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Protein

Proto-oncogene c-Fos

Gene

Fos

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. chromatin binding Source: MGI
  2. DNA binding Source: MGI
  3. double-stranded DNA binding Source: Ensembl
  4. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
  6. RNA polymerase II core promoter sequence-specific DNA binding Source: MGI
  7. R-SMAD binding Source: MGI
  8. sequence-specific DNA binding transcription factor activity Source: MGI
  9. transcription factor binding Source: MGI
  10. transcription regulatory region DNA binding 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: MGI
  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, DNA-templated Source: MGI
  11. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  12. regulation of transcription, DNA-templated Source: MGI
  13. response to cAMP Source: Ensembl
  14. response to cold Source: Ensembl
  15. response to corticosterone Source: Ensembl
  16. response to cytokine Source: Ensembl
  17. response to drug Source: MGI
  18. response to gravity Source: Ensembl
  19. response to immobilization stress Source: Ensembl
  20. response to light stimulus Source: Ensembl
  21. response to lipopolysaccharide Source: Ensembl
  22. response to muscle stretch Source: MGI
  23. response to progesterone Source: Ensembl
  24. response to toxic substance Source: Ensembl
  25. skeletal muscle cell differentiation Source: MGI
  26. sleep Source: Ensembl
  27. SMAD protein signal transduction Source: MGI
  28. transforming growth factor beta receptor signaling pathway Source: MGI
Complete GO annotation...

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_305463. Oxidative Stress Induced Senescence.
REACT_314186. FCERI mediated MAPK activation.
REACT_320943. 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 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:95574. Fos.

Subcellular locationi

  1. Nucleus PROSITE-ProRule annotation
  2. Endoplasmic reticulum By similarity
  3. Cytoplasmcytosol By similarity

  4. 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. nucleoplasm Source: MGI
  6. nucleus Source: MGI
  7. transcription factor complex Source: MGI
Complete GO annotation...

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

BgeeiP01101.
CleanExiMM_FOS.
ExpressionAtlasiP01101. baseline and differential.
GenevestigatoriP01101.

Interactioni

Subunit structurei

Heterodimer; with JUN (By similarity). Interacts with MAFB. Component of the SMAD3/SMAD4/JUN/FOS complex required for synergistic 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 – 19961Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
OMAiDWEPLYT.
OrthoDBiEOG7VTDN9.
PhylomeDBiP01101.
TreeFamiTF326301.

Family and domain databases

InterProiIPR000837. AP-1.
IPR004827. bZIP.
IPR029816. c-Fos/v-Fos.
[Graphical view]
PANTHERiPTHR23351. PTHR23351. 1 hit.
PTHR23351:SF4. PTHR23351:SF4. 1 hit.
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

        10         20         30         40         50
MMFSGFNADY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNTQDFC
60 70 80 90 100
ADLSVSSANF IPTVTAISTS PDLQWLVQPT LVSSVAPSQT RAPHPYGLPT
110 120 130 140 150
QSAGAYARAG MVKTVSGGRA QSIGRRGKVE QLSPEEEEKR RIRRERNKMA
160 170 180 190 200
AAKCRNRRRE LTDTLQAETD QLEDEKSALQ TEIANLLKEK EKLEFILAAH
210 220 230 240 250
RPACKIPDDL GFPEEMSVAS LDLTGGLPEA STPESEEAFT LPLLNDPEPK
260 270 280 290 300
PSLEPVKSIS NVELKAEPFD DFLFPASSRP SGSETSRSVP DVDLSGSFYA
310 320 330 340 350
ADWEPLHSNS LGMGPMVTEL EPLCTPVVTC TPGCTTYTSS FVFTYPEADS
360 370 380
FPSCAAAHRK GSSSNEPSSD SLSSPTLLAL
Length:380
Mass (Da):40,838
Last modified:July 21, 1986 - v1
Checksum:i475966265952B624
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiP01101.

Proteomic databases

PRIDEiP01101.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2353.
MGIiMGI:95574. Fos.

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiREACT_305463. Oxidative Stress Induced Senescence.
REACT_314186. FCERI mediated MAPK activation.
REACT_320943. Activation of the AP-1 family of transcription factors.

Miscellaneous databases

ChiTaRSiFos. mouse.
NextBioi285657.
PROiP01101.
SOURCEiSearch...

Gene expression databases

BgeeiP01101.
CleanExiMM_FOS.
ExpressionAtlasiP01101. baseline and differential.
GenevestigatoriP01101.

Family and domain databases

InterProiIPR000837. AP-1.
IPR004827. bZIP.
IPR029816. c-Fos/v-Fos.
[Graphical view]
PANTHERiPTHR23351. PTHR23351. 1 hit.
PTHR23351:SF4. PTHR23351:SF4. 1 hit.
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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: April 29, 2015
This is version 136 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.