ID   FOS_RAT                 Reviewed;         380 AA.
AC   P12841; Q4FDN1;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   02-SEP-2026, entry version 198.
DE   RecName: Full=Protein c-Fos {ECO:0000305};
DE   AltName: Full=Cellular oncogene fos;
DE   AltName: Full=Proto-oncogene c-Fos {ECO:0000305};
GN   Name=Fos;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=3325886;
RA   Curran T., Gordon M.B., Rubino K.L., Sambucetti L.C.;
RT   "Isolation and characterization of the c-fos(rat) cDNA and analysis of
RT   post-translational modification in vitro.";
RL   Oncogene 2:79-84(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RA   Weiler E.;
RT   "cFOS expression in rat.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   DNA-BINDING.
RX   PubMed=2105492; DOI=10.1073/pnas.87.3.1032;
RA   Abate C., Luk D., Gentz R., Rauscher F.J. III, Curran T.;
RT   "Expression and purification of the leucine zipper and DNA-binding domains
RT   of Fos and Jun: both Fos and Jun contact DNA directly.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:1032-1036(1990).
RN   [4]
RP   INTERACTION WITH MAFB.
RX   PubMed=9571165; DOI=10.1006/bbrc.1998.8447;
RA   Matsushima-Hibiya Y., Nishi S., Sakai M.;
RT   "Rat maf-related factors: the specificities of DNA binding and heterodimer
RT   formation.";
RL   Biochem. Biophys. Res. Commun. 245:412-418(1998).
RN   [5]
RP   PHOSPHORYLATION AT THR-232, FUNCTION, AND MUTAGENESIS OF THR-232.
RX   PubMed=7816602; DOI=10.1093/nar/22.24.5173;
RA   Bannister A.J., Brown H.J., Sutherland J.A., Kouzarides T.;
RT   "Phosphorylation of the c-Fos and c-Jun HOB1 motif stimulates its
RT   activation capacity.";
RL   Nucleic Acids Res. 22:5173-5176(1994).
RN   [6]
RP   PHOSPHORYLATION AT THR-325; THR-331; SER-362 AND SER-374, FUNCTION, AND
RP   MUTAGENESIS OF THR-325; THR-331; 343-PHE--TYR-345; SER-362 AND SER-374.
RX   PubMed=17223854; DOI=10.1111/j.1471-4159.2006.04250.x;
RA   Pellegrino M.J., Stork P.J.;
RT   "Sustained activation of extracellular signal-regulated kinase by nerve
RT   growth factor regulates c-fos protein stabilization and transactivation in
RT   PC12 cells.";
RL   J. Neurochem. 99:1480-1493(2006).
CC   -!- FUNCTION: Nuclear phosphoprotein which forms a tight but non-covalently
CC       linked complex with the JUN/AP-1 transcription factor. On TGF-beta
CC       activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the
CC       AP1/SMAD-binding site to regulate TGF-beta-mediated signaling (By
CC       similarity). Has a critical function in regulating the development of
CC       cells destined to form and maintain the skeleton. It is thought to have
CC       an important role in signal transduction, cell proliferation and
CC       differentiation. In growing cells, activates phospholipid synthesis,
CC       possibly by activating CDS1 and PI4K2A. This activity requires Tyr-
CC       dephosphorylation and association with the endoplasmic reticulum (By
CC       similarity). {ECO:0000250, ECO:0000269|PubMed:17223854,
CC       ECO:0000269|PubMed:7816602}.
CC   -!- SUBUNIT: Heterodimer; with JUN (By similarity). Component of the
CC       SMAD3/SMAD4/JUN/FOS complex required for synergistic TGF-beta-mediated
CC       transcription at the AP1-binding site (By similarity). Interacts with
CC       SMAD3; the interaction is weak even on TGF-beta activation (By
CC       similarity). Interacts with MAFB (PubMed:9571165). Interacts with
CC       TSC22D3 (via N-terminus); this interaction inhibits the binding of
CC       active AP1 to its target DNA (By similarity). Interacts with CDS1 and
CC       PI4K2A (By similarity). Interacts (via bZIP domain and leucine-zipper
CC       region) with the multiprotein chromatin-remodeling complexes SWI/SNF:
CC       SWI/SNF-A (BAF) subunits SMARCB1, SMARCC2 and SMARCD1 (By similarity).
CC       Interacts (via bZIP domain and leucine-zipper region) with ARID1A (By
CC       similarity). {ECO:0000250|UniProtKB:P01100,
CC       ECO:0000250|UniProtKB:P01101, ECO:0000269|PubMed:9571165}.
