPSI 179
Cdd:COG5126  142 DGEIDYEEFKKLIKDSPTI 160
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
67-126 5.65e-15

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 66.03  E-value: 5.65e-15
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  67 HLFTVFDKDNNGFIHFEEFITVLSTTSRGTLEEKLSWAFELYDLNHDGYITFDEMLTIVA 126
Cdd:cd00051    4 EAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
100-172 5.70e-12

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 57.94  E-value: 5.70e-12
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 398366535 100 KLSWAFELYDLNHDGYITFDEMLTIVasvyKMMGSMVTLNEdeatpemrVKKIFKLMDKNEDGYITLDEFREG 172
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAAL----KSLGEGLSEEE--------IDEMIREVDKDGDGKIDFEEFLEL 61
EF-hand_7 pfam13499
EF-hand domain pair;
98-171 8.02e-11

EF-hand domain pair;


Pssm-ID: 338778 [Multi-domain]  Cd Length: 68  Bit Score: 55.35  E-value: 8.02e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 398366535   98 EEKLSWAFELYDLNHDGYITFDEMLTIVASVYKmmgsmvtlnEDEATPEMRVKKIFKLMDKNEDGYITLDEFRE 171
Cdd:pfam13499   1 EEKLKEAFKLLDKDGDGYLDVEELKKLLRKLFE---------EGEKLSDEEVEELFKEFDLDKDGRISFEEFLE 65
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
54-168 5.00e-07

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 48.21  E-value: 5.00e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  54 QFFPFGSPEDFANHLFTVF-------DKDNNGFIHFEEFITVLSTTSRGtlEEKLSWAF-------ELYDLNHDGYITFD 119
Cdd:cd15899  144 EFLAFLHPEESPYMLDFVIketledlDKNGDGFISLEEFISDPYSADEN--EEEPEWVKvekerfvELRDKDKDGKLDGE 221
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 398366535 120 EMLTIvasvykmmgsMVTLNEDEATPEmrVKKIFKLMDKNEDGYITLDE 168
Cdd:cd15899  222 ELLSW----------VDPSNQEIALEE--AKHLIAESDENKDGKLSPEE 258
PTZ00184 PTZ00184
calmodulin; Provisional
69-170 3.22e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 44.75  E-value: 3.22e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  69 FTVFDKDNNGFIHFEEFITVLSTTSRGTLEEKLSWAFELYDLNHDGYITFDEMLTIVASvyKMMGsmvTLNEDEatpemr 148
Cdd:PTZ00184  17 FSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMAR--KMKD---TDSEEE------ 85
                         90       100
                 ....*....|....*....|..
gi 398366535 149 VKKIFKLMDKNEDGYITLDEFR 170
Cdd:PTZ00184  86 IKEAFKVFDRDGNGFISAAELR 107
EF-hand_7 pfam13499
EF-hand domain pair;
68-125 3.68e-06

EF-hand domain pair;


Pssm-ID: 338778 [Multi-domain]  Cd Length: 68  Bit Score: 42.64  E-value: 3.68e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 398366535   68 LFTVFDKDNNGFI---HFEEFITVLSTTSRGTLEEKLSWAFELYDLNHDGYITFDEMLTIV 125
Cdd:pfam13499   7 AFKLLDKDGDGYLdveELKKLLRKLFEEGEKLSDEEVEELFKEFDLDKDGRISFEEFLELY 67
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
68-170 3.77e-06

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 45.77  E-value: 3.77e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  68 LFTVFDKDNNGFIHFEEFITVLSTTSRGTLEEKLSWAFELYDLNHDGYITFDEmltIVASVYKMMGSMVTLNEDEATPEM 147
Cdd:cd16227   41 LAKKMDLNDDGFIDRKELKAWILRSFKMLDEEEANERFEEADEDGDGKVTWEE---YLADSFGYDDEDNEEMIKDSTEDD 117
                         90       100
                 ....*....|....*....|....*...
gi 398366535 148 RV-----KKIFKLMDKNEDGYITLDEFR 170
Cdd:cd16227  118 LKlleddKEMFEAADLNKDGKLDKTEFS 145
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
53-168 1.42e-05

