UniProt functional annotation for Q969V5



	UniProt functional annotation for Q969V5

UniProt code: Q969V5.

Organism: Homo sapiens (Human).

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

Function: Exhibits weak E3 ubiquitin-protein ligase activity (PubMed:18591963, PubMed:19407830, PubMed:22410793). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (PubMed:18591963, PubMed:19407830, PubMed:22410793). Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to be involved in regulation of Akt signaling by targeting phosphorylated Akt to proteosomal degradation (PubMed:22410793). Mediates polyubiquitination of cytoplasmic TP53 at 'Lys-24' which targets TP53 for proteasomal degradation, thus reducing TP53 levels in the cytoplasm and mitochondrion (PubMed:21597459). Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations (PubMed:19407830). Plays a role in the control of mitochondrial morphology by promoting mitochondrial fragmentation, and influences mitochondrial localization (PubMed:19407830, PubMed:18207745, PubMed:18213395). Likely to promote mitochondrial fission through negatively regulating the mitochondrial fusion proteins MFN1 and MFN2, acting in a pathway that is parallel to the PRKN/PINK1 regulatory pathway (PubMed:24898855). May also be involved in the sumoylation of the membrane fission protein DNM1L (PubMed:18207745, PubMed:19407830). Inhibits cell growth (PubMed:18591963, PubMed:22410793). When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis (PubMed:23399697). Involved in the modulation of innate immune defense against viruses by inhibiting DDX58-dependent antiviral response (PubMed:23399697). Can mediate DDX58 sumoylation and disrupt its polyubiquitination (PubMed:23399697). {ECO:0000269|PubMed:18207745, ECO:0000269|PubMed:18213395, ECO:0000269|PubMed:18591963, ECO:0000269|PubMed:19407830, ECO:0000269|PubMed:22410793, ECO:0000269|PubMed:23399697, ECO:0000269|PubMed:24898855}.

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:18591963, ECO:0000269|PubMed:21597459, ECO:0000269|PubMed:22410793};

Pathway: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:21597459}.

Pathway: Protein modification; protein sumoylation. {ECO:0000269|PubMed:19407830}.

Subunit: Homooligomer (PubMed:18591963). Interacts with MAP3K7/TAK1 (PubMed:18591963). Interacts with UBC9 (PubMed:19407830). Interacts with and sumoylates DNM1L (PubMed:19407830). Interacts with MAVS (PubMed:23399697). Interacts with TP53 (via N-terminus); the interaction leads to ubiquitination and proteasomal degradation of TP53 (PubMed:21597459). {ECO:0000269|PubMed:18591963, ECO:0000269|PubMed:19407830, ECO:0000269|PubMed:21597459, ECO:0000269|PubMed:23399697}.

Subcellular location: Mitochondrion outer membrane {ECO:0000269|PubMed:18207745, ECO:0000269|PubMed:18213395, ECO:0000269|PubMed:18591963, ECO:0000269|PubMed:21597459}; Multi-pass membrane protein {ECO:0000255}. Peroxisome {ECO:0000269|PubMed:18207745}. Note=Transported in mitochondrion- derived vesicles from the mitochondrion to the peroxisome. {ECO:0000269|PubMed:18207745}.

Tissue specificity: Widely expressed with highest levels in the heart, skeletal muscle, placenta, kidney and liver. Barely detectable in colon and thymus. {ECO:0000269|PubMed:18213395, ECO:0000269|PubMed:18591963}.

Domain: The zinc finger domain is required for E3 ligase activity. {ECO:0000269|PubMed:18591963}.

Ptm: Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. {ECO:0000269|PubMed:25621951}.

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:		Exhibits weak E3 ubiquitin-protein ligase activity (PubMed:18591963, PubMed:19407830, PubMed:22410793). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (PubMed:18591963, PubMed:19407830, PubMed:22410793). Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to be involved in regulation of Akt signaling by targeting phosphorylated Akt to proteosomal degradation (PubMed:22410793). Mediates polyubiquitination of cytoplasmic TP53 at 'Lys-24' which targets TP53 for proteasomal degradation, thus reducing TP53 levels in the cytoplasm and mitochondrion (PubMed:21597459). Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations (PubMed:19407830). Plays a role in the control of mitochondrial morphology by promoting mitochondrial fragmentation, and influences mitochondrial localization (PubMed:19407830, PubMed:18207745, PubMed:18213395). Likely to promote mitochondrial fission through negatively regulating the mitochondrial fusion proteins MFN1 and MFN2, acting in a pathway that is parallel to the PRKN/PINK1 regulatory pathway (PubMed:24898855). May also be involved in the sumoylation of the membrane fission protein DNM1L (PubMed:18207745, PubMed:19407830). Inhibits cell growth (PubMed:18591963, PubMed:22410793). When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis (PubMed:23399697). Involved in the modulation of innate immune defense against viruses by inhibiting DDX58-dependent antiviral response (PubMed:23399697). Can mediate DDX58 sumoylation and disrupt its polyubiquitination (PubMed:23399697). {ECO:0000269\|PubMed:18207745, ECO:0000269\|PubMed:18213395, ECO:0000269\|PubMed:18591963, ECO:0000269\|PubMed:19407830, ECO:0000269\|PubMed:22410793, ECO:0000269\|PubMed:23399697, ECO:0000269\|PubMed:24898855}.


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:18591963, ECO:0000269\|PubMed:21597459, ECO:0000269\|PubMed:22410793};
Pathway:		Protein modification; protein ubiquitination. {ECO:0000269\|PubMed:21597459}.
Pathway:		Protein modification; protein sumoylation. {ECO:0000269\|PubMed:19407830}.
Subunit:		Homooligomer (PubMed:18591963). Interacts with MAP3K7/TAK1 (PubMed:18591963). Interacts with UBC9 (PubMed:19407830). Interacts with and sumoylates DNM1L (PubMed:19407830). Interacts with MAVS (PubMed:23399697). Interacts with TP53 (via N-terminus); the interaction leads to ubiquitination and proteasomal degradation of TP53 (PubMed:21597459). {ECO:0000269\|PubMed:18591963, ECO:0000269\|PubMed:19407830, ECO:0000269\|PubMed:21597459, ECO:0000269\|PubMed:23399697}.
Subcellular location:		Mitochondrion outer membrane {ECO:0000269\|PubMed:18207745, ECO:0000269\|PubMed:18213395, ECO:0000269\|PubMed:18591963, ECO:0000269\|PubMed:21597459}; Multi-pass membrane protein {ECO:0000255}. Peroxisome {ECO:0000269\|PubMed:18207745}. Note=Transported in mitochondrion- derived vesicles from the mitochondrion to the peroxisome. {ECO:0000269\|PubMed:18207745}.
Tissue specificity:		Widely expressed with highest levels in the heart, skeletal muscle, placenta, kidney and liver. Barely detectable in colon and thymus. {ECO:0000269\|PubMed:18213395, ECO:0000269\|PubMed:18591963}.
Domain:		The zinc finger domain is required for E3 ligase activity. {ECO:0000269\|PubMed:18591963}.
Ptm:		Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. {ECO:0000269\|PubMed:25621951}.