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. Ref.1 Ref.2 Ref.3 Ref.9 Ref.12 Ref.13 Ref.15 Ref.16
Catalytic activity: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
Pathway: Protein modification; protein ubiquitination.
Subunit structure: Interacts with RNF138/NARF. Interacts with BRCA1. Ref.9 Ref.13
Subcellular location: Cytoplasm
By similarity.
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. Ref.1 Ref.2 Ref.3
Induction: By aggregated low-density lipoprotein. Ref.2 Ref.3
Post-translational modification: Sumoylation at Lys-14 impairs catalytic activity
By similarity.
Sequence similarities: Belongs to the ubiquitin-conjugating enzyme family.Contains 1 UBA domain.
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