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P01101

- FOS_MOUSE

UniProt

P01101 - FOS_MOUSE

Protein

Proto-oncogene c-Fos

Gene

Fos

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 129 (01 Oct 2014)
      Sequence version 1 (21 Jul 1986)
      Previous versions | rss
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    Functioni

    Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling By similarity. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum.By similarity5 Publications

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. double-stranded DNA binding Source: Ensembl
    3. protein binding Source: IntAct
    4. RNA polymerase II core promoter sequence-specific DNA binding Source: MGI
    5. sequence-specific DNA binding transcription factor activity Source: MGI

    GO - Biological processi

    1. aging Source: Ensembl
    2. cellular response to calcium ion Source: MGI
    3. cellular response to extracellular stimulus Source: MGI
    4. cellular response to hormone stimulus Source: Ensembl
    5. cellular response to reactive oxygen species Source: Ensembl
    6. conditioned taste aversion Source: Ensembl
    7. female pregnancy Source: Ensembl
    8. nervous system development Source: MGI
    9. positive regulation of osteoclast differentiation Source: MGI
    10. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    11. regulation of transcription, DNA-templated Source: MGI
    12. response to cAMP Source: Ensembl
    13. response to cold Source: Ensembl
    14. response to corticosterone Source: Ensembl
    15. response to cytokine Source: Ensembl
    16. response to drug Source: MGI
    17. response to gravity Source: Ensembl
    18. response to light stimulus Source: Ensembl
    19. response to lipopolysaccharide Source: Ensembl
    20. response to mechanical stimulus Source: Ensembl
    21. response to progesterone Source: Ensembl
    22. response to toxic substance Source: Ensembl
    23. skeletal muscle cell differentiation Source: MGI
    24. sleep Source: Ensembl
    25. SMAD protein signal transduction Source: Ensembl
    26. transcription from RNA polymerase II promoter Source: Ensembl
    27. transforming growth factor beta receptor signaling pathway Source: Ensembl

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_188530. FCERI mediated MAPK activation.
    REACT_188970. Oxidative Stress Induced Senescence.
    REACT_204811. Activation of the AP-1 family of transcription factors.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Proto-oncogene c-Fos
    Alternative name(s):
    Cellular oncogene fos
    Gene namesi
    Name:Fos
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 12

    Organism-specific databases

    MGIiMGI:95574. Fos.

    Subcellular locationi

    Nucleus PROSITE-ProRule annotation. Endoplasmic reticulum By similarity. Cytoplasmcytosol By similarity
    Note: In quiescent cells, present in very small amounts in the cytosol. Following induction of cell growth, first localizes to the endoplasmic reticulum and only later to the nucleus. Localization at the endoplasmic reticulum requires dephosphorylation at Tyr-10 and Tyr-30 By similarity.By similarity

    GO - Cellular componenti

    1. cytosol Source: UniProtKB-SubCell
    2. endoplasmic reticulum Source: UniProtKB-SubCell
    3. membrane Source: Ensembl
    4. neuron projection Source: Ensembl
    5. nucleus Source: MGI
    6. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi139 – 1391K → N: No effect on activation of phospholipid synthesis. 1 Publication
    Mutagenesisi144 – 1441R → N: No effect on activation of phospholipid synthesis, nor on CDS1-binding. 1 Publication
    Mutagenesisi146 – 1461R → N: Complete loss of activation of phospholipid synthesis. No effect on CDS1-binding. 1 Publication
    Mutagenesisi232 – 2321T → A: No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-325; A-331 and A-374. 1 Publication
    Mutagenesisi325 – 3251T → A: Almost no EGF-mediated phosphorylation, greatly reduced cellular transformation, and reduced AP1 activity by 20%; when associated with A-331. No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-232; A-331 and A-374. 2 Publications
    Mutagenesisi331 – 3311T → A: Almost no EGF-mediated phosphorylation, greatly reduced cellular transformation, and reduced AP1 activity by 20%; when associated with A-325. No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-232; A-325;and A-374. 2 Publications
    Mutagenesisi343 – 3431F → A: Reduced phosphorylation by ERK. Reduced AP1 activity by 65%. 1 Publication
    Mutagenesisi345 – 3451Y → A: Reduced phosphorylation by ERK. 1 Publication
    Mutagenesisi362 – 3621S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-374. 1 Publication
    Mutagenesisi362 – 3621S → E: Increased enhancement of EGF- and RSK-mediated tranformation; when associated with E-374. 1 Publication
    Mutagenesisi374 – 3741S → A: No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-232; A-325 and A-331. 2 Publications
    Mutagenesisi374 – 3741S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-362. 2 Publications
    Mutagenesisi374 – 3741S → E: Enhanced EGF- and RSK-mediated tranformation; when associated with E-362. 2 Publications