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 43.84  E-value: 1.42e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  53 KQFFPFGSPEDFAnHLFTV--------FDKDNNGFIHFEEFI--TVLSTTSRGTLEEKLSWAFElYDLNHDGYITFDEML 122
Cdd:cd16227  142 TEFSAFQHPEEYP-HMHPVlieqtlrdKDKDNDGFISFQEFLgdRAGHEDKEWLLVEKDRFDED-YDKDGDGKLDGEEIL 219
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 398366535 123 TIVasvykmmgsmVTLNEDEATPEmrVKKIFKLMDKNEDGYITLDE 168
Cdd:cd16227  220 SWL----------VPDNEEIAEEE--VDHLFASADDDHDDRLSFDE 253
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
64-171 1.85e-05

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 42.27  E-value: 1.85e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  64 FANHLFTVFDKDNNGFIHFEEFITVLS----TTSRGTLEEKlswaFELYDLNHDGYITFDEMltivasvYKMMGSMVTLN 139
Cdd:cd15898    1 WLRRQWIKADKDGDGKLSLKEIKKLLKrlniRVSEKELKKL----FKEVDTNGDGTLTFDEF-------EELYKSLTERP 69
                         90       100       110
                 ....*....|....*....|....*....|..
gi 398366535 140 EdeatpemrVKKIFKLMDKNEDGYITLDEFRE 171
Cdd:cd15898   70 E--------LEPIFKKYAGTNRDYMTLEEFIR 93
EFh_CREC_RCN3 cd16230
EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand ...
60-169 2.82e-05

EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand calcium-binding protein RLP49, is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal His-Asp-Glu-Leu (HDEL) tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320028 [Multi-domain]  Cd Length: 268  Bit Score: 43.04  E-value: 2.82e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  60 SPEDFANHLFTVFDK-----DNNGFIHFEEFITVLSTTSRGTLEEKLSWAFELYDLNHDGYITFDEMLTIV--------- 125
Cdd:cd16230   29 SPEESQARLGRIVDRmdragDGDGWVSLAELRAWIAHTQQRHIRDSVSAAWQTYDTDRDGRVGWEELRNATyghyepgee 108
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 398366535 126 ------ASVYKMM---------------GSMVTLNE------DEATPEMR---VKKIFKLMDKNEDGYITLDEF 169
Cdd:cd16230  109 fhdvedAETYKKMlarderrfrvadqdgDSMATREEltaflhPEEFPHMRdivVAETLEDLDKNKDGYVQVEEY 182
EFh_parvalbumin_like cd16251
EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes ...
52-126 1.00e-04

EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes alpha- and beta-parvalbumins, and a group of uncharacterized calglandulin-like proteins. Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI


Pssm-ID: 319994  Cd Length: 101  Bit Score: 39.82  E-value: 1.00e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  52 YKQFFP----FGSPEDFANHLFTVFDKDNNGFIHFEEFITVLSTTSRG--TLEEKLSWAF-ELYDLNHDGYITFDEMLTI 124
Cdd:cd16251   19 YKKFFEhvglKQKSEDQIKKVFQILDKDKSGFIEEEELKYILKGFSIAgrDLTDEETKALlAAGDTDGDGKIGVEEFATL 98

                 ..
gi 398366535 125 VA 126
Cdd:cd16251   99 VA 100
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
73-169 2.57e-04

