UniProt functional annotation for P55211



	UniProt functional annotation for P55211

UniProt code: P55211.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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.

Catalytic activity: Reaction=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.; EC=3.4.22.62; Evidence={ECO:0000269|PubMed:23516580};

Activity regulation: Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis. {ECO:0000269|PubMed:23516580}.

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|PubMed:23516580}.

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}.

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}.

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}.

Miscellaneous: [Isoform 3]: May function as an endogenous apoptotic inhibitor, inhibits the BAX-mediated cleavage of procaspase-3. {ECO:0000305}.

Similarity: Belongs to the peptidase C14A family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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.


Catalytic activity:		Reaction=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.; EC=3.4.22.62; Evidence={ECO:0000269\|PubMed:23516580};
Activity regulation:		Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis. {ECO:0000269\|PubMed:23516580}.
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\|PubMed:23516580}.
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}.
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}.
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}.
Miscellaneous:		[Isoform 3]: May function as an endogenous apoptotic inhibitor, inhibits the BAX-mediated cleavage of procaspase-3. {ECO:0000305}.
Similarity:		Belongs to the peptidase C14A family. {ECO:0000305}.