FGF1_HUMAN
ID FGF1_HUMAN Reviewed; 155 AA.
AC P05230; B2R5T0; D3DQF2; P07502; Q16588;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 242.
DE RecName: Full=Fibroblast growth factor 1;
DE Short=FGF-1;
DE AltName: Full=Acidic fibroblast growth factor;
DE Short=aFGF;
DE AltName: Full=Endothelial cell growth factor;
DE Short=ECGF;
DE AltName: Full=Heparin-binding growth factor 1;
DE Short=HBGF-1;
DE Flags: Precursor;
GN Name=FGF1; Synonyms=FGFA;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Brain stem;
RX PubMed=3523756; DOI=10.1126/science.3523756;
RA Jaye M., Howk R., Burgess W., Ricca G.A., Chiu I.-M., Ravera M.W.,
RA O'Brien S.J., Modi W.S., Maciag T., Drohan W.N.;
RT "Human endothelial cell growth factor: cloning, nucleotide sequence, and
RT chromosome localization.";
RL Science 233:541-545(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2590193; DOI=10.1016/0006-291x(89)91785-3;
RA Mergia A., Tischer E., Graves D., Tumolo A., Miller J., Gospodarowicz D.,
RA Abraham J.A., Shipley G.D., Fiddes J.C.;
RT "Structural analysis of the gene for human acidic fibroblast growth
RT factor.";
RL Biochem. Biophys. Res. Commun. 164:1121-1129(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain stem;
RX PubMed=2474753; DOI=10.1128/mcb.9.6.2387-2395.1989;
RA Wang W.P., Lehtoma K., Varban M.L., Krishnan I., Chiu I.M.;
RT "Cloning of the gene coding for human class 1 heparin-binding growth factor
RT and its expression in fetal tissues.";
RL Mol. Cell. Biol. 9:2387-2395(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain stem;
RX PubMed=1693186;
RA Chiu I.M., Wang W.P., Lehtoma K.;
RT "Alternative splicing generates two forms of mRNA coding for human heparin-
RT binding growth factor 1.";
RL Oncogene 5:755-762(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1717925;
RA Wang W.P., Quick D., Balcerzak S.P., Needleman S.W., Chiu I.M.;
RT "Cloning and sequence analysis of the human acidic fibroblast growth factor
RT gene and its preservation in leukemia patients.";
RL Oncogene 6:1521-1529(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1372643; DOI=10.1084/jem.175.4.1073;
RA Li Y.L., Kha H., Golden J.A., Migchielsen A.A.J., Goetzl E.J., Turck E.J.;
RT "An acidic fibroblast growth factor protein generated by alternate splicing
RT acts like an antagonist.";
RL J. Exp. Med. 175:1073-1080(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF 1-154
RP (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=7504343; DOI=10.1097/00007890-199311000-00025;
RA Zhao X.M., Yeoh T.K., Hiebert M., Frist W.H., Miller G.G.;
RT "The expression of acidic fibroblast growth factor (heparin-binding growth
RT factor-1) and cytokine genes in human cardiac allografts and T cells.";
RL Transplantation 56:1177-1182(1993).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-21.
RG NIEHS SNPs program;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
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 [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-40 (ISOFORMS 1/2).
RX PubMed=2393407; DOI=10.1016/0006-291x(90)91348-v;
RA Crumley G., Dionne C.A., Jaye M.;
RT "The gene for human acidic fibroblast growth factor encodes two upstream
RT exons alternatively spliced to the first coding exon.";
RL Biochem. Biophys. Res. Commun. 171:7-13(1990).
RN [14]
RP PROTEIN SEQUENCE OF 16-155 (ISOFORM 1).
RX PubMed=2427112; DOI=10.1021/bi00362a017;
RA Harper J.W., Strydom D.J., Lobb R.R.;
RT "Human class 1 heparin-binding growth factor: structure and homology to
RT bovine acidic brain fibroblast growth factor.";
RL Biochemistry 25:4097-4103(1986).
RN [15]
RP PROTEIN SEQUENCE OF 16-155 (ISOFORM 1).
RX PubMed=3527167; DOI=10.1016/s0006-291x(86)80540-x;
RA Gimenez-Gallego G., Conn G., Hatcher V.B., Thomas K.A.;
RT "The complete amino acid sequence of human brain-derived acidic fibroblast
RT growth factor.";
RL Biochem. Biophys. Res. Commun. 138:611-617(1986).
RN [16]
RP PROTEIN SEQUENCE OF 16-155 (ISOFORM 1).
RX PubMed=3778488; DOI=10.1016/0006-291x(86)90716-3;
RA Gautschi-Sova P., Mueller T., Boehlen P.;
RT "Amino acid sequence of human acidic fibroblast growth factor.";
RL Biochem. Biophys. Res. Commun. 140:874-880(1986).
RN [17]
RP PROTEIN SEQUENCE OF 16-47 (ISOFORMS 1/2).
RX PubMed=3964259; DOI=10.1016/0006-291x(86)90028-8;
RA Gimenez-Gallego G., Conn G., Hatcher V.B., Thomas K.A.;
RT "Human brain-derived acidic and basic fibroblast growth factors: amino
RT terminal sequences and specific mitogenic activities.";
RL Biochem. Biophys. Res. Commun. 135:541-548(1986).
RN [18]
RP PROTEIN SEQUENCE OF 16-49 (ISOFORMS 1/2).
RX PubMed=3732516; DOI=10.1016/0014-5793(86)80812-2;
RA Gautschi P., Frater-Schroeder M., Boehlen P.;
RT "Partial molecular characterization of endothelial cell mitogens from human
RT brain: acidic and basic fibroblast growth factors.";
RL FEBS Lett. 204:203-207(1986).
RN [19]
RP IDENTIFICATION IN A COMPLEX WITH FGFBP1 AND FGF2, AND INTERACTION WITH
RP FGFBP1.
RX PubMed=1885605; DOI=10.1016/s0021-9258(18)55368-0;
RA Wu D.Q., Kan M.K., Sato G.H., Okamoto T., Sato J.D.;
RT "Characterization and molecular cloning of a putative binding protein for
RT heparin-binding growth factors.";
RL J. Biol. Chem. 266:16778-16785(1991).
RN [20]
RP INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, AND FUNCTION IN CELL
RP PROLIFERATION.
RX PubMed=8663044; DOI=10.1074/jbc.271.25.15292;
RA Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A., Coulier F.,
RA Gao G., Goldfarb M.;
RT "Receptor specificity of the fibroblast growth factor family.";
RL J. Biol. Chem. 271:15292-15297(1996).
RN [21]
RP SUBCELLULAR LOCATION, COPPER-BINDING, AND INTERACTION WITH S100A13 AND
RP SYT1.
RX PubMed=11432880; DOI=10.1074/jbc.m102925200;
RA Landriscina M., Bagala C., Mandinova A., Soldi R., Micucci I., Bellum S.,
RA Prudovsky I., Maciag T.;
RT "Copper induces the assembly of a multiprotein aggregate implicated in the
RT release of fibroblast growth factor 1 in response to stress.";
RL J. Biol. Chem. 276:25549-25557(2001).
RN [22]
RP INTERACTION WITH CSNK2A; CSNK2B; FGF2; FIBP AND LRRC59, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF SER-114; SER-131 AND
RP LYS-133.
RX PubMed=11964394; DOI=10.1074/jbc.m112193200;
RA Skjerpen C.S., Wesche J., Olsnes S.;
RT "Identification of ribosome-binding protein p34 as an intracellular protein
RT that binds acidic fibroblast growth factor.";
RL J. Biol. Chem. 277:23864-23871(2002).
RN [23]
RP INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, AND FUNCTION IN STIMULATION
RP OF CELL PROLIFERATION.
RX PubMed=16597617; DOI=10.1074/jbc.m601252200;
RA Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M.;
RT "Receptor specificity of the fibroblast growth factor family. The complete
RT mammalian FGF family.";
RL J. Biol. Chem. 281:15694-15700(2006).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=18400376; DOI=10.1016/j.canlet.2008.03.001;
RA Di Serio C., Doria L., Pellerito S., Prudovsky I., Micucci I., Massi D.,
RA Landriscina M., Marchionni N., Masotti G., Tarantini F.;
RT "The release of fibroblast growth factor-1 from melanoma cells requires
RT copper ions and is mediated by phosphatidylinositol 3-kinase/Akt
RT intracellular signaling pathway.";
RL Cancer Lett. 267:67-74(2008).
RN [25]
RP FUNCTION, BINDING TO INTEGRIN; HEPARIN AND FGFR1, AND MUTAGENESIS OF
RP ASN-33; ARG-50; GLU-102; TYR-109; ASN-110; LYS-127; LYS-128; LYS-133 AND
RP ARG-134.
RX PubMed=18441324; DOI=10.1074/jbc.m801213200;
RA Mori S., Wu C.Y., Yamaji S., Saegusa J., Shi B., Ma Z., Kuwabara Y.,
RA Lam K.S., Isseroff R.R., Takada Y.K., Takada Y.;
RT "Direct binding of integrin alphavbeta3 to FGF1 plays a role in FGF1
RT signaling.";
RL J. Biol. Chem. 283:18066-18075(2008).
RN [26]
RP SUBCELLULAR LOCATION.
RX PubMed=20863990; DOI=10.1016/s0929-6646(10)60103-9;
RA Cao R., Yan B., Yang H., Zu X., Wen G., Zhong J.;
RT "Effect of human S100A13 gene silencing on FGF-1 transportation in human
RT endothelial cells.";
RL J. Formos. Med. Assoc. 109:632-640(2010).
RN [27]
RP REVIEW.
RX PubMed=15863030; DOI=10.1016/j.cytogfr.2005.01.001;
RA Eswarakumar V.P., Lax I., Schlessinger J.;
RT "Cellular signaling by fibroblast growth factor receptors.";
RL Cytokine Growth Factor Rev. 16:139-149(2005).
RN [28]
RP REVIEW.
RX PubMed=20094046; DOI=10.1038/nrc2780;
RA Turner N., Grose R.;
RT "Fibroblast growth factor signalling: from development to cancer.";
RL Nat. Rev. Cancer 10:116-129(2010).
RN [29]
RP FUNCTION, BINDING TO FGFR1, IDENTIFICATION IN A COMPLEX WITH INTEGRIN AND
RP FGFR1, AND MUTAGENESIS OF ARG-50.
RX PubMed=20422052; DOI=10.1371/journal.pone.0010273;
RA Yamaji S., Saegusa J., Ieguchi K., Fujita M., Mori S., Takada Y.K.,
RA Takada Y.;
RT "A novel fibroblast growth factor-1 (FGF1) mutant that acts as an FGF
RT antagonist.";
RL PLoS ONE 5:E10273-E10273(2010).
RN [30]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF 24-LYS--LYS-27.
RX PubMed=22321063; DOI=10.1111/j.1600-0854.2012.01341.x;
RA Zhen Y., Sorensen V., Skjerpen C.S., Haugsten E.M., Jin Y., Walchli S.,
RA Olsnes S., Wiedlocha A.;
RT "Nuclear import of exogenous FGF1 requires the ER-protein LRRC59 and the
RT importins Kpnalpha1 and Kpnbeta1.";
RL Traffic 13:650-664(2012).
RN [31]
RP FUNCTION, AND MUTAGENESIS OF ARG-50.
RX PubMed=23469107; DOI=10.1371/journal.pone.0057927;
RA Mori S., Tran V., Nishikawa K., Kaneda T., Hamada Y., Kawaguchi N.,
RA Fujita M., Saegusa J., Takada Y.K., Matsuura N., Zhao M., Takada Y.;
RT "A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis
RT and angiogenesis.";
RL PLoS ONE 8:E57927-E57927(2013).
RN [32]
RP ERRATUM OF PUBMED:23469107.
RA Mori S., Tran V., Nishikawa K., Kaneda T., Hamada Y., Kawaguchi N.,
RA Fujita M., Saegusa J., Takada Y.K., Matsuura N., Zhao M., Takada Y.;
RL PLoS ONE 8:E91599-E91599(2013).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 16-155.
RX PubMed=1702556; DOI=10.1126/science.1702556;
RA Zhu X., Komiya H., Chirino A., Faham S., Fox G.M., Arakawa T., Hsu B.T.,
RA Rees D.C.;
RT "Three-dimensional structures of acidic and basic fibroblast growth
RT factors.";
RL Science 251:90-93(1991).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 21-155.
