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UniProtKB/Swiss-Prot entry P01100


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name FOS_HUMAN
Primary accession number P01100
Secondary accession number P18849
Integrated into Swiss-Prot on July 21, 1986
Sequence was last modified on July 21, 1986 (Sequence version 1)
Annotations were last modified on    June 16, 2009 (Entry version 113)
Name and origin of the protein
Protein name Proto-oncogene protein c-fos
Synonyms Cellular oncogene fos
G0/G1 switch regulatory protein 7
Gene name
Name: FOS
Synonyms: G0S7
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1073/pnas.80.11.3183; PubMed=6574479 [NCBI, ExPASy, EBI, Israel, Japan]
van Straaten F., Mueller R., Curran T., Van Beveren C., Verma I.M.;
"Complete nucleotide sequence of a human c-onc gene: deduced amino acid sequence of the human c-fos protein.";
Proc. Natl. Acad. Sci. U.S.A. 80:3183-3187(1983).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 133-200.
PubMed=2516827 [NCBI, ExPASy, EBI, Israel, Japan]
Hai T., Liu F., Coukos W.J., Green M.R.;
"Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers.";
Genes Dev. 3:2083-2090(1989).
[3]
ERRATUM.
Hai T., Liu F., Coukos W.J., Green M.R.;
Genes Dev. 4:682-682(1990).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
NIEHS SNPs program;
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature01348; PubMed=12508121 [NCBI, ExPASy, EBI, Israel, Japan]
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.;
"The DNA sequence and analysis of human chromosome 14.";
Nature 421:601-607(2003).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Pancreas;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 1-6.
PubMed=1658710 [NCBI, ExPASy, EBI, Israel, Japan]
Roux P., Verrier B., Klein B., Niccolino M., Marty L., Alexandre C., Piechaczyk M.;
"Retrovirus-mediated gene transfer of a human c-fos cDNA into mouse bone marrow stromal cells.";
Oncogene 6:2155-2160(1991).
[8]
DNA-BINDING.
PubMed=2511004 [NCBI, ExPASy, EBI, Israel, Japan]
Nakabeppu Y., Nathans D.;
"The basic region of Fos mediates specific DNA binding.";
EMBO J. 8:3833-3841(1989).
[9]
PHOSPHORYLATION AT SER-362 AND SER-374, FUNCTION, AND MUTAGENESIS OF SER-362 AND SER-374.
PubMed=7588633 [NCBI, ExPASy, EBI, Israel, Japan]
Okazaki K., Sagata N.;
"The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells.";
EMBO J. 14:5048-5059(1995).
[10]
SUMOYLATION AT LYS-265, SUBCELLUALR LOCATION, FUNCTION, AND MUTAGENESIS OF LYS-128; LYS-192; LYS-265; THR-325; THR-331; SER-362 AND SER-374.
DOI=10.1128/MCB.25.16.6964-6979.2005; PubMed=16055710 [NCBI, ExPASy, EBI, Israel, Japan]
Bossis G., Malnou C.E., Farras R., Andermarcher E., Hipskind R., Rodriguez M., Schmidt D., Muller S., Jariel-Encontre I., Piechaczyk M.;
"Down-regulation of c-Fos/c-Jun AP-1 dimer activity by sumoylation.";
Mol. Cell. Biol. 25:6964-6979(2005).
[11]
UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-113, AND MASS SPECTROMETRY.
TISSUE=Lung adenocarcinoma;
DOI=10.1021/pr060438j; PubMed=17203973 [NCBI, ExPASy, EBI, Israel, Japan]
Vasilescu J., Zweitzig D.R., Denis N.J., Smith J.C., Ethier M., Haines D.S., Figeys D.;
"The proteomic reactor facilitates the analysis of affinity-purified proteins by mass spectrometry: application for identifying ubiquitinated proteins in human cells.";
J. Proteome Res. 6:298-305(2007).
[12]
SUMOYLATION.
DOI=10.1093/nar/gkm617; PubMed=17709345 [NCBI, ExPASy, EBI, Israel, Japan]
Jakobs A., Himstedt F., Funk M., Korn B., Gaestel M., Niedenthal R.;
"Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation.";
Nucleic Acids Res. 35:E109-E109(2007).
[13]
X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 139-198 OF COMPLEX WITH JUN.
DOI=10.1038/373257a0; PubMed=7816143 [NCBI, ExPASy, EBI, Israel, Japan]
Glover J.N., Harrison S.C.;
"Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA.";
Nature 373:257-261(1995).
Comments
