Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9WVH3 (FOXO4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Forkhead box protein O4
Alternative name(s):
Afxh
Fork head domain transcription factor AFX1
Gene names
Name:Foxo4
Synonyms:Afx, Afx1, Fkhr3, Mllt7
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length505 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. 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

Subunit structure

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.

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 By similarity.

Tissue specificity

Strongly expressed in brown adipose tissue and weakly in white adipose tissue (at protein level). Expressed in skeletal muscle. Ref.1 Ref.4

Induction

By artery ligation in proliferating neointimal smooth muscle cells. Ref.3

Post-translational modification

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.

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processCell cycle
Differentiation
Myogenesis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processblood vessel development

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell cycle arrest

Inferred from sequence or structural similarity. Source: UniProtKB

insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

mitotic G2 DNA damage checkpoint

Inferred from direct assay PubMed 12048180. Source: MGI

muscle organ development

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of G0 to G1 transition

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of stress-activated MAPK cascade

Inferred from Biological aspect of Ancestor. Source: RefGenome

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12048180PubMed 14966295. Source: MGI

regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

stem cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

tissue development

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

DNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

enzyme binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 19932102. Source: IntAct

sequence-specific DNA binding

Inferred from direct assay Ref.1. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

transcription factor binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

OgtP565582EBI-4567305,EBI-7614183From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 505505Forkhead box protein O4
PRO_0000091876

Regions

DNA binding100 – 18889Fork-head

Amino acid modifications

Modified residue321Phosphothreonine; by PKB/AKT1 By similarity
Modified residue1971Phosphoserine; by PKB/AKT1 By similarity
Modified residue2001Phosphoserine By similarity
Modified residue2621Phosphoserine; by PKB/AKT1 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9WVH3 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: ABB99B54807C7CE5

FASTA50553,649
        10         20         30         40         50         60 
MDPENKKSAT GAAAILDLDP DFEPQSRPRS CTWPLPRPDL ATEPHEPSEV EPSLGQKVPT 

        70         80         90        100        110        120 
EGHSEPILLP SRLPEPAGGP QPGILGAVTG PRKGGSRRNA WGNQSYAELI SQAIESAPEK 

       130        140        150        160        170        180 
RLTLAQIYEW MVRTVPYFKD KGDSNSSAGW KNSIRHNLSL HSKFIKVHNE ATGKSSWWML 

       190        200        210        220        230        240 
NPDGGKGGKA PRRRAASMDS SSKLLRGRSK GPKKKPSVLP APPEGATPRS PLGHFAKWSS 

       250        260        270        280        290        300 
SPCPRNREEA DVWTTFRPRS SSNASTVSTR LSPMRPESEV LAEEEMPASA SSYAGGVPPT 

       310        320        330        340        350        360 
LSEDLELLDG LNLASPHSLL SRSGLSGFSL QHPGLAGPLH SYGASLFGPI DGSLSAGEGC 

       370        380        390        400        410        420 
FSSSQSLEAL LTSDTPPPPA DVLMTQVDPI LSQAPTLLLL GGMPSSSKLG TGVSLCPTPL 

       430        440        450        460        470        480 
EGPGPSNLVP NLSVMAPPPV MAGAPIPKVL GTPVLASPTE DSSHDRMPQD LDLDMYMENL 

       490        500 
ECDMDNIISD LMDGEGLDFN FEPDP 

« Hide

References

[1]"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.
Tissue: Embryo.
[2]"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].
[3]"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.
[4]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF114260 mRNA. Translation: AAD42108.1.
AB032770 mRNA. Translation: BAA86199.1.
CCDSCCDS41077.1.
RefSeqNP_061259.1. NM_018789.2.
UniGeneMm.240299.

3D structure databases

ProteinModelPortalQ9WVH3.
SMRQ9WVH3. Positions 97-181.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9WVH3. 3 interactions.
MINTMINT-4095287.
STRING10090.ENSMUSP00000059420.

PTM databases

PhosphoSiteQ9WVH3.

Proteomic databases

PaxDbQ9WVH3.
PRIDEQ9WVH3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000062000; ENSMUSP00000059420; ENSMUSG00000042903.
GeneID54601.
KEGGmmu:54601.
UCSCuc009twz.2. mouse.

Organism-specific databases

CTD4303.
MGIMGI:1891915. Foxo4.

Phylogenomic databases

eggNOGCOG5025.
GeneTreeENSGT00390000000589.
HOGENOMHOG000251635.
HOVERGENHBG057789.
InParanoidQ9WVH3.
KOK12358.
OMAFSLQHPG.
OrthoDBEOG7SFHZ8.
PhylomeDBQ9WVH3.
TreeFamTF315583.

Gene expression databases

ArrayExpressQ9WVH3.
BgeeQ9WVH3.
CleanExMM_FOXO4.
GenevestigatorQ9WVH3.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFOXO4. mouse.
NextBio311392.
PROQ9WVH3.
SOURCESearch...

Entry information

Entry nameFOXO4_MOUSE
AccessionPrimary (citable) accession number: Q9WVH3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot