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Protein

Proto-oncogene c-Fos

Gene

Fos

Organism
Rattus norvegicus (Rat)
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 similarity).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • aging Source: RGD
  • cellular response to calcium ion Source: Ensembl
  • cellular response to extracellular stimulus Source: Ensembl
  • cellular response to hormone stimulus Source: RGD
  • cellular response to reactive oxygen species Source: Ensembl
  • conditioned taste aversion Source: RGD
  • female pregnancy Source: RGD
  • nervous system development Source: Ensembl
  • positive regulation of osteoclast differentiation Source: Ensembl
  • positive regulation of pri-miRNA transcription from RNA polymerase II promoter Source: BHF-UCL
  • response to cAMP Source: RGD
  • response to cold Source: RGD
  • response to corticosterone Source: RGD
  • response to cytokine Source: RGD
  • response to drug Source: RGD
  • response to gravity Source: RGD
  • response to immobilization stress Source: RGD
  • response to light stimulus Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to mechanical stimulus Source: RGD
  • response to muscle stretch Source: Ensembl
  • response to organic cyclic compound Source: RGD
  • response to progesterone Source: RGD
  • response to toxic substance Source: RGD
  • skeletal muscle cell differentiation Source: Ensembl
  • sleep Source: RGD
  • SMAD protein signal transduction Source: Ensembl
  • transcription from RNA polymerase II promoter Source: RGD
  • transforming growth factor beta receptor signaling pathway Source: Ensembl
Complete GO annotation...

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-RNO-2559580. Oxidative Stress Induced Senescence.
R-RNO-2871796. FCERI mediated MAPK activation.
R-RNO-450341. 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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi2626. 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

  • cytosol Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • membrane Source: RGD
  • neuron projection Source: RGD
  • nucleoplasm Source: Ensembl
  • nucleus Source: RGD
  • transcription factor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi232 – 2321T → A: Abolishes HA-RAS-mediated activation. Loss of in vitro ERK2-mediated phosphorylation. No change in sumoylation levels. 1 Publication
Mutagenesisi325 – 3251T → A: Loss of NGF-mediated phosphorylation; when associated with A-331. 1 Publication
Mutagenesisi331 – 3311T → A: Loss of NGF-mediated phosphorylation; when associated with A-325. 1 Publication
Mutagenesisi343 – 3453FTY → ATA: Decreased phosphorylation levels. Reduced NGF-mediated enhanced transactivation. 1 Publication
Mutagenesisi362 – 3621S → A: Some loss of protein stabilization on NGF-treatment; when associated with D-374. 1 Publication
Mutagenesisi362 – 3621S → D: Increased protein stabilization on NGF-treatment, but no increase when treated with MAPK-inhibitor; when associated with D-374. 1 Publication
Mutagenesisi374 – 3741S → A: Greatly reduced protein stabilization on NGF stimulation. 1 Publication
Mutagenesisi374 – 3741S → D: Increased protein stabilization on NGF-treatment, but no increase when treated with MAPK-inhibitor; when associated with D-362. Some loss of protein stablization on NGF-treatment; wnen associated with A-362. 1 Publication

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 380380Proto-oncogene c-FosPRO_0000076469Add
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
Cross-linki128 – 128Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei232 – 2321Phosphothreonine1 Publication
Cross-linki265 – 265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki265 – 265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei325 – 3251Phosphothreonine; by MAPK1 and MAPK31 Publication
Modified residuei331 – 3311Phosphothreonine; by MAPK1 and MAPK31 Publication
Modified residuei362 – 3621Phosphoserine; by MAPK1, MAPK3 and RPS6KA31 Publication
Modified residuei374 – 3741Phosphoserine; by MAPK1 and MAPK31 Publication

Post-translational modificationi

Phosphorylated in the C-terminal upon stimulation by nerve growth factor (NGF) and epidermal growth factor (EGF) (By similarity). 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 similarity2 Publications
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 (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP12841.
PRIDEiP12841.

PTM databases

iPTMnetiP12841.
PhosphoSiteiP12841.

Interactioni

Subunit structurei

Heterodimer; with JUN (By similarity). 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 DSIPI; this interaction inhibits the binding of active AP1 to its target DNA (By similarity). Interacts with MAFB. Interacts with CDS1 and PI4K2A (By similarity).By similarity

GO - Molecular functioni

  • protein heterodimerization activity Source: RGD
  • transcription factor binding Source: RGD

Protein-protein interaction databases

BioGridi260681. 1 interaction.
DIPiDIP-6001N.
IntActiP12841. 1 interaction.
MINTiMINT-220035.
STRINGi10116.ENSRNOP00000010712.

Structurei

3D structure databases

ProteinModelPortaliP12841.
SMRiP12841. Positions 140-192.
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-bindingPROSITE-ProRule annotationAdd
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

eggNOGiKOG1414. Eukaryota.
ENOG4111CH5. LUCA.
GeneTreeiENSGT00730000110541.
HOGENOMiHOG000234334.
HOVERGENiHBG005743.
InParanoidiP12841.
KOiK04379.
OMAiDWEPLYT.
OrthoDBiEOG7VTDN9.
PhylomeDBiP12841.
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.

P12841-1 [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
PSTGAYARAG VVKTMSGGRA QSIGRRGKVE QLSPEEEEKR RIRRERNKMA
160 170 180 190 200
AAKCRNRRRE LTDTLQAETD QLEDEKSALQ TEIANLLKEK EKLEFILAAH
210 220 230 240 250
RPACKIPNDL GFPEEMSVTS LDLTGGLPEA TTPESEEAFT LPLLNDPEPK
260 270 280 290 300
PSLEPVKNIS NMELKAEPFD DFLFPASSRP SGSETARSVP DVDLSGSFYA
310 320 330 340 350
ADWEPLHSSS LGMGPMVTEL EPLCTPVVTC TPSCTTYTSS FVFTYPEADS
360 370 380
FPSCAAAHRK GSSSNEPSSD SLSSPTLLAL
Length:380
Mass (Da):40,927
Last modified:October 1, 1989 - v1
Checksum:iE62D16A88CB2BEE9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06769 mRNA. Translation: CAA29937.1.
DQ089699 Genomic DNA. Translation: AAZ13764.1.
PIRiA28263. TVRTFS.
RefSeqiNP_071533.1. NM_022197.2.
UniGeneiRn.103750.

Genome annotation databases

EnsembliENSRNOT00000010712; ENSRNOP00000010712; ENSRNOG00000008015.
GeneIDi314322.
KEGGirno:314322.
UCSCiRGD:2626. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06769 mRNA. Translation: CAA29937.1.
DQ089699 Genomic DNA. Translation: AAZ13764.1.
PIRiA28263. TVRTFS.
RefSeqiNP_071533.1. NM_022197.2.
UniGeneiRn.103750.

3D structure databases

ProteinModelPortaliP12841.
SMRiP12841. Positions 140-192.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi260681. 1 interaction.
DIPiDIP-6001N.
IntActiP12841. 1 interaction.
MINTiMINT-220035.
STRINGi10116.ENSRNOP00000010712.

PTM databases

iPTMnetiP12841.
PhosphoSiteiP12841.

Proteomic databases

PaxDbiP12841.
PRIDEiP12841.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000010712; ENSRNOP00000010712; ENSRNOG00000008015.
GeneIDi314322.
KEGGirno:314322.
UCSCiRGD:2626. rat.

Organism-specific databases

CTDi2353.
RGDi2626. Fos.

Phylogenomic databases

eggNOGiKOG1414. Eukaryota.
ENOG4111CH5. LUCA.
GeneTreeiENSGT00730000110541.
HOGENOMiHOG000234334.
HOVERGENiHBG005743.
InParanoidiP12841.
KOiK04379.
OMAiDWEPLYT.
OrthoDBiEOG7VTDN9.
PhylomeDBiP12841.
TreeFamiTF326301.

Enzyme and pathway databases

ReactomeiR-RNO-2559580. Oxidative Stress Induced Senescence.
R-RNO-2871796. FCERI mediated MAPK activation.
R-RNO-450341. Activation of the AP-1 family of transcription factors.

Miscellaneous databases

PROiP12841.

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

  1. "Isolation and characterization of the c-fos(rat) cDNA and analysis of post-translational modification in vitro."
    Curran T., Gordon M.B., Rubino K.L., Sambucetti L.C.
    Oncogene 2:79-84(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "cFOS expression in rat."
    Weiler E.
    Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: Sprague-Dawley.
    Tissue: Liver.
  3. "Expression and purification of the leucine zipper and DNA-binding domains of Fos and Jun: both Fos and Jun contact DNA directly."
    Abate C., Luk D., Gentz R., Rauscher F.J. III, Curran T.
    Proc. Natl. Acad. Sci. U.S.A. 87:1032-1036(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: DNA-BINDING.
  4. "Rat maf-related factors: the specificities of DNA binding and heterodimer formation."
    Matsushima-Hibiya Y., Nishi S., Sakai M.
    Biochem. Biophys. Res. Commun. 245:412-418(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAFB.
  5. "Phosphorylation of the c-Fos and c-Jun HOB1 motif stimulates its activation capacity."
    Bannister A.J., Brown H.J., Sutherland J.A., Kouzarides T.
    Nucleic Acids Res. 22:5173-5176(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-232, FUNCTION, MUTAGENESIS OF THR-232.
  6. "Sustained activation of extracellular signal-regulated kinase by nerve growth factor regulates c-fos protein stabilization and transactivation in PC12 cells."
    Pellegrino M.J., Stork P.J.
    J. Neurochem. 99:1480-1493(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-325; THR-331; SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF THR-325; THR-331; 343-PHE--TYR-345; SER-362 AND SER-374.

Entry informationi

Entry nameiFOS_RAT
AccessioniPrimary (citable) accession number: P12841
Secondary accession number(s): Q4FDN1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: July 6, 2016
This is version 141 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. SIMILARITY comments
    Index of protein domains and families

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 one 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.