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Symbol HERC2 contributors: mct/pgu - updated : 30-10-2014
HGNC name hect domain and RLD 2
HGNC id 4868
Corresponding disease
HECD skin, hair and eye pigmentation variations
MRAGI mental retardation, autistic behavior, and gait instability
Location 15q13.1      Physical location : 28.356.189 - 28.567.295
Synonym name
  • HECT domain and RCC1-like domain-containing protein 2
  • probable E3 ubiquitin-protein ligase HERC2
  • Synonym symbol(s) D15F37S1, KIAA0393, JDF2, P528, H18, DKFZp547P028, D15S62, SHEP1
    EC.number 6.3.2.-
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem, head to head
    text ancestral gene of a superfamily of low-copy repeat sequences in the PWCR/AS breakpoint cluster region
    STRUCTURE 211.11 kb     93 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure a conserved regulatory element within intron 86 that is perfectly associated with the brown/blue eye color, having an inhibitory effect on the OCA2 promoter activity
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    93 - 15334 527.5 4834 - 2007 17952075
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   highly
     parathyroid   highly
    Nervousnerve   highly
    Reproductivefemale systemovary  highly
     male systemtestis  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    physiological period fetal
    Text highly in fetal tissues
  • 19 RCC1-like domains (RLD)
  • a ZZ type putative zinc finger motif
  • a cytochrome b5 heme-binding domain
  • a DOC domain
  • a MIB/HERC2 domain
  • six WD repeats
  • a C terminal HECT domain characteristic of (E6-AP) E3 ubiquitin ligases, homologous to the UBE3A carboxy terminus
    interspecies homolog to murine Herc2
  • HERC family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
  • centriole
  • HERC2 and NEURL4 localize to the centrosome
  • basic FUNCTION
  • guanyl-nucleotide exchange factor
  • E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates
  • factor that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes
  • function for HERC2 in regulating BRCA1 stability in opposition to BARD1, suggesting that this mechanism may play a role in breast carcinogenesis
  • stimulates the ubiquitin-protein ligase activity of UBE3A within cells and this stimulatory effect does not depend on the ubiquitin-protein ligase activity of HERC2
  • regulates DNA replication progression and origin firing by facilitating MCM2 phosphorylation
  • having a critical function in DNA repair, checkpoint activation, and DNA replication
  • HERC2 and RNF168 are novel DNA damage-dependent SUMOylation targets in human cells
  • modulates the ubiquitin ligase activity of UBE3A
  • regulates the basal turnover of FBXL5, and this ubiquitin-dependent degradation pathway contributes to the control of mammalian iron metabolism
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text vesicular transport
    a component
  • forming a complex with RNF8, complex involved in DNA damage response
  • component of the DNA replication fork complex that plays a critical role in DNA elongation and origin firing
  • NEURL4-HERC2 complex participates in the ubiquitin-dependent regulation of centrosome architecture
    small molecule
  • HERC2-RNF8 interaction requires ionising radiation-inducible phosphorylation of HERC2 at Thr 4827, which in turn binds to the forkhead-associated (FHA) domain of RNF8
  • targets BARD1-uncoupled BRCA1 for degradation
  • UBE3A interaction with HERC2 is mediated by the RCC1-like domain 2 of HERC2 and a region spanning amino acid residues 150-200 of UBE3A
  • interaction between HERC2 and SLC24A4 affecting determination of blue eye colour
  • significant interactions of a redundant character between the HERC2 and OCA2 genes affecting determination of hazel eye colour
  • E3 ubiquitin ligase that targets breast cancer suppressor BRCA1 for degradation
  • in the presence of BRCA1, interacts with CLSPN, a protein essential for G(2)-M checkpoint activation and replication fork stability
  • HERC2 and the neuralized homologue NEURL4 are novel interaction partners of the centrosomal protein CCP110, and association between CCP110 and HERC2 depends on nonoverlapping regions of NEURL4
  • both HERC2 and RNF168 were specifically modified with SUMO1 at DSB sites in a manner dependent on the SUMO E3 ligase PIAS4
  • thought to be a key regulator of E6AP
  • is an FBXL5-associated protein
  • HERC2, a HECT domain-containing E3 ligase, as being responsible for polyubiquitination of USP33
  • HERC2 interacts with the coiled-coil domain of USP16 through its C-terminal HECT domain
  • function of HERC2/USP20 in coordinating CHEK1 activation by modulating CLSPN stability, which ultimately promotes genome stability and suppresses tumor growth
  • USP20 is phosphorylated by ATR, resulting in disassociation of the E3 ubiquitin ligase HERC2 from USP20 and USP20 stabilization
  • cell & other
    corresponding disease(s) HECD , MRAGI
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    mapped within the commonly deleted PWS/AS region, with multiple duplications at the common breapoints
    Susceptibility to blue or brown eye colors
    Variant & Polymorphism SNP two SNPs perfectly associated with the blue and brown eye colors
    Candidate gene
    Therapy target