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FLASH GENE
Symbol SETDB1 contributors: mct/pgu - updated : 17-01-2019
HGNC name SET domain, bifurcated 1
HGNC id 10761
Location 1q21.3      Physical location : 150.898.814 - 150.937.220
Synonym name
  • ERG-associated protein with SET domain
  • histone-lysine N-methyltransferase, H3lysine-9 specific 4
  • histone-lysine N-methyltransferase SETDB1
  • H3-K9-HMTase 4
  • lysine N-methyltransferase 1E
  • histone H3-K9 methyltransferase 4
    • Synonym symbol(s) KIAA0067, ESET, KG1T, KMT1E
    EC.number 2.1.1.43
    DNA
    TYPE functioning gene
    STRUCTURE 38.57 kb     22 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D1S514 - D1S2347 - SETDB1 - D1S2858 - D1S305 - D1S2635 - qter
    Authors GeneMap (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 4449 - 1291 - 1994 7584044
    22 - 4446 - 1290 - -
    9 - 1507 - 397 - -
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   highly
    Lymphoid/Immunespleen    
     thymus   highly
     tonsils   highly
    Nervousbrain   highly Mus musculusFetal
    Reproductivefemale systembreastmammary gland  
     male systemtestis  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal tudor domain, mediating protein-protein interactions region and a SUMO interaction motif (SIM) whose mutation greatly reduced the ability of SETDB1 to associate with promyelocytic leukemia nuclear body (PML-NB) , related to the nuclear export of SETDB1, and having two nuclear export signal motifs
  • a pre-set and post-set domains are all required for methyltransferase activity
  • one methyl-binding (MBD) domain
  • C-terminal SET domain that catalyzes methylation of histone H3 at lysine 9, an unusual bifurcated SET domain, multifunctional chromatin regulator (130AA)
    • conjugated PhosphoP
    mono polymer complex
    HOMOLOGY
    interspecies homolog to murine Setdb1 (92.5pc)
    homolog to rattus Setdb1 (94.5pc)
    Homologene
    FAMILY
  • histone-lysine methyltransferase family
  • Suvar3-9 subfamily
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,chromatin/chromosome
    text
  • associated with non pericentromeric regions of chromatin
  • excluded from nucleoli and islands of condensed chromatin
    • basic FUNCTION
  • contributing to silencing of euchromatic genes by KRAB zinc-finger proteins
  • histone H3 (K9) methyltransferase, mediating histone methylation
  • functioning in transcription regulation and modification of local chromatin and involved in maintaining hetrochromatin
  • coordinates with AKT1 to silence gene expression
  • chromatin-associated protein, effector of SUMO-dependent changes in chromatin structure and gene expression
  • essential role in the control of developmentally regulated gene expression programs in embryonic stem (ES) cells
  • epigenetic role in the temporal and tissue-specific gene expression that results in proper control of brain development
  • controls hypertrophic differentiation of growth plate chondrocytes and endochondral ossification during embryogenesis and postnatal development
  • its expression plays an essential role in the maintenance of articular cartilage by preventing articular chondrocytes from terminal differentiation and may have implications in joint diseases such as osteoarthritis
  • is a critical regulator of osteoblast differentiation during bone development
    • CELLULAR PROCESS nucleotide, chromatin organization, methylation
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with ATF7IP/MDB1 (complex facilitating the formation of heterochromatic domains, and emphasizing the role of MCAF/AM family proteins in epigenetic control)
  • complex at least composed of the CAF-1 subunit CHAF1A, MBD1 and SETDB1
  • associating with CHAF1B-CBX5 chaperone complex and monomethylating K9 on non nucleosomal histone H3, thus providing H3K9me1 for subsequent trimethylation by SUV39H1/H2 in pericentric regions
  • forms a multimeric complex with SUV39H1 and other H3K9 methyltransferases
  • OLIG2-SETDB1 complex can mediate transcriptional repression in oligodendrocytes progenitor cells (OPCs), affecting myelination
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TRIM28, ERG
  • interacting with ESCO2
  • interacting with CBX1, CBX5, DNMT3A, HDAC1, HDAC2
  • interacting with SIN3A, SIN3B, DNMT3B and SUMO2
  • can bind to HIV-1 Tat and methylate it, thus regulating the transcriptional activity of the viral LTR
  • nuclear interacting partner of AKT1
  • ZNF274 binding sites co-localize with SETDB1, TRIM28, and H3K9me3 at the 3prime ends of zinc finger genes
  • JARID2 functions as a transcriptional repressor of target genes, including NOTCH1, through a novel process involving the modification of H3K9 methylation via specific interaction with SETDB1 during heart development
  • MAT2A interacts with histone methyltransferase SETDB1 and inhibits PTGS2 gene expression
  • associates with histone deacetylase 4 to bind and inhibit the activity of RUNX2, a hypertrophy-promoting transcription factor
  • SETDB1-TIAM1 compounds were involved in a novel pathway, which regulated epigenetic modification of gene expression in hepatocellular carcinoma (HCC)
    • cell & other
    REGULATION
    Other targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    markedly increased in Huntington's disease
    tumoral   amplification    
    focally amplified in non-small-cell lung cancer, small-cell lung cancer, ovarian cancer, hepatocellular carcinoma and breast cancer
    tumoral     --over  
    may potentially contribute to melanoma formation by abrogating oncogene-induced senescence
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativehuntington chorea
    regulation of the gene is important to neuronal survival and, as such, may be a promising treatment in HD patients
    ANIMAL & CELL MODELS
  • Eset-deficient mice are thus characterized by defective long bone growth and trabecular bone formation