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P98177

- FOXO4_HUMAN

UniProt

P98177 - FOXO4_HUMAN

Protein

Forkhead box protein O4

Gene

FOXO4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 5 (25 Jul 2006)
      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.8 Publications

    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: UniProtKB
    4. sequence-specific DNA binding Source: UniProtKB
    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. epidermal growth factor receptor signaling pathway Source: Reactome
    3. Fc-epsilon receptor signaling pathway Source: Reactome
    4. fibroblast growth factor receptor signaling pathway Source: Reactome
    5. innate immune response Source: Reactome
    6. insulin receptor signaling pathway Source: UniProtKB
    7. mitotic G2 DNA damage checkpoint Source: Ensembl
    8. muscle organ development Source: UniProtKB-KW
    9. negative regulation of angiogenesis Source: UniProtKB
    10. negative regulation of cell proliferation Source: UniProtKB
    11. negative regulation of G0 to G1 transition Source: UniProtKB
    12. negative regulation of smooth muscle cell differentiation Source: UniProtKB
    13. neurotrophin TRK receptor signaling pathway Source: Reactome
    14. phosphatidylinositol-mediated signaling Source: Reactome
    15. positive regulation of transcription, DNA-templated Source: Ensembl
    16. regulation of transcription, DNA-templated Source: UniProtKB
    17. stem cell differentiation Source: UniProtKB
    18. transcription from RNA polymerase II promoter Source: ProtInc

    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_12442. AKT phosphorylates targets in the nucleus.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    SignaLinkiP98177.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Forkhead box protein O4
    Alternative name(s):
    Fork head domain transcription factor AFX1
    Gene namesi
    Name:FOXO4
    Synonyms:AFX, AFX1, MLLT7
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome X

    Organism-specific databases

    HGNCiHGNC:7139. 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.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: UniProtKB
    3. nucleoplasm Source: Reactome
    4. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    A chromosomal aberration involving FOXO4 is found in acute leukemias. Translocation t(X;11)(q13;q23) with KMT2A/MLL1. The result is a rogue activator protein.

    Pharmaceutical usei

    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.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi32 – 321T → A: Abolishes phosphorylation. Protein is located mainly in nucleus and shows increased transcriptional activity. Increased transcriptional and proteasome activities in embryonic stem cells; when associated with A-197 and A-262. 3 Publications
    Mutagenesisi197 – 1971S → A: Abolishes phosphorylation. Protein is located mainly in nucleus and shows increased transcriptional activity. Increased transcriptional and proteasome activities in embryonic stem cells; when associated with A-32 and A-262. 4 Publications
    Mutagenesisi262 – 2621S → A: Abolishes phosphorylation. No effect on cellular location or transcriptional activity. Increased transcriptional and proteasome activities in embryonic stem cells; when associated with A-32 and A-197. 4 Publications

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    PharmGKBiPA162388882.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 505505Forkhead box protein O4PRO_0000091875Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei32 – 321Phosphothreonine; by PKB/AKT11 Publication
    Modified residuei197 – 1971Phosphoserine; by PKB/AKT14 Publications
    Modified residuei200 – 2001Phosphoserine1 Publication
    Modified residuei262 – 2621Phosphoserine; by PKB/AKT13 Publications

    Post-translational modificationi

    Acetylation by CREBBP/CBP, which is induced by peroxidase stress, inhibits transcriptional activity. Deacetylation by SIRT1 is NAD-dependent and stimulates transcriptional activity.1 Publication
    Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization. May be phosphorylated at multiple sites by NLK.4 Publications
    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.1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP98177.
    PaxDbiP98177.
    PRIDEiP98177.

    PTM databases

    PhosphoSiteiP98177.

    Expressioni

    Tissue specificityi

    Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform zeta is most abundant in the liver, kidney, and pancreas.

    Gene expression databases

    BgeeiP98177.
    CleanExiHS_FOXO4.
    GenevestigatoriP98177.

    Organism-specific databases

    HPAiHPA040232.

    Interactioni

    Subunit structurei

    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.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    SIRT1Q96EB63EBI-4481939,EBI-1802965

    Protein-protein interaction databases

    BioGridi110449. 16 interactions.
    IntActiP98177. 4 interactions.
    STRINGi9606.ENSP00000363377.

