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Protein

Proto-oncogene c-Fos

Gene

FOS

Organism
Homo sapiens (Human)
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. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. 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.5 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170345-MONOMER.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2871796. FCERI mediated MAPK activation.
R-HSA-450341. Activation of the AP-1 family of transcription factors.
R-HSA-6796648. TP53 Regulates Transcription of DNA Repair Genes.
SignaLinkiP01100.
SIGNORiP01100.

Names & Taxonomyi

Protein namesi
Recommended name:
Proto-oncogene c-Fos
Alternative name(s):
Cellular oncogene fos
G0/G1 switch regulatory protein 7
Gene namesi
Name:FOS
Synonyms:G0S7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:3796. FOS.

Subcellular locationi

  • Nucleus
  • Endoplasmic reticulum
  • Cytoplasmcytosol

  • 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.

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10Y → E: Loss of activation of phospholipid synthesis; when associated with E-30. 2 Publications1
Mutagenesisi10Y → F: Overall loss of Tyr-phosphorylation, including that of Y-30 phosphorylation. Localizes to the endoplasmic reticulum in quiescent cells. Activates phospholipid synthesis in growing cells. 2 Publications1
Mutagenesisi30Y → E: Loss of activation of phospholipid synthesis; when associated with E-10. 2 Publications1
Mutagenesisi30Y → F: Overall loss of Tyr-phosphorylation, including that of Y-10 phosphorylation. Localizes to the endoplasmic reticulum in quiescent cells. Activates phospholipid synthesis in growing cells. 2 Publications1
Mutagenesisi106Y → F: No effect on Tyr-phosphorylation. Loss of endoplasmic reticulum localization in quiescent cells. 1 Publication1
Mutagenesisi128K → R: No change in sumoylation. 1 Publication1
Mutagenesisi192K → R: No change in sumoylation. 1 Publication1
Mutagenesisi232T → D: Decreased sumoylation levels. 1
Mutagenesisi265K → R: Abolishes sumoylation. No change in nuclear location nor on protein stability. Increased AP1 transactivation activity when heterodimerized with cJUN. 1 Publication1
Mutagenesisi325T → D: No change in sumoylation levels. 1 Publication1
Mutagenesisi331T → D: No change in sumoylation levels. 1 Publication1
Mutagenesisi337Y → F: No effect on Tyr-phosphorylation. Loss of endoplasmic reticulum localization in quiescent cells. 1 Publication1
Mutagenesisi362S → A: Loss of protein stability. Reduced MOS/MAPK-mediated transforming ability; when associated with A-374. 2 Publications1
Mutagenesisi362S → D: Increased protein stability. Increased MOS/MAPK-mediated transforming ability and no change in sumoylation levels; when associated with D-374. 2 Publications1
Mutagenesisi374S → A: No change in sumoylation levels. Loss of protein stability. Reduced MOS/MAPK-mediated transforming ability; when associated with A-362. 2 Publications1
Mutagenesisi374S → D: Increased protein stability. Increased MOS/MAPK-mediated transforming ability and no change in sumoylation levels; when associated with D-362. 2 Publications1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi2353.
OpenTargetsiENSG00000170345.
Orphaneti528. Berardinelli-Seip congenital lipodystrophy.
PharmGKBiPA28212.

Chemistry databases

ChEMBLiCHEMBL2111421.
DrugBankiDB08813. Nadroparin.
DB00852. Pseudoephedrine.

Polymorphism and mutation databases

BioMutaiFOS.
DMDMi120470.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000764651 – 380Proto-oncogene c-FosAdd BLAST380

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10Phosphotyrosine; by SRC2 Publications1
Modified residuei30Phosphotyrosine; by SRC2 Publications1
Cross-linki128Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei232PhosphothreonineBy similarity1
Cross-linki265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei325Phosphothreonine; by MAPK1 and MAPK31 Publication1
Modified residuei331Phosphothreonine; by MAPK1 and MAPK31 Publication1
Modified residuei362Phosphoserine; by MAPK1, MAPK3 and RPS6KA31 Publication1
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-232.2 Publications
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.2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP01100.
PaxDbiP01100.
PeptideAtlasiP01100.
PRIDEiP01100.

PTM databases

iPTMnetiP01100.
PhosphoSitePlusiP01100.

