HUWE1, E3 ubikitiiniligaasi (E6AP-tyyppinen) , HECT, UBA ja WWE- domaanit sisältävä ,

https://www.ncbi.nlm.nih.gov/gene/10075

Official Symbol

HUWE1provided by HGNC

Official Full Name

HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1provided by HGNC

Gene type

protein coding

RefSeq status

REVIEWED

Organism

Homo sapiens

Lineage

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo

Also known as

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

Summary

This gene encodes a protein containing a C-terminal HECT (E6AP type E3 ubiquitin protein ligase) domain that functions as an E3 ubiquitin ligase. The encoded protein is required for the ubiquitination and subsequent degradation of the anti-apoptotic protein Mcl1 (myeloid cell leukemia sequence 1 (BCL2-related)). This protein also ubiquitinates the p53 tumor suppressor, core histones, and DNA polymerase beta. Mutations in this gene are associated with Turner type X-linked syndromic cognitive disability. [provided by RefSeq, Aug 2013]

Expression

Ubiquitous expression in ovary (RPKM 14.5), testis (RPKM 13.8) and 25 other tissues See more

Orthologs mouse all

Preferred Names

E3 ubiquitin-protein ligase HUWE1

Names

ARF-binding protein 1

BJ-HCC-24 tumor antigen

HECT domain protein LASU1

HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase

HECT-type E3 ubiquitin transferase HUWE1

Mcl-1 ubiquitin ligase E3

URE-binding protein 1

homologous to E6AP carboxyl terminus homologous protein 9

large structure of UREB1

upstream regulatory element-binding protein 1

https://www.ncbi.nlm.nih.gov/protein/NP_113584.3

Conserved Domains (7) summary

smart00119
Location:4043 → 4371

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:4019 → 4372

HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

cd14288
Location:1317 → 1356

UBA_HUWE1; UBA domain found in eukaryotic E3 ubiquitin-protein ligase HUWE1 and similar proteins

pfam02825
Location:1617 → 1678

WWE;

WWE domain

The WWE domain is named after three of its conserved residues and is predicted to mediate specific protein- protein interactions in ubiquitin and ADP ribose conjugation systems.

pfam06012
Location:92 → 367

DUF908; Domain of Unknown Function (DUF908)

pfam06025
Location:430 → 814

DUF913; Domain of Unknown Function (DUF913)

pfam14377
Location:2968 → 3077

DUF4414; Domain of unknown function (DUF4414)

 

Related articles in PubMed

1. HUWE1 variants cause dominant X-linked intellectual disability: a clinical study of 21 patients. Moortgat S, et al. Eur J Hum Genet, 2018 Jan. PMID 29180823, Free PMC Article
2. HUWE1 mutations in Juberg-Marsidi and Brooks syndromes: the results of an X-chromosome exome sequencing study. Friez MJ, et al. BMJ Open, 2016 Apr 29. PMID 27130160, Free PMC Article
3. Novel microduplications at Xp11.22 including HUWE1: clinical and molecular insights into these genomic rearrangements associated with intellectual disability. Santos-Rebouças CB, et al. J Hum Genet, 2015 Apr. PMID 25652354
4. Shh signaling protects Atoh1 from degradation mediated by the E3 ubiquitin ligase Huwe1 in neural precursors. Forget A, et al. Dev Cell, 2014 Jun 23. PMID 24960692
5. Copy-number gains of HUWE1 due to replication- and recombination-based rearrangements. Froyen G, et al. Am J Hum Genet, 2012 Aug 10. PMID 22840365, Free PMC Article

See all (187) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. Regulation of the intracellular WIPI2 protein level by mTORC1 and HUWE1 is a key determinant of autophagy flux.
2. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014.
3. Ubiquitination modification through the coordinated action of PAQR3 with HUWE1 plays a crucial role in regulating the activity of hepatic PPARalpha in response to starvation.
4. HUWE1 missense variants may cause syndromic ID in both males and females.
5. HUWE1 overexpression could functionally suppress prostate carcinoma development both in vitro and in vivo, possibly by inverse regulation of c-Myc.
6. RBBP7 controls the stability of HUWE1.RBBP7 promotes HUWE1 ubiquitination.
7. The data supports an indispensable role for Mule in cardiac homeostasis through the regulation of mitochondrial function via maintenance of Pgc-1alpha and Pink1 expression and persistent negative regulation of c-Myc.
8. these results suggest that HUWE1 protein could contribute to preimplantation embryo development and dysregulated expression of HUWE1 could be related to poor embryo development and miscarriage in IVF clinic.
9. The authors show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. They also demonstrate that HUWE1 is inhibited in cells and that it can be activated by disruption of the dimer interface.
10. High HUWE1 expression is associated with Ovarian cancer.

Submit: New GeneRIF Correction See all GeneRIFs (57)