RX PubMed=8652550; DOI=10.1021/bi9521755;
RA Blaber M., Disalvo J., Thomas K.A.;
RT "X-ray crystal structure of human acidic fibroblast growth factor.";
RL Biochemistry 35:2086-2094(1996).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 21-155 IN COMPLEX WITH HEPARIN,
RP AND SUBUNIT.
RX PubMed=9655399; DOI=10.1038/31741;
RA DiGabriele A.D., Lax I., Chen D.I., Svahn C.M., Jaye M., Schlessinger J.,
RA Hendrickson W.A.;
RT "Structure of a heparin-linked biologically active dimer of fibroblast
RT growth factor.";
RL Nature 393:812-817(1998).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 22-155 IN COMPLEX WITH FGFR1.
RX PubMed=10830168; DOI=10.1016/s0092-8674(00)80851-x;
RA Plotnikov A.N., Hubbard S.R., Schlessinger J., Mohammadi M.;
RT "Crystal structures of two FGF-FGFR complexes reveal the determinants of
RT ligand-receptor specificity.";
RL Cell 101:413-424(2000).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 16-155 IN COMPLEX WITH FGFR2 AND
RP HEPARIN.
RX PubMed=11069186; DOI=10.1038/35039551;
RA Pellegrini L., Burke D.F., von Delft F., Mulloy B., Blundell T.L.;
RT "Crystal structure of fibroblast growth factor receptor ectodomain bound to
RT ligand and heparin.";
RL Nature 407:1029-1034(2000).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 21-155 IN COMPLEX WITH FGFR2.
RX PubMed=10618369; DOI=10.1073/pnas.97.1.49;
RA Stauber D.J., DiGabriele A.D., Hendrickson W.A.;
RT "Structural interactions of fibroblast growth factor receptor with its
RT ligands.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:49-54(2000).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 16-155.
RX PubMed=11847269; DOI=10.1110/ps.43802;
RA Kim J., Blaber S.I., Blaber M.;
RT "Alternative type I and I' turn conformations in the beta8/beta9 beta-
RT hairpin of human acidic fibroblast growth factor.";
RL Protein Sci. 11:459-466(2002).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH FGFR3.
RX PubMed=14732692; DOI=10.1073/pnas.0307287101;
RA Olsen S.K., Ibrahimi O.A., Raucci A., Zhang F., Eliseenkova A.V., Yayon A.,
RA Basilico C., Linhardt R.J., Schlessinger J., Mohammadi M.;
RT "Insights into the molecular basis for fibroblast growth factor receptor
RT autoinhibition and ligand-binding promiscuity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:935-940(2004).
RN [41]
RP STRUCTURE BY NMR OF 24-155 IN COMPLEX WITH INOSITOL HEXASULFATE, AND
RP PROTEIN SEQUENCE OF 24-27.
RX PubMed=7521397; DOI=10.1006/jmbi.1994.1558;
RA Pineda-Lucena A., Jimenez M.A., Nieto J.L., Santoro J., Rico M.,
RA Gimenez-Gallego G.;
RT "1H-NMR assignment and solution structure of human acidic fibroblast growth
RT factor activated by inositol hexasulfate.";
RL J. Mol. Biol. 242:81-98(1994).
RN [42]
RP STRUCTURE BY NMR OF 24-155.
RX PubMed=8950275; DOI=10.1006/jmbi.1996.0631;
RA Pineda-Lucena A., Jimenez M.A., Lozano R.M., Nieto J.L., Santoro J.,
RA Rico M., Gimenez-Gallego G.;
RT "Three-dimensional structure of acidic fibroblast growth factor in
RT solution: effects of binding to a heparin functional analog.";
RL J. Mol. Biol. 264:162-178(1996).
RN [43]
RP STRUCTURE BY NMR OF 24-155.
RX PubMed=9719643; DOI=10.1006/jmbi.1998.1977;
RA Lozano R.M., Jimenez M., Santoro J., Rico M., Gimenez-Gallego G.;
RT "Solution structure of acidic fibroblast growth factor bound to 1,3, 6-
RT naphthalenetrisulfonate: a minimal model for the anti-tumoral action of
RT suramins and suradistas.";
RL J. Mol. Biol. 281:899-915(1998).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 24-153 IN COMPLEX WITH GENTISIC
RP ACID AND 2,5-DIHYDROXYPHENYLSULFONATE, FUNCTION, HEPARIN-BINDING, AND
RP INTERACTION WITH FGFR1.
RX PubMed=20145243; DOI=10.1074/jbc.m109.064618;
RA Fernandez I.S., Cuevas P., Angulo J., Lopez-Navajas P.,
RA Canales-Mayordomo A., Gonzalez-Corrochano R., Lozano R.M., Valverde S.,
RA Jimenez-Barbero J., Romero A., Gimenez-Gallego G.;
RT "Gentisic acid, a compound associated with plant defense and a metabolite
RT of aspirin, heads a new class of in vivo fibroblast growth factor
RT inhibitors.";
RL J. Biol. Chem. 285:11714-11729(2010).
RN [45]
RP STRUCTURE BY NMR OF 23-155.
RX PubMed=20220137; DOI=10.1074/jbc.m109.066357;
RA Mohan S.K., Rani S.G., Yu C.;
RT "The heterohexameric complex structure, a component in the non-classical
RT pathway for fibroblast growth factor 1 (FGF1) secretion.";
RL J. Biol. Chem. 285:15464-15475(2010).
CC -!- FUNCTION: Plays an important role in the regulation of cell survival,
CC cell division, angiogenesis, cell differentiation and cell migration.
CC Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and
CC integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1
CC dimerization and activation via sequential autophosphorylation on
CC tyrosine residues which act as docking sites for interacting proteins,
CC leading to the activation of several signaling cascades. Binds to
CC integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary
CC complex formation with integrin and FGFR1, and the recruitment of
CC PTPN11 to the complex are essential for FGF1 signaling. Induces the
CC phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2
CC and AKT1 (PubMed:18441324, PubMed:20422052). Can induce angiogenesis
CC (PubMed:23469107). {ECO:0000269|PubMed:16597617,
CC ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:20145243,
CC ECO:0000269|PubMed:20422052, ECO:0000269|PubMed:23469107,
CC ECO:0000269|PubMed:8663044}.
