UniProt functional annotation for Q8WZ73



	UniProt functional annotation for Q8WZ73

UniProt code: Q8WZ73.

Organism: Homo sapiens (Human).

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

Function: E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling. {ECO:0000269|PubMed:15069192, ECO:0000269|PubMed:17121812, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:18450452, ECO:0000269|PubMed:22609986}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269|PubMed:15069192};

Pathway: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:15069192}.

Subunit: Interacts with CASP8 and CASP10. Interacts with RIPK1 (via protein kinase domain); involved in RIPK1 ubiquitination. Interacts with PRR5L. Interacts (via RING-type zinc finger) with p53/TP53; involved in p53/TP53 ubiquitination. Interacts (via RING-type zinc finger) with MDM2; the interaction stabilizes MDM2. {ECO:0000269|PubMed:15069192, ECO:0000269|PubMed:17121812, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:18450452, ECO:0000269|PubMed:22609986}.

Subcellular location: Cytoplasm, cytosol. Cell membrane; Peripheral membrane protein. Recycling endosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=The FYVE-type zinc finger may mediate phosphatidylinositol phosphate-binding and control subcellular localization.

Tissue specificity: Ubiquitous. Detected in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. {ECO:0000269|PubMed:15069192}.

Induction: Down-regulated upon DNA damage. {ECO:0000269|PubMed:18382127}.

Domain: The RING-type zinc finger is required for the ubiquitination of target proteins. {ECO:0000269|PubMed:22609986}.

Domain: The FYVE-type zinc finger domain is required for localization to the recycling endosome membranes and the function in endocytic recycling. {ECO:0000250|UniProtKB:Q6ZQM0}.

Ptm: Autoubiquitinated. {ECO:0000250}.

Ptm: Palmitoylated. {ECO:0000250}.

Ptm: Undergoes caspase-mediated cleavage upon death-receptor activation, by TNFSF10 for instance. May be mediated by the caspases CASP8 and CASP10 in a negative feedback loop.

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:		E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling. {ECO:0000269\|PubMed:15069192, ECO:0000269\|PubMed:17121812, ECO:0000269\|PubMed:18382127, ECO:0000269\|PubMed:18450452, ECO:0000269\|PubMed:22609986}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269\|PubMed:15069192};
Pathway:		Protein modification; protein ubiquitination. {ECO:0000269\|PubMed:15069192}.
Subunit:		Interacts with CASP8 and CASP10. Interacts with RIPK1 (via protein kinase domain); involved in RIPK1 ubiquitination. Interacts with PRR5L. Interacts (via RING-type zinc finger) with p53/TP53; involved in p53/TP53 ubiquitination. Interacts (via RING-type zinc finger) with MDM2; the interaction stabilizes MDM2. {ECO:0000269\|PubMed:15069192, ECO:0000269\|PubMed:17121812, ECO:0000269\|PubMed:18382127, ECO:0000269\|PubMed:18450452, ECO:0000269\|PubMed:22609986}.
Subcellular location:		Cytoplasm, cytosol. Cell membrane; Peripheral membrane protein. Recycling endosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=The FYVE-type zinc finger may mediate phosphatidylinositol phosphate-binding and control subcellular localization.
Tissue specificity:		Ubiquitous. Detected in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. {ECO:0000269\|PubMed:15069192}.
Induction:		Down-regulated upon DNA damage. {ECO:0000269\|PubMed:18382127}.
Domain:		The RING-type zinc finger is required for the ubiquitination of target proteins. {ECO:0000269\|PubMed:22609986}.
Domain:		The FYVE-type zinc finger domain is required for localization to the recycling endosome membranes and the function in endocytic recycling. {ECO:0000250\|UniProtKB:Q6ZQM0}.
Ptm:		Autoubiquitinated. {ECO:0000250}.
Ptm:		Palmitoylated. {ECO:0000250}.
Ptm:		Undergoes caspase-mediated cleavage upon death-receptor activation, by TNFSF10 for instance. May be mediated by the caspases CASP8 and CASP10 in a negative feedback loop.