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HUWE1 HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase [ Homo sapiens (human) ]

Gene ID: 10075, updated on 20-Jan-2019

Summary

Official Symbol
HUWE1provided by HGNC
Official Full Name
HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligaseprovided by HGNC
Primary source
HGNC:HGNC:30892
See related
Ensembl:ENSG00000086758 MIM:300697
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; 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

Genomic context

See HUWE1 in Genome Data Viewer
Location:
Xp11.22
Exon count:
92
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) X NC_000023.11 (53532096..53686729, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (53559057..53713697, complement)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene TIMELESS interacting protein pseudogene Neighboring gene vault RNA 3-1, pseudogene Neighboring gene microRNA let-7f-2 Neighboring gene microRNA 98 Neighboring gene 39S ribosomal protein L32, mitochondrial pseudogene Neighboring gene mitochondrial ribosomal protein S18C pseudogene

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Mental retardation, X-linked, syndromic, turner type
MedGen: C2678046 OMIM: 300706 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated (2018-09-26)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated (2018-09-26)

ClinGen Genome Curation Page

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase (HUWE1) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Gag-Pol gag-pol Co-immunoprecipitation shows interaction of HIV-1 Gag-Pol with Huwe1 through IN domain (residues 1148-1435) PubMed
Rev rev HIV-1 Rev interacting protein, HECT, UBA and WWE domain containing 1 (HUWE1), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells PubMed
Vif vif HIV-1 Vif is identified to have a physical interaction with HECT, UBA and WWE domain containing 1 (HUWE1) in human HEK293 and/or Jurkat cell lines PubMed
integrase gag-pol Co-immunoprecipitation shows interaction of HIV-1 IN with Huwe1 through the CCD domain of IN PubMed
retropepsin gag-pol Positional proteomics analysis identifies the cleavage of human HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase (HUWE1) at amino acid residues 3686-3687 by the HIV-1 protease PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystem (from REACTOME)
    Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystemIntracellular foreign or aberrant host proteins are cleaved into peptide fragments of a precise size, such that they can be loaded on to class I MHC molecules and presented externally to cytotoxic T ...
  • Class I MHC mediated antigen processing & presentation, organism-specific biosystem (from REACTOME)
    Class I MHC mediated antigen processing & presentation, organism-specific biosystemMajor histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular b...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Neutrophil degranulation, organism-specific biosystem (from REACTOME)
    Neutrophil degranulation, organism-specific biosystemNeutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and ...
  • Ubiquitin mediated proteolysis, organism-specific biosystem (from KEGG)
    Ubiquitin mediated proteolysis, organism-specific biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
  • Ubiquitin mediated proteolysis, conserved biosystem (from KEGG)
    Ubiquitin mediated proteolysis, conserved biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
  • Validated targets of C-MYC transcriptional activation, organism-specific biosystem (from Pathway Interaction Database)
    Validated targets of C-MYC transcriptional activation, organism-specific biosystem
    Validated targets of C-MYC transcriptional activation
  • p53 pathway, organism-specific biosystem (from Pathway Interaction Database)
    p53 pathway, organism-specific biosystem
    p53 pathway

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • KIAA0312

Gene Ontology Provided by GOA

Function Evidence Code Pubs
DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
RNA binding HDA PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin-protein transferase activity EXP
Inferred from Experiment
more info
PubMed 
ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
 
Process Evidence Code Pubs
base-excision repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
base-excision repair IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell differentiation IEA
Inferred from Electronic Annotation
more info
 
histone ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
neutrophil degranulation TAS
Traceable Author Statement
more info
 
positive regulation of protein targeting to mitochondrion HMP PubMed 
protein monoubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein polyubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein polyubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein polyubiquitination TAS
Traceable Author Statement
more info
 
protein ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
extracellular exosome HDA PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
ficolin-1-rich granule lumen TAS
Traceable Author Statement
more info
 
membrane HDA PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 
secretory granule lumen TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
E3 ubiquitin-protein ligase HUWE1
Names
ARF-binding protein 1
BJ-HCC-24 tumor antigen
HECT domain protein LASU1
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
NP_113584.3
XP_005262022.1
XP_011529049.1
XP_011529053.1
XP_016884680.1
XP_016884681.1
XP_016884682.1
XP_016884683.1
XP_016884684.1
XP_016884685.1
XP_016884686.1
XP_016884687.1
XP_016884688.1
XP_016884689.1
XP_016884690.1
XP_016884691.1
XP_016884692.1
XP_016884693.1
XP_016884695.1
XP_024308090.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_016261.2 RefSeqGene

    Range
    5005..159638
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_031407.7NP_113584.3  E3 ubiquitin-protein ligase HUWE1

    Status: REVIEWED

    Source sequence(s)
    AB002310, AC231658, AY772009, BX323845, DQ097177, R60532
    Consensus CDS
    CCDS35301.1
    UniProtKB/Swiss-Prot
    Q7Z6Z7
    UniProtKB/TrEMBL
    A0A024R9W5
    Related
    ENSP00000262854.6, ENST00000262854.10
    Conserved Domains (7) summary
    smart00119
    Location:40434371
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00078
    Location:40194372
    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:13171356
    UBA_HUWE1; UBA domain found in eukaryotic E3 ubiquitin-protein ligase HUWE1 and similar proteins
    pfam02825
    Location:16171678
    WWE; WWE domain
    pfam06012
    Location:92367
    DUF908; Domain of Unknown Function (DUF908)
    pfam06025
    Location:430814
    DUF913; Domain of Unknown Function (DUF913)
    pfam14377
    Location:29683077
    DUF4414; Domain of unknown function (DUF4414)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p12 Primary Assembly