  • FUNCTION: Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, c-fos and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. 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.
  • SUBUNIT: Heterodimer with JUN. Interacts with DSIPI; this interaction inhibits the binding of active AP1 to its target DNA. Interacts with MAFB (By similarity).
  • INTERACTION:
    O60869-1:EDF1; NbExp=1; IntAct=EBI-852851, EBI-781310;
  • SUBCELLULAR LOCATION: Nucleus.
  • PTM: 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).
  • PTM: Constitutively sumoylated by 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.
  • SIMILARITY: Belongs to the bZIP family. Fos subfamily.
  • SIMILARITY: Contains 1 bZIP domain.
  • WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/fos/";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
V01512; CAA24756.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
K00650; AAA52471.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY212879; AAO21129.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF111167; AAC98315.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC004490; AAH04490.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S65138; AAB20306.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00033008; -.
PIR A01342; TVHUF1.
E34223; E34223.
RefSeq NP_005243.1; -.
UniGene Hs.25647
3D structure databases
PDB
1A02; X-ray; 2.70 A; F=139-193.[ExPASy / RCSB / EBI]
1FOS; X-ray; 3.05 A; E/G=139-200.[ExPASy / RCSB / EBI]
1S9K; X-ray; 3.10 A; D=140-192.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1A02; -.
1FOS; -.
1S9K; -.
DisProt DP00078; -.
ModBase P01100.
Protein-protein interaction databases
DIP DIP:1047N; -.
IntAct P01100; 1.
PTM databases
PhosphoSite P01100; -.
Enzyme and pathway databases
Pathway_Interaction_DB bcr_5pathway; BCR signaling pathway.
nfat_tfpathway; Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
tcrcalciumpathway; Calcium signaling in the CD4+ TCR pathway.
cd8tcrdownstreampathway; Downstream signaling in naive CD8+ T cells.
endothelinpathway; Endothelins.
fcer1pathway; Fc-epsilon receptor I signaling in mast cells.
fgf_pathway; FGF signaling pathway.
hnf3apathway; FOXA1 transcription factor network.
foxm1pathway; FOXM1 transcription factor network.
hif1_tfpathway; HIF-1-alpha transcription factor network.
il12_stat4pathway; IL12 signaling mediated by STAT4.
il12_2pathway; IL12-mediated signaling events.
il2_1pathway; IL2-mediated signaling events.
il6_7pathway; IL6-mediated signaling events.
lysophospholipid_pathway; LPA receptor mediated events.
avb3_opn_pathway; Osteopontin-mediated events.
pdgfrapathway; PDGFR-alpha signaling pathway.
ps1pathway; Presenilin action in Notch and Wnt signaling.
tcrraspathway; Ras signaling in the CD4+ TCR pathway.
smad2_3nuclearpathway; Regulation of nuclear SMAD2/3 signaling.
telomerasepathway; Regulation of Telomerase.
s1p_s1p2_pathway; S1P2 pathway.
met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
mapktrkpathway; Trk receptor signaling mediated by the MAPK pathway.
Organism-specific databases
GeneCards GC14P074815; -.
H-InvDB HIX0011826; -.
HGNC HGNC:3796; FOS.
GenAtlas FOS.
HPA CAB000461; -.
MIM 164810; gene. [NCBI / EBI]
PharmGKB PA134953249; -.
Gene expression databases
ArrayExpress P01100; -.
Bgee P01100; -.
CleanEx HS_FOS; -.
GermOnline ENSG00000170345; Homo sapiens.
Ontologies
GO
GO:0010843; Molecular function: promoter binding (inferred from direct assay from UniProtKB).
GO:0070412; Molecular function: R-SMAD binding (inferred from physical interaction from UniProtKB).
GO:0003704; Molecular function: specific RNA polymerase II transcription factor activity (traceable author statement from ProtInc).
GO:0003700; Molecular function: transcription factor activity (inferred from direct assay from UniProtKB).
GO:0034614; Biological process: cellular response to reactive oxygen species (inferred from direct assay from UniProtKB).
GO:0006306; Biological process: DNA methylation (traceable author statement from ProtInc).
