Conserved Protein Domain Family
C2D_Ferlin

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cd04017: C2D_Ferlin 
C2 domain fourth repeat in Ferlin
Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.
Statistics
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PSSM-Id: 175984
View PSSM: cd04017
Aligned: 52 rows
Threshold Bit Score: 135.363
Threshold Setting Gi: 156337232
Created: 30-Dec-2004
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
putative Ca2+
Feature 1:putative Ca2+ binding site [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                     #     #                                             
4503431      1152 YHLRCYMYQARDLAa------------mDKDSFSDPYAIVSFL-HQSQKTVVVKNTLNPTWDQTLIFYEIeifgepatVA 1218 human
XP_001599714  542 CQTELFLWLGNAKFagacwsalppgyrlEDETLGGGRLDVFPKfLEYEKSSVIKQTLDPFWDQTLVFPAIdvhgmrehVK 621  jewel wasp
XP_393799     907 CKLEIFLWLGNADYvgrf------dpgmDTSGLLDPLIRVCFH-GYSISTRVVKQTLDPFWDQTLILPPRtvhgskeyIK 979  honey bee
EEB12737      698 YECHVHVFQAKIFNg------------fDKTGLADPFIRVIAF-GETITSKVRKNTLNPIWNETIVFPQLilygpsdyLK 764  human body louse
XP_970237     613 FEARVHIFQGRFTPg------------sDKSGLSDPFVHVIIS-SQFKETQVLQKTLNPVWDQTLVFRNVelygnrdfIT 679  red flour beetle
XP_002593371   14 YELHCYIYQARDLQs------------aDRDGMDDPFLSVFFS-CRNQRTKVVKKTLNPVWDQTLVFKDLriygtpetVA 80   Florida lancelet
XP_002161264  773 YILHAHIFQGRTVFg------------sDENGLSDPFARVMFG-NNMEETWAVPKTRMPLWDQSFVFDKVtl----ygTN 835  green hydra
ABO93155      362 FLCHVYIHQAKVRPg------------gEKKNICDSHLRVLFA-DQACETYTSPGTLSPIWDAVITFNWVslpggiglYL 428  fruit fly
XP_002046792  652 FRCHVYVHQAKVRPsg-----------mENRIICDGHVRVVFA-AQAAETHTTPGTCSPIWDAVITIKGLtlpgsiswYL 719  Drosophila vi...
XP_002062288  633 FRCQVYVHQAKVRPt------------aDKNNFCDGYLRTLFG-EQVAETYTSPGTHSPIWNAVTTLKGLtlpgsigwYL 699  Drosophila wi...
Feature 1                    # #                                                                  
4503431      1219 EQPPSIVVELYDHDTY---------------GADEFMGRCICQPSLERm--------------------------PRLAW 1257 human
XP_001599714  622 NHPPKVVLEAFDRDYC---------------NSLELYGRCVARPLVKLdteths----------------ppdfpPKLRW 670  jewel wasp
XP_393799     980 LNPPIVILEVYDLDIC---------------GIKEFCGRCTAIPLVKLaeetys----------------ppdfpPKLGW 1028 honey bee
EEB12737      765 KDSVTFVVDVLDKDTS---------------KKADFIGRSFIKPKLKEikgeknk--------------kskenvEKLKW 815  human body louse
XP_970237     680 ANPPSVFIEIFDKDEC---------------QQIEVIGKCVLRPIIKTlkgeq------------------gsgsLRLTW 726  red flour beetle
XP_002593371   81 ANPPPVVVQVYDHDLWrn-----------ehLGSVEMTPLVAKDGEQQg-------------------------dTKLRW 124  Florida lancelet
XP_002161264  836 SNMPSPVVLITIFDKDs--------------NGEEFIGQAIASPRLITngy----------------------vpAKLQL 879  green hydra
ABO93155      429 KNPPLLSLEFYNSERSlpe---------dlvGMGSLAMSVVSEDRASDsnwedagvfgcsrnplrklqrlkyltpPPLKW 499  fruit fly
XP_002046792  720 QNPPMIGVELFNSEYDa-------------vGSGHIVVSVIADDNDMEnsrgdesrcwgrs-pvhkmkklknvspPPLKW 785  Drosophila vi...
XP_002062288  700 QNPPVFSMEYRNTERTsnddhvakgyitasvISAEDHVRNTEREEAAAglcwtrspvq-------kfqrlkhitpPPLKW 772  Drosophila wi...
Feature 1                                            
4503431      1258 FPLTRGsq------------pSGELLASFELIQRE 1280 human
XP_001599714  671 HRFGHDddngnddrrpaaddsGAAVLAAFELVEVC 705  jewel wasp
XP_393799    1029 YKFKSQrd------------fSGSVLAAFELIEVK 1051 honey bee
EEB12737      816 EKIRKDyn------------pTGEILIAIDLVEIT 838  human body louse
XP_970237     727 YRVHNVfd------------vSAEILAAAELLEVT 749  red flour beetle
XP_002593371  125 HPISVGgk------------hHGDVLATCKLFRVR 147  Florida lancelet
XP_002161264  880 IPLYLGkq------------sVGDILASFELFPVD 902  green hydra
ABO93155      500 VPIARKgt------------lQAEVLMSAEIIQIS 522  fruit fly
XP_002046792  786 VSMAKNgm------------vQAEVLMSVEFKELV 808  Drosophila virilis
XP_002062288  773 LPVALKgi------------vWAEVLMSVELIELV 795  Drosophila willistoni

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