NCOA4

Function

Cargo receptor for the autophagic turnover of the iron-binding ferritin complex, playing a central role in iron homeostasis (PubMed:25327288, PubMed:26436293). Acts as an adapter for delivery of ferritin to lysosomes and autophagic degradation of ferritin, a process named ferritinophagy (PubMed:25327288, PubMed:26436293). Targets the iron-binding ferritin complex to autolysosomes following starvation or iron depletion (PubMed:25327288). Ensures efficient erythropoiesis, possibly by regulating hemin-induced erythroid differentiation (PubMed:26436293). In some studies, has been shown to enhance the androgen receptor AR transcriptional activity as well as acting as ligand-independent coactivator of the peroxisome proliferator-activated receptor (PPAR) gamma (PubMed:10347167, PubMed:8643607). Another study shows only weak behavior as a coactivator for the androgen receptor and no alteration of the ligand responsiveness of the AR (PubMed:10517667). Binds to DNA replication origins, binding is not restricted to sites of active transcription and may likely be independent from the nuclear receptor transcriptional coactivator function (PubMed:24910095). May inhibit activation of DNA replication origins, possibly by obstructing DNA unwinding via interaction with the MCM2-7 complex (PubMed:24910095).

Involvement in disease

A chromosomal aberration involving NCOA4 is found in papillary thyroid carcinomas (PTCs). Inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene.

Post-translational modifications

NCOA4 levels may be regulated via HERC2-mediated ubiquitination leading to proteosomal degradation; HERC2 association is dependent on NCOA4 iron occupancy.

Tissue Specificity

Widely expressed. Also detected in adipose tissues and in different cell lines. Isoform Beta is only expressed in testis.

Cellular localization

• Cytoplasmic vesicle
• Autophagosome
• Autolysosome
• Nucleus
• Chromosome

Alternative names

ARA70, ELE1, RFG, NCOA4, Nuclear receptor coactivator 4, NCoA-4, Androgen receptor coactivator 70 kDa protein, Androgen receptor-associated protein of 70 kDa, Ferritin cargo receptor NCOA4, Ret-activating protein ELE1, 70 kDa AR-activator, 70 kDa androgen receptor coactivator

Database links

swissprot:Q13772 omim:164761 swissprot:P07949 entrezGene:8031 entrezGene:5979 omim:601984