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and
CC FGFR4. Affinity between fibroblast growth factors (FGFs) and their
CC receptors is increased by heparan sulfate glycosaminoglycans that
CC function as coreceptors. Found in a complex with FGFBP1, FGF1 and FGF2.
CC Interacts with FGFBP1. Part of a Cu(2+)-dependent multiprotein
CC aggregate containing FGF1, S100A13 and SYT1. Interacts with SYT1.
CC Interacts with S100A13. Interacts with LRRC59. Interacts with CSNKA,
CC CSNKB and FIBP. While binding with LRRC59, CSNKA and FIBP seem mutually
CC exclusive, CSNKB and FIBP may cooperatively interact with FGF1. Forms a
CC ternary complex with FGFR1 and ITGAV:ITGB3 and induces the recruitment
CC of PTPN11 to the complex (PubMed:20422052).
CC {ECO:0000269|PubMed:10618369, ECO:0000269|PubMed:10830168,
CC ECO:0000269|PubMed:11069186, ECO:0000269|PubMed:11432880,
CC ECO:0000269|PubMed:11964394, ECO:0000269|PubMed:14732692,
CC ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:1885605,
CC ECO:0000269|PubMed:20145243, ECO:0000269|PubMed:20422052,
CC ECO:0000269|PubMed:7521397, ECO:0000269|PubMed:8663044,
CC ECO:0000269|PubMed:9655399}.
CC -!- INTERACTION:
CC P05230; P11362: FGFR1; NbExp=4; IntAct=EBI-698068, EBI-1028277;
CC P05230; P21802: FGFR2; NbExp=2; IntAct=EBI-698068, EBI-1028658;
CC P05230; P22607: FGFR3; NbExp=3; IntAct=EBI-698068, EBI-348399;
CC P05230; P61758: VBP1; NbExp=3; IntAct=EBI-698068, EBI-357430;
CC P05230-1; P21802-1: FGFR2; NbExp=2; IntAct=EBI-15489950, EBI-15489960;
CC PRO_0000008908; P21802: FGFR2; NbExp=5; IntAct=EBI-6880860, EBI-1028658;
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasm. Cytoplasm, cell cortex.
CC Cytoplasm, cytosol. Nucleus. Note=Lacks a cleavable signal sequence.
CC Within the cytoplasm, it is transported to the cell membrane and then
CC secreted by a non-classical pathway that requires Cu(2+) ions and
CC S100A13. Secreted in a complex with SYT1 (By similarity). Binding of
CC exogenous FGF1 to FGFR facilitates endocytosis followed by
CC translocation of FGF1 across endosomal membrane into the cytosol.
CC Nuclear import from the cytosol requires the classical nuclear import
CC machinery, involving proteins KPNA1 and KPNB1, as well as LRRC59.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P05230-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P05230-2; Sequence=VSP_036536, VSP_036537;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in kidney and brain.
CC Detected at much lower levels in heart and skeletal muscle.
CC {ECO:0000269|PubMed:11964394, ECO:0000269|PubMed:7504343}.
CC -!- PTM: In the nucleus, phosphorylated by PKC/PRKCD.
CC {ECO:0000269|PubMed:22321063}.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fgf1/";
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DR EMBL; M13361; AAA79245.1; -; mRNA.
DR EMBL; M30492; AAA52446.1; -; Genomic_DNA.
DR EMBL; M30490; AAA52446.1; JOINED; Genomic_DNA.
DR EMBL; M30491; AAA52446.1; JOINED; Genomic_DNA.
DR EMBL; M23087; AAA52638.1; -; Genomic_DNA.
DR EMBL; M23086; AAA52638.1; JOINED; Genomic_DNA.
DR EMBL; X51943; CAA36206.1; -; mRNA.
DR EMBL; X65778; CAA46661.1; -; mRNA.
DR EMBL; S67291; AAB29057.2; -; mRNA.
DR EMBL; S67292; AAB29058.1; -; mRNA.
DR EMBL; AY601819; AAS99352.1; -; Genomic_DNA.
DR EMBL; AC005370; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK312301; BAG35227.1; -; mRNA.
DR EMBL; CH471062; EAW61881.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61882.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61885.1; -; Genomic_DNA.
DR EMBL; BC032697; AAH32697.1; -; mRNA.
DR EMBL; M60515; AAA51672.1; -; mRNA.
DR EMBL; M60516; AAA51673.1; -; mRNA.
DR CCDS; CCDS4275.1; -. [P05230-1]
DR CCDS; CCDS4276.1; -. [P05230-2]
DR PIR; A33665; A33665.
DR PIR; JH0708; JH0708.
DR RefSeq; NP_000791.1; NM_000800.4. [P05230-1]
DR RefSeq; NP_001138364.1; NM_001144892.2. [P05230-1]
DR RefSeq; NP_001138406.1; NM_001144934.1. [P05230-1]
DR RefSeq; NP_001138407.1; NM_001144935.1. [P05230-1]
DR RefSeq; NP_001244134.1; NM_001257205.1. [P05230-1]
DR RefSeq; NP_001244136.1; NM_001257207.1. [P05230-1]
DR RefSeq; NP_001244137.1; NM_001257208.1. [P05230-1]
DR RefSeq; NP_001244138.1; NM_001257209.1. [P05230-1]
DR RefSeq; NP_001244139.1; NM_001257210.1. [P05230-1]
DR RefSeq; NP_149127.1; NM_033136.3. [P05230-2]
DR PDB; 1AXM; X-ray; 3.00 A; A/B/C/D/E/F=21-155.
DR PDB; 1DJS; X-ray; 2.40 A; B=21-155.
DR PDB; 1DZC; NMR; -; A=25-155.
DR PDB; 1DZD; NMR; -; A=29-155.
DR PDB; 1E0O; X-ray; 2.80 A; A/C=16-155.
DR PDB; 1EVT; X-ray; 2.80 A; A/B=22-155.
DR PDB; 1HKN; X-ray; 2.00 A; A/B/C/D/E/F=17-155.
DR PDB; 1JQZ; X-ray; 1.65 A; A/B=16-155.