CC   -!- INTERACTION:
CC       P12841; P17325: Jun; NbExp=2; IntAct=EBI-8590661, EBI-7709365;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00978}.
CC       Endoplasmic reticulum {ECO:0000250}. Cytoplasm, cytosol {ECO:0000250}.
CC       Note=In quiescent cells, present in very small amounts in the cytosol.
CC       Following induction of cell growth, first localizes to the endoplasmic
CC       reticulum and only later to the nucleus. Localization at the
CC       endoplasmic reticulum requires dephosphorylation at Tyr-10 and Tyr-30
CC       (By similarity). {ECO:0000250}.
CC   -!- PTM: Phosphorylated in the C-terminal upon stimulation by nerve growth
CC       factor (NGF) and epidermal growth factor (EGF) (By similarity).
CC       Phosphorylated, in vitro, by MAPK and RSK1. Phosphorylation on both
CC       Ser-362 and Ser-374 by MAPK1/2 and RSK1/2 leads to protein
CC       stabilization with phosphorylation on Ser-374 being the major site for
CC       protein stabilization on NGF stimulation. Phosphorylation on Ser-362
CC       and Ser-374 primes further phosphorylations on Thr-325 and Thr-331
CC       through promoting docking of MAPK to the DEF domain. Phosphorylation on
CC       Thr-232, induced by HA-RAS, activates the transcriptional activity and
CC       antagonizes sumoylation. Phosphorylation on Ser-362 by RSK2 in
CC       osteoblasts contributes to osteoblast transformation. {ECO:0000250,
CC       ECO:0000269|PubMed:17223854, ECO:0000269|PubMed:7816602}.
CC   -!- PTM: Constitutively sumoylated with SUMO1, SUMO2 and SUMO3.
CC       Desumoylated by SENP2. Sumoylation requires heterodimerization with JUN
CC       and is enhanced by mitogen stimulation. Sumoylation inhibits the AP-1
CC       transcriptional activity and is, itself, inhibited by Ras-activated
CC       phosphorylation on Thr-232 (By similarity). {ECO:0000250}.
CC   -!- PTM: In quiescent cells, the small amount of FOS present is
CC       phosphorylated at Tyr-10 and Tyr-30 by SRC. This Tyr-phosphorylated
CC       form is cytosolic. In growing cells, dephosphorylated by PTPN2.
CC       Dephosphorylation leads to the association with endoplasmic reticulum
CC       membranes and activation of phospholipid synthesis (By similarity).
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the bZIP family. Fos subfamily. {ECO:0000305}.
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DR   EMBL; X06769; CAA29937.1; -; mRNA.
DR   EMBL; DQ089699; AAZ13764.1; -; Genomic_DNA.
DR   PIR; A28263; TVRTFS.
DR   RefSeq; NP_071533.1; NM_022197.2.
DR   AlphaFoldDB; P12841; -.
DR   SMR; P12841; -.
DR   BioGRID; 260681; 1.
DR   CORUM; P12841; -.
DR   DIP; DIP-6001N; -.
DR   FunCoup; P12841; 1049.
DR   IntAct; P12841; 2.
DR   MINT; P12841; -.
DR   STRING; 10116.ENSRNOP00000010712; -.
DR   GlyGen; P12841; 1 site.
DR   iPTMnet; P12841; -.
DR   PhosphoSitePlus; P12841; -.
DR   PaxDb; 10116-ENSRNOP00000010712; -.
DR   ABCD; P12841; 3 sequenced antibodies.
DR   Ensembl; ENSRNOT00000010712.5; ENSRNOP00000010712.2; ENSRNOG00000008015.7.
DR   Ensembl; ENSRNOT00055043608; ENSRNOP00055035598; ENSRNOG00055025291.
DR   Ensembl; ENSRNOT00060040477; ENSRNOP00060033445; ENSRNOG00060023383.
DR   Ensembl; ENSRNOT00065042954; ENSRNOP00065035153; ENSRNOG00065024997.
DR   GeneID; 314322; -.
DR   KEGG; rno:314322; -.
DR   UCSC; RGD:2626; rat.
DR   AGR; RGD:2626; -.
DR   CTD; 2353; -.
DR   RGD; 2626; Fos.
DR   eggNOG; KOG1414; Eukaryota.
DR   GeneTree; ENSGT00940000159276; -.
DR   HOGENOM; CLU_049742_2_0_1; -.
DR   InParanoid; P12841; -.
DR   OMA; NRTHPYG; -.
DR   OrthoDB; 5866312at2759; -.
DR   PhylomeDB; P12841; -.
DR   Reactome; R-RNO-2559580; Oxidative Stress Induced Senescence.
