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FLASH GENE
Symbol NCOR1 contributors: mct/pgu - updated : 11-09-2012
HGNC name nuclear receptor co-repressor 1
HGNC id 7672
Location 17p11.2      Physical location : 15.933.409 - 16.118.874
Synonym name
  • murine nuclear receptor corepressor
  • thyroid hormone- and retinoic acid receptor-associated corepressor 1
  • Synonym symbol(s) TRAC1, NCOR, KIAA1047, N-CoR, hCIT529I10, MGC104216
    DNA
    TYPE functioning gene
    STRUCTURE 185.45 kb     46 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    regionally located localized between CMT1A and SMS
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    46 - 9809 270.2 2440 - 1999 10444336
    19 - 3106 103.8 914 - -
    45 - 9301 258.5 2337 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     intestinelarge intestinecolon highly
    Endocrinethyroid   highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three N terminal (RD) repression domains with a SIAH2 and a putative SIN3 interacting motifs
  • third NR-interaction domains ID (ID3) upstream of two IDs (ID1 and ID2) and its core motif (IDVII), rather than an extended helical motif, is known to be involved directly in the exclusive interaction of ID3 with the thyroid hormone receptor (TR)
  • a deacetylase activation domain (DAD), conserved in the highly related NCOR2, for association with HDAC3
  • a domain homolog to a repeat identified in yeast SWI3, GTF3B and a second putative repression domain in the C terminal region
  • two C terminal interaction domains containing a conserved sequence referred to as the NCOR box
  • two SANT domains
  • HOMOLOGY
    interspecies homolog to murine Ncor1
    homolog to C.elegans f45e4.4
    intraspecies homolog to SMRT
    Homologene
    FAMILY
  • N-CoR nuclear receptor corepressors family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • recruiting the CoR/Sin3/HDAC1/HDAC2 complex, resulting in chromatin remodeling and repression of transcription
  • inhibiting transcription by hormone receptors in absence of ligand
  • promoting chromatin condensation
  • functions as an activating subunit for the chromatin modifying enzyme histone deacetylase 3 (HDAC3)
  • participates in DACH1 repression of TNFSF11 gene expression in marrow stromal/preosteoblast cells
  • central role to control the actions of many transcriptional factors, in large part, by recruitment and activation of a range of chromatin remodeling enzymes
  • plays an adaptive role in muscle physiology and that interference with NCOR1 action could be used to improve muscle function
  • key physiological regulator of muscle mass and function
  • negative regulator of both muscle mass and mitochondrial oxidative metabolism
  • NCOR1 and NCOR2 are coregulators of nuclear receptor (NR) action
  • is the principal mediator of thyroid hormone (TH) sensitivity
  • NCOR1 and NCOR2 collaborate to control hepatic lipid content, which likely reflects their cooperative activity in regulating the action of multiple NRs including the TH receptor (TR)
  • NCOR1 acquires the ability to repress active PPARG-mediated transcription via G-protein pathway suppressor 2 (GPS2), a component of the NCOR corepressor complex 2)
  • CELLULAR PROCESS nucleotide, chromatin organization, remodeling
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forming a large corepressor complex containing SIN3A/B and histone deacetylases HDAC1 and HDAC2,this complex associates with the thyroid and the retinoid acid receptors in the absence of ligand
  • core repression complex involves the recruitment of three proteins, HDAC3, GPS2 and TBL1X, to a highly conserved repression domain within NCOR2 and NCOR
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HDAC1, HDAC2, sin3A/B, PML-RAR, AML1-eto nuclear hormone receptor (with CoRNR box of NCOR1)
  • with HD
  • with THAP7
  • SERPINF1 is a novel transcriptional target for NCOR1 repressive action (Doyon 2009)
  • interacts with the DNA-bound thyroid receptor (TR) homodimer through two of its three receptor-interacting domains (RIDs) (Astapova 2009)
  • interacting with HDAC3 (interaction HDAC3/NCOR1 is a nodal point in the epigenetic regulation of circadian and metabolic physiology (Alenghat 2008)
  • interaction with SERPINF1 (NCOR1 expression is required to maintain intestinal epithelial cell in a proliferative state and identify SERPINF1 as a novel transcriptional target for NCOR1 repressive action) (Doyon 2009)
  • DEAF1 transcription regulation activity is mediated through interactions with cofactors such as NCOR1 and NCOR2
  • NCOR1 and NCOR2 directly bind to transcription factors and nucleate the formation of stable complexes that include HDAC3, transducin b-like protein 1/TBL1-related protein 1, and GPS2
  • GPS2 is dispensable for the intrinsic repression function of NCOR1, can mediate a novel corepressor repression pathway that allows NCOR1 to directly repress active PPARG-mediated transcription
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in malignant disorders
    tumoral     --over  
    distorts the actions of PPARA/PPARG selectively and generates a potential epigenetic lesion with diagnostic and prognostic significance in prostate carcinoma
    constitutional   deletion    
    results in a paradoxical hyporesponsiveness to TLR4 signaling
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscular  
    pharmacological inhibition of NCOR1 and/or its interaction with deacetylases may be a viable approach to improve muscle mass and oxidative metabolism
    ANIMAL & CELL MODELS
    Ncor1-/-mice