FOS_HUMAN
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 03-AUG-2022, entry version 240.
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; 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 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: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; Q9BRT8: CBWD1; NbExp=3; IntAct=EBI-852851, EBI-1054417;
CC P01100; Q96HB5: CCDC120; NbExp=3; IntAct=EBI-852851, EBI-744556;
CC P01100; Q8TAB7: 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=3; 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; 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/";
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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; 262.
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 GlyGen; P01100; 8 sites, 2 O-linked glycans (8 sites).
DR iPTMnet; P01100; -.
DR PhosphoSitePlus; P01100; -.
DR BioMuta; FOS; -.
DR DMDM; 120470; -.
DR EPD; P01100; -.
DR jPOST; P01100; -.
DR MassIVE; P01100; -.
DR MaxQB; P01100; -.
DR PaxDb; P01100; -.
DR PeptideAtlas; P01100; -.
DR PRIDE; P01100; -.
DR ProteomicsDB; 1860; -.
DR ProteomicsDB; 4848; -.
DR ProteomicsDB; 51317; -. [P01100-1]
DR ABCD; P01100; 13 sequenced antibodies.
DR Antibodypedia; 4375; 1944 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 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 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 SignaLink; P01100; -.
DR SIGNOR; P01100; -.
DR BioGRID-ORCS; 2353; 16 hits in 1106 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 202 other tissues.
DR ExpressionAtlas; P01100; baseline and differential.
DR Genevisible; P01100; HS.
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:0016020; C:membrane; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
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; IEA:Ensembl.
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:0044877; F:protein-containing complex binding; IEA:Ensembl.
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; IBA:GO_Central.
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:0007568; P:aging; IEA:Ensembl.
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:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; 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: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; IC:ComplexPortal.
DR GO; GO:0007399; P:nervous system development; IEA:Ensembl.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISS:BHF-UCL.
DR GO; GO:1901216; P:positive regulation of neuron death; ISS:ARUK-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:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR GO; GO:0051412; P:response to corticosterone; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine; 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: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:0030431; P:sleep; 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 DisProt; DP00078; -.
DR IDEAL; IID00436; -.
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 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 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 MOS/MAPK-
FT mediated transforming ability; when associated 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
