Skip Header

Contribute Send feedback
Read comments (0) or add your own

P01100 (FOS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified August 10, 2010. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
Customize displayNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

Names and origin

Protein namesRecommended name:
Proto-oncogene c-Fos
Alternative name(s):
Cellular oncogene fos
G0/G1 switch regulatory protein 7
Gene names
Name:FOS
Synonyms:G0S7
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length380 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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. 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. Ref.9 Ref.10

Subunit structure

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

Subcellular location

Nucleus Ref.10.

Post-translational modification

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. Ref.9

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. Ref.10 Ref.12

Sequence similarities

Belongs to the bZIP family. Fos subfamily.

Contains 1 bZIP domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 380380Proto-oncogene c-Fos
PRO_0000076465

Regions

Domain165 – 19329Leucine-zipper
DNA binding139 – 16022Basic motif Ref.8

Amino acid modifications

Modified residue2321Phosphothreonine By similarity
Modified residue3251Phosphothreonine By similarity
Modified residue3311Phosphothreonine By similarity
Modified residue3621Phosphoserine; by MAPK and RPS6KA3 Ref.9
Modified residue3741Phosphoserine; by MAPK Ref.9
Cross-link113Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.11
Cross-link265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Experimental info

Mutagenesis1281K → R: No change in sumoylation. Ref.10
Mutagenesis1921K → R: No change in sumoylation. Ref.10
Mutagenesis2321T → D: Decreased sumoylation levels.
Mutagenesis2651K → R: Abolishes sumoylation. No change in nuclear location nor on protein stability. Increased AP1 transactivation activity when heterodimerized with cJUN. Ref.10
Mutagenesis3251T → D: No change in sumoylation levels. Ref.10
Mutagenesis3311T → D: No change in sumoylation levels. Ref.10
Mutagenesis3621S → A: Loss of protein stability. Reduced MOS/MAPK-mediated transforming ability; when associated with A-374. Ref.9 Ref.10
Mutagenesis3621S → D: Increased protein stability. Increased MOS/MAPK-mediated transforming ability and no change in sumoylation levels; when associated with D-374. Ref.9 Ref.10
Mutagenesis3741S → A: No change in sumoylation levels. Loss of protein stability. Reduced MOS/MAPK-mediated transforming ability; when associated with A-362. Ref.9 Ref.10
Mutagenesis3741S → D: Increased protein stability. Increased MOS/MAPK-mediated transforming ability and no change in sumoylation levels; when associated with D-362. Ref.9 Ref.10
Sequence conflict133 – 14412SPEEE…RRIRR → ISRRRREKENPK Ref.6

Secondary structure

1 ..... 380
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01100-1 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 9E3B2969347C90C8