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 40.26  E-value: 2.57e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  73 DKDNNGFIHFEEFITVLSTTSRGTLEEKLSWAFELYDLNHDGYITFDEmltivasvYKMM--GSMVTLNEDEATP----E 146
Cdd:cd16226   45 DKNGDGFVTEEELKDWIKYVQKKYIREDVDRQWKEYDPNKDGKLSWEE--------YKKAtyGFLDDEEEDDDLHesykK 116
                         90       100
                 ....*....|....*....|....*
gi 398366535 147 M--RVKKIFKLMDKNEDGYITLDEF 169
Cdd:cd16226  117 MirRDERRWKAADQDGDGKLTKEEF 141
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
100-128 2.71e-04

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 36.59  E-value: 2.71e-04
                           10        20
                   ....*....|....*....|....*....
gi 398366535   100 KLSWAFELYDLNHDGYITFDEMLTIVASV 128
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
149-171 2.89e-04

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 333786 [Multi-domain]  Cd Length: 27  Bit Score: 36.59  E-value: 2.89e-04
                          10        20
                  ....*....|....*....|...
gi 398366535  149 VKKIFKLMDKNEDGYITLDEFRE 171
Cdd:pfam00036   1 LKEIFRLFDKDGDGKIDFEEFKE 23
EF-hand_8 pfam13833
EF-hand domain pair;
39-89 3.18e-04

EF-hand domain pair;


Pssm-ID: 316358 [Multi-domain]  Cd Length: 53  Bit Score: 37.17  E-value: 3.18e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 398366535   39 PSGQLAREDFVKIYKQFFPFGSPEDFANHLFTVFDKDNNGFIHFEEFITVL 89
Cdd:pfam13833   1 EKGVITREDLRRALALLGLKGLSEEEVDILFREFDTDGDGYISFEEFCVLL 51
EF-hand_8 pfam13833
EF-hand domain pair;
112-169 3.34e-04

EF-hand domain pair;


Pssm-ID: 316358 [Multi-domain]  Cd Length: 53  Bit Score: 36.79  E-value: 3.34e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 398366535  112 HDGYITFDEMLTIVASVykmmgSMVTLNEDEATpemrvkKIFKLMDKNEDGYITLDEF 169
Cdd:pfam13833   1 EKGVITREDLRRALALL-----GLKGLSEEEVD------ILFREFDTDGDGYISFEEF 47
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
68-169 3.59e-04

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 39.73  E-value: 3.59e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  68 LFTVFDKDNNGFIHFEEFITVLSTTSRGTLEEKLSWAFELYDLNHDGYITFDE----MLTIVASVYKmmGSMVTLNEDEA 143
Cdd:cd15899   40 IVSKMDVDKDGFISAKELHSWILESFKRHAMEESKEQFRAVDPDEDGHVSWDEykndTYGSVGDDEE--NVADNIKEDEE 117
                         90       100
                 ....*....|....*....|....*...
gi 398366535 144 TPEM--RVKKIFKLMDKNEDGYITLDEF 169
Cdd:cd15899  118 YKKLllKDKKRFEAADQDGDLILTLEEF 145
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
25-128 4.65e-04

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 38.66  E-value: 4.65e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  25 REIQQWHKGFLR---DcPSGQLAREDFVKIYKQFfPFGSPEDFANHLFTVFDKDNNGFIHFEEFITVLSTTSRgtleekL 101
Cdd:cd16180   64 KYIQDWRRLFRRfdrD-RSGSIDFNELQNALSSF-GYRLSPQFVQLLVRKFDRRRRGSISFDDFVEACVTLKR------L 135
                         90       100
                 ....*....|....*....|....*....
gi 398366535 102 SWAFELYDLNHDGYIT--FDEMLTIVASV 128
Cdd:cd16180  136 TDAFRKYDTNRTGYATisYEDFLTMVLSI 164
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
149-171 6.24e-04

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 35.82  E-value: 6.24e-04
                           10        20
                   ....*....|....*....|...
gi 398366535   149 VKKIFKLMDKNEDGYITLDEFRE 171
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKD 24
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
40-169 6.37e-04