DR   Reactome; R-RNO-2871796; FCERI mediated MAPK activation.
DR   Reactome; R-RNO-450341; Activation of the AP-1 family of transcription factors.
DR   Reactome; R-RNO-9018519; Estrogen-dependent gene expression.
DR   PRO; PR:P12841; -.
DR   Proteomes; UP000002494; Chromosome 6.
DR   Bgee; ENSRNOG00000008015; Expressed in jejunum and 18 other cell types or tissues.
DR   ExpressionAtlas; P12841; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR   GO; GO:0016363; C:nuclear matrix; IDA:RGD.
DR   GO; GO:0005654; C:nucleoplasm; IDA:RGD.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0032993; C:protein-DNA complex; ISO:RGD.
DR   GO; GO:0035976; C:transcription factor AP-1 complex; ISO:RGD.
DR   GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR   GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR   GO; GO:0003677; F:DNA binding; IDA:RGD.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:RGD.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; IDA:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR   GO; GO:0070412; F:R-SMAD binding; ISO:RGD.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR   GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; ISO:RGD.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR   GO; GO:0001221; F:transcription coregulator binding; ISO:RGD.
DR   GO; GO:0071277; P:cellular response to calcium ion; ISO:RGD.
DR   GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEP:RGD.
DR   GO; GO:0032870; P:cellular response to hormone stimulus; IEP:RGD.
DR   GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR   GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEP:RGD.
DR   GO; GO:1904628; P:cellular response to phorbol 13-acetate 12-myristate; IEP:RGD.
DR   GO; GO:1990646; P:cellular response to prolactin; IEP:RGD.
DR   GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:RGD.
DR   GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR   GO; GO:0034224; P:cellular response to zinc ion starvation; IEP:RGD.
DR   GO; GO:0021987; P:cerebral cortex development; IMP:RGD.
DR   GO; GO:0001661; P:conditioned taste aversion; IEP:RGD.
DR   GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR   GO; GO:0072375; P:medium-term memory; IMP:RGD.
DR   GO; GO:1903131; P:mononuclear cell differentiation; IEP:RGD.
DR   GO; GO:0051450; P:myoblast proliferation; IEP:RGD.
DR   GO; GO:0007399; P:nervous system development; ISO:RGD.
DR   GO; GO:0003407; P:neural retina development; IEP:RGD.
DR   GO; GO:0030182; P:neuron differentiation; IMP:RGD.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL.
DR   GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:RGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0014823; P:response to activity; IEP:RGD.
DR   GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR   GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR   GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR   GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR   GO; GO:1904321; P:response to forskolin; IEP:RGD.
DR   GO; GO:0009629; P:response to gravity; IEP:RGD.
DR   GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR   GO; GO:0032868; P:response to insulin; IEP:RGD.
DR   GO; GO:0009416; P:response to light stimulus; IEP:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR   GO; GO:0035994; P:response to muscle stretch; ISO:RGD.
DR   GO; GO:0032570; P:response to progesterone; IEP:RGD.
DR   GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR   GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   GO; GO:0035914; P:skeletal muscle cell differentiation; ISO:RGD.
DR   GO; GO:0014856; P:skeletal muscle cell proliferation; IEP:RGD.
DR   GO; GO:0060395; P:SMAD protein signal transduction; ISO:RGD.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; IMP:RGD.
DR   GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR   CDD; cd14721; bZIP_Fos; 1.
DR   FunFam; 1.20.5.170:FF:000006; fos-related antigen 2 isoform X1; 1.
DR   Gene3D; 1.20.5.170; -; 1.
DR   InterPro; IPR000837; AP-1.
DR   InterPro; IPR004827; bZIP.
DR   InterPro; IPR046347; bZIP_sf.
DR   PANTHER; PTHR23351; FOS TRANSCRIPTION FACTOR-RELATED; 1.
DR   PANTHER; PTHR23351:SF4; PROTEIN C-FOS; 1.
DR   Pfam; PF00170; bZIP_1; 1.
DR   PRINTS; PR00042; LEUZIPPRFOS.
DR   SMART; SM00338; BRLZ; 1.
DR   SUPFAM; SSF57959; Leucine zipper domain; 1.
DR   PROSITE; PS50217; BZIP; 1.
DR   PROSITE; PS00036; BZIP_BASIC; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; DNA-binding; Endoplasmic reticulum; Isopeptide bond; Nucleus;
KW   Phosphoprotein; Proto-oncogene; Reference proteome; Ubl conjugation.
