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FLASH GENE
Symbol NCOA3 contributors: mct/pgu - updated : 22-06-2014
HGNC name nuclear receptor coactivator 3
HGNC id 7670
Location 20q13.12      Physical location : 46.130.600 - 46.285.620
Synonym name
  • thyroid hormone receptor activator molecule 1
  • amplified in breast cancer 1
  • CBP-interacting protein
  • steroid receptor coactivator protein 3
  • receptor-associated coactivator 3
  • class E basic helix-loop-helix protein 42
  • Synonym symbol(s) ACTR, TRAM1, RAC3, AIB1, SRC3, CAGH16, TNRC14, pCIP, CTG26, TNRC16, MGC141848, AIB-1, SRC-3, KAT13B, TRAM-1, bHLHe42
    EC.number 2.3.1.48
    DNA
    TYPE functioning gene
    STRUCTURE 154.96 kb     23 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   triplet
    text structure
  • a trinucleotide CAG repeat encoding a poly Q
  • MAPPING cloned Y linked N status confirmed
    Physical map
    NCOA5 20q12-q13.2 nuclear receptor coactivator 5 RPL13P2 20q13.12 ribosomal protein L13 pseudogene 2 TNFRSF5 20q12-q13.2 tumor necrosis factor receptor superfamily, member 5 CDH22 20q12-q13.1 cadherin-like 22 SLC35C2 20q13.12 solute carrier family 35, member C2 ELMO2 20q13 engulfment and cell motility 2 (ced-12 homolog, C. elegans) DKFZp547G0215 20q13.12 hypothetical protein DKFZp547G0215 MKRNP3 20q21.1 makorin, ring finger protein, pseudogene 3 LOC343593 20q13.12 similar to BC331191_1 ZNF334 20q13.12 zinc finger protein 334 SLC13A3 20q12-q13.1 solute carrier family 13 (sodium-dependent dicarboxylate transporter), member 3 C20orf64 20q13 chromosome 20 open reading frame 64 SLC2A10 20q13.1 solute carrier family 2 (facilitated glucose transporter), member 10 EYA2 20q13.1 eyes absent homolog 2 (Drosophila) PRKCBP1 20q12-q13.1 protein kinase C binding protein 1 RPL35AP 20q12-q13.1 ribosomal protein L35a pseudogene NCOA3 20q12 nuclear receptor coactivator 3 SULF2 20q12-q13.1 Homo sapiens similar to glucosamine-6-sulfatases (SULF2), mRNA. SRMP1 20q13.13 spermidine synthase pseudogene 1 LOC388798 20 LOC388798 PREX1 20q12-q13 LOC388798 ARFGEF2 20q13.13 ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 7996 155.3 1424 - 1997 9238002
  • isoform a
  • 23 splicing 7984 154.9 1420 - 1997 9238002
  • isoform b
  • 23 - 7993 155.2 1423 - 1997 9238002
  • isoform c
  • 23 - 7969 154.4 1415 - 1997 9238002
  • isoform d
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestivemouthtongue  moderately
     stomach   predominantly
    Endocrinepancreas   highly
    Lymphoid/Immunelymph node   highly
    Nervousbraindiencephalonhypothalamus  
    Olfactoryolfactory bulb    
    Reproductivefemale systembreastmammary gland highly
     female systemuterus  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelial    
    Muscularsmooth   
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestivehepatocyte
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • basic helix-loop-helix (bHLH) domain juxtaposed to a stretch of 300 aa with the PAS (per-ARNT-Sim) domain
  • two receptor interacting domains (RIDs) with the LXXLL motif
  • a C terminal histone acetyltransferase (HAT) domain, interacting with UBE3A
  • a poly Q encoded by a trinucleotide CAG repeat
  • conjugated PhosphoP , Other
    HOMOLOGY
    interspecies homolog to rattus Ncoa3 (85.3pc)
    homolog to murine Ncoa3 (85.5pc)
    Homologene
    FAMILY
  • steroid coactivator (SRC) family
  • SRC/p160 nuclear receptor coactivator family
  • CATEGORY transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • translocated into the nucleus upon phosphorylation
  • nuclear export was required for its proteasomal degradation and involved the ubiquitin ligase, UBE3A
  • in the absence of Retinoic acid, present essentially in nuclei
  • basic FUNCTION
  • possessing an intrinsic histone acetyltransferase activity
  • required in mice for normal growth, puberty, female reproductive function and mammary gland development
  • stimulating gene expression in a hormone dependent fashion, by facilitating the assembly of basal transcription factors into a stable preinitiation complex
  • thyroid hormone receptor activator molecule
  • playing a role in tumorigenesis of breast cancer
  • enhancing Tat-stimulated HIV-1 LTR promoter transactivation
  • involved in coactivation of NFKB pathway via its interaction with NFKB1 subunit
  • acting as a transcription coactivator and a critical regulator of white adipocyte development
  • acting synergistically with CREBBP to control expression of PPARG2 and adipogenesis
  • nuclear receptor co-activator exerting an anti-apoptotic role through a cytoplasmatic action
