Conserved Protein Domain Family
C2E_Ferlin

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cd04037: C2E_Ferlin 
C2 domain fifth repeat in Ferlin
Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.
Statistics
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PSSM-Id: 176002
View PSSM: cd04037
Aligned: 47 rows
Threshold Bit Score: 113.414
Threshold Setting Gi: 67582352
Created: 27-Dec-2004
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Ca2+ binding
Feature 1:Ca2+ binding site [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                        #     #                                                          
CAI11718     1488 LVRIYIIRATDLHPADinGKADPYIVIKLGKsd----------iRDKENYISk--qLNPVFGKSFDIEATFPmesMLTVA 1555 zebrafish
XP_002142388 1414 LSNIKSTKSEGSWYLNlkTGHDQIGNSSNGIfe----------iNDSENCVQg---FSPEFYKTYILDALLPtnaLLSIT 1480 Cryptosporidi...
XP_001031491 1365 FIRIYVTRGKNIGGEG--FSPDSYLKLKLGEkv----------vDLKSKTLQqd-tNNPDYYISYDFECKLPgsaVLEVQ 1431 Tetrahymena t...
XP_001436900 1050 TIRLYVIDCSNLPPKDqdSMSDPYLKIRLGKea----------iDDVENRITd--nCNPQYYKRYDITTELPgasELTIQ 1117 Paramecium te...
XP_001017854 1083 LVRLYVLEAVNIPNADelDESDPYLIVRLGDqk----------iSTRKRFIKd--nCNPKFYEMFEFKTCLPgdpLLKIQ 1150 Tetrahymena t...
CAL50497     1467 TIRLYAIRGRDLRTSDpsGLCDPYLVVNLRGvkk--------syGKRDDHVRr--tLSPWFYKSFQVSTEVPgnsILDVH 1536 Ostreococcus ...
ACO69722       26 IVRAFVVRGKNIRPLDpsGLCDPYMKVDLLGtgk--------rfGNRRDHVKe--tLAPWFYKMFQFTTELPgssQLQFK 95   Micromonas sp...
EEE25514     1051 VVRAYVLAARGLVPPSgaSDIQTYVWIQDSEnaatlp--gglsyNIRDTGYTkkqgFKPEFNRCYTLACSLPensIVQIA 1128 Toxoplasma go...
CAX64098     1331 VVRAYIIQARGLNPPSgaTDITTYIWIKNSNdmtnipgglshniKDTGHTKKq--gYKPEFNRCYQLLCSFPdesIVQVC 1408 Plasmodium fa...
XP_001610088  921 VVRLYVLQAKGLYTSRgnSNITTYLWVRNIDgeqkrs--lsypqNVRDTTVIaq-gVKPMYNTCFNLGCALPenaILKIS 997  Babesia bovis...
Feature 1           # #    #                                                                      
CAI11718     1556 VYDWDLVgTDDLIGETKIDLEnryy-skhRATCGIASnys-----------------------vhGYNVWRDPQKPAQIL 1611 zebrafish
XP_002142388 1481 VMYKNNN-LNQSYGRTYIDIEdrff-hprYQKILSNPnsilpieirqlypfndqwnyiptnypvgSLRCWFHILPPEISL 1558 Cryptosporidi...
XP_001031491 1432 IWNDVIG-SDEMIGKTVIDMEnrlf-tgkWLQYQRKPfenrnifp-------------edesvskGNLEMWVELIPKSLI 1496 Tetrahymena t...
XP_001436900 1118 VWDYDDFmPDELIGQTVIDIEeryfqqrfRQLKQIPIet------------------------rqLIHPSSSMPQGQIRL 1173 Paramecium te...
XP_001017854 1151 LWDYDELsADDFLCETVIDLEdrf--yskRWRKLVNPpie-----------------------trPLYHYSSSMQKGELR 1205 Tetrahymena t...
CAL50497     1537 VWNWDKRgKDVLIGTVSVDVEdrf--fsqIWAQNLSDkpp----------------------levRPILLPDSNAPQGYL 1592 Ostreococcus ...
ACO69722       96 LYDWDKNgGDDVIGVNTVDLEdrwf-spiWKSQFSETppl-----------------------elRTLLNNDATGSQGSL 151  Micromonas sp...
EEE25514     1129 VMNMGRL-TDECIGRTYLDVEdrff-nkkVEQMVIEEstp----------------------ielRTLKNEGSTVSHGSL 1184 Toxoplasma go...
CAX64098     1409 IMNQGSL-SDEIIGYTYIDMEdry--fnqKIRQLMIDdlmp---------------------ielRSLKLENSTISHGSL 1464 Plasmodium fa...
XP_001610088  998 VVHQGTL-QDEVIGTTFVDCEdrf--lnhKMFQLMQDdavp---------------------ielRTLKNEDSTVSHGTL 1053 Babesia bovis...

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