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FLASH GENE
Symbol NCOA4 contributors: mct - updated : 15-02-2018
HGNC name nuclear receptor coactivator 4
HGNC id 7671
Corresponding disease
PTC3 papillary thyroid carcinoma 3
Location 10q11.22      Physical location : 51.565.107 - 51.590.733
Synonym name
  • RET-activating gene ELE1
  • androgen receptor-associated protein 70
  • RET-fused
  • Synonym symbol(s) ARA70, RFG, ELE1, RP11-481A12.4, DKFZp762E1112, PTC3
    DNA
    TYPE functioning gene
    STRUCTURE 25.62 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Physical map
    LOC118706 10q11.22 similar to ARF GTPase-activating protein LOC387674 10 similar to Ribosome biogenesis protein BMS1 homolog MGC35285 10q11.22 hypothetical protein MGC35285 MAPK8 10q11.2 mitogen-activated protein kinase 8 RhoGAP2 LOC387675 10 LOC387675 LOC159491 LOC389964 10 similar to ribosomal protein L13a; 60S ribosomal protein L13a; 23 kD highly basic protein KIAA1607 FLJ31737 LOC170370 10q11.23 hypothetical LOC170370 LOC170371 10q11.23 hypothetical protein LOC170371 LOC118461 DRG11 ERCC6 10q11 excision repair cross-complementing rodent repair deficiency, complementation group 6 PGBD3 10q11 piggyBac transposable element derived 3 CHAT 10q11.2 choline acetyltransferase SLC18A3 10q11.2 solute carrier family 18 (vesicular acetylcholine), member 3 LOC282966 10q11.23 hypothetical protein LOC282966 FLJ10851 10q11.23 hypothetical protein FLJ10851 MAPK6PS6 10q11.21 hypothetical protein FLJ10851 PARG 10q11.23 poly (ADP-ribose) glycohydrolase LOC387676 10 similar to KIAA0592 protein LOC387677 10 hypothetical gene supported by BC051717; NM_133446 LOC255319 10q11.23 similar to ARF GTPase-activating protein MSMB 10q11.2 microseminoprotein, beta- NCOA4 10q11.2 nuclear receptor coactivator 4 TIMM23 10q11.21-q11.23 translocase of inner mitochondrial membrane 23 homolog (yeast) LOC387678 10 similar to ARF GTPase-activating protein LOC389965 10 similar to Sodium/hydrogen exchanger 3 (Na(+)/H(+) exchanger 3) (NHE-3) LOC387679 10 similar to KIAA0592 protein LOC387680 10 similar to KIAA0592 protein LOC389966 10 similar to Sodium/hydrogen exchanger 3 (Na(+)/H(+) exchanger 3) (NHE-3) ASAH2 10q11.21 N-acylsphingosine amidohydrolase (non-lysosomal ceramidase) 2 LOC387681 10 hypothetical gene supported by BT007130; NM_001378 MOB 10q11.2 mob protein LOC340858 10q21.1 similar to hypothetical protein FLJ10539 FLJ31958 10q21.1 hypothetical protein FLJ31958 LOC389967 10 similar to bA182L21.1 (novel protein similar to hypothetical proteins) LOC389968 10 similar to Cathepsin L preproprotein LOC283023 10q21.1 similar to Geranylgeranyl transferase type I beta subunit (Type I protein geranyl-geranyltransferase beta subunit) (GGTase-I-beta) ACF 10q21,1 similar to Geranylgeranyl transferase type I beta subunit (Type I protein geranyl-geranyltransferase beta subunit) (GGTase-I-beta) PRKG1 10q11.2 protein kinase, cGMP-dependent, type I CSTF2T 10q22-q23 protein kinase, cGMP-dependent, type I
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 3748 73.6 650 . found in the nucleus 2010 20167864
  • ARA70 alpha
  • represses prostate cancer cell proliferation and anchorage-independent growth
  • although growth inhibition by ARA70alpha is AR-dependent, the inhibition of cell invasion is an androgen-independent process
  • 11 - 3659 71.4 630 only in testis, localized to the cytosol 2010 20167864
  • ARA70 beta
  • internally spliced ARA70 isoform, ARA70beta, promotes prostate cancer cell growth and invasion
  • regulator of tumor cell growth and metastasis by affecting gene expression
  • 10 - 3562 69.7 614 - 1996 8643607
    10 - 3502 69.7 614 - 1996 8643607
    10 - 3588 69.7 614 - 1996 8643607
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemprostate   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a nuclear receptor interaction motif (LXXLL), implicated in the interaction with AR