GO:0006954; Biological process: inflammatory response (traceable author statement from ProtInc).
GO:0060395; Biological process: SMAD protein signal transduction (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR011616; bZIP_1.
IPR000837; Leuzip_Fos.
IPR004827; TF_bZIP.
Graphical view of domain structure.
Pfam PF00170; bZIP_1; 1.
Pfam graphical view of domain structure.
PRINTS PR00042; LEUZIPPRFOS.
SMART SM00338; BRLZ; 1.
SMART graphical view of domain structure.
PROSITE PS50217; BZIP; 1.
PS00036; BZIP_BASIC; 1.
PROSITE graphical view of domain structure (profiles).
Genome annotation databases
Ensembl ENSG00000170345; Homo sapiens. [Contig view]
GeneID 2353; -.
KEGG hsa:2353; -.
Phylogenomic databases
HOGENOM P01100; -.
HOVERGEN P01100; -.
OMA P01100; TYTSSFV.
Other
NextBio 9543; -.
SOURCE FOS; Homo sapiens.
ProtoNet P01100.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Proto-oncogene; Ubl conjugation.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   380  380     Proto-oncogene protein c-fos. PRO_0000076465
DOMAIN   165   193  29     Leucine-zipper. 
DNA_BIND   139   160  22     Basic motif. 
MOD_RES   232   232        Phosphothreonine (By similarity). 
MOD_RES   325   325        Phosphothreonine (By similarity). 
MOD_RES   331   331        Phosphothreonine (By similarity). 
MOD_RES   362   362        Phosphoserine; by MAPK and RPS6KA3. 
MOD_RES   374   374        Phosphoserine; by MAPK. 
CROSSLNK   113   113        Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin). 
CROSSLNK   265   265        Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) (By similarity). 
MUTAGEN   128   128        K->R: No change in sumoylation. 
MUTAGEN   192   192        K->R: No change in sumoylation. 
MUTAGEN   232   232        T->D: Decreased sumoylation levels. 
MUTAGEN   265   265        K->R: Abolishes sumoylation. No change in nuclear location nor on protein stability. Increased AP1 transactivation activity when heterodimerized with cJUN. 
MUTAGEN   325   325        T->D: No change in sumoylation levels. 
MUTAGEN   331   331        T->D: No change in sumoylation levels. 
MUTAGEN   362   362        S->A: Loss of protein stability. Reduced MOS/MAPK-mediated transforming ability; when associated with A-374. 
MUTAGEN   362   362        S->D: Increased protein stability. Increased MOS/MAPK-mediated transforming ability and no change in sumoylation levels; when associated with D-374. 
MUTAGEN   374   374        S->A: No change in sumoylation levels. Loss of protein stability. Reduced MOS/MAPK-mediated transforming ability; when associated with A-362. 
MUTAGEN   374   374        S->D: Increased protein stability. Increased MOS/MAPK-mediated transforming ability and no change in sumoylation levels; when associated with D-362. 
CONFLICT   133   144        SPEEEEKRRIRR -> ISRRRREKENPK (in Ref. 2). 
HELIX   141   191  51      
HELIX   193   197  5      
Sequence information
Length: 380 AA [This is the length of the unprocessed precursor] Molecular weight: 40695 Da [This is the MW of the unprocessed precursor] CRC64: 9E3B2969347C90C8 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MMFSGFNADY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNAQDFC TDLAVSSANF 

        70         80         90        100        110        120 
IPTVTAISTS PDLQWLVQPA LVSSVAPSQT RAPHPFGVPA PSAGAYSRAG VVKTMTGGRA 

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

       190        200        210        220        230        240 
TEIANLLKEK EKLEFILAAH RPACKIPDDL GFPEEMSVAS LDLTGGLPEV ATPESEEAFT 

       250        260        270        280        290        300 
LPLLNDPEPK PSVEPVKSIS SMELKTEPFD DFLFPASSRP SGSETARSVP DMDLSGSFYA 

       310        320        330        340        350        360 
ADWEPLHSGS LGMGPMATEL EPLCTPVVTC TPSCTAYTSS FVFTYPEADS FPSCAAAHRK 

       370        380 
GSSSNEPSSD SLSSPTLLAL 

P01100 in FASTA format

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