3DF0,1KFX,1DF0,1U5I


Conserved Protein Domain Family
EFh_PEF_CAPN2

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cd16199: EFh_PEF_CAPN2 
Click on image for an interactive view with Cn3D
Penta-EF hand, calcium binding motifs, found in m-type calpain (CAPN2)
CAPN2, also termed millimolar-calpain (m-calpain), or calpain-2 catalytic subunit, or calcium-activated neutral proteinase 2 (CANP 2), or calpain large polypeptide L2, or calpain-2 large subunit, is a ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine protease that contains 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 catalytic subunit CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms an m-calpain heterodimer. CAPN2 acts as the key protease responsible for N-methyl-d-aspartic acid (NMDA)-induced cytoplasmic polyadenylation element-binding protein 3 (CPEB3) degradation in neurons. It cleaves several components of the focal adhesion complex, such as FAK and talin, triggering disassembly of the complex at the rear of the cell. The stimulation of CAPN2 activity is required for Golgi antiapoptotic proteins (GAAPs) to promote cleavage of FA kinase (FAK), cell spreading, and enhanced migration. calpain 2 is also involved in the onset of glial differentiation. It regulates proliferation, survival, migration, and tumorigenesis of breast cancer cells through a PP2A-Akt-FoxO-p27(Kip1) signaling cascade. Its expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer. Moreover, CAPN2 may play a role in fundamental mitotic functions, such as the maintenance of sister chromatid cohesion. The activation of CAPN2 plays an essential role in hippocampal synaptic plasticity and in learning and memory. In the eye, CAPN2, together with a lens-specific variant of CAPN3, is responsible for proteolytic cleavages of alpha and beta-crystallin. Overactivated alpha and beta-crystallin can lead to cataract formation. Sometimes, CAPN2 compensates for loss of CAPN1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation. The main phosphorylation sites in m-calpain are Ser50 and Ser369/Thr370.
Statistics
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PSSM-Id: 320074
View PSSM: cd16199
Aligned: 7 rows
Threshold Bit Score: 330.325
Threshold Setting Gi: 148237926
Created: 4-Mar-2015
Updated: 18-Aug-2016
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 15 residues -Click on image for an interactive view with Cn3D
Feature 1:Ca binding site [ion binding site]
Evidence:
  • Structure:3DF0; Rattus norvegicus m-calpain binds four Ca2+ ions through its EF1, EF2, EF3, and EF4 hands.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                    # #    #                 #              # # #      #                
3DF0_A       533 GFRRLFAQLAGEDAEISAFELQTILRRVLakreDIKSDGFSIETCKIMVDMLDEDGSGKLGLKEFYILWTKIQKYQKIYR 612
1KFX_L       532 GVRRLFAQLAGEDAEISAFELQTILRRVLakrqDIKSDGFSIETCKIMVDMLDSDGSGKLGLKEFYILWTKIQKYQKIYR 611
1DF0_A       533 GFRRLFAQLAGEDAEISAFELQTILRRVLakreDIKSDGFSIETCKIMVDMLDEDGSGKLGLKEFYILWTKIQKYQKIYR 612
1U5I_A       533 GFRRLFAQLAGEDAEISAFELQTILRRVLakreDIKSDGFSIETCKIMVDMLDEDGSGKLGLKEFYILWTKIQKYQKIYR 612
gi 148237926 532 TFKRMFLALAGDDKEISPHELFNILQKVIskreDIKSDGFSMETCRTIVDLLDSDGSGKLGLKEFNILWTKILKYQKIYS 611
gi 209892843 533 SFKKLFGQLAGSDAEISAFELRSILNKILakrqDIKSDGFSIETCKIMVDLLDNDGSGKLGLKEFHTLWTKIQKYQKIYR 612
gi 317373596 533 GFRRLFAQLAGEDAEISAFELQTILRRVLakrqDIKSDGFSIETCKIMVDMLDSDGSGKLGLKEFYILWTKIQKYQKIYR 612
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          # # #      #                               # ##                               
3DF0_A       613 EIDVDRSGTMNSYEMRKALEEAGFklpcqLHQVIVARFADDELIIDFDNFVRCLVRLEiLFKIFKQLDPENTGTIQLDLI 692
1KFX_L       612 EIDVDRSGTMNSYEMRKALEEAGFkmpcqLHQVIVARFADDQLIIDFDNFVRCLVRLEtLFKIFKQLDPENTGTIELDLI 691
1DF0_A       613 EIDVDRSGTMNSYEMRKALEEAGFklpcqLHQVIVARFADDELIIDFDNFVRCLVRLEiLFKIFKQLDPENTGTIQLDLI 692
1U5I_A       613 EIDVDRSGTMNSYEMRKALEEAGFklpcqLHQVIVARFADDELIIDFDNFVRCLVRLEiLFKIFKQLDPENTGTIQLDLI 692
gi 148237926 612 SVDKDRSGTINSYEMRGALEGAGFkvnakIIELLVARFADEDQNIDFDNFVRCLLRLEtMFKIFNKLDTEKTGVVPLKMD 691
gi 209892843 613 EIDVDRSGTMNSYEMRRALEAAGFklncqLHQIIVARFADEDLIIDFDNFVRCLIRLEtLFKMFRKLDTEKTGTIELNLI 692
gi 317373596 613 EIDVDRSGTMNSYEMRKALEEAGFkmpcqLHQVIVARFADDQLIIDFDNFVRCLVRLEtLFKIFKQLDPENTGTIELDLI 692

                 ....*...
Feature 1                
3DF0_A       693 SWLSFSVL 700
1KFX_L       692 SWLCFSVL 699
1DF0_A       693 SWLSFSVL 700
1U5I_A       693 SWLSFSVL 700
gi 148237926 692 TWLSLTVI 699
gi 209892843 693 NWLFFTVI 700
gi 317373596 693 SWLCFSVL 700

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