FASTA38040,695
        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

« Hide

References

« Hide 'large scale' references
[1]"Complete nucleotide sequence of a human c-onc gene: deduced amino acid sequence of the human c-fos protein."
van Straaten F., Mueller R., Curran T., Van Beveren C., Verma I.M.
Proc. Natl. Acad. Sci. U.S.A. 80:3183-3187(1983) [PubMed: 6574479] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]NIEHS SNPs program
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The DNA sequence and analysis of human chromosome 14."
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. expand/collapse author list , 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.
Nature 421:601-607(2003) [PubMed: 12508121] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[5]"Retrovirus-mediated gene transfer of a human c-fos cDNA into mouse bone marrow stromal cells."
Roux P., Verrier B., Klein B., Niccolino M., Marty L., Alexandre C., Piechaczyk M.
Oncogene 6:2155-2160(1991) [PubMed: 1658710] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-6.
[6]"Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers."
Hai T., Liu F., Coukos W.J., Green M.R.
Genes Dev. 3:2083-2090(1989) [PubMed: 2516827] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 133-200.
[7]Erratum
Hai T., Liu F., Coukos W.J., Green M.R.
Genes Dev. 4:682-682(1990)
[8]"The basic region of Fos mediates specific DNA binding."
Nakabeppu Y., Nathans D.
EMBO J. 8:3833-3841(1989) [PubMed: 2511004] [Abstract]
Cited for: DNA-BINDING.
[9]"The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells."
Okazaki K., Sagata N.
EMBO J. 14:5048-5059(1995) [PubMed: 7588633] [Abstract]
Cited for: PHOSPHORYLATION AT SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF SER-362 AND SER-374.
[10]"Down-regulation of c-Fos/c-Jun AP-1 dimer activity by sumoylation."
Bossis G., Malnou C.E., Farras R., Andermarcher E., Hipskind R., Rodriguez M., Schmidt D., Muller S., Jariel-Encontre I., Piechaczyk M.
Mol. Cell. Biol. 25:6964-6979(2005) [PubMed: 16055710] [Abstract]
Cited for: SUMOYLATION AT LYS-265, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF LYS-128; LYS-192; LYS-265; THR-325; THR-331; SER-362 AND SER-374.
[11]"The proteomic reactor facilitates the analysis of affinity-purified proteins by mass spectrometry: application for identifying ubiquitinated proteins in human cells."
Vasilescu J., Zweitzig D.R., Denis N.J., Smith J.C., Ethier M., Haines D.S., Figeys D.
J. Proteome Res. 6:298-305(2007) [PubMed: 17203973] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-113, MASS SPECTROMETRY.
Tissue: Lung adenocarcinoma.
[12]"Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation."
Jakobs A., Himstedt F., Funk M., Korn B., Gaestel M., Niedenthal R.
Nucleic Acids Res. 35:E109-E109(2007) [PubMed: 17709345] [Abstract]
Cited for: SUMOYLATION.
[13]"Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA."
Glover J.N., Harrison S.C.
Nature 373:257-261(1995) [PubMed: 7816143] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 139-198 OF COMPLEX WITH JUN.
+Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		V01512 Genomic DNA. Translation: CAA24756.1.
K00650 Genomic DNA. Translation: AAA52471.1.
AY212879 Genomic DNA. Translation: AAO21129.1.
AF111167 Genomic DNA. Translation: AAC98315.1.
BC004490 mRNA. Translation: AAH04490.1.
S65138 mRNA. Translation: AAB20306.1.
IPIIPI00033008.
PIRTVHUF1. A01342.
E34223.
RefSeqNP_005243.1.
UniGeneHs.25647.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A02X-ray2.70F139-193[»]
1FOSX-ray3.05E/G139-200[»]
1S9KX-ray3.10D140-192[»]
ProteinModelPortalP01100.
DisProtDP00078.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-1047N.
IntActP01100. 95 interactions.
MINTMINT-105814.
STRINGP01100.

PTM databases

PhosphoSiteP01100.

Proteomic databases

PRIDEP01100.

Genome annotation databases

EnsemblENST00000303562; ENSP00000306245; ENSG00000170345; Homo sapiens. [Genome view]
GeneID2353.
KEGGhsa:2353.
UCSCuc001xrn.1. human.

Organism-specific databases

CTD2353.
GeneCardsGC14P075745.
H-InvDBHIX0011826.
HGNCHGNC:3796. FOS.
HPAHPA018531.
MIM164810. gene.
PharmGKBPA134953249.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG06597.
HOGENOMHBG714812.
HOVERGENHBG005743.
InParanoidP01100.
OMADWEPLHG.
OrthoDBEOG91RSDG.
PhylomeDBP01100.

Enzyme and pathway databases

Pathway_Interaction_DBbcr_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.
ReactomeREACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpressP01100.
BgeeP01100.
CleanExHS_FOS.
GenevestigatorP01100.
GermOnlineENSG00000170345. Homo sapiens.

Family and domain databases

InterProIPR011616. bZIP_1.
IPR000837. Leuzip_Fos.
IPR004827. TF_bZIP.
[Graphical view]
PfamPF00170. bZIP_1. 1 hit.
[Graphical view]
PRINTSPR00042. LEUZIPPRFOS.
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio9543.
SOURCESearch...

Entry information

Entry nameFOS_HUMAN
AccessionPrimary (citable) accession number: P01100
Secondary accession number(s): P18849
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: August 10, 2010
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

Relevant documents

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents