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FLASH GENE
Symbol NCOR2 contributors: mct/pgu - updated : 24-01-2015
HGNC name nuclear receptor co-repressor 2
HGNC id 7673
Location 12q24.31      Physical location : 124.808.961 - 125.052.010
Synonym name
  • silencing mediator for retinoid and thyroid hormone receptor
  • CTG repeat protein 26
  • thyroid-, retinoic-acid-receptor-associated corepressor
  • Synonym symbol(s) SMRT, SMRTE, CTG26, TRAC1, TNRC14, EVI69, SMAP270, SMRTE-tau
    DNA
    TYPE functioning gene
    STRUCTURE 211.20 kb     48 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure 47 exons coding
    MAPPING cloned Y linked N status provisional
    Map cen - D12S340 - BDKRB2 - D12S1609 - D12S367 - D12S97 - qter
    Authors GeneMap (98)
    Physical map
    MPHOSPH9 12q24.31 M-phase phosphoprotein 9 FLJ38663 12q24.31 hypothetical protein FLJ38663 CDK2AP1 12q24.31 CDK2-associated protein 1 SBNO1 12q24.31 sno, strawberry notch homolog 1 (Drosophila) LOC387893 12 similar to SET domain-containing protein 8 MGC7036 12q24.31 hypothetical protein MGC7036 RNP24 12q24.31 coated vesicle membrane protein DDX55 12q24.31 DEAD (Asp-Glu-Ala-Asp) box polypeptide 55 EIF2B1 12q24.2-q24.31 eukaryotic translation initiation factor 2B, subunit 1 alpha, 26kDa GTF2H3 12q24.31 general transcription factor IIH, polypeptide 3, 34kDa FLJ12975 12q24.31 hypothetical protein FLJ12975 ATP6V0A2 12q24.31 ATPase, H+ transporting, lysosomal V0 subunit a isoform 2 DNAH10 13q14 dynein, axonemal, heavy polypeptide 10 FLJ22471 12q24.31 limkain beta 2 DKFZp761B128 12q24.31 hypothetical protein DKFZp761B128 LOC144347 12q24.31 hypothetical protein LOC144347 NCOR2 12q24.23-q24.31 nuclear receptor co-repressor 2 SCARB1 12q24.2-qter scavenger receptor class B, member 1 UBC 12q24.3 ubiquitin C LOC256441 12q24.31 similar to ribosomal protein L22 DHX37 12q24.32 DEAH (Asp-Glu-Ala-His) box polypeptide 37 BRI3BP 12q24.31 BRI3 binding protein AACS 12q24.31 acetoacetyl-CoA synthetase
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    49 - 8857 - 2514 - 2009 19133230
    48 - 8689 - 2458 - 2009 19133230
    48 - 8827 - 2504 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
    Respiratoryrespiratory tractlarynx  highly
    Skin/Tegumentskin   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal (RD) repression domain with a SIAH2 and a putative SIN3 interacting motifs
  • two major receptor-interacting domains (RID1 and RID2) utilized to mediate nuclear receptor (NR) signaling through epigenetic modification
  • a domain homolog to a repeat identified in yeast SWI3, GTF3B
  • a second putative repression domain in the C terminal region
  • MYB-like DNA binding domain
  • a deacetylase activation domain (DAD)
  • HOMOLOGY
    intraspecies homolog to NCOR1
    Homologene
    FAMILY
  • N-CoR nuclear receptor corepressors family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • nuclear hormone receptor co-repressor, silencing mediator of retinoic acid and thyroid hormone receptors
  • recruiting the histone deacytylation complex Sin3A/HDAC1/HDAC2, resulting in chromatin remodeling and repression of transcription
  • with HDAC4 play an important role in nuclear retention and the BACH2 focus formation in the mammalian cell nucleus, which may contribute to the local transcription repression
  • transcriptional corepressor that participates in diverse signaling pathways and diseases
  • directly involved in the VDR-mediated repression via an ID1-specific interaction with the VDR
  • central role to control the actions of many transcriptional factors, in large part, by recruitment and activation of a range of chromatin remodeling enzymes
  • role in mitochondrial oxidative metabolism and the aging process, which may serve as a drug target to improve health span
  • essential role for NCOR2 in regulating the progression, severity, and therapeutic outcome of metabolic diseases
  • co-repressor NCOR2 exerts a critical protective action against genotoxic stress-induced caspase activation, repressing a functionally important cohort of pro-apoptotic genes
  • biological role for NCOR2 in mediating DNA damage responses
  • promotes breast cancer progression through multiple pathways leading to increased proliferation and decreased apoptosis
  • NCOR1 and NCOR2 are coregulators of nuclear receptor (NR) action
  • 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)
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complex NCOR2/HDAC interacting with TBL1X
  • complexing with SCA1
  • 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
  • HDAC5, HDAC7, NCOR1, TBL1X
  • repressing STAT5A, STAT5B dependent transcription
  • mediates the HDAC4 binding to BACH2, and HDAC4 facilitates the retention of BACH2 in the foci
  • functional interaction between NCOR2 and FOXP1 is required for cardiac growth and regulation of macrophage differentiation
  • interaction with PIN1 (interaction requires the WW domain of PIN1 and SMRT phosphorylation, and regulates SMRT protein stability, thereby affecting SMRT-dependent transcriptional repression)
  • TBL1X interacts with both NCOR2 and GPS2
  • CAMK2A down-regulated the protein stability of NCOR2 through proteasomal degradation
  • WNT5A inhibited the physical association between RBPJ and NCOR2 suggesting that WNT5A induced CAMK2A activation plays a critical role in the endogenous RBPJ-NCOR2 binding
  • kinase activity of CAMK2A plays a crucial role in the proteasomal degradation of NCOR2
  • regulatory cascade containing PPARG and TWIST1 that controlled the expression of GPS2 and NCOR2 in human adipocytes
  • MAP2K1 interacts with the nuclear receptor corepressor silencing mediator of retinoid and thyroid hormone receptor (NCOR2)
  • DEAF1 transcription regulation activity is mediated through interactions with cofactors such as NCOR1 and NCOR2
  • is responsible for basal repression of PPM1D, a phosphatase that de-phosphorylates and inactivates CHEK2, thus affecting a feedback loop responsible for licensing the correct timing of CHEK2 activation and the proper execution of the DNA repair process
  • interaction with NCOR2 is essential for deacetylase-independent function of HDAC3
  • target for the ubiquitously expressed protein kinase CSNK2A1, which is known to phosphorylate a wide variety of substrates
  • (HDAC3)-dependent transcriptional corepressor
  • TP53 bound to the NCOR2 deacetylase activation domain (DAD), which mediates HDAC3 binding and activation, and HDAC3 could attenuate TP53 binding to the DAD region of 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
  • cell & other
    REGULATION
    Other regulates a wide variety of transcriptional systems important in cellular growth and differentiation
    negatively regulated by PIN1 and CDK2
    phosphorylation of the CSNK2A1 site on NCOR2 significantly increased affinity for SPEN
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    significantly reduced in obese adipose tissue, inversely correlated to inflammatory status
    tumoral     --low  
    observed in leukemias, lymphomas, and androgen-resistant prostate carcinomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    altered corepressor NCOR2 expression and recruitment to target genes is a mechanism that change the response to androgens in prostate cancer progression
    ANIMAL & CELL MODELS