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MT000107

UniProt Annotations

Entry Information

Gene Name	caspase 9, apoptosis-related cysteine peptidase
Protein Entry	CASP9_HUMAN
UniProt ID	P55211
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=4; Name=1; Synonyms=9L, Alpha; IsoId=P55211-1; Sequence=Displayed; Name=2; Synonyms=9S, Beta; IsoId=P55211-2; Sequence=VSP_000818; Name=3; Synonyms=Gamma; IsoId=P55211-3; Sequence=VSP_043910, VSP_043911; Note=May function as an endogenous apoptotic inhibitor, inhibits the BAX-mediated cleavage of procaspase-3.; Name=4; IsoId=P55211-4; Sequence=VSP_044256;
Catalytic Activity	Strict requirement for an Asp residue at position P1 and with a marked preference for His at position P2. It has a preferred cleavage sequence of Leu-Gly-His-Asp-\|-Xaa. {ECO:0000269\|Ref.24}.
Developmental Stage	Expressed at low levels in fetal heart, at moderate levels in neonate heart, and at high levels in adult heart. {ECO:0000269\|PubMed:16857965}.
Enzyme Regulation	Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis. {ECO:0000269\|Ref.24}.
Function	Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf- 1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP- ribose) polymerase (PARP).
Function	Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9.
Interaction	O14727:APAF1; NbExp=18; IntAct=EBI-516799, EBI-446492; Q13490:BIRC2; NbExp=4; IntAct=EBI-516799, EBI-514538; Q13489:BIRC3; NbExp=2; IntAct=EBI-516799, EBI-517709; O15392:BIRC5; NbExp=2; IntAct=EBI-516799, EBI-518823; Q96CA5:BIRC7; NbExp=5; IntAct=EBI-516799, EBI-517623; Q13418:ILK; NbExp=2; IntAct=EBI-516799, EBI-747644; P98170:XIAP; NbExp=6; IntAct=EBI-516799, EBI-517127;
Ptm	Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase- 3 generate the two active subunits. Caspase-8 and -10 can also be involved in these processing events.
Ptm	Phosphorylated at Thr-125 by MAPK1/ERK2. Phosphorylation at Thr-125 is sufficient to block caspase-9 processing and subsequent caspase-3 activation. Phosphorylation on Tyr-153 by ABL1/c-Abl; occurs in the response of cells to DNA damage. {ECO:0000269\|PubMed:12792650, ECO:0000269\|PubMed:15657060, ECO:0000269\|PubMed:18669648, ECO:0000269\|PubMed:20068231}.
Similarity	Belongs to the peptidase C14A family. {ECO:0000305}.
Similarity	Contains 1 CARD domain. {ECO:0000255\|PROSITE- ProRule:PRU00046}.
Subunit	Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 35 kDa (p35) and a 10 kDa (p10) subunit. Caspase-9 and APAF1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome C and ATP. Interacts (inactive form) with EFHD2. Interacts with HAX1. Interacts with BIRC2/c-IAP1, XIAP/BIRC4, BIRC5/survivin, BIRC6/bruce and BIRC7/livin. Interacts with ABL1 (via SH3 domain); the interaction is direct and increases in the response of cells to genotoxic stress and ABL1/c- Abl activation. Interacts with NleF from pathogenic E.coli. {ECO:0000269\|PubMed:11734640, ECO:0000269\|PubMed:12620238, ECO:0000269\|PubMed:15200957, ECO:0000269\|PubMed:15657060, ECO:0000269\|PubMed:16857965, ECO:0000269\|PubMed:19118655, ECO:0000269\|Ref.24}.
Tissue Specificity	Ubiquitous, with highest expression in the heart, moderate expression in liver, skeletal muscle, and pancreas. Low levels in all other tissues. Within the heart, specifically expressed in myocytes. {ECO:0000269\|PubMed:16857965}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CASP9ID423ch1p36.html";
Web Resource	Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/casp9/";
Web Resource	Name=Wikipedia; Note=Caspase-9 entry; URL="http://en.wikipedia.org/wiki/Caspase-9";