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P01101 (FOS_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
Proto-oncogene c-Fos
Alternative name(s):
Cellular oncogene fos
Gene names
Name:Fos
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length380 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Subunit structure

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. Ref.4 Ref.9

Subcellular location

Nucleus By similarity. 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.

Post-translational modification

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. Ref.5 Ref.6 Ref.7 Ref.9

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.

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. Ref.5 Ref.6 Ref.7 Ref.9

Sequence similarities

Belongs to the bZIP family. Fos subfamily.

Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
   Cellular componentCytoplasm
Endoplasmic reticulum
Nucleus
   DiseaseProto-oncogene
   LigandDNA-binding
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein signal transduction

Inferred from electronic annotation. Source: Ensembl

aging

Inferred from electronic annotation. Source: Ensembl

cellular response to calcium ion

Inferred from direct assay PubMed 19365557. Source: MGI

cellular response to extracellular stimulus

Inferred from mutant phenotype PubMed 9294610. Source: MGI

cellular response to hormone stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to reactive oxygen species

Inferred from electronic annotation. Source: Ensembl

conditioned taste aversion

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from electronic annotation. Source: Ensembl

nervous system development

Inferred from mutant phenotype PubMed 11925568. Source: MGI

positive regulation of osteoclast differentiation

Inferred from direct assay PubMed 23395171. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 9294610. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12220541. Source: MGI

response to cAMP

Inferred from electronic annotation. Source: Ensembl

response to cold

Inferred from electronic annotation. Source: Ensembl

response to corticosterone

Inferred from electronic annotation. Source: Ensembl

response to cytokine

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from direct assay PubMed 9098922. Source: MGI

response to gravity

Inferred from electronic annotation. Source: Ensembl

response to light stimulus

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

response to progesterone

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

skeletal muscle cell differentiation

Inferred from mutant phenotype PubMed 22147266. Source: MGI

sleep

Inferred from electronic annotation. Source: Ensembl

transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from electronic annotation. Source: Ensembl

neuron projection

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 11747369PubMed 7595148. Source: MGI

transcription factor complex

Inferred from direct assay PubMed 12943993. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 12486129. Source: MGI

RNA polymerase II core promoter sequence-specific DNA binding

Inferred from direct assay PubMed 23980096. Source: MGI

double-stranded DNA binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 21565615. Source: IntAct

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12220541. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Esr2O085372EBI-4288185,EBI-2526214

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 380380Proto-oncogene c-Fos
PRO_0000076467

Regions

Domain137 – 20064bZIP
Region139 – 15921Basic motif; required for the activation of phospholipid synthesis, but not for CDS1-binding
Region165 – 19329Leucine-zipper By similarity

Amino acid modifications

Modified residue101Phosphotyrosine; by SRC By similarity
Modified residue301Phosphotyrosine; by SRC By similarity
Modified residue2321Phosphothreonine Ref.6
Modified residue3251Phosphothreonine; by MAPK1 and MAPK3 Ref.5 Ref.6
Modified residue3311Phosphothreonine; by MAPK1 and MAPK3 Ref.5 Ref.6
Modified residue3621Phosphoserine; by MAPK1, MAPK3 and RPS6KA3 Ref.5 Ref.6 Ref.7
Modified residue3741Phosphoserine; by MAPK1 and MAPK3 Ref.5 Ref.6
Cross-link113Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Experimental info

Mutagenesis1391K → N: No effect on activation of phospholipid synthesis. Ref.9
Mutagenesis1441R → N: No effect on activation of phospholipid synthesis, nor on CDS1-binding. Ref.9
Mutagenesis1461R → N: Complete loss of activation of phospholipid synthesis. No effect on CDS1-binding. Ref.9
Mutagenesis2321T → 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. Ref.6
Mutagenesis3251T → 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. Ref.5 Ref.6
Mutagenesis3311T → 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. Ref.5 Ref.6
Mutagenesis3431F → A: Reduced phosphorylation by ERK. Reduced AP1 activity by 65%. Ref.5
Mutagenesis3451Y → A: Reduced phosphorylation by ERK. Ref.5
Mutagenesis3621S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-374. Ref.5
Mutagenesis3621S → E: Increased enhancement of EGF- and RSK-mediated tranformation; when associated with E-374. Ref.5
Mutagenesis3741S → 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. Ref.5 Ref.6
Mutagenesis3741S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-362. Ref.5 Ref.6
Mutagenesis3741S → E: Enhanced EGF- and RSK-mediated tranformation; when associated with E-362. Ref.5 Ref.6

