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Protein

Proto-oncogene c-Fos

Gene

Fos

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionDNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-2559580 Oxidative Stress Induced Senescence
R-MMU-2871796 FCERI mediated MAPK activation
R-MMU-450341 Activation of the AP-1 family of transcription factors
R-MMU-9018519 Estrogen-dependent gene expression

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:95574 Fos

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi139K → N: No effect on activation of phospholipid synthesis. 1 Publication1
Mutagenesisi144R → N: No effect on activation of phospholipid synthesis, nor on CDS1-binding. 1 Publication1
Mutagenesisi146R → N: Complete loss of activation of phospholipid synthesis. No effect on CDS1-binding. 1 Publication1
Mutagenesisi232T → 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 Publication1
Mutagenesisi325T → 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 Publications1
Mutagenesisi331T → 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 Publications1
Mutagenesisi343F → A: Reduced phosphorylation by ERK. Reduced AP1 activity by 65%. 1 Publication1
Mutagenesisi345Y → A: Reduced phosphorylation by ERK. 1 Publication1
Mutagenesisi362S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-374. 1 Publication1
Mutagenesisi362S → E: Increased enhancement of EGF- and RSK-mediated tranformation; when associated with E-374. 1 Publication1
Mutagenesisi374S → 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 Publications1
Mutagenesisi374S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-362. 2 Publications1
Mutagenesisi374S → E: Enhanced EGF- and RSK-mediated tranformation; when associated with E-362. 2 Publications1

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000764671 – 380Proto-oncogene c-FosAdd BLAST380

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10Phosphotyrosine; by SRCBy similarity1
Modified residuei30Phosphotyrosine; by SRCBy similarity1
Cross-linki113Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki128Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei232Phosphothreonine1 Publication1
Cross-linki265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei325Phosphothreonine; by MAPK1 and MAPK32 Publications1
Modified residuei331Phosphothreonine; by MAPK1 and MAPK32 Publications1
Modified residuei362Phosphoserine; by MAPK1, MAPK3 and RPS6KA33 Publications1
Modified residuei374Phosphoserine; by MAPK1 and MAPK32 Publications1

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

MaxQBiP01101
PaxDbiP01101
PRIDEiP01101

PTM databases

iPTMnetiP01101
PhosphoSitePlusiP01101

Expressioni

Gene expression databases

BgeeiENSMUSG00000021250
CleanExiMM_FOS
GenevisibleiP01101 MM

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199726, 20 interactors
ComplexPortaliCPX-610 AP-1 transcription factor complex FOS-JUN-NFATC2
CPX-611 AP-1 transcription factor complex FOS-JUN
DIPiDIP-1066N
ELMiP01101
IntActiP01101, 4 interactors
MINTiP01101
STRINGi10090.ENSMUSP00000021674

Structurei

Secondary structure

1380
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi139 – 199Combined sources61

3D structure databases

ProteinModelPortaliP01101
SMRiP01101
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini137 – 200bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni139 – 159Basic motif; required for the activation of phospholipid synthesis, but not for CDS1-bindingAdd BLAST21
Regioni165 – 193Leucine-zipperPROSITE-ProRule annotationAdd BLAST29

Sequence similaritiesi

Belongs to the bZIP family. Fos subfamily.Curated

Phylogenomic databases

eggNOGiKOG1414 Eukaryota
ENOG4111CH5 LUCA
GeneTreeiENSGT00730000110541
HOGENOMiHOG000234334
HOVERGENiHBG005743
InParanoidiP01101
KOiK04379
OMAiHRPACKM
OrthoDBiEOG091G0GGW
PhylomeDBiP01101
TreeFamiTF326301

Family and domain databases

InterProiView protein in InterPro
IPR000837 AP-1
IPR004827 bZIP
IPR029816 c-Fos/v-Fos
PANTHERiPTHR23351 PTHR23351, 1 hit
PTHR23351:SF4 PTHR23351:SF4, 1 hit
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
PRINTSiPR00042 LEUZIPPRFOS
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiFOS_MOUSE
AccessioniPrimary (citable) accession number: P01101
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: June 20, 2018
This is version 162 of the entry and version 1 of the sequence. See 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

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