    Keywords - Diseasei

    Proto-oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 380380Proto-oncogene c-FosPRO_0000076467Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei10 – 101Phosphotyrosine; by SRCBy similarity
    Modified residuei30 – 301Phosphotyrosine; by SRCBy similarity
    Cross-linki113 – 113Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei232 – 2321Phosphothreonine1 Publication
    Cross-linki265 – 265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
    Modified residuei325 – 3251Phosphothreonine; by MAPK1 and MAPK32 Publications
    Modified residuei331 – 3311Phosphothreonine; by MAPK1 and MAPK32 Publications
    Modified residuei362 – 3621Phosphoserine; by MAPK1, MAPK3 and RPS6KA33 Publications
    Modified residuei374 – 3741Phosphoserine; by MAPK1 and MAPK32 Publications

    Post-translational modificationi

    Phosphorylated in the C-terminal upon stimulation by nerve growth factor (NGF) and epidermal growth factor (EGF). Phosphorylated, in vitro, by MAPK and RSK1. Phosphorylation on both Ser-362 and Ser-374 by MAPK1/2 and RSK1/2 leads to protein stabilization with phosphorylation on Ser-374 being the major site for protein stabilization on NGF stimulation. Phosphorylation on Ser-362 and Ser-374 primes further phosphorylations on Thr-325 and Thr-331 through promoting docking of MAPK to the DEF domain. Phosphorylation on Thr-232, induced by HA-RAS, activates the transcriptional activity and antagonizes sumoylation. Phosphorylation on Ser-362 by RSK2 in osteoblasts contributes to osteoblast transformation By similarity.By similarity
    Constitutively sumoylated with SUMO1, SUMO2 and SUMO3. Desumoylated by SENP2. Sumoylation requires heterodimerization with JUN and is enhanced by mitogen stimulation. Sumoylation inhibits the AP-1 transcriptional activity and is, itself, inhibited by Ras-activated phosphorylation on Thr-232 By similarity.By similarity
    In quiescent cells, the small amount of FOS present is phosphorylated at Tyr-10 and Tyr-30 by SRC. This Tyr-phosphorylated form is cytosolic. In growing cells, dephosphorylated by PTPN2. Dephosphorylation leads to the association with endoplasmic reticulum membranes and activation of phospholipid synthesis.3 Publications

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiP01101.

    PTM databases

    PhosphoSiteiP01101.

    Expressioni

    Gene expression databases

    ArrayExpressiP01101.
    BgeeiP01101.
    CleanExiMM_FOS.
    GenevestigatoriP01101.

    Interactioni

    Subunit structurei

    Heterodimer; with JUN By similarity. Interacts with MAFB. Component of the SMAD3/SMAD4/JUN/FOS complex required for syngernistic TGF-beta-mediated transcription at the AP1 promoter site. Interacts with SMAD3; the interaction is weak even on TGF-beta activation. Interacts with MAFB By similarity. Interacts with DSIPI; this interaction inhibits the binding of active AP1 to its target DNA. Interacts with CDS1 and PI4K2A, but not with CDIPT, nor PI4K2B.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Esr2O085372EBI-4288185,EBI-2526214

    Protein-protein interaction databases

    BioGridi199726. 21 interactions.
    DIPiDIP-1066N.
    IntActiP01101. 2 interactions.
    MINTiMINT-1500015.

    Structurei

    Secondary structure

    1
    380
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi139 – 19961

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2WT7X-ray2.30A138-200[»]
    ProteinModelPortaliP01101.
    SMRiP01101. Positions 138-200.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini137 – 20064bZIPPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni139 – 15921Basic motif; required for the activation of phospholipid synthesis, but not for CDS1-bindingAdd
    BLAST
    Regioni165 – 19329Leucine-zipperPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the bZIP family. Fos subfamily.Curated
    Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG258795.
    GeneTreeiENSGT00730000110541.
    HOGENOMiHOG000234334.
    HOVERGENiHBG005743.
    InParanoidiP01101.
    KOiK04379.
    OMAiTPTCTTY.
    OrthoDBiEOG7VTDN9.
    PhylomeDBiP01101.
    TreeFamiTF326301.

    Family and domain databases

    InterProiIPR004827. bZIP.
    IPR000837. Leuzip_Fos.
    [Graphical view]
    PfamiPF00170. bZIP_1. 1 hit.
    [Graphical view]
    PRINTSiPR00042. LEUZIPPRFOS.
    SMARTiSM00338. BRLZ. 1 hit.
    [Graphical view]
    PROSITEiPS50217. BZIP. 1 hit.
    PS00036. BZIP_BASIC. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P01101-1 [UniParc]FASTAAdd to Basket

    « Hide

    MMFSGFNADY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNTQDFC    50
    ADLSVSSANF IPTVTAISTS PDLQWLVQPT LVSSVAPSQT RAPHPYGLPT 100
    QSAGAYARAG MVKTVSGGRA QSIGRRGKVE QLSPEEEEKR RIRRERNKMA 150
    AAKCRNRRRE LTDTLQAETD QLEDEKSALQ TEIANLLKEK EKLEFILAAH 200
    RPACKIPDDL GFPEEMSVAS LDLTGGLPEA STPESEEAFT LPLLNDPEPK 250
    PSLEPVKSIS NVELKAEPFD DFLFPASSRP SGSETSRSVP DVDLSGSFYA 300
    ADWEPLHSNS LGMGPMVTEL EPLCTPVVTC TPGCTTYTSS FVFTYPEADS 350
    FPSCAAAHRK GSSSNEPSSD SLSSPTLLAL 380
    Length:380
    Mass (Da):40,838
    Last modified:July 21, 1986 - v1
    Checksum:i475966265952B624
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    V00727 Genomic DNA. Translation: CAA24105.1.
    J00370 Genomic DNA. Translation: AAA96699.1.
    BC029814 mRNA. Translation: AAH29814.1.
    CCDSiCCDS26059.1.
    PIRiA01343. TVMSF.
    RefSeqiNP_034364.1. NM_010234.2.
    UniGeneiMm.246513.

    Genome annotation databases

    EnsembliENSMUST00000021674; ENSMUSP00000021674; ENSMUSG00000021250.
    GeneIDi14281.
    KEGGimmu:14281.
    UCSCiuc007oha.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    V00727 Genomic DNA. Translation: CAA24105.1 .
    J00370 Genomic DNA. Translation: AAA96699.1 .
    BC029814 mRNA. Translation: AAH29814.1 .
    CCDSi CCDS26059.1.
    PIRi A01343. TVMSF.
    RefSeqi NP_034364.1. NM_010234.2.
    UniGenei Mm.246513.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2WT7 X-ray 2.30 A 138-200 [» ]
    ProteinModelPortali P01101.
    SMRi P01101. Positions 138-200.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 199726. 21 interactions.
    DIPi DIP-1066N.
    IntActi P01101. 2 interactions.
    MINTi MINT-1500015.

    PTM databases

    PhosphoSitei P01101.

    Proteomic databases

    PRIDEi P01101.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000021674 ; ENSMUSP00000021674 ; ENSMUSG00000021250 .
    GeneIDi 14281.
    KEGGi mmu:14281.
    UCSCi uc007oha.2. mouse.

