Conserved Protein Domain Family
C2F_Ferlin

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cd08374: C2F_Ferlin 
C2 domain sixth 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 sixth C2 repeat, C2E, and has a type-II topology.
Statistics
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PSSM-Id: 176020
View PSSM: cd08374
Aligned: 36 rows
Threshold Bit Score: 122.002
Threshold Setting Gi: 67586366
Created: 14-Sep-2009
Updated: 2-Oct-2020
Structure
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Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
XP_001628928  184 ELRVIIWNTsd----viLEETSITGek--mSDIYVKGWLaga-------------ddPQKTDVHYrslDGEGNFNWRFIF 244  starlet sea a...
XP_626436    1457 EVRVIIWAGr------dIKTANNLDy----GDYLFKSTLdckqypefrpdfgnnnprVQQTDVHYncrTGEPVFNWRLVY 1526 Cryptosporidi...
XP_002260315 1662 EIRIIIWRCtm-----lPMDENVSKt----FDLLVTAELdcvnyn-------ganstIQSTDVHYsckNGNALFNWRVVY 1725 Plasmodium kn...
EEE32236     1226 EIRVIVWGAr-------NLNFKALGkd--fVDAMIRCNLdctgyr-------gsqpiAQQTDVHYyskTGAAIFNWRMVY 1289 Toxoplasma go...
XP_002141895 1486 EIRIVIWAGrs----ikIPKNKDYGd----FAIQVSLDCnqyhgnkv--ksreiyskQQLTDVHYncrNGEPVFNWRVVF 1555 Cryptosporidi...
XP_665186     195 QVRVVIYRLknipisklVNNTGILAfgepsISLMVKGLMspnn----------ntilEQDTDTHWnssDGTAIFNWRFVF 264  Cryptosporidi...
XP_001437572 1279 EVRVIVWETf-------NIPLNPVKk---aVDIFVRCVMdssatg-------tgseiGKETDTHMgstDGNGEFNWRMKF 1341 Paramecium te...
NP_001137915  845 EVRVVVKNLvg----iqAGDKNIFGkl--mSDVYVIGWCede-------------dkRQSTDIHYrsfAGDAAFNWRMVF 905  fruit fly
XP_001901784 1698 QLRVAVWSVrn-----vILTKRTMGkp--aADIYLKVFLngs-------------ekKEKTDVHYrslDGYGSFNWRFVF 1757 agent of lymp...
NP_001122477 1576 QLRIAVMDVrg----aiPVKRSFAEp---vSDLYVKAFIngm-------------tkGHKTDTHFrvlDGTGEFNWRFLL 1635 nematode
XP_001628928  245 PFMYLPAEKIM--VVKKKVHFWslde-----------teerVPLRLIIQIWDNDq--------------FSPDDFLGQLE 297  starlet sea a...
XP_626436    1527 PHLVTPISGCL--LQISIYHYSsfgnhefigevnldlrkyiMNVANSLEAIDEDvelpl-----vnsqsVDSSFDAGFVQ 1599 Cryptosporidi...
XP_002260315 1726 PQISHPLNTCF--LQLAAYNNNnvgvseflgevnlelskyiNKASQIVNKLELDaelklr----kkkgtDSDNNYNGYLQ 1799 Plasmodium kn...
EEE32236     1290 SRVVMPVSTCV--LQIAAYDNRnmgespfigevnlelrrylERVASTLNSIDVDaelkli----nrsreSADVSSFGFVQ 1363 Toxoplasma go...
XP_002141895 1556 PYIVTPVSGCL--LQISLLNYStlgnhdflgevnldmrkyiMNVANTLEMIDSDvelpli----ntqetDEVYRNPGYVQ 1629 Cryptosporidi...
XP_665186     265 NIPVPCHFPILr-LQVWNRGLLvfgdaisec-sfdlssylmRSRKLNSKVNISRtlin-------mchpARPNEKRGEME 335  Cryptosporidi...
XP_001437572 1342 NFKTPCQFPRMkiSVHDFSVFGaspii----------geatISLKRVLTVMKTQaiyemaptqiklssaKEPDAEKGTVM 1411 Paramecium te...
NP_001137915  906 GLKYSPNEDLM--VIRRKAGLLeei-------------efkKPPIIYLQVWDKDv--------------LTKDEYLAALE 956  fruit fly
XP_001901784 1758 DFDFDIWEKKIa-MYTKKHLFGkks-------------sllVDPILFVQIWDNNk--------------FRKDGYIGQLA 1809 agent of lymp...
NP_001122477 1636 NFDYNPWEKKVv-AYTKNRFFCkpv-------------eelVDPILVIELWDKNk--------------FRKDRLLGDIE 1687 nematode
XP_001628928  298 LTLn-RMPKPAKSARKCNL 315  starlet sea anemone
XP_626436    1600 VTIq-IIPQSEANSKKVGM 1617 Cryptosporidium parvum Iowa II
XP_002260315 1800 VTVq-FLPQTKANTKPVGL 1817 Plasmodium knowlesi strain H
EEE32236     1364 VSLq-FISQSEATSKPVGL 1381 Toxoplasma gondii VEG
XP_002141895 1630 LTIq-ILTQSEANSKKVGL 1647 Cryptosporidium muris RN66
XP_665186     336 IEIs-ILPLSLAESSPVGI 353  Cryptosporidium hominis TU502
XP_001437572 1412 LQMt-ILQKSMAEAKPVGE 1429 Paramecium tetraurelia strain d4-2
NP_001137915  957 LNLs-NMYAPYPAAQLCKP 974  fruit fly
XP_001901784 1810 LDLlsFDEAQMDADEMYNI 1828 agent of lymphatic filariasis
NP_001122477 1688 LDLl-DFIEGIGSPSDVGV 1705 nematode
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