FOS_RAT
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 03-AUG-2022, entry version 180.
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 DSIPI; this interaction inhibits the binding of active AP1 to its
CC target DNA (By similarity). Interacts with CDS1 and PI4K2A (By
CC similarity). Interacts (via bZIP domain and leucine-zipper region) with
CC the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A
CC (BAF) subunits SMARCB1, SMARCC2 and SMARCD1 (By similarity). Interacts
CC (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 IntAct; P12841; 2.
DR MINT; P12841; -.
DR STRING; 10116.ENSRNOP00000010712; -.
DR iPTMnet; P12841; -.
DR PhosphoSitePlus; P12841; -.
DR PaxDb; P12841; -.
DR ABCD; P12841; 3 sequenced antibodies.
DR Ensembl; ENSRNOT00000010712; ENSRNOP00000010712; ENSRNOG00000008015.
DR GeneID; 314322; -.
DR KEGG; rno:314322; -.
DR UCSC; RGD:2626; rat.
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; FTYPEAE; -.
DR OrthoDB; 1221590at2759; -.
DR PhylomeDB; P12841; -.
DR TreeFam; TF326301; -.
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 PRO; PR:P12841; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000008015; Expressed in jejunum and 18 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032993; C:protein-DNA complex; ISO:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator 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: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:0007568; P:aging; IEP:RGD.
DR GO; GO:0071276; P:cellular response to cadmium ion; ISO:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; ISO:RGD.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; ISO: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:1990646; P:cellular response to prolactin; IEP:RGD.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:RGD.
DR GO; GO:0001661; P:conditioned taste aversion; IEP:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL.
DR GO; GO:1901216; P:positive regulation of neuron death; IGI:ARUK-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:0045893; P:positive regulation of transcription, DNA-templated; 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:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR GO; GO:0009409; P:response to cold; 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:0009629; P:response to gravity; IEP:RGD.
DR GO; GO:0035902; P:response to immobilization stress; 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:0014070; P:response to organic cyclic compound; IEP: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:0030431; P:sleep; 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 InterPro; IPR000837; AP-1.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR029816; c-Fos/v-Fos.
DR PANTHER; PTHR23351; PTHR23351; 1.
DR PANTHER; PTHR23351:SF4; PTHR23351:SF4; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR PRINTS; PR00042; LEUZIPPRFOS.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 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 357..380
FT /note="Polar residues"
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 NGF-
FT treatment; when associated with D-374."
FT /evidence="ECO:0000269|PubMed:17223854"
FT MUTAGEN 362
FT /note="S->D: Increased protein stabilization on NGF-
FT treatment, but no increase when treated with MAPK-
FT 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 NGF-
FT treatment, but no increase when treated with MAPK-
FT inhibitor; when associated with D-362. Some loss of protein
FT stablization on NGF-treatment; wnen associated 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