Expressioni

Developmental stagei

Expressed at very low levels in quiescent cells. When cells are stimulated to reenter growth, they undergo 2 waves of expression, the first one peaks 7.5 minutes following FBS induction. At this stage, the protein is localized endoplasmic reticulum. The second wave of expression occurs at about 20 minutes after induction and peaks at 1 hour. At this stage, the protein becomes nuclear.1 Publication

Gene expression databases

BgeeiENSG00000170345.
CleanExiHS_FOS.
ExpressionAtlasiP01100. baseline and differential.
GenevisibleiP01100. HS.

Organism-specific databases

HPAiHPA018531.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
APPP050673EBI-852851,EBI-77613
ATF2P153367EBI-852851,EBI-1170906
ATF4P188483EBI-852851,EBI-492498
ATF7P175444EBI-852851,EBI-765623
CLUP109092EBI-852851,EBI-1104674
COPS4Q9BT782EBI-852851,EBI-742413
JUNP0541232EBI-852851,EBI-852823
JUNBP172758EBI-852851,EBI-748062
JUNDP175359EBI-852851,EBI-2682803
MazP566712EBI-852851,EBI-1809712From a different organism.
PPP1R12AO149742EBI-852851,EBI-351726
STAT1P422246EBI-852851,EBI-1057697
ZNF133P527364EBI-852851,EBI-2687350

GO - Molecular functioni

  • R-SMAD binding Source: BHF-UCL
  • transcription factor binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi108636. 131 interactors.
DIPiDIP-1047N.
IntActiP01100. 135 interactors.
MINTiMINT-105814.
STRINGi9606.ENSP00000306245.

Chemistry databases

BindingDBiP01100.

Structurei

Secondary structure

1380
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi141 – 191Combined sources51

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A02X-ray2.70F138-193[»]
1FOSX-ray3.05E/G139-200[»]
1S9KX-ray3.10D140-192[»]
DisProtiDP00078.
ProteinModelPortaliP01100.
SMRiP01100.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01100.

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
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1414. Eukaryota.
ENOG4111CH5. LUCA.
GeneTreeiENSGT00730000110541.
HOGENOMiHOG000234334.
HOVERGENiHBG005743.
InParanoidiP01100.
KOiK04379.
OMAiDWEPLYT.
OrthoDBiEOG091G0GGW.
PhylomeDBiP01100.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P01100-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MMFSGFNADY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNAQDFC
60 70 80 90 100
TDLAVSSANF IPTVTAISTS PDLQWLVQPA LVSSVAPSQT RAPHPFGVPA
110 120 130 140 150
PSAGAYSRAG VVKTMTGGRA QSIGRRGKVE QLSPEEEEKR RIRRERNKMA
160 170 180 190 200
AAKCRNRRRE LTDTLQAETD QLEDEKSALQ TEIANLLKEK EKLEFILAAH
210 220 230 240 250
RPACKIPDDL GFPEEMSVAS LDLTGGLPEV ATPESEEAFT LPLLNDPEPK
260 270 280 290 300
PSVEPVKSIS SMELKTEPFD DFLFPASSRP SGSETARSVP DMDLSGSFYA
310 320 330 340 350
ADWEPLHSGS LGMGPMATEL EPLCTPVVTC TPSCTAYTSS FVFTYPEADS
360 370 380
FPSCAAAHRK GSSSNEPSSD SLSSPTLLAL
Length:380
Mass (Da):40,695
Last modified:July 21, 1986 - v1
Checksum:i9E3B2969347C90C8
GO
Isoform 2 (identifier: P01100-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-114: Missing.

Note: No experimental confirmation available.
Show »
Length:266
Mass (Da):28,986
Checksum:iC57F8C4E227FB777
GO
Isoform 3 (identifier: P01100-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     132-167: Missing.

Note: No experimental confirmation available.
Show »
Length:344
Mass (Da):36,301
Checksum:i5DD706220BEB00A1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti133 – 144SPEEE…RRIRR → ISRRRREKENPK no nucleotide entry (PubMed:15489334).CuratedAdd BLAST12

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0555601 – 114Missing in isoform 2. 1 PublicationAdd BLAST114
Alternative sequenceiVSP_055561132 – 167Missing in isoform 3. 1 PublicationAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01512 Genomic DNA. Translation: CAA24756.1.
K00650 Genomic DNA. Translation: AAA52471.1.
AY212879 Genomic DNA. Translation: AAO21129.1.
AK097379 mRNA. Translation: BAG53458.1.
AK290907 mRNA. Translation: BAF83596.1.
AK298659 mRNA. Translation: BAG60827.1.
AF111167 Genomic DNA. Translation: AAC98315.1.
CH471061 Genomic DNA. Translation: EAW81229.1.
BC004490 mRNA. Translation: AAH04490.1.
S65138 mRNA. Translation: AAB20306.1.
CCDSiCCDS9841.1. [P01100-1]
PIRiA01342. TVHUF1.
E34223.
RefSeqiNP_005243.1. NM_005252.3. [P01100-1]
UniGeneiHs.25647.

