UniProt functional annotation for P42575



	UniProt functional annotation for P42575

UniProt code: P42575.

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. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival (PubMed:15073321). Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress (PubMed:15073321). {ECO:0000269|PubMed:15073321}.

Catalytic activity: Reaction=Strict requirement for an Asp residue at P1, with 316-asp being essential for proteolytic activity and has a preferred cleavage sequence of Val-Asp-Val-Ala-Asp-|-.; EC=3.4.22.55;

Subunit: Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a p18 subunit and a p12 subunit (PubMed:12920126). Forms a complex named the PIDDosome with PIDD1 and CRADD (PubMed:9044836, PubMed:8985253, PubMed:15073321, PubMed:16652156). Interacts with NOL3 (via CARD domain); inhibits CASP2 activity in a phosphorylation-dependent manner (PubMed:9560245). {ECO:0000269|PubMed:12920126, ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:16652156, ECO:0000269|PubMed:8985253, ECO:0000269|PubMed:9044836, ECO:0000269|PubMed:9560245}.

Tissue specificity: Expressed at higher levels in the embryonic lung, liver and kidney than in the heart and brain. In adults, higher level expression is seen in the placenta, lung, kidney, and pancreas than in the heart, brain, liver and skeletal muscle.

Domain: The CARD domain mediates a direct interaction with CRADD. {ECO:0000269|PubMed:8985253}.

Ptm: The mature protease can process its own propeptide, but not that of other caspases. {ECO:0000269|PubMed:8654923}.

Miscellaneous: [Isoform 1]: Acts as a positive regulator of apoptosis.

Miscellaneous: [Isoform 2]: Acts as a negative regulator of apoptosis. {ECO:0000305}.

Miscellaneous: [Isoform 3]: May function as an endogenous apoptosis inhibitor that antagonizes caspase activation and cell death. {ECO:0000305}.

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

Sequence caution: Sequence=AAA58959.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAO25653.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAP22346.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAP22349.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAD92877.1; Type=Erroneous initiation; Evidence={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. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival (PubMed:15073321). Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress (PubMed:15073321). {ECO:0000269\|PubMed:15073321}.


Catalytic activity:		Reaction=Strict requirement for an Asp residue at P1, with 316-asp being essential for proteolytic activity and has a preferred cleavage sequence of Val-Asp-Val-Ala-Asp-\|-.; EC=3.4.22.55;
Subunit:		Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a p18 subunit and a p12 subunit (PubMed:12920126). Forms a complex named the PIDDosome with PIDD1 and CRADD (PubMed:9044836, PubMed:8985253, PubMed:15073321, PubMed:16652156). Interacts with NOL3 (via CARD domain); inhibits CASP2 activity in a phosphorylation-dependent manner (PubMed:9560245). {ECO:0000269\|PubMed:12920126, ECO:0000269\|PubMed:15073321, ECO:0000269\|PubMed:16652156, ECO:0000269\|PubMed:8985253, ECO:0000269\|PubMed:9044836, ECO:0000269\|PubMed:9560245}.
Tissue specificity:		Expressed at higher levels in the embryonic lung, liver and kidney than in the heart and brain. In adults, higher level expression is seen in the placenta, lung, kidney, and pancreas than in the heart, brain, liver and skeletal muscle.
Domain:		The CARD domain mediates a direct interaction with CRADD. {ECO:0000269\|PubMed:8985253}.
Ptm:		The mature protease can process its own propeptide, but not that of other caspases. {ECO:0000269\|PubMed:8654923}.
Miscellaneous:		[Isoform 1]: Acts as a positive regulator of apoptosis.
Miscellaneous:		[Isoform 2]: Acts as a negative regulator of apoptosis. {ECO:0000305}.
Miscellaneous:		[Isoform 3]: May function as an endogenous apoptosis inhibitor that antagonizes caspase activation and cell death. {ECO:0000305}.
Similarity:		Belongs to the peptidase C14A family. {ECO:0000305}.
Sequence caution:		Sequence=AAA58959.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAO25653.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAP22346.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAP22349.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAD92877.1; Type=Erroneous initiation; Evidence={ECO:0000305};