    Structurei

    Secondary structure

    1
    505
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi106 – 11611
    Beta strandi117 – 1193
    Helixi124 – 13411
    Helixi136 – 1383
    Helixi139 – 1424
    Helixi149 – 16012
    Beta strandi164 – 1674
    Turni170 – 1723
    Beta strandi173 – 1753
    Beta strandi177 – 1804

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1E17NMR-A86-211[»]
    3L2CX-ray1.87A86-187[»]
    ProteinModelPortaliP98177.
    SMRiP98177. Positions 97-181.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP98177.

    Family & Domainsi

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiCOG5025.
    HOGENOMiHOG000251635.
    HOVERGENiHBG057789.
    KOiK12358.
    OMAiFSLQHPG.
    OrthoDBiEOG7SFHZ8.
    PhylomeDBiP98177.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P98177-1) [UniParc]FASTAAdd to Basket

    Also known as: FOXO4a

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDPGNENSAT EAAAIIDLDP DFEPQSRPRS CTWPLPRPEI ANQPSEPPEV    50
    EPDLGEKVHT EGRSEPILLP SRLPEPAGGP QPGILGAVTG PRKGGSRRNA 100
    WGNQSYAELI SQAIESAPEK RLTLAQIYEW MVRTVPYFKD KGDSNSSAGW 150
    KNSIRHNLSL HSKFIKVHNE ATGKSSWWML NPEGGKSGKA PRRRAASMDS 200
    SSKLLRGRSK APKKKPSVLP APPEGATPTS PVGHFAKWSG SPCSRNREEA 250
    DMWTTFRPRS SSNASSVSTR LSPLRPESEV LAEEIPASVS SYAGGVPPTL 300
    NEGLELLDGL NLTSSHSLLS RSGLSGFSLQ HPGVTGPLHT YSSSLFSPAE 350
    GPLSAGEGCF SSSQALEALL TSDTPPPPAD VLMTQVDPIL SQAPTLLLLG 400
    GLPSSSKLAT GVGLCPKPLE APGPSSLVPT LSMIAPPPVM ASAPIPKALG 450
    TPVLTPPTEA ASQDRMPQDL DLDMYMENLE CDMDNIISDL MDEGEGLDFN 500
    FEPDP 505
    Length:505
    Mass (Da):53,684
    Last modified:July 25, 2006 - v5
    Checksum:i0C71C8E2167CEE68
    GO
    Isoform Zeta (identifier: P98177-2) [UniParc]FASTAAdd to Basket

    Also known as: AFXzeta, FOXO4b

    The sequence of this isoform differs from the canonical sequence as follows:
         58-112: Missing.

    Show »
    Length:450
    Mass (Da):47,941
    Checksum:iD44C18FAD9C2A747
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti1 – 1111MDPGNENSATE → MRIQPQK in CAA63819. (PubMed:9010221)CuratedAdd
    BLAST
    Sequence conflicti25 – 3410QSRPRSCTWP → RAVPLLHLA in CAA72156. (PubMed:9341872)Curated
    Sequence conflicti74 – 741P → S in CAA63819. (PubMed:9010221)Curated
    Sequence conflicti79 – 791G → A in CAA72156. (PubMed:9341872)Curated
    Sequence conflicti109 – 1091L → F in CAA63819. (PubMed:9010221)Curated
    Sequence conflicti422 – 4221P → R in CAA63819. (PubMed:9010221)Curated
    Sequence conflicti422 – 4221P → R in AAL85197. (PubMed:11779849)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei58 – 11255Missing in isoform Zeta. 1 PublicationVSP_001552Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y11284, Y11285, Y11286 Genomic DNA. Translation: CAA72156.1.
    X93996 mRNA. Translation: CAA63819.1.
    AF384029 mRNA. Translation: AAL85197.1.
    AL590764 Genomic DNA. No translation available.
    CH471132 Genomic DNA. Translation: EAX05321.1.
    BC106761 mRNA. Translation: AAI06762.1.
    U10072 mRNA. Translation: AAA82171.1. Sequence problems.
    CCDSiCCDS43969.1. [P98177-1]
    CCDS55440.1. [P98177-2]
    PIRiI38654.
    RefSeqiNP_001164402.1. NM_001170931.1. [P98177-2]
    NP_005929.2. NM_005938.3. [P98177-1]
    UniGeneiHs.584654.