DR PDB; 1JT3; X-ray; 1.95 A; A/B=16-155.
DR PDB; 1JT4; X-ray; 1.78 A; A/B=16-155.
DR PDB; 1JT5; X-ray; 1.85 A; A/B=16-155.
DR PDB; 1JT7; X-ray; 1.70 A; A/B/C/D=16-155.
DR PDB; 1JTC; X-ray; 1.70 A; A/B/C/D=16-155.
DR PDB; 1JY0; X-ray; 1.70 A; A/B=16-155.
DR PDB; 1K5U; X-ray; 2.00 A; A/B/C=16-154.
DR PDB; 1K5V; X-ray; 2.10 A; A/B=16-154.
DR PDB; 1M16; X-ray; 1.70 A; A/B=16-155.
DR PDB; 1NZK; X-ray; 1.95 A; A/B/C/D=16-152.
DR PDB; 1P63; X-ray; 1.60 A; A/B=16-155.
DR PDB; 1PZZ; X-ray; 2.00 A; A/B=16-155.
DR PDB; 1Q03; X-ray; 2.05 A; A/B=16-152.
DR PDB; 1Q04; X-ray; 1.80 A; A/B=16-155.
DR PDB; 1RG8; X-ray; 1.10 A; A/B=16-155.
DR PDB; 1RML; NMR; -; A=1-155.
DR PDB; 1RY7; X-ray; 3.20 A; A=1-155.
DR PDB; 1YTO; X-ray; 2.10 A; A/B/C/D=16-155.
DR PDB; 1Z2V; X-ray; 1.90 A; A/B=16-155.
DR PDB; 1Z4S; X-ray; 2.60 A; A/B/C/D=16-155.
DR PDB; 2AFG; X-ray; 2.00 A; A/B/C/D=16-155.
DR PDB; 2AQZ; X-ray; 1.85 A; A/B=16-155.
DR PDB; 2AXM; X-ray; 3.00 A; A/B=21-155.
DR PDB; 2ERM; NMR; -; A=17-155.
DR PDB; 2HW9; X-ray; 1.60 A; A/B=16-155.
DR PDB; 2HWA; X-ray; 1.65 A; A/B=16-155.
DR PDB; 2HWM; X-ray; 1.60 A; A/B=16-155.
DR PDB; 2HZ9; X-ray; 1.70 A; A/B=16-155.
DR PDB; 2K43; NMR; -; A=23-155.
DR PDB; 2K4A; NMR; -; B=23-155.
DR PDB; 2K8R; NMR; -; A=23-155.
DR PDB; 2KI4; NMR; -; A/D=23-155.
DR PDB; 2KI6; NMR; -; B/E=23-155.
DR PDB; 2NTD; X-ray; 2.52 A; A/B/C/D=16-155.
DR PDB; 2Q9X; X-ray; 1.70 A; A=16-155.
DR PDB; 2RQ9; NMR; -; A=22-155.
DR PDB; 3B9U; X-ray; 1.55 A; A=16-155.
DR PDB; 3BA4; X-ray; 1.80 A; A/B=16-155.
DR PDB; 3BA5; X-ray; 1.75 A; A/B=16-155.
DR PDB; 3BA7; X-ray; 1.60 A; A/B=16-155.
DR PDB; 3BAD; X-ray; 2.00 A; A/B=16-155.
DR PDB; 3BAG; X-ray; 1.75 A; A/B=16-155.
DR PDB; 3BAH; X-ray; 1.65 A; A/B=16-155.
DR PDB; 3BAO; X-ray; 1.55 A; A/B=16-155.
DR PDB; 3BAQ; X-ray; 1.80 A; A/B=16-155.
DR PDB; 3BAU; X-ray; 1.60 A; A/B=16-155.
DR PDB; 3BAV; X-ray; 1.62 A; A/B=16-155.
DR PDB; 3BB2; X-ray; 1.50 A; A/B=16-155.
DR PDB; 3CQA; X-ray; 1.80 A; A/B=16-155.
DR PDB; 3CRG; X-ray; 1.85 A; A/B=16-155.
DR PDB; 3CRH; X-ray; 2.15 A; A/B=16-155.
DR PDB; 3CRI; X-ray; 2.10 A; A/B=16-155.
DR PDB; 3CU1; X-ray; 2.60 A; B/D=22-152.
DR PDB; 3FGM; X-ray; 1.95 A; A/B=16-155.
DR PDB; 3FJ8; X-ray; 2.00 A; A/B=16-155.
DR PDB; 3FJ9; X-ray; 1.90 A; A/B=16-155.
DR PDB; 3FJA; X-ray; 1.95 A; A/B=16-155.
DR PDB; 3FJB; X-ray; 2.00 A; A/B=16-155.
DR PDB; 3FJC; X-ray; 2.00 A; A/B=16-155.
DR PDB; 3FJD; X-ray; 1.90 A; A/B=16-155.
DR PDB; 3FJE; X-ray; 2.10 A; A/B=16-155.
DR PDB; 3FJF; X-ray; 1.90 A; A/B=16-155.
DR PDB; 3FJH; X-ray; 1.90 A; A/B=16-155.
DR PDB; 3FJI; X-ray; 2.55 A; A/B/C/D=16-155.
DR PDB; 3FJJ; X-ray; 1.90 A; A/B=16-155.
DR PDB; 3FJK; X-ray; 2.15 A; A/B/C/D=16-155.
DR PDB; 3HOM; X-ray; 2.30 A; A/B=16-155.
DR PDB; 3JUT; X-ray; 2.25 A; A/B/C/D/E/F=24-153.
DR PDB; 3K1X; X-ray; 1.98 A; A/B/C/D/E/F=24-153.
DR PDB; 3O3Q; X-ray; 1.60 A; A/B/C/D=16-155.
DR PDB; 3OJ2; X-ray; 2.20 A; A/B=1-155.
DR PDB; 3OJM; X-ray; 2.10 A; A=1-155.
DR PDB; 3OJV; X-ray; 2.60 A; A/B=21-155.
DR PDB; 3UD7; X-ray; 2.80 A; A/B/C=16-155.
DR PDB; 3UD8; X-ray; 2.37 A; A/B/C=16-155.
DR PDB; 3UD9; X-ray; 2.34 A; A/B/C=16-155.
