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

Gene ID: 8031, updated on 2-Nov-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
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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 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

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