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    NCOA4 nuclear receptor coactivator 4 [ Homo sapiens (human) ]

    Gene ID: 8031, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NCOA4provided by HGNC
    Official Full Name
    nuclear receptor coactivator 4provided by HGNC
    Primary source
    HGNC:HGNC:7671
    See related
    Ensembl:ENSG00000266412 MIM:601984; AllianceGenome:HGNC:7671
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    RFG; ELE1; PTC3; ARA70
    Summary
    This gene encodes an androgen receptor coactivator. The encoded protein interacts with the androgen receptor in a ligand-dependent manner to enhance its transcriptional activity. Chromosomal translocations between this gene and the ret tyrosine kinase gene, also located on chromosome 10, have been associated with papillary thyroid carcinoma. Alternatively spliced transcript variants have been described. Pseudogenes are present on chromosomes 4, 5, 10, and 14. [provided by RefSeq, Feb 2009]
    Expression
    Ubiquitous expression in duodenum (RPKM 113.8), liver (RPKM 75.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NCOA4 in Genome Data Viewer
    Location:
    10q11.22
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (46005088..46030623, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (46885972..46911498, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (51565199..51590734)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene PARGP1-AGAP4 readthrough Neighboring gene PARG pseudogene 1 Neighboring gene ribosomal protein L35a pseudogene 23 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:51370889-51371579 Neighboring gene small nucleolar RNA, H/ACA box 74C-1 Neighboring gene translocase of inner mitochondrial membrane 23 Neighboring gene NANOG hESC enhancer GRCh37_chr10:51396871-51397413 Neighboring gene Sharpr-MPRA regulatory region 10440 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:51574030-51574225 Neighboring gene Sharpr-MPRA regulatory region 5969 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2350 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3324 Neighboring gene uncharacterized LOC105378287 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:51551103-51551604 Neighboring gene Sharpr-MPRA regulatory region 2638 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:51541582-51542406 Neighboring gene microseminoprotein beta Neighboring gene ribosomal protein L23a pseudogene 61

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Comparison of the breakpoint regions of ELE1 and RET genes involved in the generation of RET/PTC3 oncogene in sporadic and in radiation-associated papillary thyroid carcinomas. Bongarzone I, et al. Genomics, 1997 Jun 1. PMID 9192845
    2. Reducing the agonist activity of antiandrogens by a dominant-negative androgen receptor coregulator ARA70 in prostate cancer cells. Rahman MM, et al. J Biol Chem, 2003 May 30. PMID 12649293
    3. Iron Supply via NCOA4-Mediated Ferritin Degradation Maintains Mitochondrial Functions. Fujimaki M, et al. Mol Cell Biol, 2019 Jul 15. PMID 31061094, Free PMC Article
    4. Ferritinophagy is not required for colon cancer cell growth. Hasan M, et al. Cell Biol Int, 2020 Nov. PMID 32767706
    5. Tyrosine kinase oncoprotein, RET/PTC3, induces the secretion of myeloid growth and chemotactic factors. Russell JP, et al. Oncogene, 2003 Jul 17. PMID 12881713

    See all (114) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Lactylation of nuclear receptor coactivator 4 promotes ferritinophagy and glycolysis of neuronal cells after cerebral ischemic injury.
      Title: Lactylation of nuclear receptor coactivator 4 promotes ferritinophagy and glycolysis of neuronal cells after cerebral ischemic injury.
    2. NCOA4 requires a [3Fe-4S] to sense and maintain the iron homeostasis.
      Title: NCOA4 requires a [3Fe-4S] to sense and maintain the iron homeostasis.
    3. HECW1 induces NCOA4-regulated ferroptosis in glioma through the ubiquitination and degradation of ZNF350.
      Title: HECW1 induces NCOA4-regulated ferroptosis in glioma through the ubiquitination and degradation of ZNF350.
    4. JNK-JUN-NCOA4 axis contributes to chondrocyte ferroptosis and aggravates osteoarthritis via ferritinophagy.
      Title: JNK-JUN-NCOA4 axis contributes to chondrocyte ferroptosis and aggravates osteoarthritis via ferritinophagy.
    5. RET rearrangements are relevant to histopathologic subtypes and clinicopathological features in Thai papillary thyroid carcinoma patients.
      Title: RET rearrangements are relevant to histopathologic subtypes and clinicopathological features in Thai papillary thyroid carcinoma patients.
    6. The PTBP1NCOA4 axis promotes ferroptosis in liver cancer cells.
      Title: The PTBP1‑NCOA4 axis promotes ferroptosis in liver cancer cells.
    7. C-MYC Inhibited Ferroptosis and Promoted Immune Evasion in Ovarian Cancer Cells through NCOA4 Mediated Ferritin Autophagy.
      Title: C-MYC Inhibited Ferroptosis and Promoted Immune Evasion in Ovarian Cancer Cells through NCOA4 Mediated Ferritin Autophagy.
    8. TRIM7 modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells.
      Title: TRIM7 modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells.
    9. NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema.
      Title: NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema.
    10. Intraductal carcinoma of the salivary gland with NCOA4-RET: expanding the morphologic spectrum and an algorithmic diagnostic approach.
      Title: Intraductal carcinoma of the salivary gland with NCOA4-RET: expanding the morphologic spectrum and an algorithmic diagnostic approach.
    Submit: New GeneRIF Correction See all GeneRIFs (51)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association study of hematological and biochemical traits in a Japanese population.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • DKFZp762E1112

