ID FOS_HUMAN Reviewed; 380 AA. AC P01100; A8K4E2; B4DQ65; P18849; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 27-MAR-2024, entry version 249. DE RecName: Full=Protein c-Fos {ECO:0000305}; DE AltName: Full=Cellular oncogene fos; DE AltName: Full=Fos proto-oncogene, AP-1 transcription factor subunit {ECO:0000312|HGNC:HGNC:3796}; DE AltName: Full=G0/G1 switch regulatory protein 7; DE AltName: Full=Proto-oncogene c-Fos; DE AltName: Full=Transcription factor AP-1 subunit c-Fos {ECO:0000305}; GN Name=FOS; Synonyms=G0S7; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6574479; DOI=10.1073/pnas.80.11.3183; RA van Straaten F., Mueller R., Curran T., Van Beveren C., Verma I.M.; RT "Complete nucleotide sequence of a human c-onc gene: deduced amino acid RT sequence of the human c-fos protein."; RL Proc. Natl. Acad. Sci. U.S.A. 80:3183-3187(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Colon; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-6 (ISOFORM 1/2). RX PubMed=1658710; RA Roux P., Verrier B., Klein B., Niccolino M., Marty L., Alexandre C., RA Piechaczyk M.; RT "Retrovirus-mediated gene transfer of a human c-fos cDNA into mouse bone RT marrow stromal cells."; RL Oncogene 6:2155-2160(1991). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 133-200 (ISOFORM 1), DNA-BINDING, AND RP SUBUNIT. RX PubMed=2516827; DOI=10.1101/gad.3.12b.2083; RA Hai T., Liu F., Coukos W.J., Green M.R.; RT "Transcription factor ATF cDNA clones: an extensive family of leucine RT zipper proteins able to selectively form DNA-binding heterodimers."; RL Genes Dev. 3:2083-2090(1989). RN [9] RP ERRATUM OF PUBMED:2516827. RA Hai T., Liu F., Coukos W.J., Green M.R.; RL Genes Dev. 4:682-682(1990). RN [10] RP DNA-BINDING. RX PubMed=2511004; DOI=10.1002/j.1460-2075.1989.tb08561.x; RA Nakabeppu Y., Nathans D.; RT "The basic region of Fos mediates specific DNA binding."; RL EMBO J. 8:3833-3841(1989). RN [11] RP PHOSPHORYLATION AT SER-362 AND SER-374, FUNCTION, AND MUTAGENESIS OF RP SER-362 AND SER-374. RX PubMed=7588633; DOI=10.1002/j.1460-2075.1995.tb00187.x; RA Okazaki K., Sagata N.; RT "The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and RT augments its transforming activity in NIH 3T3 cells."; RL EMBO J. 14:5048-5059(1995). RN [12] RP IDENTIFICATION AS A COMPONENT OF THE SMAD3/SMAD4/JUN/FOS COMPLEX, FUNCTION, RP AND INTERACTION WITH SMAD3. RX PubMed=9732876; DOI=10.1038/29814; RA Zhang Y., Feng X.H., Derynck R.; RT "Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced RT transcription."; RL Nature 394:909-913(1998). RN [13] RP PHOSPHORYLATION AT THR-325; THR-331 AND SER-374. RX PubMed=12134156; DOI=10.1038/ncb822; RA Murphy L.O., Smith S., Chen R.H., Fingar D.C., Blenis J.; RT "Molecular interpretation of ERK signal duration by immediate early gene RT products."; RL Nat. Cell Biol. 4:556-564(2002). RN [14] RP SUMOYLATION AT LYS-265, SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF RP LYS-128; LYS-192; THR-232; LYS-265; THR-325; THR-331; SER-362 AND SER-374. RX PubMed=16055710; DOI=10.1128/mcb.25.16.6964-6979.2005; RA Bossis G., Malnou C.E., Farras R., Andermarcher E., Hipskind R., RA Rodriguez M., Schmidt D., Muller S., Jariel-Encontre I., Piechaczyk M.; RT "Down-regulation of c-Fos/c-Jun AP-1 dimer activity by sumoylation."; RL Mol. Cell. Biol. 25:6964-6979(2005). RN [15] RP SUMOYLATION. RX PubMed=17709345; DOI=10.1093/nar/gkm617; RA Jakobs A., Himstedt F., Funk M., Korn B., Gaestel M., Niedenthal R.; RT "Ubc9 fusion-directed SUMOylation identifies constitutive and inducible RT SUMOylation."; RL Nucleic Acids Res. 35:E109-E109(2007). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, PHOSPHORYLATION AT RP TYR-10 AND TYR-30, AND MUTAGENESIS OF TYR-10; TYR-30; TYR-106 AND TYR-337. RX PubMed=17160021; DOI=10.1038/sj.onc.1210137; RA Portal M.M., Ferrero G.O., Caputto B.L.; RT "N-Terminal c-Fos tyrosine phosphorylation regulates c-Fos/ER association RT and c-Fos-dependent phospholipid synthesis activation."; RL Oncogene 26:3551-3558(2007). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-10 AND TYR-30, AND RP MUTAGENESIS OF TYR-10 AND TYR-30. RX PubMed=22105363; DOI=10.1038/onc.2011.510; RA Ferrero G.O., Velazquez F.N., Caputto B.L.; RT "The kinase c-Src and the phosphatase TC45 coordinately regulate c-Fos RT tyrosine phosphorylation and c-Fos phospholipid synthesis activation RT capacity."; RL Oncogene 31:3381-3391(2012). RN [19] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-128 AND LYS-265, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [20] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-265, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [21] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-113; LYS-128 AND LYS-265, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [22] RP X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 139-198 OF COMPLEX WITH JUN. RX PubMed=7816143; DOI=10.1038/373257a0; RA Glover J.N., Harrison S.C.; RT "Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c- RT Jun bound to DNA."; RL Nature 373:257-261(1995). CC -!- FUNCTION: Nuclear phosphoprotein which forms a tight but non-covalently CC linked complex with the JUN/AP-1 transcription factor. In the CC heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with CC symmetrical DNA half sites. On TGF-beta activation, forms a multimeric CC SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate CC TGF-beta-mediated signaling. Has a critical function in regulating the CC development of cells destined to form and maintain the skeleton. It is CC thought to have an important role in signal transduction, cell CC proliferation and differentiation. In growing cells, activates CC phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This CC activity requires Tyr-dephosphorylation and association with the CC endoplasmic reticulum. {ECO:0000269|PubMed:16055710, CC ECO:0000269|PubMed:17160021, ECO:0000269|PubMed:22105363, CC ECO:0000269|PubMed:7588633, ECO:0000269|PubMed:9732876}. 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 promoter site (PubMed:9732876). Interacts with CC SMAD3; the interaction is weak even on TGF-beta activation CC (PubMed:9732876). Interacts with MAFB (By similarity). 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:P01101, CC ECO:0000250|UniProtKB:P12841, ECO:0000269|PubMed:9732876}. CC -!- INTERACTION: CC P01100; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-852851, EBI-10173507; CC P01100; P05067: APP; NbExp=3; IntAct=EBI-852851, EBI-77613; CC P01100; P52566: ARHGDIB; NbExp=3; IntAct=EBI-852851, EBI-2806617; CC P01100; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-852851, EBI-10254793; CC P01100; P15336: ATF2; NbExp=13; IntAct=EBI-852851, EBI-1170906; CC P01100; P18847: ATF3; NbExp=2; IntAct=EBI-852851, EBI-712767; CC P01100; P18848: ATF4; NbExp=4; IntAct=EBI-852851, EBI-492498; CC P01100; P17544: ATF7; NbExp=4; IntAct=EBI-852851, EBI-765623; CC P01100; Q14457: BECN1; NbExp=3; IntAct=EBI-852851, EBI-949378; CC P01100; Q9UFG5: C19orf25; NbExp=3; IntAct=EBI-852851, EBI-741214; CC P01100; Q96HB5: CCDC120; NbExp=3; IntAct=EBI-852851, EBI-744556; CC P01100; A0A024R9H7: CCDC26; NbExp=3; IntAct=EBI-852851, EBI-10271580; CC P01100; P49715: CEBPA; NbExp=2; IntAct=EBI-852851, EBI-1172054; CC P01100; P53567: CEBPG; NbExp=2; IntAct=EBI-852851, EBI-740209; CC P01100; P10909: CLU; NbExp=2; IntAct=EBI-852851, EBI-1104674; CC P01100; Q9Y6G5: COMMD10; NbExp=3; IntAct=EBI-852851, EBI-1550310; CC P01100; Q9BT78: COPS4; NbExp=2; IntAct=EBI-852851, EBI-742413; CC P01100; Q02930-3: CREB5; NbExp=3; IntAct=EBI-852851, EBI-10192698; CC P01100; P35638: DDIT3; NbExp=8; IntAct=EBI-852851, EBI-742651; CC P01100; Q9UI10: EIF2B4; NbExp=3; IntAct=EBI-852851, EBI-2340132; CC P01100; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-852851, EBI-744099; CC P01100; P01100: FOS; NbExp=2; IntAct=EBI-852851, EBI-852851; CC P01100; Q9HC44: GPBP1L1; NbExp=3; IntAct=EBI-852851, EBI-746674; CC P01100; Q13322-4: GRB10; NbExp=3; IntAct=EBI-852851, EBI-12353035; CC P01100; Q13352: ITGB3BP; NbExp=3; IntAct=EBI-852851, EBI-712105; CC P01100; Q9NQC1-2: JADE2; NbExp=3; IntAct=EBI-852851, EBI-10311936; CC P01100; P05412: JUN; NbExp=42; IntAct=EBI-852851, EBI-852823; CC P01100; P17275: JUNB; NbExp=13; IntAct=EBI-852851, EBI-748062; CC P01100; P17535: JUND; NbExp=12; IntAct=EBI-852851, EBI-2682803; CC P01100; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-852851, EBI-2796400; CC P01100; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-852851, EBI-1048945; CC P01100; Q14693: LPIN1; NbExp=3; IntAct=EBI-852851, EBI-5278370; CC P01100; Q9Y5Q3: MAFB; NbExp=2; IntAct=EBI-852851, EBI-3649340; CC P01100; Q03112: MECOM; NbExp=4; IntAct=EBI-852851, EBI-1384862; CC P01100; Q14994: NR1I3; NbExp=3; IntAct=EBI-852851, EBI-960794; CC P01100; P42336: PIK3CA; NbExp=3; IntAct=EBI-852851, EBI-2116585; CC P01100; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-852851, EBI-9090282; CC P01100; Q13526: PIN1; NbExp=3; IntAct=EBI-852851, EBI-714158; CC P01100; O14974: PPP1R12A; NbExp=2; IntAct=EBI-852851, EBI-351726; CC P01100; O14744: PRMT5; NbExp=3; IntAct=EBI-852851, EBI-351098; CC P01100; Q15907: RAB11B; NbExp=3; IntAct=EBI-852851, EBI-722234; CC P01100; Q9BWF3-2: RBM4; NbExp=3; IntAct=EBI-852851, EBI-25856809; CC P01100; Q96CM3: RPUSD4; NbExp=4; IntAct=EBI-852851, EBI-7825200; CC P01100; P11684: SCGB1A1; NbExp=3; IntAct=EBI-852851, EBI-7797649; CC P01100; O60880: SH2D1A; NbExp=3; IntAct=EBI-852851, EBI-6983382; CC P01100; O14796: SH2D1B; NbExp=3; IntAct=EBI-852851, EBI-3923013; CC P01100; Q9P1W8: SIRPG; NbExp=3; IntAct=EBI-852851, EBI-1268284; CC P01100; P42224: STAT1; NbExp=6; IntAct=EBI-852851, EBI-1057697; CC P01100; P56279: TCL1A; NbExp=4; IntAct=EBI-852851, EBI-749995; CC P01100; Q96A09: TENT5B; NbExp=3; IntAct=EBI-852851, EBI-752030; CC P01100; Q8NFB2: TMEM185A; NbExp=3; IntAct=EBI-852851, EBI-21757569; CC P01100; Q13829: TNFAIP1; NbExp=3; IntAct=EBI-852851, EBI-2505861; CC P01100; Q9BZM4: ULBP3; NbExp=3; IntAct=EBI-852851, EBI-1032551; CC P01100; Q6ZMY6-2: WDR88; NbExp=3; IntAct=EBI-852851, EBI-25857007; CC P01100; P52736: ZNF133; NbExp=4; IntAct=EBI-852851, EBI-2687350; CC P01100; Q9UNY5: ZNF232; NbExp=3; IntAct=EBI-852851, EBI-749023; CC P01100; Q9BRT8: ZNG1A; NbExp=3; IntAct=EBI-852851, EBI-1054417; CC P01100; P56671: Maz; Xeno; NbExp=2; IntAct=EBI-852851, EBI-1809712; CC -!- SUBCELLULAR LOCATION: Nucleus. Endoplasmic reticulum. Cytoplasm, CC cytosol. Note=In quiescent cells, present in very small amounts in the CC cytosol. Following induction of cell growth, first localizes to the CC endoplasmic reticulum and only later to the nucleus. Localization at CC the endoplasmic reticulum requires dephosphorylation at Tyr-10 and Tyr- CC 30. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P01100-1; Sequence=Displayed; CC Name=2; CC IsoId=P01100-2; Sequence=VSP_055560; CC Name=3; CC IsoId=P01100-3; Sequence=VSP_055561; CC -!- DEVELOPMENTAL STAGE: Expressed at very low levels in quiescent cells. CC When cells are stimulated to reenter growth, they undergo 2 waves of CC expression, the first one peaks 7.5 minutes following FBS induction. At CC this stage, the protein is localized endoplasmic reticulum. The second CC wave of expression occurs at about 20 minutes after induction and peaks CC at 1 hour. At this stage, the protein becomes nuclear. CC {ECO:0000269|PubMed:17160021}. CC -!- PTM: Phosphorylated in the C-terminal upon stimulation by nerve growth CC factor (NGF) and epidermal growth factor (EGF). Phosphorylated, in CC vitro, by MAPK and RSK1. Phosphorylation on both Ser-362 and Ser-374 by CC MAPK1/2 and RSK1/2 leads to protein stabilization with phosphorylation CC on Ser-374 being the major site for protein stabilization on NGF CC stimulation. Phosphorylation on Ser-362 and Ser-374 primes further CC phosphorylations on Thr-325 and Thr-331 through promoting docking of CC MAPK to the DEF domain. Phosphorylation on Thr-232, induced by HA-RAS, CC activates the transcriptional activity and antagonizes sumoylation. CC Phosphorylation on Ser-362 by RSK2 in osteoblasts contributes to CC osteoblast transformation (By similarity). {ECO:0000250}. 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. {ECO:0000269|PubMed:16055710, CC ECO:0000269|PubMed:17709345}. 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. CC {ECO:0000269|PubMed:17160021, ECO:0000269|PubMed:22105363}. CC -!- SIMILARITY: Belongs to the bZIP family. Fos subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/fos/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; V01512; CAA24756.1; -; Genomic_DNA. DR EMBL; K00650; AAA52471.1; -; Genomic_DNA. DR EMBL; AY212879; AAO21129.1; -; Genomic_DNA. DR EMBL; AK097379; BAG53458.1; -; mRNA. DR EMBL; AK290907; BAF83596.1; -; mRNA. DR EMBL; AK298659; BAG60827.1; -; mRNA. DR EMBL; AF111167; AAC98315.1; -; Genomic_DNA. DR EMBL; CH471061; EAW81229.1; -; Genomic_DNA. DR EMBL; BC004490; AAH04490.1; -; mRNA. DR EMBL; S65138; AAB20306.1; -; mRNA. DR CCDS; CCDS9841.1; -. [P01100-1] DR PIR; A01342; TVHUF1. DR PIR; E34223; E34223. DR RefSeq; NP_005243.1; NM_005252.3. [P01100-1] DR PDB; 1A02; X-ray; 2.70 A; F=138-193. DR PDB; 1FOS; X-ray; 3.05 A; E/G=139-200. DR PDB; 1S9K; X-ray; 3.10 A; D=140-192. DR PDBsum; 1A02; -. DR PDBsum; 1FOS; -. DR PDBsum; 1S9K; -. DR AlphaFoldDB; P01100; -. DR SMR; P01100; -. DR BioGRID; 108636; 265. DR ComplexPortal; CPX-2491; bZIP transcription factor complex, BACH1-FOS. DR ComplexPortal; CPX-480; AP-1 transcription factor complex FOS-JUN-NFATC2. DR ComplexPortal; CPX-486; bZIP transcription factor complex, FOS-JUN. DR ComplexPortal; CPX-6416; bZIP transcription factor complex, ATF2-FOS. DR ComplexPortal; CPX-6477; bZIP transcription factor complex, ATF3-FOS. DR ComplexPortal; CPX-6564; bZIP transcription factor complex, ATF4-FOS. DR ComplexPortal; CPX-6783; bZIP transcription factor complex, ATF7-FOS. DR CORUM; P01100; -. DR DIP; DIP-1047N; -. DR ELM; P01100; -. DR IntAct; P01100; 262. DR MINT; P01100; -. DR STRING; 9606.ENSP00000306245; -. DR BindingDB; P01100; -. DR ChEMBL; CHEMBL5029; -. DR DrugBank; DB08813; Nadroparin. DR DrugBank; DB08804; Nandrolone decanoate. DR DrugBank; DB00852; Pseudoephedrine. DR