Search
forkhead box protein O4; forkhead domain transcription factor AFX1 (FOXO4, AFX1)
Function:
- transcription factor
- role in regulation of insulin signaling pathway
- binds to insulin-response elements (IREs) & can activate transcription of IGFBP1
- down-regulates expression of HIF1A & suppresses hypoxia- induced transcriptional activation of HIF1A-modulated genes
- role in negative regulation of the cell cycle
- interacts with CBP, MYOCD, SIRT1, SRF & YWHAZ
- acetylated by CBP & deacetylated by SIRT1
- binding of YWHAZ inhibits DNA-binding
- acetylation by CBP, which is induced by peroxidase stress, inhibits transcriptional activity
- deacetylation by SIRT1 is NAD-dependent & stimulates transcriptional activity
- phosphorylation by PKB/AKT1 inhibits transcriptional activity & is responsible for cytoplasmic localization
Compartment:
- cytoplasm, nucleus
- when phosphorylated, translocated from nucleus to cytoplasm
- dephosphorylation triggers nuclear translocation
Alternative splicing: named isoforms=2
Expression:
- expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney & pancreas
- isoform zeta is most abundant in liver, kidney, & pancreas
Pathology: -chromosomal translocation t(X;11)(q13;q23) involving FOXO4 with MLL/HRX is found in acute leukemias The result is a rogue activator protein
Related
AFX1 gene or MLLT7 gene
General
forkhead family transcription factor
phosphoprotein
Properties
SIZE: MW = 54 kD
entity length = 505 aa
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: Thr phosphorylation site {T32}
fork head domain
NAME: fork head domain
SITE: 100-188
Ser phosphorylation site {S197}
Ser phosphorylation site {S262}
Database Correlations
OMIM 300033
UniProt P98177
References
- UniProt :accession P98177
- Atlas of Genetics and Cytogenetics in Oncology and Haematology
http://atlasgeneticsoncology.org/Genes/AFX1ID57.html