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FLASH GENE
Symbol HERC2 contributors: mct/pgu - updated : 30-10-2014
HGNC name hect domain and RLD 2
HGNC id 4868
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Endocrineadrenal gland   highly
 parathyroid   highly
Nervousnerve   highly
Reproductivefemale systemovary  highly
 male systemtestis  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumcardiac  
Muscularstriatumskeletal  
Nervouscentral   
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text highly in fetal tissues
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 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
  • HOMOLOGY
    interspecies homolog to murine Herc2
    Homologene
    FAMILY
  • HERC family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text
  • 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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text vesicular transport
    PATHWAY
    metabolism
    signaling
    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
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
    REGULATION
    ASSOCIATED DISORDERS
    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
    Marker
    Therapy target
    ANIMAL & CELL MODELS