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory , transcription factor , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus
    basic FUNCTION
  • transcriptional activation of target genes, mediating estrogen-androgen synergism
  • amplifies the activity of several ligand-activated nuclear transcription factors, including the aryl hydrocarbon receptor (AHR) and androgen receptor (AR)
  • coactivator that may play a role in modulating nuclear receptor activity, particularly that of the AHR, during development
  • role for autophagy and NCOA4 in the control of iron homeostasis
  • is a selective cargo receptor for the autophagic turnover of ferritin, a process critical for regulation of intracellular iron bioavailability
  • NCOA4 prevents iron accumulation and ensures efficient erythropoiesis, playing a central role in balancing iron levels
  • NCOA4 was a selective cargo receptor for the selective autophagic turnover of ferritin (namely ferritinophagy) in ferroptosis
  • ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis
  • importance of ferritin for the vectorial transfer of imported iron to mitochondria in developing red cells and of PCBP1 and NCOA4 in mediating iron flux through ferritin
  • iron-dependent, highly-specific formation of the remarkably stable FTH1-NCOA4 complex may be important for the characterization of the mechanism of ferritinophagy 7)
  • THRB and NCOA4 regulate terminal erythrocyte differentiation
  • roles of PCBP1 and nuclear coactivator 4 (NCOA4) in mediating the flux of iron through ferritin in developing erythroid cells
  • implicated in ovarian cancer biology in which it could be involved in the transition from precursors to ovarian cancers (OVCAs)
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling hormonal
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • androgen receptor in a ligand-dependent manner
  • retinoid X receptor in a ligand-dependent manner
  • coactivator of the androgen receptor and PPARgamma and repressor of PPARalpha (but coactivator of PPARA in prostate cancer cell lines)
  • interacts with and amplifies AHR action (NCOA4-facilitation of AHR activity was abolished by overexpression of AR, suggesting a potential competition of AHR and AR for NCOA4)
  • both MSMB and an adjacent gene, NCOA4, are subjected to transcriptional control via androgen response elements
  • NCOA4 interacts directly with AR as a co-activator to enhance AR transcriptional activity
  • NCOA4 is a minichromosome maintenance 7 (MCM7)-interacting protein that is able to control DNA replication
  • NCOA4 directly binds ferritin heavy chain-1 (FTH1) to target the iron-binding ferritin complex
  • direct association via a key surface arginine in FTH1 and a C-terminal element in NCOA4 is required for delivery of ferritin to the lysosome via autophagosomes
  • cell & other
    REGULATION
    induced by specific induction by androgens
    Other ligand dependent
    regulated in a proteasome- and autophagy-independent manner
    NCOA4 activity also exhibited developmental regulation and regulation by cellular iron levels
    ASSOCIATED DISORDERS
    corresponding disease(s) PTC3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    NCOA4 overexpression promotes anchorage-independent growth of prostate epithelial cells, but not growth of breast epithelial cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Ncoa4-/- mice are anemic in perinatal periods and fail to respond to TH by enhanced erythropoiesis
  • despite signs of iron overload, Ncoa4-null mice had mild microcytic hypochromic anemia
  • Ncoa4(-/-) mice exhibit a profound accumulation of iron in splenic macrophages, which are critical for the reutilization of iron from engulfed red blood cells