FGF2_HUMAN
ID FGF2_HUMAN Reviewed; 288 AA.
AC P09038; A4LBB8; O00527; P78443; Q16443; Q5PY50; Q7KZ11; Q7KZ72; Q9UC54;
AC Q9UCS5; Q9UCS6;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 13-OCT-2009, sequence version 3.
DT 03-AUG-2022, entry version 245.
DE RecName: Full=Fibroblast growth factor 2;
DE Short=FGF-2;
DE AltName: Full=Basic fibroblast growth factor;
DE Short=bFGF;
DE AltName: Full=Heparin-binding growth factor 2;
DE Short=HBGF-2;
DE Flags: Precursor;
GN Name=FGF2; Synonyms=FGFB;
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=3472745; DOI=10.1101/sqb.1986.051.01.078;
RA Abraham J.A., Whang J.L., Tumolo A., Mergia A., Fiddes J.C.;
RT "Human basic fibroblast growth factor: nucleotide sequence, genomic
RT organization, and expression in mammalian cells.";
RL Cold Spring Harb. Symp. Quant. Biol. 51:657-668(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=3780670; DOI=10.1002/j.1460-2075.1986.tb04530.x;
RA Abraham J.A., Whang J.L., Tumolo A., Mergia A., Friedman J.,
RA Gospodarowicz D., Fiddes J.C.;
RT "Human basic fibroblast growth factor: nucleotide sequence and genomic
RT organization.";
RL EMBO J. 5:2523-2528(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), PROTEIN SEQUENCE OF
RP 126-145 (ISOFORMS 1/2/4), AND ALTERNATIVE INITIATION.
RC TISSUE=Hepatoma;
RX PubMed=2538817; DOI=10.1073/pnas.86.6.1836;
RA Prats H., Kaghad M., Prats A.C., Klagsbrun M., Lelias J.M., Liauzun P.,
RA Chalon P., Tauber J.P., Amalric F., Smith J.A., Caput D.;
RT "High molecular mass forms of basic fibroblast growth factor are initiated
RT by alternative CUG codons.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:1836-1840(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-192.
RX PubMed=1785797; DOI=10.1111/j.1749-6632.1991.tb49022.x;
RA Florkiewicz R.Z., Shibata F., Barankiewicz T., Baird A., Gonzalez A.M.,
RA Florkiewicz E., Shah N.;
RT "Basic fibroblast growth factor gene expression.";
RL Ann. N. Y. Acad. Sci. 638:109-126(1991).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-192.
RC TISSUE=Blood;
RA Handschug K., Archoukieh E., Glaeser C.;
RT "Mutations in the 5' untranslated region of the FGF-2 gene.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-288 (ISOFORM 1).
RX PubMed=2435575; DOI=10.1016/0014-5793(87)81489-8;
RA Kurokawa T., Sasada R., Iwane M., Igarashi K.;
RT "Cloning and expression of cDNA encoding human basic fibroblast growth
RT factor.";
RL FEBS Lett. 213:189-194(1987).
RN [11]
RP PROTEIN SEQUENCE OF 94-107 AND 162-173, FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Hepatoma;
RX PubMed=1721615; DOI=10.1111/j.1349-7006.1991.tb01791.x;
RA Shimoyama Y., Gotoh M., Ino Y., Sakamoto M., Kato K., Hirohashi S.;
RT "Characterization of high-molecular-mass forms of basic fibroblast growth
RT factor produced by hepatocellular carcinoma cells: possible involvement of
RT basic fibroblast growth factor in hepatocarcinogenesis.";
RL Jpn. J. Cancer Res. 82:1263-1270(1991).
RN [12]
RP PROTEIN SEQUENCE OF 125-140 (ISOFORMS 1/2/4).
RX PubMed=8564983;
RA Izbicka E., Dunstan C., Esparza J., Jacobs C., Sabatini M., Mundy G.R.;
RT "Human amniotic tumor that induces new bone formation in vivo produces
RT growth-regulatory activity in vitro for osteoblasts identified as an
RT extended form of basic fibroblast growth factor.";
RL Cancer Res. 56:633-636(1996).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 132-288 (ISOFORMS 1/2/4), AND PROTEIN
RP SEQUENCE OF 132-148; 153-160; 165-247; 252-261 AND 267-288 (ISOFORMS 2/4).
