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Protein

Proto-oncogene c-Fos

Gene

FOS

Organism
Homo sapiens (Human)
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. 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

Keywordsi

Molecular functionDNA-binding

Enzyme and pathway databases

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-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes
R-HSA-9018519 Estrogen-dependent gene expression
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

EuPathDBiHostDB:ENSG00000170345.9
HGNCiHGNC:3796 FOS
MIMi164810 gene
neXtProtiNX_P01100

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
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-linki113Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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
ProteomicsDBi51317

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 Expressed in 237 organ(s), highest expression level in mucosa of stomach
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108636, 135 interactors
ComplexPortaliCPX-480 AP-1 transcription factor complex FOS-JUN-NFATC2
CPX-486 AP-1 transcription factor complex FOS-JUN
CORUMiP01100
DIPiDIP-1047N
ELMiP01100
IntActiP01100, 143 interactors
MINTiP01100
STRINGi9606.ENSP00000306245

Chemistry databases

BindingDBiP01100

Structurei

Secondary structure

1380
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

eggNOGiKOG1414 Eukaryota
ENOG4111CH5 LUCA
GeneTreeiENSGT00730000110541
HOGENOMiHOG000234334
HOVERGENiHBG005743
InParanoidiP01100
KOiK04379
OMAiHRPACKM
OrthoDBiEOG091G0GGW
PhylomeDBiP01100
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

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3V2V7G3V2V7_HUMAN
Proto-oncogene c-Fos
FOS
232Annotation score:
G3V5J9G3V5J9_HUMAN
Proto-oncogene c-Fos
FOS
176Annotation score:
G3V5N7G3V5N7_HUMAN
Proto-oncogene c-Fos
FOS
142Annotation score:
H0YJM3H0YJM3_HUMAN
Proto-oncogene c-Fos
FOS
83Annotation score:
G3V289G3V289_HUMAN
Proto-oncogene c-Fos
FOS
170Annotation score:
G3V5N9G3V5N9_HUMAN
Proto-oncogene c-Fos
FOS
137Annotation score:

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

Similar proteinsi

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, 135 interactors
ComplexPortaliCPX-480 AP-1 transcription factor complex FOS-JUN-NFATC2
CPX-486 AP-1 transcription factor complex FOS-JUN
CORUMiP01100
DIPiDIP-1047N
ELMiP01100
IntActiP01100, 143 interactors
MINTiP01100
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
ProteomicsDBi51317

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
EuPathDBiHostDB:ENSG00000170345.9
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
OMAiHRPACKM
OrthoDBiEOG091G0GGW
PhylomeDBiP01100
TreeFamiTF326301

Enzyme and pathway databases

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-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiP01100
SIGNORiP01100

Miscellaneous databases

ChiTaRSiFOS human
EvolutionaryTraceiP01100
GeneWikiiC-Fos
GenomeRNAii2353
PROiPR:P01100
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170345 Expressed in 237 organ(s), highest expression level in mucosa of stomach
CleanExiHS_FOS
ExpressionAtlasiP01100 baseline and differential
GenevisibleiP01100 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiFOS_HUMAN
AccessioniPrimary (citable) accession number: P01100
Secondary accession number(s): A8K4E2, B4DQ65, P18849
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 10, 2018
This is version 216 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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