DR PDB; 3UDA; X-ray; 2.51 A; A/B/C=16-155.
DR PDB; 4J23; X-ray; 3.88 A; B=21-155.
DR PDB; 4Q91; X-ray; 1.80 A; A/B=16-155.
DR PDB; 4Q9G; X-ray; 1.55 A; A/B=16-155.
DR PDB; 4Q9P; X-ray; 1.80 A; A/B=16-155.
DR PDB; 4QAL; X-ray; 1.50 A; A/B=16-155.
DR PDB; 4QBC; X-ray; 1.52 A; A/B=16-155.
DR PDB; 4QBV; X-ray; 1.50 A; A/B=16-155.
DR PDB; 4QC4; X-ray; 1.49 A; A/B=16-155.
DR PDB; 4QO3; X-ray; 2.05 A; A/B=16-155.
DR PDB; 4XKI; X-ray; 2.00 A; A/B=16-155.
DR PDB; 4YOL; X-ray; 1.97 A; A/B=16-155.
DR PDBsum; 1AXM; -.
DR PDBsum; 1DJS; -.
DR PDBsum; 1DZC; -.
DR PDBsum; 1DZD; -.
DR PDBsum; 1E0O; -.
DR PDBsum; 1EVT; -.
DR PDBsum; 1HKN; -.
DR PDBsum; 1JQZ; -.
DR PDBsum; 1JT3; -.
DR PDBsum; 1JT4; -.
DR PDBsum; 1JT5; -.
DR PDBsum; 1JT7; -.
DR PDBsum; 1JTC; -.
DR PDBsum; 1JY0; -.
DR PDBsum; 1K5U; -.
DR PDBsum; 1K5V; -.
DR PDBsum; 1M16; -.
DR PDBsum; 1NZK; -.
DR PDBsum; 1P63; -.
DR PDBsum; 1PZZ; -.
DR PDBsum; 1Q03; -.
DR PDBsum; 1Q04; -.
DR PDBsum; 1RG8; -.
DR PDBsum; 1RML; -.
DR PDBsum; 1RY7; -.
DR PDBsum; 1YTO; -.
DR PDBsum; 1Z2V; -.
DR PDBsum; 1Z4S; -.
DR PDBsum; 2AFG; -.
DR PDBsum; 2AQZ; -.
DR PDBsum; 2AXM; -.
DR PDBsum; 2ERM; -.
DR PDBsum; 2HW9; -.
DR PDBsum; 2HWA; -.
DR PDBsum; 2HWM; -.
DR PDBsum; 2HZ9; -.
DR PDBsum; 2K43; -.
DR PDBsum; 2K4A; -.
DR PDBsum; 2K8R; -.
DR PDBsum; 2KI4; -.
DR PDBsum; 2KI6; -.
DR PDBsum; 2NTD; -.
DR PDBsum; 2Q9X; -.
DR PDBsum; 2RQ9; -.
DR PDBsum; 3B9U; -.
DR PDBsum; 3BA4; -.
DR PDBsum; 3BA5; -.
DR PDBsum; 3BA7; -.
DR PDBsum; 3BAD; -.
DR PDBsum; 3BAG; -.
DR PDBsum; 3BAH; -.
DR PDBsum; 3BAO; -.
DR PDBsum; 3BAQ; -.
DR PDBsum; 3BAU; -.
DR PDBsum; 3BAV; -.
DR PDBsum; 3BB2; -.
DR PDBsum; 3CQA; -.
DR PDBsum; 3CRG; -.
DR PDBsum; 3CRH; -.
DR PDBsum; 3CRI; -.
DR PDBsum; 3CU1; -.
DR PDBsum; 3FGM; -.
DR PDBsum; 3FJ8; -.
DR PDBsum; 3FJ9; -.
DR PDBsum; 3FJA; -.
DR PDBsum; 3FJB; -.
DR PDBsum; 3FJC; -.
DR PDBsum; 3FJD; -.
DR PDBsum; 3FJE; -.
DR PDBsum; 3FJF; -.
DR PDBsum; 3FJH; -.
DR PDBsum; 3FJI; -.
DR PDBsum; 3FJJ; -.
DR PDBsum; 3FJK; -.
DR PDBsum; 3HOM; -.
DR PDBsum; 3JUT; -.
DR PDBsum; 3K1X; -.
DR PDBsum; 3O3Q; -.
DR PDBsum; 3OJ2; -.
DR PDBsum; 3OJM; -.
DR PDBsum; 3OJV; -.
DR PDBsum; 3UD7; -.
DR PDBsum; 3UD8; -.
DR PDBsum; 3UD9; -.
DR PDBsum; 3UDA; -.
DR PDBsum; 4J23; -.
DR PDBsum; 4Q91; -.
DR PDBsum; 4Q9G; -.
DR PDBsum; 4Q9P; -.
DR PDBsum; 4QAL; -.
DR PDBsum; 4QBC; -.
DR PDBsum; 4QBV; -.
DR PDBsum; 4QC4; -.
DR PDBsum; 4QO3; -.
DR PDBsum; 4XKI; -.
DR PDBsum; 4YOL; -.
DR AlphaFoldDB; P05230; -.
DR BMRB; P05230; -.
DR SMR; P05230; -.
DR BioGRID; 108537; 43.
DR CORUM; P05230; -.
DR DIP; DIP-3787N; -.
DR IntAct; P05230; 18.
DR MINT; P05230; -.
DR STRING; 9606.ENSP00000480791; -.
DR BindingDB; P05230; -.
DR ChEMBL; CHEMBL2120; -.
DR DrugBank; DB08238; 5-aminonaphthalene-2-sulfonic acid.
DR DrugBank; DB01025; Amlexanox.
DR DrugBank; DB10770; Foreskin fibroblast (neonatal).
DR DrugBank; DB10772; Foreskin keratinocyte (neonatal).
DR DrugBank; DB01942; Formic acid.
DR DrugBank; DB01109; Heparin.
DR DrugBank; DB03959; N,O6-Disulfo-Glucosamine.
DR DrugBank; DB04409; Naphthalene Trisulfonate.
DR DrugBank; DB02264; O2-Sulfo-Glucuronic Acid.
DR DrugBank; DB06589; Pazopanib.