    Range
    53532096..53686729 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011530747.1XP_011529049.1  E3 ubiquitin-protein ligase HUWE1 isoform X9

    Conserved Domains (7) summary
    cd00078
    Location:41024455
    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:14001439
    UBA_HUWE1; UBA domain found in eukaryotic E3 ubiquitin-protein ligase HUWE1 and similar proteins
    pfam02825
    Location:17001761
    WWE; WWE domain
    pfam06012
    Location:92367
    DUF908; Domain of Unknown Function (DUF908)
    pfam06025
    Location:430897
    DUF913; Domain of Unknown Function (DUF913)
    pfam14377
    Location:30513160
    DUF4414; Domain of unknown function (DUF4414)
    cl26464
    Location:28183149
    Atrophin-1; Atrophin-1 family
  2. XM_017029199.1XP_016884688.1  E3 ubiquitin-protein ligase HUWE1 isoform X8

  3. XM_017029202.1XP_016884691.1  E3 ubiquitin-protein ligase HUWE1 isoform X8

  4. XM_024452322.1XP_024308090.1  E3 ubiquitin-protein ligase HUWE1 isoform X9

    Conserved Domains (7) summary
    cd00078
    Location:41024455
    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:14001439
    UBA_HUWE1; UBA domain found in eukaryotic E3 ubiquitin-protein ligase HUWE1 and similar proteins
    pfam02825
    Location:17001761
    WWE; WWE domain
    pfam06012
    Location:92367
    DUF908; Domain of Unknown Function (DUF908)
    pfam06025
    Location:430897
    DUF913; Domain of Unknown Function (DUF913)
    pfam14377
    Location:30513160
    DUF4414; Domain of unknown function (DUF4414)
    cl26464
    Location:28183149
    Atrophin-1; Atrophin-1 family
  5. XM_017029200.1XP_016884689.1  E3 ubiquitin-protein ligase HUWE1 isoform X8

  6. XM_005261965.4XP_005262022.1  E3 ubiquitin-protein ligase HUWE1 isoform X11

    UniProtKB/Swiss-Prot
    Q7Z6Z7
    UniProtKB/TrEMBL
    A0A024R9W5
    Related
    ENSP00000340648.3, ENST00000342160.7
    Conserved Domains (7) summary
    smart00119
    Location:40434371
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    cd00078
    Location:40194372
    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:13171356
    UBA_HUWE1; UBA domain found in eukaryotic E3 ubiquitin-protein ligase HUWE1 and similar proteins
    pfam02825
    Location:16171678
    WWE; WWE domain
    pfam06012
    Location:92367
    DUF908; Domain of Unknown Function (DUF908)
    pfam06025
    Location:430814
    DUF913; Domain of Unknown Function (DUF913)
    pfam14377
    Location:29683077
    DUF4414; Domain of unknown function (DUF4414)
  7. XM_017029198.2XP_016884687.1  E3 ubiquitin-protein ligase HUWE1 isoform X8

  8. XM_017029203.1XP_016884692.1  E3 ubiquitin-protein ligase HUWE1 isoform X8

  9. XM_011530751.2XP_011529053.1  E3 ubiquitin-protein ligase HUWE1 isoform X9

    Conserved Domains (7) summary
    cd00078
    Location:41024455
    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:14001439
    UBA_HUWE1; UBA domain found in eukaryotic E3 ubiquitin-protein ligase HUWE1 and similar proteins
    pfam02825
    Location:17001761
    WWE; WWE domain
    pfam06012
    Location:92367
    DUF908; Domain of Unknown Function (DUF908)
    pfam06025
    Location:430897
    DUF913; Domain of Unknown Function (DUF913)
    pfam14377
    Location:30513160
    DUF4414; Domain of unknown function (DUF4414)
    cl26464
    Location:28183149
    Atrophin-1; Atrophin-1 family
  10. XM_017029201.1XP_016884690.1  E3 ubiquitin-protein ligase HUWE1 isoform X8

  11. XM_017029193.1XP_016884682.1  E3 ubiquitin-protein ligase HUWE1 isoform X3

  12. XM_017029196.1XP_016884685.1  E3 ubiquitin-protein ligase HUWE1 isoform X6

  13. XM_017029192.1XP_016884681.1  E3 ubiquitin-protein ligase HUWE1 isoform X2

  14. XM_017029206.1XP_016884695.1  E3 ubiquitin-protein ligase HUWE1 isoform X12

  15. XM_017029197.1XP_016884686.1  E3 ubiquitin-protein ligase HUWE1 isoform X7

  16. XM_017029195.1XP_016884684.1  E3 ubiquitin-protein ligase HUWE1 isoform X5

  17. XM_017029194.1XP_016884683.1  E3 ubiquitin-protein ligase HUWE1 isoform X4

  18. XM_017029191.1XP_016884680.1  E3 ubiquitin-protein ligase HUWE1 isoform X1

  19. XM_017029204.1XP_016884693.1  E3 ubiquitin-protein ligase HUWE1 isoform X10

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