Reviewed,
UniProtKB/Swiss-Prot P12841 (FOS_RAT)
Last modified
June 16, 2009.
Version 77.
History...
Clusters with 100%,
90%,
50% identity |
Documents (1) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Proto-oncogene protein c-fos Alternative name(s): Cellular oncogene fos | ||
| Gene names |
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| Organism | Rattus norvegicus (Rat) | ||
| Taxonomic identifier | 10116 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus |
Protein attributes
| Sequence length | 380 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| 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. 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.5 Ref.6 |
| Subunit structure | Heterodimer. Interacts with DSIPI; this interaction inhibits the binding of active AP1 to its target DNA By similarity. Interacts with MAFB. |
| 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. 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 By similarity. |
| Sequence similarities | Belongs to the bZIP family. Fos subfamily. Contains 1 bZIP domain. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 380 | 380 | Proto-oncogene protein c-fos | PRO_0000076469 | |||||
Regions | |||||||||
| Domain | 165 – 193 | 29 | Leucine-zipper | ||||||
| DNA binding | 139 – 160 | 22 | Basic motif Ref.3 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 232 | 1 | Phosphothreonine Ref.5 | ||||||
| Modified residue | 325 | 1 | Phosphothreonine Ref.6 | ||||||
| Modified residue | 331 | 1 | Phosphothreonine Ref.6 | ||||||
| Modified residue | 362 | 1 | Phosphoserine; by MAPK and RPS6KA3 Ref.6 | ||||||
| Modified residue | 374 | 1 | Phosphoserine; by MAPK Ref.6 | ||||||
| Cross-link | 113 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity | |||||||
| Cross-link | 265 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity | |||||||
Experimental info | |||||||||
| Mutagenesis | 232 | 1 | T → A: Abolishes HA-RAS-mediated activation. Loss of in vitro ERK2-mediated phosphorylation. No change in sumoylation levels. Ref.5 | ||||||
| Mutagenesis | 325 | 1 | T → A: Loss of NGF-mediated phosphorylation; when associated with A-331. Ref.6 | ||||||
| Mutagenesis | 331 | 1 | T → A: Loss of NGF-mediated phosphorylation; when associated with A-325. Ref.6 | ||||||
| Mutagenesis | 343 – 345 | 3 | FTY → ATA: Decreased phosphorylation levels. Reduced NGF-mediated enhanced transactivation. Ref.6 | ||||||
| Mutagenesis | 362 | 1 | S → A: Some loss of protein stabilization on NGF-treatment; when associated with D-374. Ref.6 | ||||||
| Mutagenesis | 362 | 1 | S → D: Increased protein stabilization on NGF-treatment, but no increase when treated with MAPK-inhibitor; when associated with D-374. Ref.6 | ||||||
| Mutagenesis | 374 | 1 | S → A: Greatly reduced protein stabilization on NGF stimulation. Ref.6 | ||||||
| Mutagenesis | 374 | 1 | S → D: Increased protein stabilization on NGF-treatment, but no increase when treated with MAPK-inhibitor; when associated with D-362. Some loss of protein stablization on NGF-treatment; wnen associated with A-362. Ref.6 | ||||||
Sequences
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References
| [1] | "Isolation and characterization of the c-fos(rat) cDNA and analysis of post-translational modification in vitro." Curran T., Gordon M.B., Rubino K.L., Sambucetti L.C. Oncogene 2:79-84(1987) [PubMed: 3325886] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | "cFOS expression in rat." Weiler E. Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Sprague-Dawley. Tissue: Liver. |
| [3] | "Expression and purification of the leucine zipper and DNA-binding domains of Fos and Jun: both Fos and Jun contact DNA directly." Abate C., Luk D., Gentz R., Rauscher F.J. III, Curran T. Proc. Natl. Acad. Sci. U.S.A. 87:1032-1036(1990) [PubMed: 2105492] [Abstract] Cited for: DNA-BINDING. |
| [4] | "Rat maf-related factors: the specificities of DNA binding and heterodimer formation." Matsushima-Hibiya Y., Nishi S., Sakai M. Biochem. Biophys. Res. Commun. 245:412-418(1998) [PubMed: 9571165] [Abstract] Cited for: INTERACTION WITH MAFB. |
| [5] | "Phosphorylation of the c-Fos and c-Jun HOB1 motif stimulates its activation capacity." Bannister A.J., Brown H.J., Sutherland J.A., Kouzarides T. Nucleic Acids Res. 22:5173-5176(1994) [PubMed: 7816602] [Abstract] Cited for: PHOSPHORYLATION AT THR-232, FUNCTION, MUTAGENESIS OF THR-232. |
| [6] | "Sustained activation of extracellular signal-regulated kinase by nerve growth factor regulates c-fos protein stabilization and transactivation in PC12 cells." Pellegrino M.J., Stork P.J. J. Neurochem. 99:1480-1493(2006) [PubMed: 17223854] [Abstract] Cited for: PHOSPHORYLATION AT THR-325; THR-331; SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF THR-325; THR-331; 343-PHE--TYR-345; SER-362 AND SER-374. |
Cross-references
Sequence databases | |
|---|---|
| X06769 mRNA. Translation: CAA29937.1. DQ089699 Genomic DNA. Translation: AAZ13764.1. | |
| IPI | IPI00368000. |
| PIR | TVRTFS. A28263. |
| RefSeq | NP_071533.1. |
| UniGene | Rn.103750 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1FOS based on UniProtKB P01100. |
| SMR | P12841. Positions 139-198. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP:6001N. |
PTM databases | |
| PhosphoSite | P12841. |
Genome annotation databases | |
| Ensembl | ENSRNOG00000008015. Rattus norvegicus. [Contig view] |
| GeneID | 314322. |
| KEGG | rno:314322. |
Organism-specific databases | |
| RGD | 2626. Fos. |
Phylogenomic databases | |
| HOVERGEN | P12841. |
| OMA | P12841. TYTSSFV. |
Gene expression databases | |
| ArrayExpress | P12841. |
| GermOnline | ENSRNOG00000008015. Rattus norvegicus. |
Family and domain databases | |
| InterPro | IPR011616. bZIP_1. IPR000837. Leuzip_Fos. IPR004827. TF_bZIP. [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 Resources | |
| NextBio | 667476. |
Entry information
| Entry name | FOS_RAT | ||||||||
| Accession | Primary (citable) accession number: P12841 Secondary accession number(s): Q4FDN1 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||

Clusters with