    Organism-specific databases

    CTDi 2353.
    MGIi MGI:95574. Fos.

    Phylogenomic databases

    eggNOGi NOG258795.
    GeneTreei ENSGT00730000110541.
    HOGENOMi HOG000234334.
    HOVERGENi HBG005743.
    InParanoidi P01101.
    KOi K04379.
    OMAi TPTCTTY.
    OrthoDBi EOG7VTDN9.
    PhylomeDBi P01101.
    TreeFami TF326301.

    Enzyme and pathway databases

    Reactomei REACT_188530. FCERI mediated MAPK activation.
    REACT_188970. Oxidative Stress Induced Senescence.
    REACT_204811. Activation of the AP-1 family of transcription factors.

    Miscellaneous databases

    NextBioi 285657.
    PROi P01101.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P01101.
    Bgeei P01101.
    CleanExi MM_FOS.
    Genevestigatori P01101.

    Family and domain databases

    InterProi IPR004827. bZIP.
    IPR000837. Leuzip_Fos.
    [Graphical view ]
    Pfami PF00170. bZIP_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00042. LEUZIPPRFOS.
    SMARTi SM00338. BRLZ. 1 hit.
    [Graphical view ]
    PROSITEi PS50217. BZIP. 1 hit.
    PS00036. BZIP_BASIC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Analysis of FBJ-MuSV provirus and c-fos (mouse) gene reveals that viral and cellular fos gene products have different carboxy termini."
      van Beveren C., van Straaten F., Curran T., Mueller R., Verma I.M.
      Cell 32:1241-1255(1983) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Removal of a 67-base-pair sequence in the noncoding region of protooncogene fos converts it to a transforming gene."
      Meijlink F., Curran T., Miller A.D., Verma I.M.
      Proc. Natl. Acad. Sci. U.S.A. 82:4987-4991(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "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].
      Strain: FVB/N.
      Tissue: Mammary gland.
    4. "Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ."
      Mittelstadt P.R., Ashwell J.D.
      J. Biol. Chem. 276:29603-29610(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DSIPI.
    5. "Molecular interpretation of ERK signal duration by immediate early gene products."
      Murphy L.O., Smith S., Chen R.H., Fingar D.C., Blenis J.
      Nat. Cell Biol. 4:556-564(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-325; THR-331; SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF THR-325; THR-331; PHE-343; TYR-345; SER-362 AND SER-374.
    6. "Phosphorylation of the carboxyl-terminal transactivation domain of c-Fos by extracellular signal-regulated kinase mediates the transcriptional activation of AP-1 and cellular transformation induced by platelet-derived growth factor."
      Monje P., Marinissen M.J., Gutkind J.S.
      Mol. Cell. Biol. 23:7030-7043(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-232; THR-325; THR-331; SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF THR-232; THR-325; THR-331 AND SER-374.
    7. Cited for: PHOSPHORYLATION AT SER-362, FUNCTION.
    8. "c-Fos activates and physically interacts with specific enzymes of the pathway of synthesis of polyphosphoinositides."
      Alfonso Pecchio A.R., Cardozo Gizzi A.M., Renner M.L., Molina-Calavita M., Caputto B.L.
      Mol. Biol. Cell 22:4716-4725(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    9. "The kinase c-Src and the phosphatase TC45 coordinately regulate c-Fos tyrosine phosphorylation and c-Fos phospholipid synthesis activation capacity."
      Ferrero G.O., Velazquez F.N., Caputto B.L.
      Oncogene 31:3381-3391(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CDS1 AND PI4K2A, TYROSINE PHOSPHORYLATION BY SRC, MUTAGENESIS OF LYS-139; ARG-144 AND ARG-146.

    Entry informationi

    Entry nameiFOS_MOUSE
    AccessioniPrimary (citable) accession number: P01101
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 21, 1986
    Last modified: October 1, 2014
    This is version 129 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

    3D-structure, Complete proteome, Reference proteome

    Documents

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

    External Data

    Dasty 3