logo CaMPDB: Calpain for Modulatory Proteolysis Database

SB0042 : Caspase 9

[ CaMP Format ]

* Basic Information

OrganismHomo sapiens (human)
Protein Namescaspase-9 isoform alpha precursor [Homo sapiens]; caspase-9 isoform alpha precursor; apoptotic protease MCH-6; apoptotic protease activating factor 3; ICE-like apoptotic protease 6; protein phosphatase 1, regulatory subunit 56; Caspase-9; CASP-9; 3.4.22.62; Apoptotic protease Mch-6; Apoptotic protease-activating factor 3; APAF-3; ICE-LAP6; Caspase-9 subunit p35; Caspase-9 subunit p10
Gene NamesCASP9; MCH6; caspase 9, apoptosis-related cysteine peptidase
Gene Locus1p36.21; chromosome 1
GO FunctionNot available
Entrez Protein Entrez Nucleotide Entrez Gene UniProt OMIM HGNC HPRD KEGG
NP_001220 NM_001229 842 P55211 602234 HGNC:1511 03756 hsa:842

* Information From OMIM

Function: Li et al. (1997) determined that caspase-9 and APAF1 (OMIM:602233) bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c (OMIM:123970) and dATP, an event that leads to caspase-9 activation. Activated caspase-9 in turn cleaves and activates caspase-3. Depletion of caspase-9 from S-100 extracts diminished caspase-3 activation. Mutation of the active site of caspase-9 (cys287 to ala) attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.

* Structure Information

1. Primary Information

Length: 416 aa

Average Mass: 46.280 kDa

Monoisotopic Mass: 46.251 kDa

2. Domain Information

Annotated Domains: interpro / pfam / smart / prosite

Computationally Assigned Domains (Pfam+HMMER):

domain namebeginendscoree-value
Caspase recruitment domain 1. 7902.00.4
--- cleavage 115 ---
Anti-Sigma Factor A 1. 16719731.00.0
--- cleavage 330 ---
Caspase recruitment domain 2. 3804049.00.0

3. Sequence Information

Fasta Sequence: SB0042.fasta

Amino Acid Sequence and Secondary Structures (PsiPred):

4. 3D Information

Known Structures in PDB: 1JXQ (X-ray; 280 A; A/B/C/D=140-416), 1NW9 (X-ray; 240 A; B=140-416), 2AR9 (X-ray; 280 A; A/B/C/D=139-416), 3D9T (X-ray; 150 A; C/D=316-321), 3V3K (X-ray; 349 A; A/C/E/G/I/K/M/O=141-416), 3YGS (X-ray; 250 A; P=1-95), 4RHW (X-ray; 210 A; E/F=1-100)

* Cleavage Information

2 [sites] cleaved by Calpain 2

Source Reference: [PubMed ID: 10671558] Chua BT, Guo K, Li P, Direct cleavage by the calcium-activated protease calpain can lead to inactivation of caspases. J Biol Chem. 2000 Feb 18;275(7):5131-5.

Cleavage sites (±10aa)

[Site 1] LTPVVLRPEI115-RKPEVLRPET

Ile115 Arg

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Leu106Thr107Pro108Val109Val110Leu111Arg112Pro113Glu114Ile115
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Arg116Lys117Pro118Glu119Val120Leu121Arg122Pro123Glu124Thr125

Sequence conservation (by blast)

[Site 2] EGLRTFDQLD330-AISSLPTPSD

Asp330 Ala

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Glu321Gly322Leu323Arg324Thr325Phe326Asp327Gln328Leu329Asp330
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Ala331Ile332Ser333Ser334Leu335Pro336Thr337Pro338Ser339Asp340

Sequence conservation (by blast)

* References

[PubMed ID: 24424093] Sharoar MG, Islam MI, Shahnawaz M, Shin SY, Park IS, Amyloid beta binds procaspase-9 to inhibit assembly of Apaf-1 apoptosome and intrinsic apoptosis pathway. Biochim Biophys Acta. 2014 Apr;1843(4):685-93. doi: 10.1016/j.bbamcr.2014.01.008.

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