RC TISSUE=Hepatoma, and Placenta;
RX PubMed=3579930; DOI=10.1016/s0006-291x(87)80001-3;
RA Sommer A., Brewer M.T., Thompson R.C., Moscatelli D., Presta M.,
RA Rifkin D.B.;
RT "A form of human basic fibroblast growth factor with an extended amino
RT terminus.";
RL Biochem. Biophys. Res. Commun. 144:543-550(1987).
RN [14]
RP PROTEIN SEQUENCE OF 135-155 (ISOFORMS 1/2/3/4).
RX PubMed=2435284; DOI=10.1016/0006-291x(87)91471-9;
RA Story M.T., Esch F., Shimasaki S., Sasse J., Jacobs S.C., Lawson R.K.;
RT "Amino-terminal sequence of a large form of basic fibroblast growth factor
RT isolated from human benign prostatic hyperplastic tissue.";
RL Biochem. Biophys. Res. Commun. 142:702-709(1987).
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 143-288 (ISOFORMS 1/2/3/4).
RA Zhang H.J., Zhang S.M., Zhuang H.;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [16]
RP PROTEIN SEQUENCE OF 143-172 (ISOFORMS 1/2/3/4), AND FUNCTION.
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 [17]
RP PROTEIN SEQUENCE OF 143-168 (ISOFORMS 1/2/3/4), AND FUNCTION.
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 [18]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 173-260 (ISOFORMS 1/2/3/4), AND TISSUE
RP SPECIFICITY.
RX PubMed=1417798; DOI=10.1016/0006-291x(92)90434-m;
RA Watson R., Anthony F., Pickett M., Lambden P., Masson G.M., Thomas E.J.;
RT "Reverse transcription with nested polymerase chain reaction shows
RT expression of basic fibroblast growth factor transcripts in human granulosa
RT and cumulus cells from in vitro fertilisation patients.";
RL Biochem. Biophys. Res. Commun. 187:1227-1231(1992).
RN [19]
RP IDENTIFICATION IN A COMPLEX WITH FGFBP1 AND FGF1.
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 FUNCTION, AND INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4.
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 INTERACTION WITH CSPG4.
RX PubMed=10358027; DOI=10.1074/jbc.274.24.16831;
RA Goretzki L., Burg M.A., Grako K.A., Stallcup W.B.;
RT "High-affinity binding of basic fibroblast growth factor and platelet-
RT derived growth factor-AA to the core protein of the NG2 proteoglycan.";
RL J. Biol. Chem. 274:16831-16837(1999).
RN [22]
RP INTERACTION WITH FGFBP1.
RX PubMed=11509569; DOI=10.1074/jbc.m104933200;
RA Tassi E., Al-Attar A., Aigner A., Swift M.R., McDonnell K., Karavanov A.,
RA Wellstein A.;
RT "Enhancement of fibroblast growth factor (FGF) activity by an FGF-binding
RT protein.";
RL J. Biol. Chem. 276:40247-40253(2001).
RN [23]
RP INTERACTION WITH FGF1.
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 [24]
RP INTERACTION WITH FGFBP1.
RX PubMed=16257968; DOI=10.1074/jbc.m510754200;
RA Xie B., Tassi E., Swift M.R., McDonnell K., Bowden E.T., Wang S., Ueda Y.,
RA Tomita Y., Riegel A.T., Wellstein A.;
RT "Identification of the fibroblast growth factor (FGF)-interacting domain in
RT a secreted FGF-binding protein by phage display.";
RL J. Biol. Chem. 281:1137-1144(2006).
RN [25]
RP INTERACTION WITH FGFBP3.
RX PubMed=18669637; DOI=10.1074/jbc.m802144200;
RA Zhang W., Chen Y., Swift M.R., Tassi E., Stylianou D.C., Gibby K.A.,
RA Riegel A.T., Wellstein A.;
RT "Effect of FGF-binding protein 3 on vascular permeability.";
RL J. Biol. Chem. 283:28329-28337(2008).
RN [26]
RP PHOSPHORYLATION AT TYR-215, INTERACTION WITH TEC, AND SUBCELLULAR LOCATION.
