E3 ubiquitin-protein ligase HUWE1; ARF-binding protein 1; ARF-BP1; HECT, UBA & WWE domain-containing protein 1; homologous to E6AP carboxyl terminus homologous protein 9; HectH9; large structure of UREB1; LASU1; Mcl-1 ubiquitin ligase E3; mule; upstream regulatory element-binding protein 1; URE-B1; URE-binding protein 1 (HUWE1, KIAA0312, KIAA1578, UREB1, HSPC272)

Function: - E3 ubiquitin-protein ligase - mediates ubiquitination & subsequent proteasomal degradation of target proteins - regulates apoptosis by catalyzing polyubiquitination & degradation of MCL1 - also ubiquitinates the p53 tumor suppressor & core histones including H1, H2A, H2B, H3 & H4 - binds to an upstream initiator-like sequence in the preprodynorphin gene - regulates neural differentiation & proliferation by catalyzing polyubiquitination & degradation of MYCN - may regulate abundance of CDC6 after DNA damage by polyubiquitinating & targeting CDC6 to degradation - protein modification; protein ubiquitination - phosphorylated on Tyr; phosphorylation is probably required for its ability to inhibit TP53 transactivation - phosphorylated upon DNA damage, probably by ATM or ATR - interacts with isoform p14ARF of CDKN2A which strongly inhibits HUWE1 ubiquitin ligase activity - interacts with MYCN & CDC6 Structure: - the HECT domain mediates inhibition of the transcriptional activity of p53 - belongs to the TOM1/PTR1 family - contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain - contains 1 UBA domain - contains 1 UIM (ubiquitin-interacting motif) repeat - contains 1 WWE domain Compartment: - cytoplasm, nucleus - mainly expressed in the cytoplasm of most tissues, - in the nucleus of spermatogonia, primary spermatocytes & neuronal cells - predominantly cytosolic or perinuclear in some colorectal carcinoma cells Alternative splicing: named isoforms=3 Expression: - weakly expressed in heart, brain & placenta - expressed in a number of cell lines, predominantly in those from colorectal carcinomas Pathology: - defects in HUWE1 are the cause of mental retardation syndromic X-linked Turner type - chromosomal microduplication involving HUWE1 & HSD17B10 is the cause of mental retardation X-linked type 17

General

phosphoprotein E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein

Properties

SIZE: entity length = 4374 aa MW = 482 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Ser phosphorylation site {S1084} UBA domain {1316-1355} Ser phosphorylation site {S1368} UIM {1370-1389} MOTIF: Ser phosphorylation site {S1370} Ser phosphorylation site {S1395} WWE {1603-1680} Ser phosphorylation site {S1903} Ser phosphorylation site {S1907} glutamate-rich region {2295-2469} MOTIF: glutamate residue (SEVERAL) Ser phosphorylation site {S2362} Ser phosphorylation site {S2365} Thr phosphorylation site {T2366} Ser phosphorylation site {S2377} Ser phosphorylation site {S2391} Ser phosphorylation site {S2526} Ser phosphorylation site {S2595} Ser phosphorylation site {S2619} Thr phosphorylation site {T2746} Thr phosphorylation site {T2751} Ser phosphorylation site {S2887} Ser phosphorylation site {S2888} Thr phosphorylation site {T2889} Ser phosphorylation site {S2918} Ser phosphorylation site {S3116} Ser phosphorylation site {S3373} Ser phosphorylation site {S3377} threonine-rich region {3483-3550} MOTIF: threonine residue (SEVERAL) Ser phosphorylation site {S3662} Ser phosphorylation site {S3752} Ser phosphorylation site {S3757} Ser phosphorylation site {S3759} Ser phosphorylation site {S3797} Ser phosphorylation site {S3808} Ser phosphorylation site {S3816} Thr phosphorylation site {T3822} Ser phosphorylation site {S3919} Thr phosphorylation site {T3924} Thr phosphorylation site {T3927} HECT domain {4038-4374} MOTIF: Tyr phosphorylation site {Y4271} cysteine residue {C4341}

Database Correlations

OMIM correlations MORBIDMAP 300697 UniProt Q7Z6Z7 PFAM correlations Entrez Gene 10075 Kegg hsa:10075

References

UniProt :accession Q7Z6Z7