P01100 (FOS_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 157.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Proto-oncogene c-Fos Alternative name(s): Cellular oncogene fos G0/G1 switch regulatory protein 7 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 380 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence 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. 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. Ref.9 Ref.10 Ref.12 |
| Subunit structure | Heterodimer; with JUN By similarity. Interacts with MAFB By similarity. Component of the SMAD3/SMAD4/JUN/FOS complex required for syngernistic 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. Ref.6 Ref.10 |
| Subcellular location | |
| 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 Ref.11 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. Ref.12 Ref.14 |
| Sequence similarities | Belongs to the bZIP family. Fos subfamily. Contains 1 bZIP (basic-leucine zipper) domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| APP | P05067 | 3 | EBI-852851,EBI-77613 | |
| ATF2 | P15336 | 4 | EBI-852851,EBI-1170906 | |
| CLU | P10909 | 2 | EBI-852851,EBI-1104674 | |
| COPS4 | Q9BT78 | 2 | EBI-852851,EBI-742413 | |
| JUN | P05412 | 6 | EBI-852851,EBI-852823 | |
| JUND | P17535 | 3 | EBI-852851,EBI-2682803 | |
| ZNF133 | P52736 | 4 | EBI-852851,EBI-2687350 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 380 | 380 | Proto-oncogene c-Fos | PRO_0000076465 | |||||||
Regions | |||||||||||
| Domain | 137 – 200 | 64 | bZIP | ||||||||
| Region | 139 – 159 | 21 | Basic motif By similarity | ||||||||
| Region | 165 – 193 | 29 | Leucine-zipper By similarity | ||||||||
Amino acid modifications | |||||||||||
| Modified residue | 232 | 1 | Phosphothreonine By similarity | ||||||||
| Modified residue | 325 | 1 | Phosphothreonine; by MAPK1 and MAPK3 Ref.11 | ||||||||
| Modified residue | 331 | 1 | Phosphothreonine; by MAPK1 and MAPK3 Ref.11 | ||||||||
| Modified residue | 362 | 1 | Phosphoserine; by MAPK1, MAPK3 and RPS6KA3 Ref.9 | ||||||||
| Modified residue | 374 | 1 | Phosphoserine; by MAPK1 and MAPK3 Ref.9 Ref.11 | ||||||||
| Cross-link | 113 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.13 | |||||||||
| Cross-link | 265 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity | |||||||||
Experimental info | |||||||||||
| Mutagenesis | 128 | 1 | K → R: No change in sumoylation. Ref.12 | ||||||||
| Mutagenesis | 192 | 1 | K → R: No change in sumoylation. Ref.12 | ||||||||
| Mutagenesis | 232 | 1 | T → D: Decreased sumoylation levels. | ||||||||
| Mutagenesis | 265 | 1 | K → R: Abolishes sumoylation. No change in nuclear location nor on protein stability. Increased AP1 transactivation activity when heterodimerized with cJUN. Ref.12 | ||||||||
| Mutagenesis | 325 | 1 | T → D: No change in sumoylation levels. Ref.12 | ||||||||
| Mutagenesis | 331 | 1 | T → D: No change in sumoylation levels. Ref.12 | ||||||||
| Mutagenesis | 362 | 1 | S → A: Loss of protein stability. Reduced MOS/MAPK-mediated transforming ability; when associated with A-374. Ref.9 Ref.12 | ||||||||
| Mutagenesis | 362 | 1 | S → D: Increased protein stability. Increased MOS/MAPK-mediated transforming ability and no change in sumoylation levels; when associated with D-374. Ref.9 Ref.12 | ||||||||
| Mutagenesis | 374 | 1 | S → A: No change in sumoylation levels. Loss of protein stability. Reduced MOS/MAPK-mediated transforming ability; when associated with A-362. Ref.9 Ref.12 | ||||||||
| Mutagenesis | 374 | 1 | S → D: Increased protein stability. Increased MOS/MAPK-mediated transforming ability and no change in sumoylation levels; when associated with D-362. Ref.9 Ref.12 | ||||||||
| Sequence conflict | 133 – 144 | 12 | SPEEE…RRIRR → ISRRRREKENPK no nucleotide entry Ref.6 | ||||||||
Secondary structure | |||||||||||
Helix Strand Turn | |||||||||||
| Helix | 141 – 191 | 51 | |||||||||
Sequences
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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] [Europe PMC] [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. Weissenbach J.Nature 421:601-607(2003) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 133-200, DNA-BINDING, SUBUNIT. |
| [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF SER-362 AND SER-374. |
| [10] | "Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription." Zhang Y., Feng X.H., Derynck R. Nature 394:909-913(1998) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A COMPONENT OF THE SMAD3/SMAD4/JUN/FOS COMPLEX, FUNCTION, INTERACTION WITH SMAD3. |
