InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HUWE1

Summary

InnateDB Protein

IDBP-70118.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HUWE1

Protein Name

HECT, UBA and WWE domain containing 1

Synonyms

ARF-BP1; HECTH9; HSPC272; Ib772; LASU1; MULE; URE-B1; UREB1;

Species

Homo sapiens

Ensembl Protein

ENSP00000340648

InnateDB Gene

IDBG-70116 (HUWE1)

Protein Structure

UniProt Annotation

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. 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. {ECO:0000269PubMed:15567145, ECO:0000269PubMed:15767685, ECO:0000269PubMed:15989956, ECO:0000269PubMed:15989957, ECO:0000269PubMed:17567951, ECO:0000269PubMed:18488021, ECO:0000269PubMed:19713937}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:19713937}. Nucleus {ECO:0000269PubMed:19713937}. Note=Mainly expressed in the cytoplasm of most tissues, except in the nucleus of spermatogonia, primary spermatocytes and neuronal cells (By similarity). Predominantly cytosolic or perinuclear in some colorectal carcinoma cells. {ECO:0000250}.

Disease Associations

Mental retardation, X-linked, syndromic, Turner type (MRXST) [MIM:300706]: A syndrome characterized by the association of mental retardation with macrocephaly and variable contractures. Note=The disease is caused by mutations affecting the gene represented in this entry.Mental retardation, X-linked 17 (MRX17) [MIM:300705]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non- syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269PubMed:18252223}. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal microduplication involving HSD17B10 and HUWE1 has been found in patients with mental retardation.

Tissue Specificity

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. {ECO:0000269PubMed:15567145}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 409 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	409 [view]
Protein-Protein	408 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0004842	ubiquitin-protein transferase activity
GO:0005488	binding
GO:0005515	protein binding
GO:0016874	ligase activity
GO:0044822	poly(A) RNA binding

Biological Process

GO:0000209	protein polyubiquitination
GO:0006284	base-excision repair
GO:0006513	protein monoubiquitination
GO:0016574	histone ubiquitination
GO:0030154	cell differentiation
GO:0042787	protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0016020	membrane
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000449 Ubiquitin-associated domain/translation elongation factor EF-Ts, N-terminal
IPR000569 HECT
IPR004170 WWE domain
IPR009060 UBA-like
IPR010309 E3 ubiquitin ligase, domain of unknown function DUF908
IPR010314 E3 ubiquitin ligase, domain of unknown function DUF913
IPR015940 Ubiquitin-associated/translation elongation factor EF1B, N-terminal, eukaryote
IPR016024 Armadillo-type fold

PFAM

PF00627
PF00632
PF02825
PF06012
PF06025

PRINTS

PIRSF

SMART

SM00119
SM00165

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q7Z6Z7