UniProt functional annotation for Q8IWV8



	UniProt functional annotation for Q8IWV8

UniProt code: Q8IWV8.

Organism: Homo sapiens (Human).

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

Function: E3 ubiquitin-protein ligase which is a component of the N-end rule pathway (PubMed:15548684, PubMed:20835242). Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (By similarity). Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A (By similarity). Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (PubMed:20298436). Required for spermatogenesis, promotes, with Tex19.1, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis (By similarity). Polyubiquitinates LINE-1 retrotransposon encoded, LIRE1, which induces degradation, inhibiting LINE-1 retrotransposon mobilization (By similarity). Catalyzes ubiquitination and degradation of the N-terminal part of NLRP1 following NLRP1 activation by pathogens and other damage-associated signals: ubiquitination promotes degradation of the N-terminal part and subsequent release of the cleaved C-terminal part of NLRP1, which polymerizes and forms the NLRP1 inflammasome followed by host cell pyroptosis (By similarity). {ECO:0000250|UniProtKB:Q6WKZ8, ECO:0000269|PubMed:15548684, ECO:0000269|PubMed:20298436, ECO:0000269|PubMed:20835242}.

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:0000250|UniProtKB:Q6WKZ8};

Pathway: Protein modification; protein ubiquitination. {ECO:0000250|UniProtKB:Q6WKZ8}.

Subunit: Interacts with UBE2B; promotes the UBE2B-H2A interaction and the ubiquitination of histone H2A by UBE2B and UBR2 (By similarity). Interacts with RECQL4 (PubMed:15317757, PubMed:20835242). Interacts with TEX19; does not lead to TEX19 degradation and stabilizes it (By similarity). Interacts with CASP8 (PubMed:28602583). Interacts with ATXN3 (PubMed:30455355). Interacts with UBE2O (By similarity). {ECO:0000250|UniProtKB:Q6WKZ8, ECO:0000269|PubMed:15317757, ECO:0000269|PubMed:20835242, ECO:0000269|PubMed:28602583, ECO:0000269|PubMed:30455355}.

Subcellular location: Nucleus {ECO:0000250|UniProtKB:Q6WKZ8}. Chromosome {ECO:0000250|UniProtKB:Q6WKZ8}. Note=Associated with chromatin during meiosis. {ECO:0000250|UniProtKB:Q6WKZ8}.

Tissue specificity: Broadly expressed, with highest levels in skeletal muscle, kidney and pancreas. Present in acinar cells of the pancreas (at protein level). {ECO:0000269|PubMed:15548684, ECO:0000269|PubMed:16311597}.

Developmental stage: Expressed in fetal pancreas. {ECO:0000269|PubMed:16311597}.

Domain: The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif. {ECO:0000269|PubMed:20835242}.

Domain: The UBR-type zinc finger forms a pocket that mediates recognition of type 1 N-degrons. It exhibits preference for Arginine in first position, has poor affinity for histidine, and doesn't bind acetylated peptides. {ECO:0000269|PubMed:20835242}.

Miscellaneous: [Isoform 4]: Derived from mouse cDNA data. {ECO:0000305}.

Similarity: Belongs to the UBR1 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:		E3 ubiquitin-protein ligase which is a component of the N-end rule pathway (PubMed:15548684, PubMed:20835242). Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (By similarity). Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A (By similarity). Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (PubMed:20298436). Required for spermatogenesis, promotes, with Tex19.1, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis (By similarity). Polyubiquitinates LINE-1 retrotransposon encoded, LIRE1, which induces degradation, inhibiting LINE-1 retrotransposon mobilization (By similarity). Catalyzes ubiquitination and degradation of the N-terminal part of NLRP1 following NLRP1 activation by pathogens and other damage-associated signals: ubiquitination promotes degradation of the N-terminal part and subsequent release of the cleaved C-terminal part of NLRP1, which polymerizes and forms the NLRP1 inflammasome followed by host cell pyroptosis (By similarity). {ECO:0000250\|UniProtKB:Q6WKZ8, ECO:0000269\|PubMed:15548684, ECO:0000269\|PubMed:20298436, ECO:0000269\|PubMed:20835242}.


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:0000250\|UniProtKB:Q6WKZ8};
Pathway:		Protein modification; protein ubiquitination. {ECO:0000250\|UniProtKB:Q6WKZ8}.
Subunit:		Interacts with UBE2B; promotes the UBE2B-H2A interaction and the ubiquitination of histone H2A by UBE2B and UBR2 (By similarity). Interacts with RECQL4 (PubMed:15317757, PubMed:20835242). Interacts with TEX19; does not lead to TEX19 degradation and stabilizes it (By similarity). Interacts with CASP8 (PubMed:28602583). Interacts with ATXN3 (PubMed:30455355). Interacts with UBE2O (By similarity). {ECO:0000250\|UniProtKB:Q6WKZ8, ECO:0000269\|PubMed:15317757, ECO:0000269\|PubMed:20835242, ECO:0000269\|PubMed:28602583, ECO:0000269\|PubMed:30455355}.
Subcellular location:		Nucleus {ECO:0000250\|UniProtKB:Q6WKZ8}. Chromosome {ECO:0000250\|UniProtKB:Q6WKZ8}. Note=Associated with chromatin during meiosis. {ECO:0000250\|UniProtKB:Q6WKZ8}.
Tissue specificity:		Broadly expressed, with highest levels in skeletal muscle, kidney and pancreas. Present in acinar cells of the pancreas (at protein level). {ECO:0000269\|PubMed:15548684, ECO:0000269\|PubMed:16311597}.
Developmental stage:		Expressed in fetal pancreas. {ECO:0000269\|PubMed:16311597}.
Domain:		The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif. {ECO:0000269\|PubMed:20835242}.
Domain:		The UBR-type zinc finger forms a pocket that mediates recognition of type 1 N-degrons. It exhibits preference for Arginine in first position, has poor affinity for histidine, and doesn't bind acetylated peptides. {ECO:0000269\|PubMed:20835242}.
Miscellaneous:		[Isoform 4]: Derived from mouse cDNA data. {ECO:0000305}.
Similarity:		Belongs to the UBR1 family. {ECO:0000305}.