P12841 (FOS_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified May 29, 2013. Version 113. History...
Names and origin
|Protein names||Recommended name:|
Cellular oncogene fos
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||380 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling By similarity. 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 By similarity. Ref.5 Ref.6
Heterodimer; with JUN 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 DSIPI; this interaction inhibits the binding of active AP1 to its target DNA By similarity. Interacts with MAFB. Interacts with CDS1 and PI4K2A By similarity. Ref.4
Nucleus By similarity. Endoplasmic reticulum By similarity. Cytoplasm › cytosol By similarity. Note: In quiescent cells, present in very small amounts in the cytosol. Following induction of cell growth, first localizes to the endoplasmic reticulum and only later to the nucleus. Localization at the endoplasmic reticulum requires dephosphorylation at Tyr-10 and Tyr-30 By similarity.
Phosphorylated in the C-terminal upon stimulation by nerve growth factor (NGF) and epidermal growth factor (EGF) By similarity. 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. Ref.5 Ref.6
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 By similarity.
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 By similarity. Ref.5 Ref.6
Contains 1 bZIP (basic-leucine zipper) domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 380||380||Proto-oncogene c-Fos||PRO_0000076469|
|Domain||137 – 200||64||bZIP|
|Region||139 – 159||21||Basic motif; required for the activation of phospholipid synthesis, but not for CDS1-binding By similarity|
|Region||165 – 193||29||Leucine-zipper By similarity|
Amino acid modifications
|Modified residue||10||1||Phosphotyrosine; by SRC By similarity|
|Modified residue||30||1||Phosphotyrosine; by SRC By similarity|
|Modified residue||232||1||Phosphothreonine Ref.5|
|Modified residue||325||1||Phosphothreonine; by MAPK1 and MAPK3 Ref.6|
|Modified residue||331||1||Phosphothreonine; by MAPK1 and MAPK3 Ref.6|
|Modified residue||362||1||Phosphoserine; by MAPK1, MAPK3 and RPS6KA3 Ref.6|
|Modified residue||374||1||Phosphoserine; by MAPK1 and MAPK3 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|
|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|
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"cFOS expression in rat."|
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"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] [Europe PMC] [Abstract]
Cited for: DNA-BINDING.
|||"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAFB.
|||"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-232, FUNCTION, MUTAGENESIS OF THR-232.
|||"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] [Europe PMC] [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.
|+||Additional computationally mapped references.|
|X06769 mRNA. Translation: CAA29937.1.|
DQ089699 Genomic DNA. Translation: AAZ13764.1.
|PIR||TVRTFS. A28263. |
|RefSeq||NP_071533.1. NM_022197.2. |
3D structure databases
|SMR||P12841. Positions 140-192. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000010712; ENSRNOP00000010712; ENSRNOG00000008015. |
|UCSC||RGD:2626. rat. |
|RGD||2626. Fos. |
Gene expression databases
|GermOnline||ENSRNOG00000008015. Rattus norvegicus. |
Family and domain databases
|InterPro||IPR004827. bZIP. |
|Pfam||PF00170. bZIP_1. 1 hit. |
|PRINTS||PR00042. LEUZIPPRFOS. |
|SMART||SM00338. BRLZ. 1 hit. |
|PROSITE||PS50217. BZIP. 1 hit. |
PS00036. BZIP_BASIC. 1 hit.
|Accession||Primary (citable) accession number: P12841|
Secondary accession number(s): Q4FDN1
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families