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription coactivator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in cellular response to estrogen stimulus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in cellular response to testosterone stimulus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in estrogen receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in intracellular iron ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in male gonad development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of DNA-templated transcription IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within protein targeting to lysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to hormone IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in autolysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in autophagosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in chromosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytoplasmic vesicle IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    nuclear receptor coactivator 4
    Names
    70 kDa AR-activator
    70 kDa androgen receptor coactivator
    NCoA-4
    RET-activating gene ELE1
    androgen receptor-associated protein of 70 kDa
    ferritin cargo receptor NCOA4
    ret fused

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_023372.1 RefSeqGene

      Range
      5001..30627
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001145260.2 → NP_001138732.1  nuclear receptor coactivator 4 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AK310849, AL162047, BC012736, DA415606, DB075100
      Consensus CDS
      CCDS73094.1
      UniProtKB/TrEMBL
      B2R5V0
      Related
      ENSP00000463027.1, ENST00000578454.5

    2. NM_001145261.2 → NP_001138733.1  nuclear receptor coactivator 4 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an exon in the coding region, which results in a frameshift and use of a downstream stop codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AK304123, AK310849, BC012736, DA415606, DB075100
      Consensus CDS
      CCDS73093.1
      UniProtKB/TrEMBL
      B2R5V0
      Related
      ENSP00000463455.1, ENST00000579039.2
      Conserved Domains (1) summary
      pfam12489
      Location:215 → 344
      ARA70; Nuclear coactivator

    3. NM_001145262.2 → NP_001138734.1  nuclear receptor coactivator 4 isoform 3

      See identical proteins and their annotated locations for NP_001138734.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains a distinct 5' UTR and lacks an in-frame portion of the 5' coding region, compared to variant 1. These differences cause translation initiation at a downstream AUG. This variant (3) also lacks an exon in the 3' coding region, which results in a frameshift and use of a downstream stop codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus and a shorter, distinct C-terminus compared to isoform 1. Variants 3, 4, and 5 encode the same protein.
      Source sequence(s)
      AK292480, AL450342, BC012736
      Consensus CDS
      CCDS73092.1
      UniProtKB/Swiss-Prot
      A8K8W5, B4E260, E9PAV7, J3KQN8, Q13772, Q14239
      UniProtKB/TrEMBL
      B2R5V0
      Related
      ENSP00000463476.1, ENST00000583565.5
      Conserved Domains (1) summary
      pfam12489
      Location:231 → 320
      ARA70; Nuclear coactivator

    4. NM_001145263.2 → NP_001138735.1  nuclear receptor coactivator 4 isoform 3

      See identical proteins and their annotated locations for NP_001138735.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an alternate in-frame exon in the 5' coding region and uses a downstream start codon, compared to variant 1. This variant (4) also lacks an exon in the 3' coding region, which results in a frameshift and use of a downstream stop codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus and a shorter, distinct C-terminus compared to isoform 1. Variants 3, 4, and 5 encode the same protein.
      Source sequence(s)
      AK292480, AK312325, BC012736
      Consensus CDS
      CCDS73092.1
      UniProtKB/Swiss-Prot
      A8K8W5, B4E260, E9PAV7, J3KQN8, Q13772, Q14239
      UniProtKB/TrEMBL
      B2R5V0
      Related
      ENSP00000462943.1, ENST00000581486.6
      Conserved Domains (1) summary
      pfam12489
      Location:231 → 320
      ARA70; Nuclear coactivator

    5. NM_005437.4 → NP_005428.1  nuclear receptor coactivator 4 isoform 3

      See identical proteins and their annotated locations for NP_005428.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) contains a distinct 5' UTR and lacks an in-frame portion of the 5' coding region, compared to variant 1. These differences cause translation initiation at a downstream AUG. This variant (5) also lacks an exon in the 3' coding region, which results in a frameshift and use of a downstream stop codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus and a shorter, distinct C-terminus compared to isoform 1. Variants 3, 4, and 5 encode the same protein.
      Source sequence(s)
      AL162047, BC012736
      Consensus CDS
      CCDS73092.1
      UniProtKB/Swiss-Prot
      A8K8W5, B4E260, E9PAV7, J3KQN8, Q13772, Q14239
      UniProtKB/TrEMBL
      B2R5V0
      Related
      ENSP00000464054.1, ENST00000585132.5
      Conserved Domains (1) summary
      pfam12489
      Location:231 → 320
      ARA70; Nuclear coactivator

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      46005088..46030623 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      46885972..46911498 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13772.1 GenPept UniProtKB/Swiss-Prot:Q13772

    Gene LinkOut

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