Q9WVH3 (FOXO4_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 113. History...
Names and origin
|Protein names||Recommended name:|
Forkhead box protein O4
Fork head domain transcription factor AFX1
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||505 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity By similarity. Represses smooth muscle cell differentiation by inhibiting the transcriptional coactivator activity of myocardin. Ref.3
Interacts with CREBBP/CBP, 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 By similarity.
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 By similarity.
By artery ligation in proliferating neointimal smooth muscle cells. Ref.3
Acetylation by CREBBP/CBP is induced by oxidative stress and inhibits transcriptional activity. Deacetylation by SIRT1 is NAD-dependent and stimulates transcriptional activity By similarity.
Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization. May be phosphorylated at multiple sites by NLK By similarity.
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 By similarity.
Contains 1 fork-head DNA-binding domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 505||505||Forkhead box protein O4||PRO_0000091876|
|DNA binding||100 – 188||89||Fork-head|
Amino acid modifications
|Modified residue||32||1||Phosphothreonine; by PKB/AKT1 By similarity|
|Modified residue||197||1||Phosphoserine; by PKB/AKT1 By similarity|
|Modified residue||200||1||Phosphoserine By similarity|
|Modified residue||262||1||Phosphoserine; by PKB/AKT1 By similarity|
|||"Identification and characterization of members of the FKHR (FOX O) subclass of winged-helix transcription factors in the mouse."|
Biggs W.H. III, Cavenee W.K., Arden K.C.
Mamm. Genome 12:416-425(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
|||"Mouse AFX, a forkhead type transcription factor."|
Furuyama T., Nakazawa T., Mori N.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin."|
Liu Z.-P., Wang Z., Yanagisawa H., Olson E.N.
Dev. Cell 9:261-270(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
|||"Novel repressor regulates insulin sensitivity through interaction with Foxo1."|
Nakae J., Cao Y., Hakuno F., Takemori H., Kawano Y., Sekioka R., Abe T., Kiyonari H., Tanaka T., Sakai J., Takahashi S., Itoh H.
EMBO J. 31:2275-2295(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
|+||Additional computationally mapped references.|
|AF114260 mRNA. Translation: AAD42108.1.|
AB032770 mRNA. Translation: BAA86199.1.
|RefSeq||NP_061259.1. NM_018789.2. |
3D structure databases
|SMR||Q9WVH3. Positions 97-181. |
Protein-protein interaction databases
|IntAct||Q9WVH3. 3 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000062000; ENSMUSP00000059420; ENSMUSG00000042903. |
|UCSC||uc009twz.2. mouse. |
|MGI||MGI:1891915. Foxo4. |
Gene expression databases
Family and domain databases
|Gene3D||22.214.171.124. 1 hit. |
|InterPro||IPR001766. TF_fork_head. |
|Pfam||PF00250. Fork_head. 1 hit. |
|PRINTS||PR00053. FORKHEAD. |
|SMART||SM00339. FH. 1 hit. |
|PROSITE||PS00658. FORK_HEAD_2. 1 hit. |
PS50039. FORK_HEAD_3. 1 hit.
|ChiTaRS||FOXO4. mouse. |
|Accession||Primary (citable) accession number: Q9WVH3|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|