Linked Life Data

P98177

Source:http://identifiers.org/uniprot/P98177

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
biopax3:comment
FUNCTION: Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. SUBUNIT: Interacts with CREBBP/CBP, CTNNB1, MYOCD, SIRT1, SRF and YWHAZ. Acetylated by CREBBP/CBP and deacetylated by SIRT1. Binding of YWHAZ inhibits DNA-binding. Interacts with USP7; the interaction is enhanced in presence of hydrogen peroxide and occurs independently of TP53. Interacts with NLK, and this inhibits monoubiquitination and transcriptional activity. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=When phosphorylated, translocated from nucleus to cytoplasm. Dephosphorylation triggers nuclear translocation. Monoubiquitination increases nuclear localization. When deubiquitinated, translocated from nucleus to cytoplasm. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=FOXO4a; IsoId=P98177-1; Sequence=Displayed; Name=Zeta; Synonyms=AFXzeta, FOXO4b; IsoId=P98177-2; Sequence=VSP_001552; TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform zeta is most abundant in the liver, kidney, and pancreas. PTM: Acetylation by CREBBP/CBP, which is induced by peroxidase stress, inhibits transcriptional activity. Deacetylation by SIRT1 is NAD-dependent and stimulates transcriptional activity. PTM: Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization. May be phosphorylated at multiple sites by NLK. PTM: Monoubiquitinated; monoubiquitination is induced by oxidative stress and reduced by deacetylase inhibitors; results in its relocalization to the nucleus and its increased transcriptional activity. Deubiquitinated by USP7; deubiquitination is induced by oxidative stress; enhances its interaction with USP7 and consequently, deubiquitination; increases its translocation to the cytoplasm and inhibits its transcriptional activity. Hydrogene- peroxide-induced ubiquitination and USP7-mediated deubiquitination have no major effect on its protein stability. DISEASE: Note=A chromosomal aberration involving FOXO4 is found in acute leukemias. Translocation t(X;11)(q13;q23) with MLL/HRX. The result is a rogue activator protein. PHARMACEUTICAL: A constitutively active FOXO4 mutant where phosphorylation sites Thr-32, Ser-197 and Ser-262 have been mutated to alanine may have therapeutic potential in ERBB2/HER2- overexpressing cancers as it inhibits ERBB2-mediated cell survival, transformation and tumorigenicity. SIMILARITY: Contains 1 fork-head DNA-binding domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/AFX1ID57.html"; GENE SYNONYMS:FOXO4 AFX AFX1 MLLT7. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 505 AA; 53684 MW; 0C71C8E2167CEE68 CRC64;
biopax3:xref
biopax3:displayName
FOXO4_HUMAN
biopax3:name
FOXO4, Fork head domain transcription factor AFX1
biopax3:entityFeature
biopax3:organism
biopax3:sequence
MDPGNENSATEAAAIIDLDPDFEPQSRPRSCTWPLPRPEIANQPSEPPEVEPDLGEKVHTEGRSEPILLPSRLPEPAGGPQPGILGAVTGPRKGGSRRNAWGNQSYAELISQAIESAPEKRLTLAQIYEWMVRTVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIKVHNEATGKSSWWMLNPEGGKSGKAPRRRAASMDSSSKLLRGRSKAPKKKPSVLPAPPEGATPTSPVGHFAKWSGSPCSRNREEADMWTTFRPRSSSNASSVSTRLSPLRPESEVLAEEIPASVSSYAGGVPPTLNEGLELLDGLNLTSSHSLLSRSGLSGFSLQHPGVTGPLHTYSSSLFSPAEGPLSAGEGCFSSSQALEALLTSDTPPPPADVLMTQVDPILSQAPTLLLLGGLPSSSKLATGVGLCPKPLEAPGPSSLVPTLSMIAPPPVMASAPIPKALGTPVLTPPTEAASQDRMPQDLDLDMYMENLECDMDNIISDLMDEGEGLDFNFEPDP
biopax3:standardName
Forkhead box protein O4