GlyCosmos; P01100; 8 sites, 2 glycans. DR GlyGen; P01100; 8 sites, 2 O-linked glycans (8 sites). DR iPTMnet; P01100; -. DR PhosphoSitePlus; P01100; -. DR BioMuta; FOS; -. DR DMDM; 120470; -. DR CPTAC; CPTAC-5781; -. DR CPTAC; CPTAC-5782; -. DR CPTAC; CPTAC-5783; -. DR CPTAC; non-CPTAC-5397; -. DR CPTAC; non-CPTAC-5398; -. DR CPTAC; non-CPTAC-5551; -. DR CPTAC; non-CPTAC-5552; -. DR CPTAC; non-CPTAC-5553; -. DR EPD; P01100; -. DR jPOST; P01100; -. DR MassIVE; P01100; -. DR MaxQB; P01100; -. DR PaxDb; 9606-ENSP00000306245; -. DR PeptideAtlas; P01100; -. DR ProteomicsDB; 1860; -. DR ProteomicsDB; 4848; -. DR ProteomicsDB; 51317; -. [P01100-1] DR ABCD; P01100; 13 sequenced antibodies. DR Antibodypedia; 4375; 2337 antibodies from 51 providers. DR CPTC; P01100; 4 antibodies. DR DNASU; 2353; -. DR Ensembl; ENST00000303562.9; ENSP00000306245.4; ENSG00000170345.10. [P01100-1] DR Ensembl; ENST00000535987.5; ENSP00000442268.1; ENSG00000170345.10. [P01100-3] DR Ensembl; ENST00000555686.1; ENSP00000452590.1; ENSG00000170345.10. [P01100-2] DR GeneID; 2353; -. DR KEGG; hsa:2353; -. DR MANE-Select; ENST00000303562.9; ENSP00000306245.4; NM_005252.4; NP_005243.1. DR UCSC; uc010asi.4; human. [P01100-1] DR AGR; HGNC:3796; -. DR CTD; 2353; -. DR DisGeNET; 2353; -. DR GeneCards; FOS; -. DR HGNC; HGNC:3796; FOS. DR HPA; ENSG00000170345; Low tissue specificity. DR MalaCards; FOS; -. DR MIM; 164810; gene. DR neXtProt; NX_P01100; -. DR OpenTargets; ENSG00000170345; -. DR Orphanet; 528; Congenital generalized lipodystrophy. DR PharmGKB; PA28212; -. DR VEuPathDB; HostDB:ENSG00000170345; -. DR eggNOG; KOG1414; Eukaryota. DR GeneTree; ENSGT00940000159276; -. DR HOGENOM; CLU_049742_2_0_1; -. DR InParanoid; P01100; -. DR OMA; FTYPEAE; -. DR OrthoDB; 4614365at2759; -. DR PhylomeDB; P01100; -. DR TreeFam; TF326301; -. DR PathwayCommons; P01100; -. DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. DR Reactome; R-HSA-450341; Activation of the AP-1 family of transcription factors. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes. DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression. DR Reactome; R-HSA-9031628; NGF-stimulated transcription. DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling. DR Reactome; R-HSA-9768919; NPAS4 regulates expression of target genes. DR SignaLink; P01100; -. DR SIGNOR; P01100; -. DR BioGRID-ORCS; 2353; 17 hits in 1182 CRISPR screens. DR ChiTaRS; FOS; human. DR EvolutionaryTrace; P01100; -. DR GeneWiki; C-Fos; -. DR GenomeRNAi; 2353; -. DR Pharos; P01100; Tbio. DR PRO; PR:P01100; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P01100; Protein. DR Bgee; ENSG00000170345; Expressed in mucosa of stomach and 204 other cell types or tissues. DR ExpressionAtlas; P01100; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0032993; C:protein-DNA complex; IMP:CAFA. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal. DR GO; GO:0035976; C:transcription factor AP-1 complex; IDA:CAFA. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0070412; F:R-SMAD binding; IPI:BHF-UCL. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IMP:CAFA. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:CAFA. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL. DR GO; GO:0001221; F:transcription coregulator binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0071276; P:cellular response to cadmium ion; IMP:CAFA. DR GO; GO:0071277; P:cellular response to calcium ion; IEA:Ensembl. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl. DR GO; GO:1904628; P:cellular response to phorbol 13-acetate 12-myristate; IEA:Ensembl. DR GO; GO:1990646; P:cellular response to prolactin; IEA:Ensembl. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:BHF-UCL. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0034224; P:cellular response to zinc ion starvation; IEA:Ensembl. DR GO; GO:0001661; P:conditioned taste aversion; IEA:Ensembl. DR GO; GO:0006306; P:DNA methylation; TAS:ProtInc. DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl. DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc. DR GO; GO:0140467; P:integrated stress response signaling; NAS:ComplexPortal. DR GO; GO:1903131; P:mononuclear cell differentiation; IEA:Ensembl. DR GO; GO:0051450; P:myoblast proliferation; IEA:Ensembl. DR GO; GO:0007399; P:nervous system development; IEA:Ensembl. DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:CAFA. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:ComplexPortal. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl. DR GO; GO:0051412; P:response to corticosterone; IEA:Ensembl. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0009629; P:response to gravity; IEA:Ensembl. DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl. DR GO; GO:0032868; P:response to insulin; IEA:Ensembl. DR GO; GO:0009416; P:response to light stimulus; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl. DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl. DR GO; GO:0014856; P:skeletal muscle cell proliferation; IEA:Ensembl. DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:BHF-UCL. DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR CDD; cd14721; bZIP_Fos; 1. DR DisProt; DP00078; -. DR Gene3D; 1.20.5.170; -; 1. DR IDEAL; IID00436; -. 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. DR Genevisible; P01100; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; DNA-binding; KW Endoplasmic reticulum; Isopeptide bond; Nucleus; Phosphoprotein; KW Proto-oncogene; Reference proteome; Ubl conjugation. FT CHAIN 1..380 FT /note="Protein c-Fos" FT /id="PRO_0000076465" FT DOMAIN 137..200 FT /note="bZIP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978" FT REGION 119..138 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 139..159 FT /note="Basic motif; required for the activation of FT phospholipid synthesis, but not for CDS1-binding" 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:0000269|PubMed:17160021, FT ECO:0000269|PubMed:22105363" FT MOD_RES 30 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:17160021, FT ECO:0000269|PubMed:22105363" FT MOD_RES 232 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P01101" FT MOD_RES 325 FT /note="Phosphothreonine; by MAPK1 and MAPK3" FT /evidence="ECO:0000269|PubMed:12134156" FT MOD_RES 331 FT /note="Phosphothreonine; by MAPK1 and MAPK3" FT /evidence="ECO:0000269|PubMed:12134156" FT MOD_RES 362 FT /note="Phosphoserine; by MAPK1, MAPK3 and RPS6KA3" FT /evidence="ECO:0000269|PubMed:7588633" FT MOD_RES 374 FT /note="Phosphoserine; by MAPK1 and MAPK3" FT /evidence="ECO:0000269|PubMed:12134156, FT ECO:0000269|PubMed:7588633" FT CROSSLNK 113 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 128 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 265 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..114 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055560" FT VAR_SEQ 132..167 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055561" FT MUTAGEN 10 FT /note="Y->E: Loss of activation of phospholipid synthesis; FT when associated with E-30." FT /evidence="ECO:0000269|PubMed:17160021, FT