HUWE1 — HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1
HUWE1 belongs to a gene co-expression module in 4 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
HUWE1's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD4⁺ T cells | PD-L1 checkpoint Immune regulation | ADAM12, CASS4, CCDC88B, CD274, GALNT10, INPP5D, KIF3B, LASP1 +13 more | View in SCUBA |
| Gamma-delta T cells | Chromatin Epigenetic Regulation DNA/chromatin regulation | ACIN1, ASH1L, BDP1, BLTP1, CLTC, EPS15, EXOC2, FAM120B +24 more | |
| Macrophages | Ubiquitin-Proteasome Regulation Housekeeping | ABCA1, AVL9, EHMT1, GIGYF2, LCORL, PAXBP1, PPP2R2D, PPP2R5C +4 more | View in SCUBA |
| Mucosal-associated invariant T cell | Cellular Maintenance Housekeeping | DCTN4, FAM13B, GBF1, GOLGA4, GPRIN3, ITSN2, PAFAH1B1, PPP6R3 +4 more |
About the gene
| Synonyms | Ib772, KIAA0312, UREB1 |
|---|---|
| Chromosome | X: 53532096-53686752 |
| Predicted location | Intracellular, Membrane |
| Essential gene | Yes |
| Protein class | Cancer-related genes, Disease related genes, Enzymes, Essential proteins, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins |
| Molecular function | DNA-binding, Transferase |
| Biological process | Biological rhythms, Differentiation, DNA damage, DNA repair, Ubl conjugation pathway |
Function
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. Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC. Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination. 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. Mediates polyubiquitination of isoform 2 of PA2G4. Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1. Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling. Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys- 48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6. 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination. Ubiquitinates PPARA in hepatocytes (By similarity).
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.