| [11] | "Molecular interpretation of ERK signal duration by immediate early gene products." Murphy L.O., Smith S., Chen R.H., Fingar D.C., Blenis J. Nat. Cell Biol. 4:556-564(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-325; THR-331 AND SER-374. |
| [12] | "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] [Europe PMC] [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. |
| [13] | "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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-113, MASS SPECTROMETRY. Tissue: Lung adenocarcinoma. |
| [14] | "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] [Europe PMC] [Abstract] Cited for: SUMOYLATION. |
| [15] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell. |
| [16] | "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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 139-198 OF COMPLEX WITH JUN. |
| + | Additional computationally mapped references. |
Web resources
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. | ||||||||||||||||||||||||
| IPI | IPI00033008. | ||||||||||||||||||||||||
| PIR | TVHUF1. A01342. E34223. | ||||||||||||||||||||||||
| RefSeq | NP_005243.1. NM_005252.3. | ||||||||||||||||||||||||
| UniGene | Hs.25647. | ||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||
| PDBe RCSB PDB PDBj |
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| DisProt | DP00078. | ||||||||||||||||||||||||
| ProteinModelPortal | P01100. | ||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||
| DIP | DIP-1047N. | ||||||||||||||||||||||||
| IntAct | P01100. 82 interactions. | ||||||||||||||||||||||||
| MINT | MINT-105814. | ||||||||||||||||||||||||
| STRING | 9606.ENSP00000306245. | ||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||
| PhosphoSite | P01100. | ||||||||||||||||||||||||
Polymorphism databases | |||||||||||||||||||||||||
| DMDM | 120470. | ||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||
| PaxDb | P01100. | ||||||||||||||||||||||||
| PRIDE | P01100. | ||||||||||||||||||||||||
Protocols and materials databases | |||||||||||||||||||||||||
| DNASU | 2353. | ||||||||||||||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||
| Ensembl | ENST00000303562; ENSP00000306245; ENSG00000170345. | ||||||||||||||||||||||||
| GeneID | 2353. | ||||||||||||||||||||||||
| KEGG | hsa:2353. | ||||||||||||||||||||||||
| UCSC | uc001xrn.3. human. | ||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||
| CTD | 2353. | ||||||||||||||||||||||||
| GeneCards | GC14P075745. | ||||||||||||||||||||||||
| HGNC | HGNC:3796. FOS. | ||||||||||||||||||||||||
| HPA | HPA018531. | ||||||||||||||||||||||||
| MIM | 164810. gene. | ||||||||||||||||||||||||
| neXtProt | NX_P01100. | ||||||||||||||||||||||||
| PharmGKB | PA28212. | ||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||
| eggNOG | NOG258795. | ||||||||||||||||||||||||
| HOGENOM | HOG000234334. | ||||||||||||||||||||||||
| HOVERGEN | HBG005743. | ||||||||||||||||||||||||
| InParanoid | P01100. | ||||||||||||||||||||||||
| KO | K04379. | ||||||||||||||||||||||||
| OMA | YYPSPAG. | ||||||||||||||||||||||||
| OrthoDB | EOG42BX9D. | ||||||||||||||||||||||||
| PhylomeDB | 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. | ||||||||||||||||||||||||
| Reactome | REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines. REACT_6900. Immune System. | ||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||
| ArrayExpress | P01100. | ||||||||||||||||||||||||
| Bgee | P01100. | ||||||||||||||||||||||||
| CleanEx | HS_FOS. | ||||||||||||||||||||||||
| Genevestigator | P01100. | ||||||||||||||||||||||||
| GermOnline | ENSG00000170345. Homo sapiens. | ||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||
| InterPro | IPR004827. bZIP. IPR000837. Leuzip_Fos. [Graphical view] | ||||||||||||||||||||||||
| Pfam | PF00170. bZIP_1. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| PRINTS | PR00042. LEUZIPPRFOS. | ||||||||||||||||||||||||
| SMART | SM00338. BRLZ. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| PROSITE | PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||
Other | |||||||||||||||||||||||||
| BindingDB | P01100. | ||||||||||||||||||||||||
| ChEMBL | CHEMBL5029. | ||||||||||||||||||||||||
| ChiTaRS | Fos. human. | ||||||||||||||||||||||||
| EvolutionaryTrace | P01100. | ||||||||||||||||||||||||
| GenomeRNAi | 2353. | ||||||||||||||||||||||||
| NextBio | 9543. | ||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||
Entry information
| Entry name | FOS_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P01100 Secondary accession number(s): P18849 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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 |

Clusters with