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 38.03  E-value: 6.37e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  40 SGQLAREDFVKIYKQFFpFGSPEDFANHLFTVFDKDNNGFIHFEEFITVLST-TSRGTLEEklswAFELYDLNHDGYITF 118
Cdd:cd15898   14 DGKLSLKEIKKLLKRLN-IRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSlTERPELEP----IFKKYAGTNRDYMTL 88
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 398366535 119 DEMLTIVASVykmmgsmvtlnEDEATPEMRVKKIFKLMDKN-EDGYITLDEF 169
Cdd:cd15898   89 EEFIRFLREE-----------QGENVSEEECEELIEKYEPErENRQLSFEGF 129
EFh_DMD_DYTN_DTN cd15901
EF-hand-like motif found in the dystrophin/dystrobrevin/dystrotelin family; The dystrophin ...
66-123 7.10e-04

EF-hand-like motif found in the dystrophin/dystrobrevin/dystrotelin family; The dystrophin/dystrobrevin/dystrotelin family has been characterized by a compact cluster of domains comprising four EF-hand-like motifs and a ZZ-domain, followed by a looser region with two coiled-coils. Dystrophin is the founder member of this family. It is a sub-membrane cytoskeletal protein associated with the inner surface membrane. Dystrophin and its close paralog utrophin have a large N-terminal extension of actin-binding CH domains, up to 24 spectrin repeats, and a WW domain. Its further paralog, dystrophin-related protein 2 (DRP-2), retains only two of the spectrin repeats. Dystrophin, utrophin or DRP2 can form the core of a membrane-bound complex consisting of dystroglycan, sarcoglycans and syntrophins, known as the dystrophin-glycoprotein complex (DGC) that plays an important role in brain development and disease, as well as in the prevention of muscle damage. Dystrobrevins, including alpha- and beta-dystrobrevin, lack the large N-terminal extension found in dystrophin, but alpha-dystrobrevin has a characteristic C-terminal extension. Dystrobrevins are part of the DGC. They physically associate with members of the dystrophin family and with the syntrophins through their homologous C-terminal coiled coil motifs. In contrast, dystrotelins lack both the large N-terminal extension found in dystrophin and the obvious syntrophin-binding sites (SBSs). Dystrotelins are not critical for mammalian development. They may be involved in other forms of cytokinesis. Moreover, dystrotelin is unable to heterodimerize with members of the dystrophin or dystrobrevin families, or to homodimerize.


Pssm-ID: 319999  Cd Length: 163  Bit Score: 38.41  E-value: 7.10e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 398366535  66 NHLFTVFDKDNNGFIHFEEFITVLSTTSRGTLEEKLSWAFELYDlNHDGYITFdEMLT 123
Cdd:cd15901   57 NWLLNLYDRNRTGCIRLLSVKIALITLCAASLLDKYRYLFGQLA-DSSGFISR-ERLT 112
EF-hand_7 pfam13499
EF-hand domain pair;
40-90 8.20e-04

EF-hand domain pair;


Pssm-ID: 338778 [Multi-domain]  Cd Length: 68  Bit Score: 36.48  E-value: 8.20e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 398366535   40 SGQLAREDFVKIYKQFFPFGSP--EDFANHLFTVFDKDNNGFIHFEEFITVLS 90
Cdd:pfam13499  16 DGYLDVEELKKLLRKLFEEGEKlsDEEVEELFKEFDLDKDGRISFEEFLELYR 68
EF-hand_6 pfam13405
EF-hand domain;
148-171 1.32e-03

EF-hand domain;


Pssm-ID: 338723 [Multi-domain]  Cd Length: 30  Bit Score: 34.86  E-value: 1.32e-03
                          10        20
                  ....*....|....*....|....
gi 398366535  148 RVKKIFKLMDKNEDGYITLDEFRE 171
Cdd:pfam13405   1 ELREAFKLFDKDGDGYISLEELRK 24
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
101-127 1.67e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 333786 [Multi-domain]  Cd Length: 27  Bit Score: 34.28  E-value: 1.67e-03
                          10        20
                  ....*....|....*....|....*..
gi 398366535  101 LSWAFELYDLNHDGYITFDEMLTIVAS 127
Cdd:pfam00036   1 LKEIFRLFDKDGDGKIDFEEFKELLKK 27
EFh_CREC_cab45 cd16225
EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also ...
53-168 2.02e-03

