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

    Gene ID: 10075, updated on 11-May-2012
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    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:30892
    Locus tag
    RP3-339A18.4
    See related
    Ensembl:ENSG00000086758; HPRD:06608; MIM:300697; Vega:OTTHUMG00000021617
    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; KIAA0312
    Summary
    This gene encodes a member of the HECT E3 ubiquitin ligase family. The HECT domain lies in the C-terminus and contains the active-site cysteine which forms an intermediate ubiquitin-thioester bond. E3 family members are divided into three subfamilies based on their protein-protein interaction domains; this gene encodes a member of the SI(ngle)-HECT E3 subfamily. In lung, breast, and colorectal carcinomas, this gene is highly expressed. Mutations in this gene has been found in 3 unrelated families with X-linked syndromic mental retardation, Turner type. [provided by RefSeq, Nov 2009]
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    Genomic context

    Location :
    Xp11.22
    Sequence :
    Chromosome: X; NC_000023.10 (53559063..53713673, complement)
    See HUWE1 in Epigenomics, MapViewer

    Chromosome X - NC_000023.10Genomic 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-like Neighboring gene mitochondrial ribosomal protein S18C pseudogene

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. HUWE1 ubiquitinates MyoD and targets it for proteasomal degradation. Noy T, et al. Biochem Biophys Res Commun, 2012 Feb 10. PMID 22277673.
    2. Regulation of oxidative DNA damage repair by DNA polymerase λ and MutYH by cross-talk of phosphorylation and ubiquitination. Markkanen E, et al. Proc Natl Acad Sci U S A, 2012 Jan 10. PMID 22203964.
    3. Identification of ubiquitinated proteins from human multiple myeloma U266 cells by proteomics. Jia H, et al. Biomed Environ Sci, 2011 Aug. PMID 22108332.
    4. Mule determines the apoptotic response to HDAC inhibitors by targeted ubiquitination and destruction of HDAC2. Zhang J, et al. Genes Dev, 2011 Dec 15. PMID 22016339.
    5. Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels. Lee KA, et al. J Biol Chem, 2011 Dec 2. PMID 21987572.

    See all (63) citations in PubMed

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

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. the involvement of HUWE1 in the ubiquitination and proteasomal degradation of MyoD was described.
      Title: HUWE1 ubiquitinates MyoD and targets it for proteasomal degradation.
    2. The E3 ligase Mule mediates the degradation of Pol lambda and the control of Pol lambda levels by Mule has functional consequences for the ability of mammalian cells to deal with 8-oxo-G lesions.
      Title: Regulation of oxidative DNA damage repair by DNA polymerase λ and MutYH by cross-talk of phosphorylation and ubiquitination.
    3. The present study reveals a novel regulation of RASSF1C and the potentially important role of RASSF1C in DNA damage responses via SCFbeta-TrCP and Mule.
      Title: Targeted polyubiquitylation of RASSF1C by the Mule and SCFβ-TrCP ligases in response to DNA damage.
    4. a critical regulatory mechanism of HDAC2 by Mule and suggest this pathway determines the cellular response to HDACis and DNA damage
      Title: Mule determines the apoptotic response to HDAC inhibitors by targeted ubiquitination and destruction of HDAC2.
    5. Mitochondrion-dependent N-terminal processing of outer membrane Mcl-1 protein removes an essential Mule/Lasu1 protein-binding site.
      Title: Mitochondrion-dependent N-terminal processing of outer membrane Mcl-1 protein removes an essential Mule/Lasu1 protein-binding site.
    6. Studies indicate that ARF is induced in response to DNA damage and inhibits, by direct interaction, the E3 ubiquitin ligase Mule.
      Title: The emerging role of Mule and ARF in the regulation of base excision repair.
    7. findings suggest that reduced Mule/Mcl-1 complex has a significant role in increasing the stability of Mcl-1 in breast cancer cells and increased resistance to apoptosis
      Title: Reduced association of anti-apoptotic protein Mcl-1 with E3 ligase Mule increases the stability of Mcl-1 in breast cancer cells.
    8. Huwe1 interacted with HIV-1 Gag-Pol precursor protein through an IN domain
      Title: Huwe1, a novel cellular interactor of Gag-Pol through integrase binding, negatively influences HIV-1 infectivity.
    9. Arf-bp1 and Pam are novel regulators of circadian gene expression that target Rev-erb alpha for degradation
      Title: E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the circadian heme receptor Rev-erb alpha.
    10. A structural element within the HUWE1 HECT domain modulates self-ubiquitination and substrate ubiquitination activities.
      Title: A structural element within the HUWE1 HECT domain modulates self-ubiquitination and substrate ubiquitination activities.
    Submit: New GeneRIF Correction See all (24)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Mental retardation, X-linked syndromic 10

