P01101 (FOS_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 125. History...
Names and origin
|Protein names||Recommended name:|
Cellular oncogene fos
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9
Heterodimer; with JUN By similarity. Interacts with MAFB. 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 By similarity. Interacts with DSIPI; this interaction inhibits the binding of active AP1 to its target DNA. Interacts with CDS1 and PI4K2A, but not with CDIPT, nor PI4K2B. Ref.4 Ref.9
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). 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.5 Ref.6 Ref.7 Ref.9
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. Ref.5 Ref.6 Ref.7 Ref.9
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_0000076467|
|Domain||137 – 200||64||bZIP|
|Region||139 – 159||21||Basic motif; required for the activation of phospholipid synthesis, but not for CDS1-binding|
|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.6|
|Modified residue||325||1||Phosphothreonine; by MAPK1 and MAPK3 Ref.5 Ref.6|
|Modified residue||331||1||Phosphothreonine; by MAPK1 and MAPK3 Ref.5 Ref.6|
|Modified residue||362||1||Phosphoserine; by MAPK1, MAPK3 and RPS6KA3 Ref.5 Ref.6 Ref.7|
|Modified residue||374||1||Phosphoserine; by MAPK1 and MAPK3 Ref.5 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||139||1||K → N: No effect on activation of phospholipid synthesis. Ref.9|
|Mutagenesis||144||1||R → N: No effect on activation of phospholipid synthesis, nor on CDS1-binding. Ref.9|
|Mutagenesis||146||1||R → N: Complete loss of activation of phospholipid synthesis. No effect on CDS1-binding. Ref.9|
|Mutagenesis||232||1||T → A: No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-325; A-331 and A-374. Ref.6|
|Mutagenesis||325||1||T → A: Almost no EGF-mediated phosphorylation, greatly reduced cellular transformation, and reduced AP1 activity by 20%; when associated with A-331. No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-232; A-331 and A-374. Ref.5 Ref.6|
|Mutagenesis||331||1||T → A: Almost no EGF-mediated phosphorylation, greatly reduced cellular transformation, and reduced AP1 activity by 20%; when associated with A-325. No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-232; A-325;and A-374. Ref.5 Ref.6|
|Mutagenesis||343||1||F → A: Reduced phosphorylation by ERK. Reduced AP1 activity by 65%. Ref.5|
|Mutagenesis||345||1||Y → A: Reduced phosphorylation by ERK. Ref.5|
|Mutagenesis||362||1||S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-374. Ref.5|
|Mutagenesis||362||1||S → E: Increased enhancement of EGF- and RSK-mediated tranformation; when associated with E-374. Ref.5|
|Mutagenesis||374||1||S → A: No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-232; A-325 and A-331. Ref.5 Ref.6|
|Mutagenesis||374||1||S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-362. Ref.5 Ref.6|
|Mutagenesis||374||1||S → E: Enhanced EGF- and RSK-mediated tranformation; when associated with E-362. Ref.5 Ref.6|
Helix Strand Turn
|Helix||139 – 199||61|
|||"Analysis of FBJ-MuSV provirus and c-fos (mouse) gene reveals that viral and cellular fos gene products have different carboxy termini."|
van Beveren C., van Straaten F., Curran T., Mueller R., Verma I.M.
Cell 32:1241-1255(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"Removal of a 67-base-pair sequence in the noncoding region of protooncogene fos converts it to a transforming gene."|
Meijlink F., Curran T., Miller A.D., Verma I.M.
Proc. Natl. Acad. Sci. U.S.A. 82:4987-4991(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"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: Mammary gland.
|||"Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ."|
Mittelstadt P.R., Ashwell J.D.
J. Biol. Chem. 276:29603-29610(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DSIPI.
|||"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; SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF THR-325; THR-331; PHE-343; TYR-345; SER-362 AND SER-374.
|||"Phosphorylation of the carboxyl-terminal transactivation domain of c-Fos by extracellular signal-regulated kinase mediates the transcriptional activation of AP-1 and cellular transformation induced by platelet-derived growth factor."|
Monje P., Marinissen M.J., Gutkind J.S.
Mol. Cell. Biol. 23:7030-7043(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-232; THR-325; THR-331; SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF THR-232; THR-325; THR-331 AND SER-374.
|||"Essential role of RSK2 in c-Fos-dependent osteosarcoma development."|
David J.-P., Mehic D., Bakiri L., Schilling A.F., Mandic V., Priemel M., Idarraga M.H., Reschke M.O., Hoffmann O., Amling M., Wagner E.F.
J. Clin. Invest. 115:664-672(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-362, FUNCTION.
|||"c-Fos activates and physically interacts with specific enzymes of the pathway of synthesis of polyphosphoinositides."|
Alfonso Pecchio A.R., Cardozo Gizzi A.M., Renner M.L., Molina-Calavita M., Caputto B.L.
Mol. Biol. Cell 22:4716-4725(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"The kinase c-Src and the phosphatase TC45 coordinately regulate c-Fos tyrosine phosphorylation and c-Fos phospholipid synthesis activation capacity."|
Ferrero G.O., Velazquez F.N., Caputto B.L.
Oncogene 31:3381-3391(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CDS1 AND PI4K2A, TYROSINE PHOSPHORYLATION BY SRC, MUTAGENESIS OF LYS-139; ARG-144 AND ARG-146.
|+||Additional computationally mapped references.|
|V00727 Genomic DNA. Translation: CAA24105.1.|
J00370 Genomic DNA. Translation: AAA96699.1.
BC029814 mRNA. Translation: AAH29814.1.
|PIR||TVMSF. A01343. |
|RefSeq||NP_034364.1. NM_010234.2. |
3D structure databases
|SMR||P01101. Positions 138-200. |
Protein-protein interaction databases
|BioGrid||199726. 21 interactions.|
|IntAct||P01101. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000021674; ENSMUSP00000021674; ENSMUSG00000021250. |
|UCSC||uc007oha.2. mouse. |
|MGI||MGI:95574. Fos. |
Gene expression databases
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: P01101|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|