UniProt functional annotation for P61086



	UniProt functional annotation for P61086

UniProt code: P61086.

Organism: Homo sapiens (Human).

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

Function: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1. {ECO:0000269|PubMed:10634809, ECO:0000269|PubMed:10675012, ECO:0000269|PubMed:16714285, ECO:0000269|PubMed:16868077, ECO:0000269|PubMed:17873885, ECO:0000269|PubMed:19906396, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:8702625}.

Catalytic activity: Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin- activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin- conjugating enzyme]-L-cysteine.; EC=2.3.2.23; Evidence={ECO:0000255|PROSITE-ProRule:PRU00388, ECO:0000255|PROSITE- ProRule:PRU10133, ECO:0000269|PubMed:20061386};

Pathway: Protein modification; protein ubiquitination. {ECO:0000255|PROSITE-ProRule:PRU00388}.

Subunit: Interacts with RNF138/NARF. Interacts with BRCA1. {ECO:0000269|PubMed:16714285, ECO:0000269|PubMed:17873885, ECO:0000269|Ref.25}.

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:P61085}.

Tissue specificity: Expressed in all tissues tested, including spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocytes, T-lymphocytes, monocytes, granulocytes and bone marrow mononuclear cells. Highly expressed in brain, with highest levels found in cortex and striatum and at lower levels in cerebellum and brainstem. {ECO:0000269|PubMed:10634809, ECO:0000269|PubMed:10675012, ECO:0000269|PubMed:8702625}.

Induction: By aggregated low-density lipoprotein. {ECO:0000269|PubMed:10634809, ECO:0000269|PubMed:10675012}.

Ptm: Sumoylation at Lys-14 impairs catalytic activity. {ECO:0000250|UniProtKB:P61085}.

Miscellaneous: [Isoform 2]: May be inactive. {ECO:0000305}.

Similarity: Belongs to the ubiquitin-conjugating enzyme family. {ECO:0000255|PROSITE-ProRule:PRU00388}.

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:		Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1. {ECO:0000269\|PubMed:10634809, ECO:0000269\|PubMed:10675012, ECO:0000269\|PubMed:16714285, ECO:0000269\|PubMed:16868077, ECO:0000269\|PubMed:17873885, ECO:0000269\|PubMed:19906396, ECO:0000269\|PubMed:20061386, ECO:0000269\|PubMed:8702625}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin- activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin- conjugating enzyme]-L-cysteine.; EC=2.3.2.23; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00388, ECO:0000255\|PROSITE- ProRule:PRU10133, ECO:0000269\|PubMed:20061386};
Pathway:		Protein modification; protein ubiquitination. {ECO:0000255\|PROSITE-ProRule:PRU00388}.
Subunit:		Interacts with RNF138/NARF. Interacts with BRCA1. {ECO:0000269\|PubMed:16714285, ECO:0000269\|PubMed:17873885, ECO:0000269\|Ref.25}.
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:P61085}.
Tissue specificity:		Expressed in all tissues tested, including spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocytes, T-lymphocytes, monocytes, granulocytes and bone marrow mononuclear cells. Highly expressed in brain, with highest levels found in cortex and striatum and at lower levels in cerebellum and brainstem. {ECO:0000269\|PubMed:10634809, ECO:0000269\|PubMed:10675012, ECO:0000269\|PubMed:8702625}.
Induction:		By aggregated low-density lipoprotein. {ECO:0000269\|PubMed:10634809, ECO:0000269\|PubMed:10675012}.
Ptm:		Sumoylation at Lys-14 impairs catalytic activity. {ECO:0000250\|UniProtKB:P61085}.
Miscellaneous:		[Isoform 2]: May be inactive. {ECO:0000305}.
Similarity:		Belongs to the ubiquitin-conjugating enzyme family. {ECO:0000255\|PROSITE-ProRule:PRU00388}.