  • having roles in both steroid-dependent and steroid-independent transcription during tumor progression
  • contributes to the transcription of RARA(RARalpha)-target genes in several cell types
  • served as a ETV4 coactivator and formed complexes with ETV4 on matrix metalloproteinase 2 (MMP2) and MMP9 promoters to enhance their expression in both mouse and human breast cancer cell
  • 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
  • coactivator for hormone-activated androgen receptor, may be a prostate cancer oncogene
  • can exert its oncogenicity through tissue-specific estrogen-dependent and estrogen-independent functions
  • with NCOA1 cooperatively regulate placental morphogenesis and embryo survival
  • NCOA2 and NCOA3 concomitantly promote adipocyte differentiation by attenuating phospho-PPARG-S114 and modulating PPARG cellular heterogeneity
  • critical for tumor formation induced by the synovial sarcoma oncoprotein SS18-SSX1
  • its functions are facilitated by changes in the posttranslational code of the protein that involves mainly phosphorylation and ubiquitination
  • importance of phosphorylation and ubiquitination processes in the regulation of RA target genes through the control of NCOA3 turnover
  • not only contributes to self-renewal by activating NANOG but also facilitates ESC differentiation as a break point to disrupt the core transcriptional circuitry of pluripotency
  • is critical for both the induction and maintenance of pluripotency
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling hormonal , signal transduction
    a component
  • component of a complex containing NCOA2, IKKA, IKKB, IKBKG and CREBBP
  • methylated by CARM1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • CREBBP
  • PCAF
  • OR (enhancing OR dependent transcription)
  • HIV-TAT
  • ER
  • GR
  • TR
  • RAR
  • VDR
  • PPAR
  • IKK
  • PSME3
  • is a coactivator not only for RARs, but also for several nuclear receptors such as the estrogen receptor
  • associated with a protein complex containing AIFM1, Hsp90 and dynein, suggesting a role for the co-activator in the cytoplasmatic nuclear transport of these proteins associated with cytoskeleton
  • in breast tumors, its expression was found to be positively associated with ETV4, MMP2, and MMP9
  • PSMC5 interacting with NCOA3 (mediates the proteasomal degradation of NCOA3)
  • functionally relevant cofactor for ESR1 in breast carcinoma (ESR1/NCOA3 complexes may control estradiol-regulated genes in a hormone-independent manner)
  • TDG-NCOA3 interaction is important for broad range activation of steroid hormone nuclear receptors, and may also contribute significantly to further understanding of TDG-related nuclear receptor regulation
  • interacting strongly with AR
  • interacting with HOXC8 (blocks the AR-dependent recruitment of the steroid receptor coactivators steroid receptor NCOA3)
  • SPOP is a cullin 3 (CUL3)-based ubiquitin ligase, responsible for NCOA3 ubiquitination and proteolysis
  • CCDC80 is an NCOA3-targeted tumor suppressor, providing a novel mechanism for NCOA3-dependent inhibition of apoptosis
  • NCOA3-ubiquitination by the CUL3 complex depends on the prior phosphorylation of NCOA3
  • role of MAPK4 in promoting lung cancer cell invasiveness by phosphorylating NCOA3 and regulating NCOA3 proinvasive activity by site-specific phosphorylation
  • NCOA3 interacts with ESRRB via its ligand-binding domain and bridges ESRRBb to RNA polymerase II complexes
  • PTEN might act as a negative regulator of NCOA3 whereby the association of PTEN with NCOA3 and FBXW7 could lead to the downregulation of NCOA3 transcriptional activity
  • FOXG1 can function as a pro-apoptotic factor in part through suppression of NCOA3 coactivator transcription complex formation, thereby reducing the expression of the NCOA3 oncogene
  • cell & other
    REGULATION
    Other hormone dependent
    phosphorylated by IKK or MAPKs
    acetylated by CREBBP
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification --over  
    in breast, ovarian and pancreatic cancers
    Susceptibility prostate cancer in Chinese men
    Variant & Polymorphism repeat CAG/CAA repeat
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    alternative strategy for controlling the deleterious roles of MMP2and MMP9 in breast cancer by inhibiting their upstream coregulator NCOA3
    cancermuscle 
    therapy target to treat synovial sarcoma
    ANIMAL & CELL MODELS
  • SRC-3 deficient mice developed fat redistribution under high-fat diet