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Q9WVH3

- FOXO4_MOUSE

UniProt

Q9WVH3 - FOXO4_MOUSE

Protein

Forkhead box protein O4

Gene

Foxo4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
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    Functioni

    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.By similarity1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi100 – 18889Fork-headPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB
    2. enzyme binding Source: UniProtKB
    3. protein binding Source: IntAct
    4. sequence-specific DNA binding Source: MGI
    5. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    6. transcription factor binding Source: UniProtKB

    GO - Biological processi

    1. cell cycle arrest Source: UniProtKB
    2. insulin receptor signaling pathway Source: UniProtKB
    3. mitotic G2 DNA damage checkpoint Source: MGI
    4. muscle organ development Source: UniProtKB-KW
    5. negative regulation of angiogenesis Source: UniProtKB
    6. negative regulation of cell proliferation Source: UniProtKB
    7. negative regulation of G0 to G1 transition Source: UniProtKB
    8. negative regulation of smooth muscle cell differentiation Source: UniProtKB
    9. positive regulation of transcription, DNA-templated Source: MGI
    10. regulation of transcription, DNA-templated Source: UniProtKB
    11. stem cell differentiation Source: UniProtKB
    12. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Developmental protein

    Keywords - Biological processi

    Cell cycle, Differentiation, Myogenesis, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_218211. AKT phosphorylates targets in the nucleus.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Forkhead box protein O4
    Alternative name(s):
    Afxh
    Fork head domain transcription factor AFX1
    Gene namesi
    Name:Foxo4
    Synonyms:Afx, Afx1, Fkhr3, Mllt7
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome X

    Organism-specific databases

    MGIiMGI:1891915. Foxo4.

    Subcellular locationi

    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 similarity

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 505505Forkhead box protein O4PRO_0000091876Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei32 – 321Phosphothreonine; by PKB/AKT1By similarity
    Modified residuei197 – 1971Phosphoserine; by PKB/AKT1By similarity
    Modified residuei200 – 2001PhosphoserineBy similarity
    Modified residuei262 – 2621Phosphoserine; by PKB/AKT1By similarity

    Post-translational modificationi

    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.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.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.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ9WVH3.
    PRIDEiQ9WVH3.

    PTM databases

    PhosphoSiteiQ9WVH3.

    Expressioni

    Tissue specificityi

    Strongly expressed in brown adipose tissue and weakly in white adipose tissue (at protein level). Expressed in skeletal muscle.2 Publications

    Inductioni

    By artery ligation in proliferating neointimal smooth muscle cells.1 Publication

    Gene expression databases

    ArrayExpressiQ9WVH3.
    BgeeiQ9WVH3.
    CleanExiMM_FOXO4.
    GenevestigatoriQ9WVH3.

    Interactioni

    Subunit structurei

    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.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    OgtP565582EBI-4567305,EBI-7614183From a different organism.

    Protein-protein interaction databases

    IntActiQ9WVH3. 3 interactions.
    MINTiMINT-4095287.
    STRINGi10090.ENSMUSP00000059420.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9WVH3.
    SMRiQ9WVH3. Positions 97-181.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG5025.
    GeneTreeiENSGT00390000000589.
    HOGENOMiHOG000251635.
    HOVERGENiHBG057789.
    InParanoidiQ9WVH3.
    KOiK12358.
    OMAiFSLQHPG.
    OrthoDBiEOG7SFHZ8.
    PhylomeDBiQ9WVH3.
    TreeFamiTF315583.

