Conserved Protein Domain Family
EFh_PEF_CalpA_B

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cd16196: EFh_PEF_CalpA_B 
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), calpain-B (CalpB), and similar proteins
The family contains two calpains that have been found in Drosophila, CalpA and CalpB. CalpA, also termed calcium-activated neutral proteinase A (CANP A), or calpain-A catalytic subunit, is a Drosophila calpain homolog specifically expressed in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. CalpB, also termed calcium-activated neutral proteinase B (CANP B), contains calpain-B catalytic subunit 1 and calpain-B catalytic subunit 2. Both CalpA and CalpB are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. Besides, CalpA and CalpB display some distinguishing structural features that are not found in mammalian typical calpains. CalpA harbors a 76 amino acid long hydrophobic stretch inserted in domain IV, which may be involved in membrane attachment of this enzyme. CalpB has an unusually long N-terminal tail of 224 amino acids, which belongs to the class of intrinsically unstructured proteins (IUP) and may become ordered upon binding to target protein(s). Moreover, they do not need small regulatory subunits for their catalytic activity, and their proteolytic function is not regulated by an intrinsic inhibitor as the Drosophila genome contains neither regulatory subunit nor calpastatin orthologs. As a result, they may exist as a monomer or perhaps as a homo- or heterodimer together with a second large subunit. Furthermore, both CalpA and CalpB are dispensable for viability and fertility and do not share vital functions during Drosophila development. Phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid can stimulate the activity and the rate of activation of CalpA, but not CalpB. Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis. CalpB directly interacts with talin, an important component of the focal adhesion complex, and functions as an important modulator in border cell migration within egg chambers, which may act via the digestion of talin. CalpB can be phosphorylated by cAMP-dependent protein kinase (protein kinase A, PKA; EC 2.7.11.11) at Ser240 and Ser845, as well as by mitogen-activated protein kinase (ERK1 and ERK2; EC 2.7.11.24) at Thr747. The activation of the ERK pathway by extracellular signals results in the phosphorylation and activation of calpain B. In Schneider cells (S2), calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.
Statistics
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PSSM-Id: 320071
View PSSM: cd16196
Aligned: 24 rows
Threshold Bit Score: 212.062
Threshold Setting Gi: 674589455
Created: 19-Feb-2015
Updated: 18-Aug-2016
Structure
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Aligned Rows:
  next features
Feature 1:Ca binding site [ion binding site]
Evidence:
  • Comment:Based on the structure evidence that Rattus norvegicus m-calpain (3DF0) 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:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                     # #    #                 #              # # #      #                
gi 62510466   758 ALRRLFDSVAGSDEEVDWQELKRILDHSMrdv-mvgSDGFSkDAVRSMVAMLDKDRSGRLGFEEFEALLTDIAKWRAVFK 836
gi 195996895  515 AFHEIFDRVAGTDEEVDAFELQQILNQGLvkmfgqsSATFSlEACRSMVAMVDQDRSGKLNYDEFRNLWQTIKSWKDNFQ 594
gi 674593068  835 KLRAAFDDIAGESSDIEAEDLRNILNRVFekkvgesFEGFSlETARSMVALMDVDTSGTLGFEEFKTLWYELRLWLTIFK 914
gi 353229533  580 RLRRLFYEASGESMAVDAFQLEPILNCLLrddhrapYSMVStDACRSLVALLDRDGTGRLCESDFRRVWDILRSWSRLFA 659
gi 390347433   18 RFRRAFEERSGQDMAVDAWELLDILNTSSlqq-dlrHDYFSlEACRSMVALSDEDRTGMLSFEEFMELWGNICAWKGFFK 96
gi 353230605  607 ALQKAFNKVAGDDGEIDADELRDILNCAFtrd--ftFDGFSlESCRSMIAMMDVDRSGMLNFSEFRKLWDLLRVWKSAFK 684
gi 353228578  552 KLEVVFNKIAGPSGAITYTQLQDILNEAFtkd--fpFDGFSrETARSMMALMDADLSGGLGFEEFKKLWMELRIWKTIFK 629
gi 684410979   57 KLRAAFTDVAGPDGVLSYPELRDILNAAFike--faFEGFSrETARSMVALMDTDLSGSLDFMQFKKLWMDLRLWKSIFK 134
gi 156381406  512 KFKEFFDNLSGRDGEIDAKELQQILSTALknd--lgGKPFSlEGARSIISMYDEDASGKLGFEEFKETWLQVKKWMKIFQ 589
gi 675862812   98 DGRWAFLALAGIDGAIDAYELQDILNRIFlsd--fkFDGFGaDMTRSLVAMRDYDLSGKLGFDGFRGLWTDLAWCKRAFV 175
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           # # #      #                               # ##                               
gi 62510466   837 LYDtRRTGSIDGFHLRGALNSAGYhlnnrLLNALAHRYGSrEGQIPFDDFLMCAIKVRTFIEMFRERDt-dNSDTAFFNL 915
gi 195996895  595 KFDtDKSGSFSSYELRAALTASGFrlstsVMRSIALRYASkDGSICFNDYLLCMMKVTTMFDKFIEHDa-sKRGKAQFSL 673
gi 674593068  915 EADsENTGRLRTYDLRTVLSDAGIsisneIFKAIVCRYAH-NGVIIFDDFILLLVLLITFFGKFKENLdrrGGNRATFNV 993
gi 353229533  660 SFDpQRTAHVTSLDFRIIVEQAGYtlphtLFSKLVNRFVNvDWRLDYPHFISAMSLITKAVAIFKNFD---HGGRAVLPL 736
gi 390347433   97 RADtDGSGMISIDEMTVALTSLGFklendTFRALGLRYGNkENNLSLASFIHVAIRVRFMYNKFASKS---RGSNARFNL 173
gi 353230605  685 QFDtDKSGSMNSIELRNALKHVGFsinnaTFSTLVLRFSRrDGSVPFDSYVICCARLQILFEVFKATPk-nDQLQALFTE 763
gi 353228578  630 KFD-GHTGSLEAFELRNVMRTVGFhvsnmIFKAIACRYANeKGQILFDDYILLLIRLSTVFETFKAQEr-tRDGRAVFEA 707
gi 684410979  135 RFDrNGNGTMDAFELRDLLRAVGIsvsnrVYHAIVCRYANrKGEIFFDDYVLLLVRLSTVIETFKAQKr-lDDGRAAFDI 213
gi 156381406  590 VFDeDKSGEMDTYELRGALKEAGFtlsnsVLYAVSARYSTgDGKVNVDDFMEILTRLNILSAAFQKQAg-qGGRRAAFDI 668
gi 675862812  176 MFDvNKSGAFCKNEFTKALEVMGLtvtpkTHKAMLMRYTDkDGNIRFDDFVLCYIRLKTMMTIYQNKDp-rGMGNSDFER 254
                         170
                  ....*....|
Feature 1                   
gi 62510466   916 DDWLERTIYS 925
gi 195996895  674 DQECSSCIAT 683
gi 674593068  994 DVFLRCVLYT 1003
gi 353229533  737 EQFVEIAMTM 746
gi 390347433  174 EELLMVHFYS 183
gi 353230605  764 SEFVNSALYM 773
gi 353228578  708 DDFIRSVIYI 717
gi 684410979  214 EEFTRSVIYI 223
gi 156381406  669 DQFLEMGVIL 678
gi 675862812  255 DEFVQLAIYS 264

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