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HUWE1 E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1. Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair. Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4. Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN. May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation. Interacts with isoform p14ARF of CDKN2A which strongly inhibits HUWE1 ubiquitin ligase activity. Interacts with MYCN, POLB and CDC6. Weakly expressed in heart, brain and placenta but not in other tissues. Expressed in a number of cell lines, predominantly in those from colorectal carcinomas. Belongs to the TOM1/PTR1 family. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: EC 6.3.2.-; EC; Ligase; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of Human Ortholog: Xp11.22
Cellular Component: cytoplasm; cytosol; extracellular region; membrane; nucleoplasm; nucleus
Molecular Function: DNA binding; protein binding; RNA binding; ubiquitin-protein ligase activity
Biological Process: base-excision repair; histone ubiquitination; neutrophil degranulation; protein monoubiquitination; protein polyubiquitination; protein ubiquitination during ubiquitin-dependent protein catabolic process
Disease: Mental Retardation, X-linked, Syndromic, Turner Type
Reference #:  Q7Z6Z7 (UniProtKB)
Alt. Names/Synonyms: ARF binding protein 1; ARF-binding protein 1; ARF-BP1; BJ-HCC-24 tumor antigen; E3 ubiquitin-protein ligase HUWE1; HECT domain protein LASU1; HECT, UBA and WWE domain containing 1; HECT, UBA and WWE domain-containing protein 1; HectH9; Homologous to E6AP carboxyl terminus homologous protein 9; HSPC272; HUWE1; Ib772; KIAA0312; KIAA1578; Large structure of UREB1; LASU1; Mcl-1 ubiquitin ligase E3; Mule; Upstream regulatory element-binding protein 1; URE-B1; URE-binding protein 1; UREB1
Gene Symbols: HUWE1
Molecular weight: 481,891 Da
Basal Isoelectric point: 5.1  Predict pI for various phosphorylation states
CST Pathways:  Apoptosis Regulation  |  Inhibition of Apoptosis  |  Mitochondrial Control of Apoptosis
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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