4PHJ,1KFX,2I7A,4OKH


Conserved Protein Domain Family
EFh_PEF_Group_II_CAPN_like

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cd16182: EFh_PEF_Group_II_CAPN_like 
Click on image for an interactive view with Cn3D
Penta-EF hand, calcium binding motifs, found in PEF calpain family
The PEF calpain family belongs to the second group of penta-EF hand (PEF) proteins. It includes classical (also called conventional or typical) calpain (referring to a calcium-dependent papain-like enzymes, EC 3.4.22.17) large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14) and two calpain small subunits (CAPNS1 and CAPNS2), which are largely confined to animals (metazoans). These PEF-containing are nonlysosomal intracellular calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates in response to calcium signalling. The classical mu- and m-calpains are heterodimers consisting of homologous but a distinct (large) L-subunit/chain (CAPN1 or CAPN2) and a common (small) S-subunit/chain (CAPNS1 or CAPNS2). These L-subunits (CAPN1 and CAPN2) and S-subunit CAPNS1 are ubiquitously found in all tissues. Other calpains likely consist of an isolated L-subunit/chain alone. Many of them, such as CAPNS2, CAPN3 (in skeletal muscle, or lens), CAPN8 (in stomach), CAPN9 (in digestive tracts), CAPN11 (in testis), CAPN12 (in follicles), are tissue-specific and have specific functions in distinct organs. The L-subunits of similar structure (called CALPA and B) also have been found in Drosophila melanogaster. The S-subunit seems to have a chaperone-like function for proper folding of the L-subunit. The catalytic L-subunits contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The S-subunits only have the PEF domain following an N-terminal Gly-rich hydrophobic domain. The calpains undergo a rearrangement of the protein backbone upon Ca2+-binding.
Statistics
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PSSM-Id: 320057
View PSSM: cd16182
Aligned: 26 rows
Threshold Bit Score: 162.778
Threshold Setting Gi: 524874153
Created: 18-Nov-2014
Updated: 18-Aug-2016
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 14 residues -Click on image for an interactive view with Cn3D
Feature 1:Ca binding site [ion binding site]
Evidence:
  • Structure:4PHJ; Homo sapiens calpain small subunit 1 binds four Ca2+ ions, through its EF1, EF2, EF3, and EF4 hands.
    View structure with Cn3D
  • Structure:4OKH; Homo sapiens calpain-3 binds four Ca2+ ions through its EF1, EF2, EF3, an EF5 hands.
    View structure with Cn3D
  • Comment:Ca2+ binding at EF5 of the calpain-3 PEF domain is a distinct feature not observed in other calpain isoforms.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                      #      #                     #              # # #      #           
4PHJ_A          5 QFRRLFAQLAG-DDMEVSATELMNILNKVVtrhp----dlkTDGFGidTCRSMVAVMDSDTTgkLGFEEFKYLWNNIKRW 79
gi 115615     589 EIEQKFLAIRDpKTNAINAVKLGELLNNSTlqd-----ipnFQGFNkeLCRSMVASVDNNLTghVELNEFMDLWIQAKGW 663
gi 62510466   758 ALRRLFDSVAG-SDEEVDWQELKRILDHSMrdv-----mvgSDGFSkdAVRSMVAMLDKDRSgrLGFEEFEALLTDIAKW 831
gi 229541100  515 QYEPVYMQLAD-ENKTINCFELHELLEACLpnd------yiKGCANidICRQVIALQDRSGSgrITFQQFKTFMVNLKSW 587
gi 353230291  600 SLELNFKQLCNpVTEKINSRILGTILDQSNfgey----mdgFTEFPsnLCSSLISSASTNLTgqIDLEEYLYLLIDLKGW 675
gi 358334968  567 WLTKRFEEVCDqESHSIHAGQLQKIINESRlrd-----lpnFQPFSleVCRSLVATMDSNHSgrMELSELLEFWNRIEQW 641
gi 674562206  584 FVDSLFNSAKDpVTNSINAEQLRDILNKSTmkss----ctdPNGFQleAVRSMLASMDNNMTgkMEYDEFKRLWENCQCW 659
gi 358253196  599 EIKERFDQLCDkKTASINATDLQNLLNGSSlqd-----mpgFEGFNreMCRSMVAAVDHNLTgrVEFSEFMDLWQHAKGW 673
gi 270011904  532 EGKSILSKLLTkFPPEVDASQLQKILRAHWks-------ylSEKPSleLCKSLIMLRDYNISgrINLMDIPVLMHMLQFW 604
gi 270003154  139 PWLEVFKKISH-NGNEIGIDGVRKALNHQFgekrllgliksKIEFSkeTCKNILALWDLDHSgkLDLNEFECLMQDVYEL 217
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                #  # #      #                                # ##                        
4PHJ_A         80 QAIYKQFDt-DRSGTICSSELPGAFEAAGFhlnehLYNMIIRRYSDe-SGNMDFDNFISCLVRLDaMFRAFKSLDkd-gT 156
gi 115615     664 KHIFIKHDv-DQSGYFSAYEFREALNDAGYhvsnrLINAIINRYQDpgTDKISFEDFMLCMVRLKtAFETIEAHPkn-iE 741
gi 62510466   832 RAVFKLYDt-RRTGSIDGFHLRGALNSAGYhlnnrLLNALAHRYGSr-EGQIPFDDFLMCAIKVRtFIEMFRERDtd-nS 908
gi 229541100  588 QGVFKMYTk-EKAGILRAERLRDALCDIGFqlstdIMNCLIQRYIRk-DGTLRLSDFVSAVIHLTtAFNQFHLKNyg-qV 664
gi 353230291  676 MLTFNKYD--DRKGCVSWFKFRDLLKSSGYkvsnrVFSVLAHRHIDhkRGHISLESYLHCMANLKfAFDVTSYHPks-dK 752
gi 358334968  642 KHAYLMSEe-DLNGGLTACQLRETLQLAGFelsnlVLNSVSLRYAHpqTGLVTFEDFIHCCARLKaAFETFEAHPkn-hS 719
gi 674562206  660 RDVFAQRDr-DASKTLNVTELREALMSAGFhlsglVFTVVVQRFVTqkLNAVTFEDWLICCVRLKnSFETMKAQFkt-nD 737
gi 358253196  674 KNVFLKHDv-DRSGKFQAEEFREALRSCGYtvsnkFFNALVHRYQDpdTEVMRFEDFMLCVIRLKnVFETSAAQPkt-yE 751
gi 270011904  605 RCAFQKFErgHGNGKTSSYHLRALLWEAGCtvsnkVLECLVLRFAK--NRILTTENYVMALVRLHlAHERYHNIDt--kM 680
gi 270003154  218 QQKFKKYDt-DDTGKLSGFDLRNILNDCGFkvnpnILTQLMFRYGD--KGSMKFANLVVCIFKLKtIIVEFSRRQsqetT 294
                         170
                  ....*....|....*.
Feature 1                         
4PHJ_A        157 GQIQVNIQEWLQLTMY 172
gi 115615     742 GTSLFSAEDYLRFSVY 757
gi 62510466   909 DTAFFNLDDWLERTIY 924
gi 229541100  665 NVIEVHLHDWIKSILS 680
gi 353230291  753 GILMFNKEDVYSPDEN 768
gi 358334968  720 GEAIFTHEDFLRMTTY 735
gi 674562206  738 GNLMFTEDDFLRLTIN 753
gi 358253196  752 GAPMFTTDDYLRCSVY 767
gi 270011904  681 KSNPLSLEEMILMTIY 696
gi 270003154  295 DHIVLNQKDLLAITLH 310

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