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also termed stromal cell-derived factor 4 (SDF-4), is a soluble, lumenal Golgi resident low-affinity Ca2+-binding protein that contains six copies of the EF-hand Ca2+-binding motif. It is required for secretory pathway calcium ATPase1 (SPCA1)-dependent Ca2+ import into the trans-Golgi network (TGN) and plays an essential role in Ca2+-dependent secretory cargo sorting at the TGN.


Pssm-ID: 320023 [Multi-domain]  Cd Length: 278  Bit Score: 37.66  E-value: 2.02e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  53 KQFFPFGSPE-------DFANHLFTVFDKDNNGFIHFEEFITVLSTTSRGTLEEKLS-WA------F-ELYDLNHDGYIT 117
Cdd:cd16225  151 EEFLSFRHPEhsrgmlkNMVKEILHDLDQDGDEKLTLDEFVSLPPGTVEEQQAEDDDeWKkerkkeFeEVIDLNHDGKVT 230
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 398366535 118 FDEMltivasvYKMMGSMvtlNEDEAtpEMRVKKIFKLMDKNEDGYITLDE 168
Cdd:cd16225  231 KEEL-------EEYMDPR---NERHA--LNEAKQLIAVADENKDGKLSLEE 269
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
66-92 2.27e-03

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 34.28  E-value: 2.27e-03
                           10        20
                   ....*....|....*....|....*..
gi 398366535    66 NHLFTVFDKDNNGFIHFEEFITVLSTT 92
Cdd:smart00054   3 KEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
63-128 2.51e-03

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination.


Pssm-ID: 320058 [Multi-domain]  Cd Length: 165  Bit Score: 36.85  E-value: 2.51e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 398366535  63 DFANHLFTVFDKDNNGFIHFEEFI---TVLSTtsrgtleekLSWAFELYDLNHDGYIT--FDEMLTIVASV 128
Cdd:cd16183  103 QFYDILVRKFDRQGRGTIAFDDFIqccVVLQT---------LTDSFRRYDTDQDGWIQisYEQFLEMVFSN 164
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
105-169 3.15e-03

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 34.50  E-value: 3.15e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 398366535 105 FELYDLNHDGYITFDEMLTIvasvykMMGSmvTLNEDEAtpemrvKKIFKLMDKNEDGYITLDEF 169
Cdd:cd00052    5 FRSLDPDGDGLISGDEARPF------LGKS--GLPRSVL------AQIWDLADTDKDGKLDKEEF 55
EFh_parvalbumin_alpha cd16254
EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2 ...
52-126 4.67e-03

EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2+/Mg2+-binding protein expressed mainly in fast-twitch skeletal myofibrils, where it may act as a soluble relaxing factor facilitating the Ca2+-mediated relaxation phase. It is also expressed in rapidly firing neurons, particularly GABA-ergic neurons, and thus may confer protection against Ca2+ toxicity. The major role of alpha-parvalbumin is metal buffering and transport of Ca2+. It binds different metal cations, and exhibits very high affinity for Ca2+ and physiologically significant affinity for Mg2+. Alpha-parvalbumin is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Both metal ion-binding sites in alpha-parvalbumin are high-affinity sites. Additionally, in contrast to beta-parvalbumin, alpha-parvalbumin is less acidic and has an additional residue in the C-terminal helix.


