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FLASH GENE
Symbol SETDB1 contributors: mct/pgu - updated : 17-01-2017
HGNC name SET domain, bifurcated 1
HGNC id 10761
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
  • 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