    Mental retardation, X-linked syndromic, Turner type

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_113584.3 AAP35666.1 CDKN2A    BIND  PubMed ARF interacts with ARF-BP1. 
    NP_113584.3 NP_113584.3 HUWE1    BIND  PubMed ARF-BP1 autoubiquitinates itself. 
    NP_113584.3 MCL1    BIND  PubMed Mule interacts with and ubiquitinates Mcl-1. 
    NP_113584.3 NP_000537.2 TP53    BIND  PubMed ARF-BP1 interacts with and ubiquitinates p53. 
    Q7Z6Z7 P22362 CCL1    HPRD  PubMed  
    Q7Z6Z7 Q8N726 CDKN2A    HPRD  PubMed  
    Q7Z6Z7 Q13571 LAPTM5    HPRD  PubMed  
    Q7Z6Z7 Q07820 MCL1    HPRD  PubMed  
    Q7Z6Z7 Q9Y3C5 RNF11    HPRD  PubMed  
    Q7Z6Z7 Q15796 SMAD2    HPRD  PubMed  
    Q7Z6Z7 O15198 SMAD9    HPRD  PubMed  
    Q7Z6Z7 P04637 TP53    HPRD  PubMed  
    BioGRID:115385 BioGRID:106962 ATM    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115385 BioGRID:107252 CALM1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:115385 BioGRID:107426 CDC6    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:115385 BioGRID:123213 CDK5RAP3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115385 BioGRID:107463 CDKN2A    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex 
    BioGRID:115385 BioGRID:116806 FAF2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115385 BioGRID:115385 HUWE1    BioGRID  PubMed Biochemical Activity 
    BioGRID:115385 BioGRID:110338 MCL1    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity; Reconstituted Complex 
    BioGRID:115385 BioGRID:110694 MYC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Biochemical Activity; Reconstituted Complex 
    BioGRID:115385 BioGRID:114941 NR1D1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:115385 BioGRID:111142 PCNA    BioGRID  PubMed Biochemical Activity 
    BioGRID:115385 BioGRID:114523 PIAS2    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity; Reconstituted Complex 
    BioGRID:115385 BioGRID:111379 PMAIP1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115385 BioGRID:111419 POLB    BioGRID  PubMed Biochemical Activity 
    BioGRID:115385 BioGRID:122479 SLX1B    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115385 BioGRID:113010 TP53    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity; Reconstituted Complex 
    BioGRID:115385 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex 
    BioGRID:115385 BioGRID:113885 UBL4A    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115385 BioGRID:119239 UBXN1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115385 BioGRID:113221 USP4    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:115385 BioGRID:117382 USP49    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115385 BioGRID:131884 USP50    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115385 BioGRID:113622 USP7    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115385 BioGRID:113867 USP9X    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115385 BioGRID:123125 VCPIP1    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    acid-amino acid ligase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    ligase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    ubiquitin-protein ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    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 
    protein modification process IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein monoubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein polyubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein ubiquitination involved in ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    intracellular IEA
    Inferred from Electronic Annotation
    more info
    		  
    NOT nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
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    General protein information