Secondary structure

... 380
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01101 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 475966265952B624

FASTA38040,838
        10         20         30         40         50         60 
MMFSGFNADY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNTQDFC ADLSVSSANF 

        70         80         90        100        110        120 
IPTVTAISTS PDLQWLVQPT LVSSVAPSQT RAPHPYGLPT QSAGAYARAG MVKTVSGGRA 

       130        140        150        160        170        180 
QSIGRRGKVE QLSPEEEEKR RIRRERNKMA AAKCRNRRRE LTDTLQAETD QLEDEKSALQ 

       190        200        210        220        230        240 
TEIANLLKEK EKLEFILAAH RPACKIPDDL GFPEEMSVAS LDLTGGLPEA STPESEEAFT 

       250        260        270        280        290        300 
LPLLNDPEPK PSLEPVKSIS NVELKAEPFD DFLFPASSRP SGSETSRSVP DVDLSGSFYA 

       310        320        330        340        350        360 
ADWEPLHSNS LGMGPMVTEL EPLCTPVVTC TPGCTTYTSS FVFTYPEADS FPSCAAAHRK 

       370        380 
GSSSNEPSSD SLSSPTLLAL 

« Hide

References

« Hide 'large scale' references
[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]"Essential role of RSK2 in c-Fos-dependent osteosarcoma development."
David J.-P., Mehic D., Bakiri L., Schilling A.F., Mandic V., Priemel M., Idarraga M.H., Reschke M.O., Hoffmann O., Amling M., Wagner E.F.
J. Clin. Invest. 115:664-672(2005) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
V00727 Genomic DNA. Translation: CAA24105.1.
J00370 Genomic DNA. Translation: AAA96699.1.
BC029814 mRNA. Translation: AAH29814.1.
CCDSCCDS26059.1.
PIRTVMSF. A01343.
RefSeqNP_034364.1. NM_010234.2.
UniGeneMm.246513.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WT7X-ray2.30A138-200[»]
ProteinModelPortalP01101.
SMRP01101. Positions 138-200.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199726. 21 interactions.
DIPDIP-1066N.
IntActP01101. 2 interactions.
MINTMINT-1500015.

PTM databases

PhosphoSiteP01101.

Proteomic databases

PRIDEP01101.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000021674; ENSMUSP00000021674; ENSMUSG00000021250.
GeneID14281.
KEGGmmu:14281.
UCSCuc007oha.2. mouse.

Organism-specific databases

CTD2353.
MGIMGI:95574. Fos.

Phylogenomic databases

eggNOGNOG258795.
GeneTreeENSGT00730000110541.
HOGENOMHOG000234334.
HOVERGENHBG005743.
InParanoidP01101.
KOK04379.
OMATPTCTTY.
OrthoDBEOG7VTDN9.
PhylomeDBP01101.
TreeFamTF326301.

Gene expression databases

ArrayExpressP01101.
BgeeP01101.
CleanExMM_FOS.
GenevestigatorP01101.

Family and domain databases

InterProIPR004827. bZIP.
IPR000837. Leuzip_Fos.
[Graphical view]
PfamPF00170. bZIP_1. 1 hit.
[Graphical view]
PRINTSPR00042. LEUZIPPRFOS.
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio285657.
PROP01101.
SOURCESearch...

Entry information

Entry nameFOS_MOUSE
AccessionPrimary (citable) accession number: P01101
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 9, 2014
This is version 127 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

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