ECO:0000269|PubMed:22105363" FT MUTAGEN 10 FT /note="Y->F: Overall loss of Tyr-phosphorylation, including FT that of Y-30 phosphorylation. Localizes to the endoplasmic FT reticulum in quiescent cells. Activates phospholipid FT synthesis in growing cells." FT /evidence="ECO:0000269|PubMed:17160021, FT ECO:0000269|PubMed:22105363" FT MUTAGEN 30 FT /note="Y->E: Loss of activation of phospholipid synthesis; FT when associated with E-10." FT /evidence="ECO:0000269|PubMed:17160021, FT ECO:0000269|PubMed:22105363" FT MUTAGEN 30 FT /note="Y->F: Overall loss of Tyr-phosphorylation, including FT that of Y-10 phosphorylation. Localizes to the endoplasmic FT reticulum in quiescent cells. Activates phospholipid FT synthesis in growing cells." FT /evidence="ECO:0000269|PubMed:17160021, FT ECO:0000269|PubMed:22105363" FT MUTAGEN 106 FT /note="Y->F: No effect on Tyr-phosphorylation. Loss of FT endoplasmic reticulum localization in quiescent cells." FT /evidence="ECO:0000269|PubMed:17160021" FT MUTAGEN 128 FT /note="K->R: No change in sumoylation." FT /evidence="ECO:0000269|PubMed:16055710" FT MUTAGEN 192 FT /note="K->R: No change in sumoylation." FT /evidence="ECO:0000269|PubMed:16055710" FT MUTAGEN 232 FT /note="T->D: Decreased sumoylation levels." FT /evidence="ECO:0000269|PubMed:16055710" FT MUTAGEN 265 FT /note="K->R: Abolishes sumoylation. No change in nuclear FT location nor on protein stability. Increased AP1 FT transactivation activity when heterodimerized with cJUN." FT /evidence="ECO:0000269|PubMed:16055710" FT MUTAGEN 325 FT /note="T->D: No change in sumoylation levels." FT /evidence="ECO:0000269|PubMed:16055710" FT MUTAGEN 331 FT /note="T->D: No change in sumoylation levels." FT /evidence="ECO:0000269|PubMed:16055710" FT MUTAGEN 337 FT /note="Y->F: No effect on Tyr-phosphorylation. Loss of FT endoplasmic reticulum localization in quiescent cells." FT /evidence="ECO:0000269|PubMed:17160021" FT MUTAGEN 362 FT /note="S->A: Loss of protein stability. Reduced FT MOS/MAPK-mediated transforming ability; when associated FT with A-374." FT /evidence="ECO:0000269|PubMed:16055710, FT ECO:0000269|PubMed:7588633" FT MUTAGEN 362 FT /note="S->D: Increased protein stability. Increased FT MOS/MAPK-mediated transforming ability and no change in FT sumoylation levels; when associated with D-374." FT /evidence="ECO:0000269|PubMed:16055710, FT ECO:0000269|PubMed:7588633" FT MUTAGEN 374 FT /note="S->A: No change in sumoylation levels. Loss of FT protein stability. Reduced MOS/MAPK-mediated transforming FT ability; when associated with A-362." FT /evidence="ECO:0000269|PubMed:16055710, FT ECO:0000269|PubMed:7588633" FT MUTAGEN 374 FT /note="S->D: Increased protein stability. Increased FT MOS/MAPK-mediated transforming ability and no change in FT sumoylation levels; when associated with D-362." FT /evidence="ECO:0000269|PubMed:16055710, FT ECO:0000269|PubMed:7588633" FT CONFLICT 133..144 FT /note="SPEEEEKRRIRR -> ISRRRREKENPK (in Ref. 6; no FT nucleotide entry)" FT /evidence="ECO:0000305" FT HELIX 141..191 FT /evidence="ECO:0007829|PDB:1A02" SQ SEQUENCE 380 AA; 40695 MW; 9E3B2969347C90C8 CRC64; MMFSGFNADY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNAQDFC TDLAVSSANF IPTVTAISTS PDLQWLVQPA LVSSVAPSQT RAPHPFGVPA PSAGAYSRAG VVKTMTGGRA QSIGRRGKVE QLSPEEEEKR RIRRERNKMA AAKCRNRRRE LTDTLQAETD QLEDEKSALQ TEIANLLKEK EKLEFILAAH RPACKIPDDL GFPEEMSVAS LDLTGGLPEV ATPESEEAFT LPLLNDPEPK PSVEPVKSIS SMELKTEPFD DFLFPASSRP SGSETARSVP DMDLSGSFYA ADWEPLHSGS LGMGPMATEL EPLCTPVVTC TPSCTAYTSS FVFTYPEADS FPSCAAAHRK GSSSNEPSSD SLSSPTLLAL //