    Preferred Names
    E3 ubiquitin-protein ligase HUWE1
    Names
    E3 ubiquitin-protein ligase HUWE1
    ARF-binding protein 1
    URE-binding protein 1
    BJ-HCC-24 tumor antigen
    large structure of UREB1
    HECT domain protein LASU1
    Mcl-1 ubiquitin ligase E3
    upstream regulatory element-binding protein 1
    homologous to E6AP carboxyl terminus homologous protein 9
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    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_016261.1 RefSeqGene

      Range
      4977..159617
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_031407.5 → NP_113584.3  E3 ubiquitin-protein ligase HUWE1

      Status: REVIEWED

      Source sequence(s)
      AY772009, BU619074, CK002817, DQ097177, R60532, Z94044
      Consensus CDS
      CCDS35301.1
      UniProtKB/Swiss-Prot
      Q7Z6Z7
      Related
      ENSP00000262854, ENST00000262854
      Conserved Domains (6) summary
      cd00078
      Location:4019 – 4372
      Blast Score: 1163
      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 ...
      pfam06025
      Location:429 – 815
      Blast Score: 1058
      DUF913; Domain of Unknown Function (DUF913)
      smart00119
      Location:4043 – 4371
      Blast Score: 1249
      HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
      pfam06012
      Location:104 – 370
      Blast Score: 639
      DUF908; Domain of Unknown Function (DUF908)
      pfam14377
      Location:2968 – 3079
      Blast Score: 235
      DUF4414; Domain of unknown function (DUF4414)
      cl02729
      Location:1617 – 1678
      Blast Score: 155
      WWE; WWE domain

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000023.10 Reference GRCh37.p5 Primary Assembly

      Range
      53559063..53713673, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000155.1 Alternate HuRef

      Range
      50615907..50769886, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL592046.7 CAI39578.1
      CAI39579.1
      CAI39580.1
      CAI39581.1
    genomic CH471154.1 EAW93160.1
      EAW93161.1
      EAW93162.1
      EAW93163.1
      EAW93164.1
      EAW93165.1
      EAW93166.1
    genomic CS228272.1 CAJ47378.1
    genomic Z94044.2 CAI42351.1
      CAI42352.1
      CAI42353.1
      CAI42354.1
    genomic Z97054.1 CAI42644.1
      CAI42654.1
      CAI42656.1
    mRNA AB002310.3 BAA20771.3
    mRNA AB071605.1 BAC06833.1
    mRNA AF057569.1 AAC62492.1
    mRNA AF161390.1 AAF28950.1
    mRNA AK056671.1 None
    mRNA AK091352.1 None
    mRNA AK223167.1 BAD96887.1
    mRNA AK294575.1 BAG57767.1
    mRNA AL162050.1 CAB82393.1
    mRNA AY772009.1 AAV90838.1
    mRNA AY929612.1 AAX24125.1
    mRNA BC002602.2 AAH02602.2
    mRNA BC018750.1 AAH18750.1
    mRNA BC038184.1 AAH38184.1
    mRNA BC063505.1 AAH63505.1
    mRNA BC072421.1 None
    mRNA BC107576.1 AAI07577.1
    mRNA BU619074.1 None
    mRNA CK002817.1 None
    mRNA CR456813.1 CAG33094.1
    mRNA DQ097177.1 AAY98258.1
    mRNA R60532.1 None
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q3B7K0 GenPept UniProtKB/TrEMBL:Q3B7K0
    Q53FW4 GenPept UniProtKB/TrEMBL:Q53FW4
    Q5H924 GenPept UniProtKB/TrEMBL:Q5H924
    Q5H935 GenPept UniProtKB/TrEMBL:Q5H935
    Q5H962 GenPept UniProtKB/TrEMBL:Q5H962
    Q5H963 GenPept UniProtKB/TrEMBL:Q5H963
    Q7Z6Z7.3 GenPept UniProtKB/Swiss-Prot:Q7Z6Z7
    Q8IWJ0 GenPept UniProtKB/TrEMBL:Q8IWJ0
    Q9NXW1 GenPept UniProtKB/TrEMBL:Q9NXW1
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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