4PHJ,1AJ5,1ALW,1DF0,1DVI,1QXP,1KFX,4PHN


Conserved Protein Domain Family
EFh_PEF_CPNS1_2

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cd16188: EFh_PEF_CPNS1_2 
Click on image for an interactive view with Cn3D
Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit CAPNS1 and CAPNS2
CAPNS1, also termed calpain small subunit 1 (CSS1), or calcium-activated neutral proteinase small subunit (CANP small subunit), or calcium-dependent protease small subunit (CDPS), or calpain regulatory subunit, is a common 28-kDa regulatory calpain subunit encoded by the calpain small 1 (Capns1, also known as Capn4) gene. It acts as a binding partner to form a heterodimer with the 80 kDa calpain large catalytic subunit and is required in maintaining the activity of calpain. CAPNS1 plays a significant role in tumor progression of human cancer, and functions as a potential therapeutic target in human hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC), glioma, and clear cell renal cell carcinoma (ccRCC). It may be involved in regulating migration and cell survival through binding to the SH3 domain of Ras GTPase-activating protein (RasGAP). It may also modulate Akt/FoxO3A signaling and apoptosis through PP2A. CAPNS1 contains an N-terminal glycine rich domain and a C-terminal PEF-hand domain. CAPNS2, also termed calpain small subunit 2 (CSS2), is a novel tissue-specific 30 kDa calpain small subunit that lacks two oligo-Gly stretches characteristic of the N-terminal Gly-rich domain of CAPNS1. CAPNS2 acts as a chaperone for the calpain large subunit, and appears to be the functional equivalent of CAPNS1. However, CAPNS2 binds the large subunit much more weakly than CAPNS1 and it does not undergo the autolytic conversion typical of CAPNS1.
Statistics
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PSSM-Id: 320063
Aligned: 17 rows
Threshold Bit Score: 310.134
Created: 13-Feb-2015
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 13 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.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                    #      #                 #                # #      #                
4PHJ_A         5 QFRRLFAQLAGDDMEVSATELMNILNKVVtrhpDLKTDGFGiDTCRSMVAVMDSDTTGKLGFEEFKYLWNNIKRWQAIYK 84  human
1ALW_A         5 QFRRLFAQLAGDDMEVSATELMNILNKVVtrhpDLKTDGFGiDTCRSMVAVMDSDTTGKLGFEEFKYLWNNIKKWQAIYK 84  pig
4PHN_A         5 QFRRLFAQLAGDDMEVSATELMNILNKVVtrhpDLKTDGFGiDTCRSMVAVMDSDTTGKLGFEEFKYLWNNIKKWQAIYK 84  pig
BAA22638      46 QFRRLFTQLAGDDMEVSPTELMNILNKVVtrhpDLKTDGFGlDTCRSMVAVMDSDTTGKLGFEEFKYLWNNIKKWQLVYK 125 chicken
Q96L46        80 RFRQQFTQLAGPDMEVGATDLMNILNKVLskhkDLKTDGFSlDTCRSIVSVMDSDTTGKLGFEEFKYLWNNIKKWQCVYK 159 human
AAH78469      59 QFRRLFSQLAGDDMEVSAAELMGILNKVVarhqDLKTDGFSvDSCRSMVAVMDSDSTGKLGFEEFKYLWDNIKKWQGVYK 138 African clawed ...
NP_001017899  48 QFRKVFNQLAGDDMEVSPTELMNILNKIIskhgDLKTDGFTiESCRSMVAVMDSDSTGKLGFHEFKHLWNNIKKWQGIYK 127 zebrafish
NP_001087910 164 QFRRLFKQLAGEDMEVNADELKNVLDKVVakhqDLKTSGFSiDTCRSMVAIMDSDGTGKLGFEEFKYLWNNIKKWQCIYK 243 African clawed ...
XP_004944228  80 QFRRLFVQLAGDDMEVSATELRNILNKVLsrhqDLKTDGFSlDTCRSMVAVMDTDTNGKLGFEEFKYLWNNIKKWQCAYK 159 chicken
XP_005507187  80 RFRRLFAQLAGDDMEVCATELRDILNKVVsrhqDLKTNGFSlDTCRSMVAVMDTDTNGKLGFEEFKYLWNNIKKWQGVYK 159 rock pigeon
Feature 1          # # #      #                               # ##                               
4PHJ_A        85 QFDTDRSGTICSSELPGAFEAAGFhlnehLYNMIIRRYSDESGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQ 164 human
1ALW_A        85 QFDVDRSGTIGSSELPGAFEAAGFhlnehLYSMIIRRYSDEGGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQ 164 pig
4PHN_A        85 QFDVDRSGTIGSSELPGAFEAAGFhlnehLYSMIIRRYSDEGGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQ 164 pig
BAA22638     126 RFDTDRSGTIGVQELPGAFEAAGFrlppeLWGVLGRRYGDEGGNLDFDNFISCLVRLDAMFRAFKSLDRDGSGQIRVSLQ 205 chicken
Q96L46       160 QYDRDHSGSLGSSQLRGALQAAGFqlneqLYQMIVRRYANEDGDMDFNNFISCLVRLDAMFRAFKSLDRDRDGLIQVSIK 239 human
AAH78469     139 RYDTDRSGTIGRNELPGAFSSAGFqlngqLYEMIVRRYSDENGEMDFDNYICCLVRLDAMFRAFKTLDKDGDGQIKVTIE 218 African clawed ...
NP_001017899 128 TYDRDHSGTIGADELPAAFRAAGFpltdqLFQMIIRRYSDESGNMDFDNYIGCLVRLDAMCHAFKTLDKDNDGTIKVNVQ 207 zebrafish
NP_001087910 244 QFDTERSGYINCQALPGALKAAGFdlhdqLHVLLARRYADESGNINFDSFISALVRLDAMYRAFKALDRENTGQVQVRMP 323 African clawed ...
XP_004944228 160 RCDTNQSGILERAQLPAALRAAGFqlneqLCQVIMRRYASEDGSMDFNNFISCLVRLDSMFRAFKSLDRNGNGQIKMTIE 239 chicken
XP_005507187 160 QYDTNQSGTVGRAQLPDALKAAGFhlneqLCQVIVRRYADEDGSMDFNSFISCLVRLDGMFRAFKSLDRDGNGQIKVTIE 239 rock pigeon
Feature 1                 
4PHJ_A       165 EWLQLTMYS 173 human
1ALW_A       165 EWLQLTMYS 173 pig
4PHN_A       165 EWLQLTMYS 173 pig
BAA22638     206 EWLQLTMYS 214 chicken
Q96L46       240 EWLQLTMYS 248 human
AAH78469     219 EWLQLTMYS 227 African clawed frog
NP_001017899 208 EWLQLTMYS 216 zebrafish
NP_001087910 324 EWLKLTIYS 332 African clawed frog
XP_004944228 240 DWLQLTMYS 248 chicken
XP_005507187 240 DWLQLTMYS 248 rock pigeon

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