Pssm-ID: 319997  Cd Length: 101  Bit Score: 35.18  E-value: 4.67e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  52 YKQFFPF----GSPEDFANHLFTVFDKDNNGFIHFEEFITVL---STTSRGTLEEKLSWAFELYDLNHDGYITFDEMLTI 124
Cdd:cd16254   19 YKKFFEMvglkKKSADDVKKVFHILDKDKSGFIEEDELKFVLkgfSPDGRDLSDKETKALLAAGDKDGDGKIGIDEFATL 98

                 ..
gi 398366535 125 VA 126
Cdd:cd16254   99 VA 100
EFh_CREC_RCN2 cd16224
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed ...
73-171 5.25e-03

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed calcium-binding protein ERC-55, or E6-binding protein (E6BP), or TCBP-49, is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. It is associated with tumorigenesis, in particular with transformation of cells of the cervix induced by human papillomavirus (HPV), through binding to human papillomavirus (HPV) E6 oncogenic protein. It specifically interacts with vitamin D receptor among nuclear receptors. RCN2 contains an N-terminal signal sequence followed by six copies of the EF-hand Ca2+-binding motif, and a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320022 [Multi-domain]  Cd Length: 268  Bit Score: 36.26  E-value: 5.25e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  73 DKDNNGFIHFEEFITVLSTTSrgTLEEKLSWAFE-------LYDLNHDGYITFDEMLTIVasvykmmgsmVTLNEDEATP 145
Cdd:cd16224  171 DKDGDGFISLEEFLGDYRKDP--TANEDPEWIIVekdrfvnDYDKDNDGKLDPQELLPWV----------VPNNYGIAQE 238
                         90       100
                 ....*....|....*....|....*.
gi 398366535 146 EmrVKKIFKLMDKNEDGYITLDEFRE 171
Cdd:cd16224  239 E--ALHLIDEMDLNGDGRLSEEEILE 262
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
68-91 5.87e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 333786 [Multi-domain]  Cd Length: 27  Bit Score: 32.74  E-value: 5.87e-03
                          10        20
                  ....*....|....*....|....
gi 398366535   68 LFTVFDKDNNGFIHFEEFITVLST 91
Cdd:pfam00036   4 IFRLFDKDGDGKIDFEEFKELLKK 27
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
99-173 5.90e-03

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 36.02  E-value: 5.90e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 398366535  99 EKLSWAFELYDLNHDGYITFDEMLTIVASVYKMMgsmvtLNEDeatpemrVKKIFKLMDKNEDGYITLDEFREGS 173
Cdd:cd16226   35 ERLGIIVDKIDKNGDGFVTEEELKDWIKYVQKKY-----IRED-------VDRQWKEYDPNKDGKLSWEEYKKAT 97
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
69-171 7.37e-03

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 36.02  E-value: 7.37e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398366535  69 FTVFDKDNNG---------FIHFEEFITVLSTTSRGTLEEklswafelYDLNHDGYITFDEmltivasvYkmMGSMVTLN 139
Cdd:cd16226  125 WKAADQDGDGkltkeeftaFLHPEEFPHMRDIVVQETLED--------IDKNKDGFISLEE--------Y--IGDMYRDD 186
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 398366535 140 EDEATPE--MRVKKIFKL-MDKNEDGYITLDEFRE 171
Cdd:cd16226  187 DEEEDPDwvKSEREQFKEfRDKNKDGKMDREEVKD 221
PLN02964 PLN02964
phosphatidylserine decarboxylase
64-126 8.86e-03

phosphatidylserine decarboxylase


Pssm-ID: 215520 [Multi-domain]  Cd Length: 644  Bit Score: 35.99  E-value: 8.86e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 398366535  64 FANHLFTVFDKDNNGFIHFEEFITVLSTTSRGTLEEKLSWAFELYDLNHDGYITFDEMLTIVA 126
Cdd:PLN02964 180 FARRILAIVDYDEDGQLSFSEFSDLIKAFGNLVAANKKEELFKAADLNGDGVVTIDELAALLA 242
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.17
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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