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FLASH GENE
Symbol NCOA2 contributors: mct/npt - updated : 06-05-2019
HGNC name nuclear receptor coactivator 2
HGNC id 7669
Location 8q13.3      Physical location : 71.024.266 - 71.316.020
Synonym name
  • glucocorticoid receptor interacting protein 1
  • transcriptional intermediary factor 2
  • MYST3/NCOA2 fusion protein
  • class E basic helix-loop-helix protein 75
  • p160 steroid receptor coactivator 2
  • Synonym symbol(s) GRIP1, TIF2, SRC2, EVI32, NCoA-2, KAT13C, bHLHe75, MGC138808
    DNA
    TYPE functioning gene
    STRUCTURE 295.63 kb     23 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    MAPPING cloned Y linked N status provisional
    Physical map
    FLJ11267 8q13.1 hypothetical protein FLJ11267 PTTG3 8q13.1 hypothetical protein FLJ11267 SGKL 8q12.3-q13.1 serum/glucocorticoid regulated kinase-like FLJ25692 8q13.1 hypothetical protein FLJ25692 LOC392228 8 similar to hypothetical class II basic helix-loop-helix protein LOC286187 8q13.1 similar to RIKEN cDNA 1700011J18 COPS5 8q13.1 COP9 constitutive photomorphogenic homolog subunit 5 (Arabidopsis) FLJ22490 8q13.1 hypothetical protein FLJ22490 BIG1 8q13 hypothetical protein FLJ22490 LOC389666 8 LOC389666 LOC392229 8 similar to 60S ribosomal protein L17 (L23) (Amino acid starvation-induced protein) (ASI) CPA6 8q12.3 carboxypeptidase A6 FLJ12987 8q13.1 hypothetical protein FLJ12987 VEST1 8q13 vestibule-1 protein LOC389667 8 similar to tropomyosin 4 SULF1 8q13.1 similar to tropomyosin 4 SLCO5A1 8q13.2 solute carrier family 21 (organic anion transporter), member 15 LOC392230 8 similar to BAG-family molecular chaperone regulator-4 (Silencer of death domains) PRDM14 8p21-p12 PR domain containing 14 LOC346990 8q13.2 similar to H2A histone family, member Z NCOA2 8q13.1 nuclear receptor coactivator 2 LOC392231 8 similar to basic transcription factor 3 TRAM1 8q13.1 translocation associated membrane protein 1 CGI-83 LOC389668 8 similar to hypothetical protein FLJ10307 EYA1 8q13.3 eyes absent homolog 1 (Drosophila) MSC 8q21.1-q21.2 musculin (activated B-cell factor-1) TRPA1 8q13 transient receptor potential cation channel, subfamily A, member 1 LOC392232 8 similar to ankyrin-like protein 1; ankyrin-like with transmembrane domains 1 KCNB2 8q13.2 potassium voltage-gated channel, Shab-related subfamily, member 2 TERF1 8q13 telomeric repeat binding factor (NIMA-interacting) 1 RPESP 8q13.3 RPE-spondin LOC392233 8 similar to Hspcb protein LOC389669 8 LOC389669 RPL7 8q12-q22 ribosomal protein L7 RDH10 8q13.3 retinol dehydrogenase 10 (all-trans)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 8430 160 1464 - 2017 28890360
    23 - 8566 160 1464 - 2017 28890360
    22 - 8287 - 1395 - 2017 28890360
    23 - 8412 160 1464 - 2017 28890360
    22 - 8307 - 1310 - 2017 28890360
    - - - - 627 - 2012 23132854
  • N-terminal 627 amino acids of p160 NCOA2
  • lacks the two major activation domains (AD1 and AD2)
  • is missing the nuclear receptor interaction domain containing three RIDs that are responsible for NCOA2 binding via LXXLL sequences to steroid/nuclear receptors
  • TIF2.0-induced structure in AF1 is not confined to secondary structural elements but that tertiary structural changes are also taking place in the protein
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbraindiencephalonhypothalamus highly Homo sapiens
     brainlimbic system  highly Homo sapiens
     braindiencephalonamygdala   Homo sapiens
     spinal cord   highly
    Reproductivemale systemtestis    Homo sapiensFetal
     male systemprostate   
    Respiratoryrespiratory tractlarynx  highly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Muscularmyoblast
    ReproductiveSertoli cell Homo sapiensAdult
    ReproductiveSertoli cell Homo sapiensFetal
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • basic helix-loop-helix (HLH) domain, juxtaposed to a stretch of 300 AA,with the PAS (Per - ARNT - Sim) domain
  • three receptor interacting domains (LXXLL)
  • two ADs (activation domains), AD1, a binding site for the related co-activators, CBP (cAMP-response-element-binding protein-binding protein) and p300, whereas AD2 binds to another co-activator, co-activator-associated arginine methyltransferase 1 (CARM1)
  • a C terminal histone acetyltransferase domain
  • both N-terminal and middle sequences participate in competing with corepressor for regulating the gene transcriptional responses of glucocorticoid and progesterone receptors (Wang 2007), and N-terminal domain of TIF2, in the form of the fragment TIF2.0, is capable of interacting with, and conformationally reorganizing, the unstructured dominant transactivation domain of NR3C1, the AF1 domain
  • HOMOLOGY
