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forkhead box protein O1A; forkhead in rhabdomyosarcoma; FKHR protein (FOXO1A)

Function: 1) transcription factor 2) phosphorylation by AKT1 is induced by insulin IGF1 rapidly induces phosphorylation of Thr-24, Ser-256 & Ser-319 phosphorylation of Ser-256 decreases DNA-binding activity & promotes phosphorylation of Thr-24, & Ser-319, which leads to nuclear exclusion & loss of function 3) LXXLL motif of murine forkhead transcription factor FoxO1 mediates Sirt1-dependent transcriptional activity [4] Structure: contains 1 fork-head DNA-binding domain Compartment: - cytoplasm, nucleus - shuttles between cytoplasm & nucleus Expression: ubiquitous Pathology: - chromosomal translocation t(2;13)(q35;q14) involving FOXO1A with PAX3 & t(1;13)(p36;q14) with PAX7 are a cause of alveolar rhabdomyosarcoma resulting protein is a transcriptional activator Polymorphism: - SNPs of FOXO1A are associated with longevity in women [5]

Related

forkhead in rhabdomyosarcoma (FKHR) gene

General

forkhead family transcription factor phosphoprotein

Properties

SIZE: MW = 70 kD entity length = 655 aa COMPARTMENT: cytoplasm cell nucleus MOTIF: Thr phosphorylation site {T24} alanine-rich region {91-102} MOTIF: alanine residue (SEVERAL) proline-rich region SITE: 120-130 MOTIF: proline residue (SEVERAL) serine-rich region {152-155} MOTIF: serine residue (SEVERAL) fork head domain NAME: fork head domain SITE: 159-235 Ser phosphorylation site {S256} Ser phosphorylation site {S319} LXXLL {462-466}

Database Correlations

OMIM 136533 UniProt Q12778 Entrez Gene 2308

References

  1. OMIM :accession 136533
  2. Entrez Gene :accession 2308
  3. UniProt :accession Q12778
  4. Nakae J, Cao Y, Daitoku H, Fukamizu A, Ogawa W, Yano Y, Hayashi Y. The LXXLL motif of murine forkhead transcription factor FoxO1 mediates Sirt1-dependent transcriptional activity. J Clin Invest. 2006 Sep;116(9):2473-83. Epub 2006 Aug 17. PMID: 16917544
  5. Li Y et al Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum Mol Genet. 2009 Dec 15;18(24):4897-904. PMID: 19793722