    Genome annotation databases

    EnsembliENST00000341558; ENSP00000342209; ENSG00000184481. [P98177-2]
    ENST00000374259; ENSP00000363377; ENSG00000184481. [P98177-1]
    GeneIDi4303.
    KEGGihsa:4303.
    UCSCiuc004dys.2. human. [P98177-1]
    uc004dyt.2. human. [P98177-2]

    Polymorphism databases

    DMDMi110825720.

    Keywords - Coding sequence diversityi

    Alternative splicing, Chromosomal rearrangement

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y11284 , Y11285 , Y11286 Genomic DNA. Translation: CAA72156.1 .
    X93996 mRNA. Translation: CAA63819.1 .
    AF384029 mRNA. Translation: AAL85197.1 .
    AL590764 Genomic DNA. No translation available.
    CH471132 Genomic DNA. Translation: EAX05321.1 .
    BC106761 mRNA. Translation: AAI06762.1 .
    U10072 mRNA. Translation: AAA82171.1 . Sequence problems.
    CCDSi CCDS43969.1. [P98177-1 ]
    CCDS55440.1. [P98177-2 ]
    PIRi I38654.
    RefSeqi NP_001164402.1. NM_001170931.1. [P98177-2 ]
    NP_005929.2. NM_005938.3. [P98177-1 ]
    UniGenei Hs.584654.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1E17 NMR - A 86-211 [» ]
    3L2C X-ray 1.87 A 86-187 [» ]
    ProteinModelPortali P98177.
    SMRi P98177. Positions 97-181.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110449. 16 interactions.
    IntActi P98177. 4 interactions.
    STRINGi 9606.ENSP00000363377.

    PTM databases

    PhosphoSitei P98177.

    Polymorphism databases

    DMDMi 110825720.

    Proteomic databases

    MaxQBi P98177.
    PaxDbi P98177.
    PRIDEi P98177.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000341558 ; ENSP00000342209 ; ENSG00000184481 . [P98177-2 ]
    ENST00000374259 ; ENSP00000363377 ; ENSG00000184481 . [P98177-1 ]
    GeneIDi 4303.
    KEGGi hsa:4303.
    UCSCi uc004dys.2. human. [P98177-1 ]
    uc004dyt.2. human. [P98177-2 ]

    Organism-specific databases

    CTDi 4303.
    GeneCardsi GC0XP070316.
    HGNCi HGNC:7139. FOXO4.
    HPAi HPA040232.
    MIMi 300033. gene.
    neXtProti NX_P98177.
    PharmGKBi PA162388882.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5025.
    HOGENOMi HOG000251635.
    HOVERGENi HBG057789.
    KOi K12358.
    OMAi FSLQHPG.
    OrthoDBi EOG7SFHZ8.
    PhylomeDBi P98177.
    TreeFami TF315583.

    Enzyme and pathway databases

    Reactomei REACT_12442. AKT phosphorylates targets in the nucleus.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    SignaLinki P98177.

    Miscellaneous databases

    EvolutionaryTracei P98177.
    GeneWikii FOXO4.
    GenomeRNAii 4303.
    NextBioi 16943.
    PROi P98177.
    SOURCEi Search...

    Gene expression databases

    Bgeei P98177.
    CleanExi HS_FOXO4.
    Genevestigatori P98177.