Genome annotation databases

EnsembliENST00000303562; ENSP00000306245; ENSG00000170345. [P01100-1]
ENST00000535987; ENSP00000442268; ENSG00000170345. [P01100-3]
ENST00000555686; ENSP00000452590; ENSG00000170345. [P01100-2]
GeneIDi2353.
KEGGihsa:2353.
UCSCiuc010asi.4. human. [P01100-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01512 Genomic DNA. Translation: CAA24756.1.
K00650 Genomic DNA. Translation: AAA52471.1.
AY212879 Genomic DNA. Translation: AAO21129.1.
AK097379 mRNA. Translation: BAG53458.1.
AK290907 mRNA. Translation: BAF83596.1.
AK298659 mRNA. Translation: BAG60827.1.
AF111167 Genomic DNA. Translation: AAC98315.1.
CH471061 Genomic DNA. Translation: EAW81229.1.
BC004490 mRNA. Translation: AAH04490.1.
S65138 mRNA. Translation: AAB20306.1.
CCDSiCCDS9841.1. [P01100-1]
PIRiA01342. TVHUF1.
E34223.
RefSeqiNP_005243.1. NM_005252.3. [P01100-1]
UniGeneiHs.25647.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A02X-ray2.70F138-193[»]
1FOSX-ray3.05E/G139-200[»]
1S9KX-ray3.10D140-192[»]
DisProtiDP00078.
ProteinModelPortaliP01100.
SMRiP01100.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108636. 131 interactors.
DIPiDIP-1047N.
IntActiP01100. 135 interactors.
MINTiMINT-105814.
STRINGi9606.ENSP00000306245.

Chemistry databases

BindingDBiP01100.
ChEMBLiCHEMBL2111421.
DrugBankiDB08813. Nadroparin.
DB00852. Pseudoephedrine.

PTM databases

iPTMnetiP01100.
PhosphoSitePlusiP01100.

Polymorphism and mutation databases

BioMutaiFOS.
DMDMi120470.

Proteomic databases

EPDiP01100.
PaxDbiP01100.
PeptideAtlasiP01100.
PRIDEiP01100.

Protocols and materials databases

DNASUi2353.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000303562; ENSP00000306245; ENSG00000170345. [P01100-1]
ENST00000535987; ENSP00000442268; ENSG00000170345. [P01100-3]
ENST00000555686; ENSP00000452590; ENSG00000170345. [P01100-2]
GeneIDi2353.
KEGGihsa:2353.
UCSCiuc010asi.4. human. [P01100-1]

Organism-specific databases

CTDi2353.
DisGeNETi2353.
GeneCardsiFOS.
HGNCiHGNC:3796. FOS.
HPAiHPA018531.
MIMi164810. gene.
neXtProtiNX_P01100.
OpenTargetsiENSG00000170345.
Orphaneti528. Berardinelli-Seip congenital lipodystrophy.
PharmGKBiPA28212.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1414. Eukaryota.
ENOG4111CH5. LUCA.
GeneTreeiENSGT00730000110541.
HOGENOMiHOG000234334.
HOVERGENiHBG005743.
InParanoidiP01100.
KOiK04379.
OMAiDWEPLYT.
OrthoDBiEOG091G0GGW.
PhylomeDBiP01100.
TreeFamiTF326301.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170345-MONOMER.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2871796. FCERI mediated MAPK activation.
R-HSA-450341. Activation of the AP-1 family of transcription factors.
R-HSA-6796648. TP53 Regulates Transcription of DNA Repair Genes.
SignaLinkiP01100.
SIGNORiP01100.

Miscellaneous databases

ChiTaRSiFOS. human.
EvolutionaryTraceiP01100.
GeneWikiiC-Fos.
GenomeRNAii2353.
PROiP01100.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170345.
CleanExiHS_FOS.
ExpressionAtlasiP01100. baseline and differential.
GenevisibleiP01100. HS.

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...

Entry informationi

Entry nameiFOS_HUMAN
AccessioniPrimary (citable) accession number: P01100
Secondary accession number(s): A8K4E2, B4DQ65, P18849
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 30, 2016
This is version 197 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.