    interspecies homolog to murine Ncoa2
    Homologene
    FAMILY
  • SRC/p160 nuclear receptor coactivator family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm,nuclear bodies
    basic FUNCTION
  • nuclear receptor coactivator required for myogenic differentiation
  • possessing an intrinsic histone acetyltransferase activity
  • stimulating gene expression in a hormone dependent fashion by facilitating the assembly of basal transcription factors into a stable preinitiation complex
  • controlling with NCOA1 energy balance between White and Brown adipose tissues and involved in the pathogenesis of obesity
  • involved in postnatal survival and male reproduction
  • mediating the interaction between the amino- and carboxyl-termini of the androgen receptor
  • NCOA1, NCOA2, NCOA3, are not functionally redundant in breast cancer cells because they play gene-specific roles in regulating mRNA and protein expression, and they therefore are likely to make unique contributions to breast tumorigenesis
  • VDR and coactivators NCOA2 and NCOA3, which are also involved in other nuclear receptors as well, are critical for epidermis-specific sphingolipid production and barrier formation
  • playing a cofactor role in innate immunity
  • interacts with ESR1, ESR2 and PGR in a subtype-specific manner, which may contribute to the functional differences of these steroid receptor subtypes in brain
  • NCOA1 and NCOA2 can modulate the expression of the uncoupling protein 3 (UCP3) in an antagonistic manner, and have important metabolic functions in white and brown adipose tissues as well as in the liver
  • NCOA2 and NCOA3 concomitantly promote adipocyte differentiation by attenuating phospho-PPARG-S114 and modulating PPARG cellular heterogeneity
  • function as coactivator for glucocorticoid receptor (GR), a ligand-dependent transcription factor of the nuclear receptor superfamily
  • undergoes glucocorticoid-induced, GR interaction-dependent phosphorylation
  • is a critical positive regulator of the mammalian circadian clock
  • through regulation of cardiac transcription factor expression and activity, NCOA2 is a critical transcriptional regulator of genes important for cardiac growth, structure, and metabolism
  • NCOA2 is a novel negative growth regulatory gene repressing the WNT/CTNNB1 pathway in Colorectal cancer, where recurrent fusion with LACTB2 contributes to its disruption
  • fetal lungs produce signals to initiate labor when mature and NCOA1/NCOA2-dependent production of SFTPA1B and platelet-activating factor (PAF) is crucial for this process
  • biphasic role of NCOA2 between AHR and hypoxic conditions, thus providing a novel mechanism underlying the cross talk between AHR and hypoxia that affects disease development and progression
  • controls activation of several key cardiac transcription factors and NCOA2 loss results in extensive cardiac transcriptional remodeling
  • coordinates likely cardiomyocyte secretion of VEGFA downstream of the two major angiogenic stimuli occurring during pressure overload bridging both hypertrophic and hypoxia-stimulated paracrine signaling
  • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling hormonal
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • CREBBP and PCAF
  • MYOG and MEF2C in the regulation of muscle-specific gene expression
  • NCOA1
  • corepressor of MYOD1
  • interaction of beta-catenin with NCOA2 in transcriptional activation by the androgen receptor
  • potentiates glucocorticoid receptor-mediated repression of AP1 and NFKB targets and, surprisingly, transcriptional activation by interferon regulatory factors
  • inhibition of senescence by KAT6A-NCOA2 is associated with increased apoptosis, suggesting a role for the fusion protein in TP53 apoptosis-versus-senescence balance
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with MYST3 in acute myeloid leukemia with inversion inv(8)(p11;q13)
    tumoral fusion      
    fusion genes, such as KAT6A-NCOA2, in acute myeloid leukemia (AML) by chromosomal translocation (Katsumoto 2008)
    tumoral fusion      
    HEY1-NCOA2 fusion in mesenchymal chondrosarcoma
    tumoral fusion      
    LACTB2-NCOA2 transcript was detected in 6 p100 of colorectal cancer (CRC) cases
    tumoral   translocation    
    recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target GRIP1/IRF3 interaction is a novel target for glucocorticoid immunosuppression
    SystemTypeDisorderPubmed
    diabetemetabolic syndrom 
    modulation of the expression and/or activity of NCOA1, NCOA2, represents an attractive way to prevent or treat metabolic disorders
    immunologyimmunodeficiency 
    GRIP1/IRF3 interaction is a novel target for glucocorticoid immunosuppression
    ANIMAL & CELL MODELS