FT   CHAIN           1..380
FT                   /note="Protein c-Fos"
FT                   /id="PRO_0000076469"
FT   DOMAIN          137..200
FT                   /note="bZIP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT   REGION          139..159
FT                   /note="Basic motif; required for the activation of
FT                   phospholipid synthesis, but not for CDS1-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT   REGION          165..193
FT                   /note="Leucine-zipper"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT   REGION          354..380
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        362..374
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         10
FT                   /note="Phosphotyrosine; by SRC"
FT                   /evidence="ECO:0000250|UniProtKB:P01100"
FT   MOD_RES         30
FT                   /note="Phosphotyrosine; by SRC"
FT                   /evidence="ECO:0000250|UniProtKB:P01100"
FT   MOD_RES         232
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:7816602"
FT   MOD_RES         325
FT                   /note="Phosphothreonine; by MAPK1 and MAPK3"
FT                   /evidence="ECO:0000269|PubMed:17223854"
FT   MOD_RES         331
FT                   /note="Phosphothreonine; by MAPK1 and MAPK3"
FT                   /evidence="ECO:0000269|PubMed:17223854"
FT   MOD_RES         362
FT                   /note="Phosphoserine; by MAPK1, MAPK3 and RPS6KA3"
FT                   /evidence="ECO:0000269|PubMed:17223854"
FT   MOD_RES         374
FT                   /note="Phosphoserine; by MAPK1 and MAPK3"
FT                   /evidence="ECO:0000269|PubMed:17223854"
FT   CROSSLNK        113
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P01100"
FT   CROSSLNK        128
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P01100"
FT   CROSSLNK        265
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT                   /evidence="ECO:0000250"
FT   CROSSLNK        265
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P01100"
FT   MUTAGEN         232
FT                   /note="T->A: Abolishes HA-RAS-mediated activation. Loss of
FT                   in vitro ERK2-mediated phosphorylation. No change in
FT                   sumoylation levels."
FT                   /evidence="ECO:0000269|PubMed:7816602"
FT   MUTAGEN         325
FT                   /note="T->A: Loss of NGF-mediated phosphorylation; when
FT                   associated with A-331."
FT                   /evidence="ECO:0000269|PubMed:17223854"
FT   MUTAGEN         331
FT                   /note="T->A: Loss of NGF-mediated phosphorylation; when
FT                   associated with A-325."
FT                   /evidence="ECO:0000269|PubMed:17223854"
FT   MUTAGEN         343..345
FT                   /note="FTY->ATA: Decreased phosphorylation levels. Reduced
FT                   NGF-mediated enhanced transactivation."
FT                   /evidence="ECO:0000269|PubMed:17223854"
FT   MUTAGEN         362
FT                   /note="S->A: Some loss of protein stabilization on
FT                   NGF-treatment; when associated with D-374."
FT                   /evidence="ECO:0000269|PubMed:17223854"
FT   MUTAGEN         362
FT                   /note="S->D: Increased protein stabilization on
FT                   NGF-treatment, but no increase when treated with
FT                   MAPK-inhibitor; when associated with D-374."
FT                   /evidence="ECO:0000269|PubMed:17223854"
FT   MUTAGEN         374
FT                   /note="S->A: Greatly reduced protein stabilization on NGF
FT                   stimulation."
FT                   /evidence="ECO:0000269|PubMed:17223854"
FT   MUTAGEN         374
FT                   /note="S->D: Increased protein stabilization on
FT                   NGF-treatment, but no increase when treated with
FT                   MAPK-inhibitor; when associated with D-362. Some loss of
FT                   protein stabilization on NGF-treatment; wnen associated
FT                   with A-362."
FT                   /evidence="ECO:0000269|PubMed:17223854"
SQ   SEQUENCE   380 AA;  40927 MW;  E62D16A88CB2BEE9 CRC64;
     MMFSGFNADY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNTQDFC ADLSVSSANF
     IPTVTAISTS PDLQWLVQPT LVSSVAPSQT RAPHPYGLPT PSTGAYARAG VVKTMSGGRA
     QSIGRRGKVE QLSPEEEEKR RIRRERNKMA AAKCRNRRRE LTDTLQAETD QLEDEKSALQ
     TEIANLLKEK EKLEFILAAH RPACKIPNDL GFPEEMSVTS LDLTGGLPEA TTPESEEAFT
     LPLLNDPEPK PSLEPVKNIS NMELKAEPFD DFLFPASSRP SGSETARSVP DVDLSGSFYA
     ADWEPLHSSS LGMGPMVTEL EPLCTPVVTC TPSCTTYTSS FVFTYPEADS FPSCAAAHRK
     GSSSNEPSSD SLSSPTLLAL
//