    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. "AFX1 and p54nrb: fine mapping, genomic structure, and exclusion as candidate genes of X-linked dystonia parkinsonism."
      Peters U., Haberhausen G., Kostrzewa M., Nolte D., Mueller U.
      Hum. Genet. 100:569-572(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Blood.
    2. "Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23)."
      Borkhardt A., Repp R., Haas O.A., Leis T., Harbott J., Kreuder J., Hammermann J., Henn T., Lampert F.
      Oncogene 14:195-202(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "An mRNA splice variant of the AFX gene with altered transcriptional activity."
      Yang Z., Whelan J., Babb R., Bowen B.R.
      J. Biol. Chem. 277:8068-8075(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ZETA).
    4. "The DNA sequence of the human X chromosome."
      Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.
      , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
      Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    7. "Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family."
      Parry P., Wei Y., Evans G.
      Genes Chromosomes Cancer 11:79-84(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHROMOSOMAL TRANSLOCATION.
      Tissue: Bone marrow.
    8. "Direct control of the forkhead transcription factor AFX by protein kinase B."
      Kops G.J.P.L., de Ruiter N.D., De Vries-Smits A.M.M., Powell D.R., Bos J.L., Burgering B.M.T.
      Nature 398:630-634(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT SER-197 AND SER-262, MUTAGENESIS OF SER-197 AND SER-262.
    9. "Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B."
      Takaishi H., Konishi H., Matsuzaki H., Ono Y., Shirai Y., Saito N., Kitamura T., Ogawa W., Kasuga M., Kikkawa U., Nishizuka Y.
      Proc. Natl. Acad. Sci. U.S.A. 96:11836-11841(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-197 AND SER-262, MUTAGENESIS OF THR-32; SER-197 AND SER-262.
    10. "AFX-like forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1."
      Medema R.H., Kops G.J.P.L., Bos J.L., Burgering B.M.T.
      Nature 404:782-787(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    11. "The forkhead transcription factor FOXO4 induces the down-regulation of hypoxia-inducible factor 1 alpha by a von Hippel-Lindau protein-independent mechanism."
      Tang T.T.-L., Lasky L.A.
      J. Biol. Chem. 278:30125-30135(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1)."
      van der Horst A., Tertoolen L.G.J., de Vries-Smits L.M.M., Frye R.A., Medema R.H., Burgering B.M.T.
      J. Biol. Chem. 279:28873-28879(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CREBBP AND SIRT1, ACETYLATION.
    13. "14-3-3 protein interacts with nuclear localization sequence of forkhead transcription factor FoxO4."
      Obsilova V., Vecer J., Herman P., Pabianova A., Sulc M., Teisinger J., Boura E., Obsil T.
      Biochemistry 44:11608-11617(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH YWHAZ, SUBCELLULAR LOCATION.
    14. "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, INTERACTION WITH MYOCD AND SRF.
    15. "Regulation of intracellular localization and transcriptional activity of FOXO4 by protein kinase B through phosphorylation at the motif sites conserved among the FOXO family."
      Matsuzaki H., Ichino A., Hayashi T., Yamamoto T., Kikkawa U.
      J. Biochem. 138:485-491(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-32; SER-197 AND SER-262, MUTAGENESIS OF THR-32; SER-197 AND SER-262.
    16. "Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity."
      Yang H., Zhao R., Yang H.-Y., Lee M.-H.
      Oncogene 24:1924-1935(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHARMACEUTICAL USE.
    17. Cited for: FUNCTION, INTERACTION WITH USP7, UBIQUITINATION, DEUBIQUITINATION BY USP7, SUBCELLULAR LOCATION.
    18. Carrascal M., Abian J.
      Submitted (JAN-2008) to UniProtKB
      Cited for: PHOSPHORYLATION AT SER-197 AND SER-200, IDENTIFICATION BY MASS SPECTROMETRY.
    19. "Oxidative stress-dependent regulation of Forkhead box O4 activity by nemo-like kinase."
      Szypowska A.A., de Ruiter H., Meijer L.A.T., Smits L.M.M., Burgering B.M.T.
      Antioxid. Redox Signal. 14:563-578(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH NLK; CTNNB1 AND CREBBP.
    20. "Increased proteasome activity in human embryonic stem cells is regulated by PSMD11."
      Vilchez D., Boyer L., Morantte I., Lutz M., Merkwirth C., Joyce D., Spencer B., Page L., Masliah E., Berggren W.T., Gage F.H., Dillin A.
      Nature 489:304-308(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF THR-32; SER-197 AND SER-262.
    21. "1H, 13C and 15N resonance assignments of the DNA binding domain of the human forkhead transcription factor AFX."
      Weigelt J., Climent I., Dahlman-Wright K., Wikstrom M.
      J. Biomol. NMR 17:181-182(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 86-211.
    22. "Solution structure of the DNA binding domain of the human forkhead transcription factor AFX (FOXO4)."
      Weigelt J., Climent I., Dahlman-Wright K., Wikstrom M.
      Biochemistry 40:5861-5869(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 86-211.

    Entry informationi

    Entry nameiFOXO4_HUMAN
    AccessioniPrimary (citable) accession number: P98177
    Secondary accession number(s): B7WPJ7
    , O43821, Q13720, Q3KPF1, Q8TDK9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: July 25, 2006
    Last modified: October 1, 2014
    This is version 150 of the entry and version 5 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Pharmaceutical, Reference proteome

    Documents

    1. Human chromosome X
      Human chromosome X: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3