Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol SETD2 contributors: mct - updated : 11-05-2016
HGNC name SET domain containing 2
HGNC id 18420
Corresponding disease
STOL2 Sotos-like syndrome 2
Location 3p21.31      Physical location : 47.057.899 - 47.205.467
Synonym name
  • huntington interacting protein B
  • histone-lysine N-methyltransferase SETD2
  • huntingtin yeast partner B
  • huntingtin-interacting protein 1
  • huntingtin-interacting protein B
  • lysine N-methyltransferase 3A
  • Synonym symbol(s) HSPC069, KIAA1732, p231HBP, HYPB, FLJ45883, FLJ16420, FLJ22472, FLJ23184, HIF-1, KMT3A, SET2, HBP231, FLJ46217
    EC.number 2.1.1.43
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 147.57 kb     21 Exon(s)
    regulatory sequence Binding site
    text structure DNA binding site in the proximal E1A promoter
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 8452 - 2564 - 2005 16118227
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousnerve   highly
    Reproductivefemale systemuterus  highly
     male systemprostate  highly
    Respiratorylung   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a single mildly related WW domain
  • a triplicate AWS-SET-PostSET domains mediating a histone H3 lysine 36 specific HMTase activity
  • a low charged region rich in glutamine and proline characterized as a novel transcriptional activation domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Setd2 (87.4pc)
    homolog to rattus Setd2 (80.8pc)
    Homologene
    FAMILY
  • histone-lysine methyltransferase family
  • SET2 subfamily
  • CATEGORY enzyme , regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,chromatin/chromosome
    text colocated in nuclear speckles with HD mutant protein
    basic FUNCTION
  • premRNA splicing
  • coordinating histone methylation and transcriptional regulation
  • having a potential roles in hematopoiesis and pathogenesis of Huntington disease
  • histone methyltransferase specific for lys-36 of histone H3
  • probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POL2RA
  • may act as a transcription activator that binds to promoters
  • can interact with TP53 and selectively regulate its transcription factor activity (Xie 2008)
  • may be a tumor suppressor for breast cancer (Al Sarakbi 2009)
  • histone methyltransferase that is involved in transcriptional elongation
  • SETD2 function of histone methylation could be the missing link in this chain which could explain the potential tumour suppressor function of SETD2 (20944102)
  • both ASH1L and SETD2 are H3K36 specific methyltransferases but only SETD2 can trimethylate this mark
  • essential role of SETD2 in myoblast proliferation and differentiation
  • CELLULAR PROCESS nucleotide, transcription, regulation
    nucleotide, RNA splicing
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • associated with hyperphosphorylated RNA pol II
  • IWS1 connects two distinct C-terminal domain-binding proteins, SUPT6H and SETD2, in a megacomplex that affects mRNA export as well as the histone modification state of active genes (Yoh 2008)
  • INTERACTION
    DNA
  • binding DNA at promoters
  • binding to the promoter of adenovirus 12E1A gene in case of infection, possibly leading to regulate its expression
  • RNA
    small molecule
    protein
  • huntingtin (HD) N terminal proline rich region, enhanced by lengthening the adjacent glutamine tract
  • SETD2 activity modulates SSRP1 recruitment and nucleosome dynamics, thereby repressing cryptic transcription initiation
  • SETD2-dependent trimethylation of histone H3K36 is associated with active transcription
  • deficiency in SETD2 also resulted in repression of Myogenin (MYOG) expression, a key myogenic regulator during differentiation
  • SETD2 is required for expression of ACRBP and protamines and essential for spermiogenesis
  • cell & other
    REGULATION
    activated by low charge region
    Other may be automethylated
    ASSOCIATED DISORDERS
    corresponding disease(s) STOL2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    lower transcription levels in cancerous tissues and in patients who developed progressive breast cancer (Al Sarakbi 2009)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • ZFHX3, MACF1, RBM15, and SETD2 are Orofacial cleft candidate risk genes
  • Marker
    Therapy target
    ANIMAL & CELL MODELS