DR DrugBank; DB00686; Pentosan polysulfate.
DR DrugBank; DB01901; Sucrosofate.
DR iPTMnet; P05230; -.
DR PhosphoSitePlus; P05230; -.
DR BioMuta; FGF1; -.
DR DMDM; 122737; -.
DR EPD; P05230; -.
DR MassIVE; P05230; -.
DR MaxQB; P05230; -.
DR PaxDb; P05230; -.
DR PeptideAtlas; P05230; -.
DR PRIDE; P05230; -.
DR ProteomicsDB; 51826; -. [P05230-1]
DR ProteomicsDB; 51827; -. [P05230-2]
DR TopDownProteomics; P05230-1; -. [P05230-1]
DR ABCD; P05230; 1 sequenced antibody.
DR Antibodypedia; 1009; 777 antibodies from 44 providers.
DR DNASU; 2246; -.
DR Ensembl; ENST00000337706.7; ENSP00000338548.2; ENSG00000113578.18. [P05230-1]
DR Ensembl; ENST00000359370.10; ENSP00000352329.6; ENSG00000113578.18. [P05230-1]
DR Ensembl; ENST00000360966.9; ENSP00000354231.5; ENSG00000113578.18. [P05230-2]
DR Ensembl; ENST00000378046.5; ENSP00000367285.1; ENSG00000113578.18. [P05230-1]
DR Ensembl; ENST00000419524.6; ENSP00000396195.2; ENSG00000113578.18. [P05230-1]
DR Ensembl; ENST00000441680.6; ENSP00000404742.2; ENSG00000113578.18. [P05230-1]
DR Ensembl; ENST00000610990.4; ENSP00000481868.1; ENSG00000113578.18. [P05230-1]
DR Ensembl; ENST00000612258.4; ENSP00000479024.1; ENSG00000113578.18. [P05230-1]
DR Ensembl; ENST00000619447.4; ENSP00000480980.1; ENSG00000113578.18. [P05230-1]
DR Ensembl; ENST00000621536.4; ENSP00000480791.1; ENSG00000113578.18. [P05230-1]
DR GeneID; 2246; -.
DR KEGG; hsa:2246; -.
DR MANE-Select; ENST00000337706.7; ENSP00000338548.2; NM_000800.5; NP_000791.1.
DR UCSC; uc003lmm.5; human. [P05230-1]
DR CTD; 2246; -.
DR DisGeNET; 2246; -.
DR GeneCards; FGF1; -.
DR HGNC; HGNC:3665; FGF1.
DR HPA; ENSG00000113578; Tissue enhanced (brain, choroid plexus).
DR MIM; 131220; gene.
DR neXtProt; NX_P05230; -.
DR OpenTargets; ENSG00000113578; -.
DR PharmGKB; PA28105; -.
DR VEuPathDB; HostDB:ENSG00000113578; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000160557; -.
DR HOGENOM; CLU_081609_5_1_1; -.
DR InParanoid; P05230; -.
DR OMA; MHADKNW; -.
DR OrthoDB; 1157770at2759; -.
DR PhylomeDB; P05230; -.
DR TreeFam; TF317805; -.
DR PathwayCommons; P05230; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1839122; Signaling by activated point mutants of FGFR1.
DR Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3.
DR Reactome; R-HSA-190322; FGFR4 ligand binding and activation.
DR Reactome; R-HSA-190370; FGFR1b ligand binding and activation.
DR Reactome; R-HSA-190371; FGFR3b ligand binding and activation.
DR Reactome; R-HSA-190372; FGFR3c ligand binding and activation.
DR Reactome; R-HSA-190373; FGFR1c ligand binding and activation.
DR Reactome; R-HSA-190375; FGFR2c ligand binding and activation.
DR Reactome; R-HSA-190377; FGFR2b ligand binding and activation.
DR Reactome; R-HSA-2033519; Activated point mutants of FGFR2.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1.
DR Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2.
DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3.
DR Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4.
DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1.
DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1.
DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1.
DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling.
DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2.
DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling.
DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3.
DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4.
DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease.
DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease.
DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-8851708; Signaling by FGFR2 IIIa TM.
DR SignaLink; P05230; -.
DR SIGNOR; P05230; -.
DR BioGRID-ORCS; 2246; 16 hits in 1071 CRISPR screens.
DR ChiTaRS; FGF1; human.
DR EvolutionaryTrace; P05230; -.
DR GeneWiki; FGF1; -.
DR GenomeRNAi; 2246; -.
DR Pharos; P05230; Tchem.
DR PRO; PR:P05230; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P05230; protein.
DR Bgee; ENSG00000113578; Expressed in renal glomerulus and 159 other tissues.
DR ExpressionAtlas; P05230; baseline and differential.
DR Genevisible; P05230; HS.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IMP:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IEA:Ensembl.
DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB.
DR GO; GO:0044548; F:S100 protein binding; IPI:UniProtKB.
DR GO; GO:0032148; P:activation of protein kinase B activity; IMP:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0060681; P:branch elongation involved in ureteric bud branching; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0030324; P:lung development; IBA:GO_Central.
DR GO; GO:0072163; P:mesonephric epithelium development; IDA:UniProtKB.
DR GO; GO:0001759; P:organ induction; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; IDA:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IBA:GO_Central.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IEA:Ensembl.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; IDA:BHF-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR GO; GO:2000544; P:regulation of endothelial cell chemotaxis to fibroblast growth factor; IDA:UniProtKB.
DR GO; GO:1901509; P:regulation of endothelial tube morphogenesis; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0042060; P:wound healing; IDA:UniProtKB.
DR CDD; cd00058; FGF; 1.
DR InterPro; IPR028210; FGF1.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; PTHR11486; 1.
DR PANTHER; PTHR11486:SF86; PTHR11486:SF86; 1.
DR Pfam; PF00167; FGF; 1.
DR PRINTS; PR00263; HBGFFGF.
DR SMART; SM00442; FGF; 1.
DR SUPFAM; SSF50353; SSF50353; 1.