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    InterProiIPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view]
    PfamiPF00250. Fork_head. 1 hit.
    [Graphical view]
    PRINTSiPR00053. FORKHEAD.
    SMARTiSM00339. FH. 1 hit.
    [Graphical view]
    PROSITEiPS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9WVH3-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDPENKKSAT GAAAILDLDP DFEPQSRPRS CTWPLPRPDL ATEPHEPSEV    50
    EPSLGQKVPT EGHSEPILLP SRLPEPAGGP QPGILGAVTG PRKGGSRRNA 100
    WGNQSYAELI SQAIESAPEK RLTLAQIYEW MVRTVPYFKD KGDSNSSAGW 150
    KNSIRHNLSL HSKFIKVHNE ATGKSSWWML NPDGGKGGKA PRRRAASMDS 200
    SSKLLRGRSK GPKKKPSVLP APPEGATPRS PLGHFAKWSS SPCPRNREEA 250
    DVWTTFRPRS SSNASTVSTR LSPMRPESEV LAEEEMPASA SSYAGGVPPT 300
    LSEDLELLDG LNLASPHSLL SRSGLSGFSL QHPGLAGPLH SYGASLFGPI 350
    DGSLSAGEGC FSSSQSLEAL LTSDTPPPPA DVLMTQVDPI LSQAPTLLLL 400
    GGMPSSSKLG TGVSLCPTPL EGPGPSNLVP NLSVMAPPPV MAGAPIPKVL 450
    GTPVLASPTE DSSHDRMPQD LDLDMYMENL ECDMDNIISD LMDGEGLDFN 500
    FEPDP 505
    Length:505
    Mass (Da):53,649
    Last modified:November 1, 1999 - v1
    Checksum:iABB99B54807C7CE5
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF114260 mRNA. Translation: AAD42108.1.
    AB032770 mRNA. Translation: BAA86199.1.
    CCDSiCCDS41077.1.
    RefSeqiNP_061259.1. NM_018789.2.
    UniGeneiMm.240299.

    Genome annotation databases

    EnsembliENSMUST00000062000; ENSMUSP00000059420; ENSMUSG00000042903.
    GeneIDi54601.
    KEGGimmu:54601.
    UCSCiuc009twz.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF114260 mRNA. Translation: AAD42108.1 .
    AB032770 mRNA. Translation: BAA86199.1 .
    CCDSi CCDS41077.1.
    RefSeqi NP_061259.1. NM_018789.2.
    UniGenei Mm.240299.

    3D structure databases

    ProteinModelPortali Q9WVH3.
    SMRi Q9WVH3. Positions 97-181.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q9WVH3. 3 interactions.
    MINTi MINT-4095287.
    STRINGi 10090.ENSMUSP00000059420.

    PTM databases

    PhosphoSitei Q9WVH3.

    Proteomic databases

    PaxDbi Q9WVH3.
    PRIDEi Q9WVH3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000062000 ; ENSMUSP00000059420 ; ENSMUSG00000042903 .
    GeneIDi 54601.
    KEGGi mmu:54601.
    UCSCi uc009twz.2. mouse.

    Organism-specific databases

    CTDi 4303.
    MGIi MGI:1891915. Foxo4.

    Phylogenomic databases

    eggNOGi COG5025.
    GeneTreei ENSGT00390000000589.
    HOGENOMi HOG000251635.
    HOVERGENi HBG057789.
    InParanoidi Q9WVH3.
    KOi K12358.
    OMAi FSLQHPG.
    OrthoDBi EOG7SFHZ8.
    PhylomeDBi Q9WVH3.
    TreeFami TF315583.

    Enzyme and pathway databases

    Reactomei REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_218211. AKT phosphorylates targets in the nucleus.

    Miscellaneous databases

    ChiTaRSi FOXO4. mouse.
    NextBioi 311392.
    PROi Q9WVH3.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9WVH3.
    Bgeei Q9WVH3.
    CleanExi MM_FOXO4.
    Genevestigatori Q9WVH3.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    InterProi IPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    Pfami PF00250. Fork_head. 1 hit.
    [Graphical view ]
    PRINTSi PR00053. FORKHEAD.
    SMARTi SM00339. FH. 1 hit.
    [Graphical view ]
    PROSITEi PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiFOXO4_MOUSE
    AccessioniPrimary (citable) accession number: Q9WVH3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 11, 2001
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 115 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3