NCOA4

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).

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.

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

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

• Cytoplasmic vesicle
• Autophagosome
• Autolysosome
• Nucleus
• Chromosome

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

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

Proteins

Oncology

69726Da