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 16-JUN-2009, entry version 77. DE RecName: Full=Proto-oncogene protein c-fos; DE AltName: Full=Cellular oncogene fos; GN Name=Fos; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=88143713; 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 MEDLINE=90138931; 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 RT domains 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 MEDLINE=98238651; 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 RT heterodimer 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, RP AND MUTAGENESIS OF THR-325; THR-331; 343-PHE--TYR-345; SER-362 AND RP 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 RT nerve growth factor regulates c-fos protein stabilization and RT transactivation in PC12 cells."; RL J. Neurochem. 99:1480-1493(2006). CC -!- FUNCTION: Nuclear phosphoprotein which forms a tight but non- CC covalently linked complex with the JUN/AP-1 transcription factor. CC Has a critical function in regulating the development of cells CC destined to form and maintain the skeleton. It is thought to have CC an important role in signal transduction, cell proliferation and CC differentiation. CC -!- SUBUNIT: Heterodimer. Interacts with DSIPI; this interaction CC inhibits the binding of active AP1 to its target DNA (By CC similarity). Interacts with MAFB. CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- PTM: Phosphorylated in the C-terminal upon stimulation by nerve CC growth factor (NGF) and epidermal growth factor (EGF). CC Phosphorylated, in vitro, by MAPK and RSK1. Phosphorylation on CC both 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 CC for protein stabilization on NGF stimulation. Phosphorylation on CC Ser-362 and Ser-374 primes further phosphorylations on Thr-325 and CC Thr-331 through promoting docking of MAPK to the DEF domain. CC Phosphorylation on Thr-232, induced by HA-RAS, activates the CC transcriptional activity and antagonizes sumoylation. CC Phosphorylation on Ser-362 by RSK2 in osteoblasts contributes to CC osteoblast transformation (By similarity). CC -!- PTM: Constitutively sumoylated by SUMO1, SUMO2 and SUMO3. CC Desumoylated by SENP2. Sumoylation requires heterodimerization CC with JUN and is enhanced by mitogen stimulation. Sumoylation CC inhibits the AP-1 transcriptional activity and is, itself, CC inhibited by Ras-activated phosphorylation on Thr-232 (By CC similarity). CC -!- SIMILARITY: Belongs to the bZIP family. Fos subfamily. CC -!- SIMILARITY: Contains 1 bZIP domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X06769; CAA29937.1; -; mRNA. DR EMBL; DQ089699; AAZ13764.1; -; Genomic_DNA. DR IPI; IPI00368000; -. DR PIR; A28263; TVRTFS. DR RefSeq; NP_071533.1; -. DR UniGene; Rn.103750; -. DR HSSP; P01100; 1FOS. DR SMR; P12841; 139-198. DR DIP; DIP:6001N; -. DR PhosphoSite; P12841; -. DR Ensembl; ENSRNOG00000008015; Rattus norvegicus. DR GeneID; 314322; -. DR KEGG; rno:314322; -. DR RGD; 2626; Fos. DR HOVERGEN; P12841; -. DR OMA; P12841; TYTSSFV. DR NextBio; 667476; -. DR ArrayExpress; P12841; -. DR GermOnline; ENSRNOG00000008015; Rattus norvegicus. DR GO; GO:0019717; C:synaptosome; IDA:RGD. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:RGD. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD. DR GO; GO:0003700; F:transcription factor activity; IMP:RGD. DR GO; GO:0007568; P:aging; IEP:RGD. DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:RGD. DR GO; GO:0001661; P:conditioned taste aversion; IEP:RGD. DR GO; GO:0007565; P:female pregnancy; IEP: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 stimulus; IEP:RGD. DR GO; GO:0034097; P:response to cytokine stimulus; IEP:RGD. DR GO; GO:0042493; P:response to drug; IEP:RGD. DR GO; GO:0009629; P:response to gravity; 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:0014070; P:response to organic cyclic substance; IEP:RGD. DR GO; GO:0032570; P:response to progesterone stimulus; IEP:RGD. DR GO; GO:0009636; P:response to toxin; IEP:RGD. DR GO; GO:0030431; P:sleep; IEP:RGD. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IMP:RGD. DR InterPro; IPR011616; bZIP_1. DR InterPro; IPR000837; Leuzip_Fos. DR InterPro; IPR004827; TF_bZIP. DR Pfam; PF00170; bZIP_1; 1. DR PRINTS; PR00042; LEUZIPPRFOS. DR SMART; SM00338; BRLZ; 1. DR PROSITE; PS50217; BZIP; 1. DR PROSITE; PS00036; BZIP_BASIC; 1. PE 1: Evidence at protein level; KW DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Proto-oncogene; KW Ubl conjugation. FT CHAIN 1 380 Proto-oncogene protein c-fos. FT /FTId=PRO_0000076469. FT DOMAIN 165 193 Leucine-zipper. FT DNA_BIND 139 160 Basic motif. FT MOD_RES 232 232 Phosphothreonine. FT MOD_RES 325 325 Phosphothreonine. FT MOD_RES 331 331 Phosphothreonine. FT MOD_RES 362 362 Phosphoserine; by MAPK and RPS6KA3. FT MOD_RES 374 374 Phosphoserine; by MAPK. FT CROSSLNK 113 113 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin) (By FT similarity). FT CROSSLNK 265 265 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO) (By FT similarity). FT MUTAGEN 232 232 T->A: Abolishes HA-RAS-mediated FT activation. Loss of in vitro ERK2- FT mediated phosphorylation. No change in FT sumoylation levels. FT MUTAGEN 325 325 T->A: Loss of NGF-mediated FT phosphorylation; when associated with A- FT 331. FT MUTAGEN 331 331 T->A: Loss of NGF-mediated FT phosphorylation; when associated with A- FT 325. FT MUTAGEN 343 345 FTY->ATA: Decreased phosphorylation FT levels. Reduced NGF-mediated enhanced FT transactivation. FT MUTAGEN 362 362 S->A: Some loss of protein stabilization FT on NGF-treatment; when associated with D- FT 374. FT MUTAGEN 362 362 S->D: Increased protein stabilization on FT NGF-treatment, but no increase when FT treated with MAPK-inhibitor; when FT associated with D-374. FT MUTAGEN 374 374 S->A: Greatly reduced protein FT stabilization on NGF stimulation. FT MUTAGEN 374 374 S->D: Increased protein stabilization on FT NGF-treatment, but no increase when FT treated with MAPK-inhibitor; when FT associated with D-362. Some loss of FT protein stablization on NGF-treatment; FT wnen associated with A-362. 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 //