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. Belongs to the ubiquitin-conjugating enzyme family. 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. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 126.96.36.199; Ligase; Ubiquitin conjugating system; Ubiquitin ligase
Molecular Function: ATP binding; protein binding; ubiquitin protein ligase binding; ubiquitin-protein transferase activity; ubiquitin-ubiquitin ligase activity
Biological Process: cellular response to interferon-beta; free ubiquitin chain polymerization; intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; positive regulation of peptidyl-threonine phosphorylation; positive regulation of type I interferon-mediated signaling pathway; protein K48-linked ubiquitination; protein ubiquitination; regulation of proteasomal ubiquitin-dependent protein catabolic process; ubiquitin-dependent protein catabolic process