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FLASH GENE
Symbol HUWE1 contributors: mct - updated : 07-01-2020
HGNC name HECT, UBA and WWE domain containing 1
HGNC id 30892
Corresponding disease
DUPXPP chromosome Xp proximal interstitial duplication
SYMYS SAY-MEYER syndrome
Location Xp11.22      Physical location : 53.559.071 - 53.713.673
Synonym name
  • homologous to E6AP carboxyl terminus homologous protein 9
  • upstream regulatory element binding protein 1
  • cDNA sequence, expressed in brain, >100kDa, homolog to rat DNA binding protein UREB1
  • BJ-HCC-24 tumor antigen
  • Mcl-1 ubiquitin ligase E3
  • ARF binding protein 1
  • HECT domain protein LASU1
  • URE-binding protein 1
  • large structure of UREB1
  • Synonym symbol(s) KIAA0312, UREB1, MULE, LASU1, ARF-BP1, HectH9, Ib772, HSPC272
    EC.number 6.3.2.-/ 2.3.2.26
    DNA
    TYPE functioning gene
    STRUCTURE 154.60 kb     84 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    84 - 14734 - 4374 - 2019 31279706
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     mouthtongue  moderately
    Lymphoid/Immunethymus   moderately
    Nervousbrain    
    Reproductivefemale systemuteruscervix moderately
     female systemovary  moderately
     female systemplacenta  moderately
     female systembreastmammary gland moderately
     male systemtestis    Homo sapiens
    Respiratorylung   moderately
     respiratory tractlarynx  predominantly
    Urinarybladder   moderately
    cell lineage
    cell lines colorectal carcinoma cells
    fluid/secretion blood, sperm
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a HECT (E6AP-type E3 ubiquitin-protein ligase) domain
  • a UBA domain
  • a UIM (ubiquitin-interacting motif) repeat
  • a WWE domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to murine Huwe1
    Homologene
    FAMILY
  • TOM1/PTR1 family
  • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus,nucleoplasm
    text predominantly cytosolic or perinuclear in some colorectal carcinoma cells
    basic FUNCTION
  • acting as a ligase
  • mediating ubiquitination and subsequent proteasomal degradation of target proteins
  • regulating apoptosis by catalyzing the polyubiquitination and degradation of MCL1
  • ubiquitinating core histones including H1, H2A, H2B, H3 and H4
  • being essential for proliferation of a subset of tumor cells, and negative regulator of TP53 during the colorectal carcinoma progression through the ubiquitination pathway mediated by the HECT domain
  • implicated in TP53-associated regulation of the neuronal cell cycle
  • operates upstream of the MYCN-DLL3-NOTCH1 pathway to control neural stem cell activity and promote neurogenesis
  • having a role in regulating Berg-mann glia differentiation and this ubiquitin ligase orchestrates the programming of the neural progenitors that give rise to neurons and glia in the cerebellum
  • required for PMAIP1-induced MCL1 degradation
  • involvement of HUWE1 in the ubiquitination and proteasomal degradation of MYOD1
  • dosage-sensitive gene for which a 2-fold increase in expression results in mild to moderate intellectual disability in males
  • HUWE1 and TRIP12 function likely in parallel during ubiquitin fusion degradation (UFD)
  • HUWE1 is a novel player involved in regulating ERK1/2 signal transmission through the SHOC2 scaffold complex
  • HUWE1 and NEDD4, are involved in the post-translational regulation of the ABCG1 and ABCG4 lipid transporters
  • acts as an intestinal tumor suppressor by regulation of the intestinal stem cell niche
  • HECT domain containing ubiquitin ligase implicated in neurogenesis, spermatogenesis and cancer development
  • is a bona fide tumour suppressor gene in the intestinal epithelium
  • role of HUWE1 in orchestrating the physiological DNA damage response in the male germline that contributes to the establishment and maintenance of spermatogonia
  • regulates essential processes such as genome integrity maintenance
  • critical role as a modulator of the DNA damage response pathway in the earliest steps of spermatogonial differentiation
  • HUWE1 is a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors
  • HUWE1 is required for a wide array of important functions in cell biology
  • regulates effectors of DNA replication and genotoxic stress tolerance
  • CELLULAR PROCESS nucleotide, transcription, regulation
    protein, degradation
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text
  • histone ubiquitination
  • mRNA transport
  • ubiquitin conjugation pathway
  • PATHWAY
    metabolism
    signaling
    a component
  • phosphorylated on tyrosine (phosphorylation is probably required for its ability to inhibit TP53 transactivation)
  • INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • ubiquitinating TP53
  • USP4 interacts directly with and deubiquitinates HUWE1, leading to the stabilization of HUWE1 and subsequent reduction of TP53 levels
  • PMAIP1 favors the interaction between MCL1 and HUWE1 and consequently affects MCL1 ubiquitination
  • involvement of HUWE1 in the ubiquitination and proteasomal degradation of MYOD1
  • functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage
  • HUWE1 is a binding partner and regulator of SHOC2 function
  • TNF activates HUWE1 by inducing the dissociation of HUWE1 from its inhibitor CDKN2A
  • upregulation of HUWE1 expression during myogenesis induces TBP degradation and myotube differentiation
  • regulates the intestinal stem cell niche via the WNT pathway and targets EPHB3 for proteasomal and lysosomal degradation
  • interacts directly with CTNNB1 and targets it for degradation under conditions of hyperactive WNT signaling
  • HUWE1 primes histone H1 with ubiquitin to allow ubiquitin chain elongation by RNF8, thereby stimulating the RNF8-RNF168 mediated DNA damage response (DDR)
  • WIPI2 is a phosphorylation substrate of CRTC1 and a ubiquitination target of HUWE1
  • LIMCH1 was a negative regulator implicated in the pathogenesis of lung cancer via modulating HUWE1 and TP53
  • MCL1 stability is regulated by the kinase GSK3B and the E3 ubiquitin ligase HUWE1 in regulating AMBRA1-mediated mitophagy
  • HUWE1 plays a significant role in the regulation of the DNA damage repair (DDR) signaling pathway by directly modulating the abundance of CHEK1 protein
  • cell & other
    REGULATION
    inhibited by interaction with isoform p14ARF of CDKN2A
    ASSOCIATED DISORDERS
    corresponding disease(s) DUPXPP , SYMYS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in multiple human tumors
    tumoral     --over  
    in colorectal carcinoma
    constitutional   amplification    
    duplicated in mental retardation
    constitutional     --low  
    significantly reduced expression of HUWE1 was observed in the villi of miscarriage embryos compared with the normal control, indicating that reduced expression of HUWE1 is related to poor embryo development
    Susceptibility
    Variant & Polymorphism
    Candidate gene potential candidate gene mutation for Say-Meyer syndrome
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Huwe1-null cerebellum exhibited defective cell cycle withdrawal and differentiation of cerebellar granule neuron precursors and disruption of the scaffold organization of radial glia, leading to impaired granule neuron migration and heterotopic granule neuron clusters at the pial surface