Conserved Protein Domain Family
C2_Perforin

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cd04032: C2_Perforin 
C2 domain of Perforin
Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. 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.
Statistics
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PSSM-Id: 175998
View PSSM: cd04032
Aligned: 18 rows
Threshold Bit Score: 191.706
Threshold Setting Gi: 149472392
Created: 11-Jan-2005
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                                                    #     #                             
1411296A     389 HDSCQCECQDSk----VTNQDCCPRQRGLAHLVVSNFRAEHLWGDyttaTDAYLKVFFGGqEFRTGVVWNnnNPRWTDKM 464 house mouse
XP_001345782 412 SARDRCACVCEss--qVIKSNCCPAENGLATLKVYNLRANGLYGDvrtqTDGTVLVKYGKtIKRTETIDNndNPRWRDTF 489 zebrafish
AAH84651     359 SQREDCSCSCSps--kYTNSDCCPTRKGLAKLIIEIRSATGLNGDyfssTDSYVNFYFNGyEKETETIFDndDPMWNETL 436 African clawed ...
CAG10870     372 REDQLGSKNCSpt--pNLDHNCCPLRSGRGTLRLMIHRAAGLRADtftkTDAYVKIFYNGmYEETETVMDdnDPVWNATY 449 Tetraodon nigro...
XP_425355    331 SAVGLCQCGCAan--nAVSADCCSKHRGMAQVTVTVLEGSGWRGDfftpTDAYVLLYFNGqRVRTATVWNnnRPRWGARF 408 chicken
ACI33854     390 SAHDSCQCVCKas--kEMTSQCCPQEKGLAHLTVTVKYARDLWGDttseTDGLVKVIMDNeARQTKVIHNknNPVWNSFY 467 Atlantic salmon
XP_001345710 376 SARDPCVCVCEss--kIMKSNCCPTEKGLATLKVYNLRANGLFGDtltqTDGYVEIKHQGqNKRTQTIVDndNPRWSETF 453 zebrafish
AAI54629     370 ISVDHKENQGCsq-tpNLDHNCCPMRAGRGTLIVLVQRAAGLKADlftrTDGYVKVWYNFmYEETEVVMDnnDPEWNISY 448 zebrafish
XP_001517199 388 SAHDPCRCVCHes--wGMNEECCPKKRGLAKLQVKIIKASGLWGDyftsTDAYVRVFFGGfEQRTPTIWNnnNPVWQTDI 465 platypus
XP_001375097 390 KKSPQNPCHCVcqastLTNGDCCPRERGLAHLEVTGLSARNLYGDifslTDGYIKAFFGNkELRTYVVWNnnNPKWDQNL 469 gray short-tail...
Feature 1                          # #        #                       
1411296A     465 DFENVllstggPLRVQVWDADYGw---DDDLLGSCDRSPh-SGFHEVTCELNH 513 house mouse
XP_001345782 490 DFGPVkitmaeRLCFEVYDADSNw---NSDLLGKCSFKLr-SGVVTDACVFNY 538 zebrafish
AAH84651     437 DFGMVelgplkKYTIEVWDEDITt---DNDLLLTCKGILk-AGNNKMSCQYSD 485 African clawed frog
CAG10870     450 NFGSVev--gqELRLEVWDRDVL----YNDVAGRCVAVPe-RGTHSFSCQLKK 495 Tetraodon nigroviridis
XP_425355    409 DFGWVmlhphqKMKVEVWDQDNGw---NDDRLGVCELPV--QATGRQQRNVVC 456 chicken
ACI33854     468 DFGFVklslasELKFEVYDEDKNwykwWNDLLGNCSTRPivPGSDKQLCALNH 520 Atlantic salmon
XP_001345710 454 NFGHInikigsTLTLEVYDEDDFw---NRDHLGTCSVKVs-SGVVNDGCALDH 502 zebrafish
AAI54629     449 DLGSVef--ghELIFEVWDSDVI----YNDMVGRCVVSPe-RGIHSHSCKLKK 494 zebrafish
XP_001517199 466 DFGPVqlnsggPLRIQVWDADNGw---DDDLLGTCDWAPhtEDSKIQDCYLNH 515 platypus
XP_001375097 470 DFGAVslmaggPLRLQVWDADHGw---DDDLLGSCDRVPv-AGGRKEQCHLNH 518 gray short-tailed opossum

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