DR PROSITE; PS00247; HBGF_FGF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Angiogenesis; Cytoplasm;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Growth factor; Heparin-binding; Mitogen; Nucleus; Phosphoprotein;
KW Reference proteome; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P03968"
FT PROPEP 2..15
FT /id="PRO_0000008907"
FT CHAIN 16..155
FT /note="Fibroblast growth factor 1"
FT /id="PRO_0000008908"
FT REGION 127..143
FT /note="Heparin-binding"
FT MOTIF 24..27
FT /note="Nuclear localization signal"
FT BINDING 33
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000269|PubMed:11069186,
FT ECO:0000269|PubMed:9655399"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P03968"
FT VAR_SEQ 57..60
FT /note="IQLQ -> TDTK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7504343"
FT /id="VSP_036536"
FT VAR_SEQ 61..155
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7504343"
FT /id="VSP_036537"
FT VARIANT 21
FT /note="G -> E (in dbSNP:rs17223632)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_021357"
FT MUTAGEN 24..27
FT /note="KKPK->AAPA: Loss of nuclear import leading to loss
FT of phosphorylation by PKC/PRKCD."
FT /evidence="ECO:0000269|PubMed:22321063"
FT MUTAGEN 33
FT /note="N->A: No effect on integrin-binding."
FT /evidence="ECO:0000269|PubMed:18441324"
FT MUTAGEN 50
FT /note="R->E: Dominant-negative mutant. Defective in
FT integrin-binding and in ternary complex formation with
FT integrin and FGFR1. No effect on heparin- and FGFR1-
FT binding. Defective in inducing FGF1 signaling, cell
FT proliferation and cell migration. Defective in inducing
FT angiogenesis, and suppression of angiogenesis in different
FT in vitro and in vivo angiogenesis models."
FT /evidence="ECO:0000269|PubMed:18441324,
FT ECO:0000269|PubMed:20422052, ECO:0000269|PubMed:23469107"
FT MUTAGEN 102
FT /note="E->A: No effect on integrin-binding. No effect on
FT integrin- and heparin-binding, loss of FGFR1-binding,
FT defective in inducing FGF1 signaling, cell proliferation
FT and cell migration; when associated with A-109 and A-110."
FT /evidence="ECO:0000269|PubMed:18441324"
FT MUTAGEN 109
FT /note="Y->A: No effect on integrin- and heparin-binding,
FT loss of FGFR1-binding, defective in inducing FGF1
FT signaling, cell proliferation and cell migration; when
FT associated with A-102 and A-110."
FT /evidence="ECO:0000269|PubMed:18441324"
FT MUTAGEN 110
FT /note="N->A: No effect on integrin-binding. No effect on
FT integrin- and heparin-binding, loss of FGFR1-binding,
FT defective in inducing FGF1 signaling, cell proliferation
FT and cell migration; when associated with A-102 and A-109."
FT /evidence="ECO:0000269|PubMed:18441324"
FT MUTAGEN 114
FT /note="S->A: Decrease in LRRC59-binding."
FT /evidence="ECO:0000269|PubMed:11964394"
FT MUTAGEN 127
FT /note="K->E: Reduced integrin-binding; when associated with
FT E-128. Defective in integrin-, heparin- and FGFR1-binding,
FT and defective in inducing FGF1 signaling, cell
FT proliferation and cell migration; when associated with E-
FT 128; E-133 and E-134."
FT /evidence="ECO:0000269|PubMed:18441324"
FT MUTAGEN 128
FT /note="K->E: Reduced integrin-binding; when associated with
FT E-127. Defective in integrin-, heparin- and FGFR1-binding,
FT and defective in inducing FGF1 signaling, cell
FT proliferation and cell migration; when associated with E-
FT 127; E-133 and E-134."
FT /evidence="ECO:0000269|PubMed:18441324"
FT MUTAGEN 131
FT /note="S->A: Decrease in LRRC59-binding."
FT /evidence="ECO:0000269|PubMed:11964394"
FT MUTAGEN 131
FT /note="S->E: Decrease in LRRC59-binding."
FT /evidence="ECO:0000269|PubMed:11964394"
FT MUTAGEN 133
FT /note="K->A: Loss of LRRC59-binding."
FT /evidence="ECO:0000269|PubMed:11964394"
FT MUTAGEN 133
FT /note="K->E: Loss of CSNK2A-, CSNK2B- and LRRC59-binding.
FT Reduced integrin-binding; when associated with E-134.
FT Defective in integrin-, heparin- and FGFR1-binding, and
FT defective in inducing FGF1 signaling, cell proliferation
FT and cell migration; when associated with E-128; E-133 and
FT E-134."
FT /evidence="ECO:0000269|PubMed:11964394,
FT ECO:0000269|PubMed:18441324"
FT MUTAGEN 133
FT /note="K->R: No effect on LRRC59-binding."
FT /evidence="ECO:0000269|PubMed:11964394"
FT MUTAGEN 134
FT /note="R->E: Reduced integrin-binding; when associated with
FT E-133. Defective in integrin-, heparin- and FGFR1-binding,
FT and defective in inducing FGF1 signaling, cell
FT proliferation and cell migration; when associated with E-
FT 127; E-128 and E-133."
FT /evidence="ECO:0000269|PubMed:18441324"
FT TURN 11..13
FT /evidence="ECO:0007829|PDB:3OJM"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:1RG8"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:1RG8"
FT TURN 32..35
FT /evidence="ECO:0007829|PDB:1RG8"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:1RG8"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:1DZC"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:1RG8"
FT HELIX 55..57
FT /evidence="ECO:0007829|PDB:3B9U"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:1RG8"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:1RG8"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:1RG8"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:1RG8"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:3OJ2"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:1RG8"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:1RG8"
FT STRAND 100..105
FT /evidence="ECO:0007829|PDB:1RG8"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:1RG8"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:1RG8"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:1RG8"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:3O3Q"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:4QC4"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:1RG8"
FT TURN 138..141
FT /evidence="ECO:0007829|PDB:2K43"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:3B9U"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:1RG8"
SQ SEQUENCE 155 AA; 17460 MW; F586E8BFB09F1580 CRC64;
MAEGEITTFT ALTEKFNLPP GNYKKPKLLY CSNGGHFLRI LPDGTVDGTR DRSDQHIQLQ
LSAESVGEVY IKSTETGQYL AMDTDGLLYG SQTPNEECLF LERLEENHYN TYISKKHAEK
NWFVGLKKNG SCKRGPRTHY GQKAILFLPL PVSSD