RX PubMed=20230531; DOI=10.1111/j.1600-0854.2010.01059.x;
RA Ebert A.D., Laussmann M., Wegehingel S., Kaderali L., Erfle H.,
RA Reichert J., Lechner J., Beer H.D., Pepperkok R., Nickel W.;
RT "Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is
RT essential for unconventional secretion.";
RL Traffic 11:813-826(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 SUBCELLULAR LOCATION.
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 [30]
RP FUNCTION.
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 [31]
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 [32]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-228, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [33]
RP FUNCTION, INTERACTION WITH INTEGRIN ITGAV:ITGB3, SITES IMPORTANT FOR
RP INTEGRIN BINDING, AND MUTAGENESIS OF ARG-181; ARG-186; LYS-188;
RP 261-LYS-ARG-262 AND LYS-267.
RX PubMed=28302677; DOI=10.1042/bsr20170173;
RA Mori S., Hatori N., Kawaguchi N., Hamada Y., Shih T.C., Wu C.Y., Lam K.S.,
RA Matsuura N., Yamamoto H., Takada Y.K., Takada Y.;
RT "The integrin-binding defective FGF2 mutants potently suppress FGF2
RT signalling and angiogenesis.";
RL Biosci. Rep. 37:0-0(2017).
RN [34]
RP FUNCTION.
RX PubMed=29501879; DOI=10.1016/j.exer.2018.02.025;
RA Zhao G., Bailey C.G., Feng Y., Rasko J., Lovicu F.J.;
RT "Negative regulation of lens fiber cell differentiation by RTK antagonists
RT Spry and Spred.";
RL Exp. Eye Res. 170:148-159(2018).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 143-288.
RX PubMed=1769963; DOI=10.1093/oxfordjournals.jbchem.a123586;
RA Ago H., Kitagawa Y., Fujishima A., Matsuura Y., Katsube Y.;
RT "Crystal structure of basic fibroblast growth factor at 1.6-A resolution.";
RL J. Biochem. 110:360-363(1991).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 143-288.
RX PubMed=1707542; DOI=10.1073/pnas.88.8.3441;
RA Eriksson A.E., Cousens L.S., Weaver L.H., Matthews B.W.;
RT "Three-dimensional structure of human basic fibroblast growth factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:3441-3445(1991).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 143-288.
RX PubMed=1849658; DOI=10.1073/pnas.88.8.3446;
RA Zhang J., Cousens L.S., Barr P.J., Sprang S.R.;
RT "Three-dimensional structure of human basic fibroblast growth factor, a
RT structural homolog of interleukin 1 beta.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:3446-3450(1991).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 135-288.
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 [39]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 143-288.
RX PubMed=7691311; DOI=10.1002/pro.5560020810;
RA Eriksson A.E., Cousens L.S., Matthews B.W.;
RT "Refinement of the structure of human basic fibroblast growth factor at
RT 1.6-A resolution and analysis of presumed heparin binding sites by selenate
RT substitution.";
RL Protein Sci. 2:1274-1284(1993).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 134-288 IN COMPLEX WITH FGFR2.
RX PubMed=11390973; DOI=10.1073/pnas.121183798;
RA Ibrahimi O.A., Eliseenkova A.V., Plotnikov A.N., Yu K., Ornitz D.M.,
RA Mohammadi M.;
RT "Structural basis for fibroblast growth factor receptor 2 activation in
RT Apert syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7182-7187(2001).
RN [41]
RP STRUCTURE BY NMR OF 134-288.
RX PubMed=8885834; DOI=10.1021/bi961260p;
RA Moy F.J., Seddon A.P., Boehlen P., Powers R.;
RT "High-resolution solution structure of basic fibroblast growth factor
RT determined by multidimensional heteronuclear magnetic resonance
RT spectroscopy.";
RL Biochemistry 35:13552-13561(1996).
CC -!- FUNCTION: Acts as a ligand for FGFR1, FGFR2, FGFR3 and FGFR4
CC (PubMed:8663044). Also acts as an integrin ligand which is required for
CC FGF2 signaling (PubMed:28302677). Binds to integrin ITGAV:ITGB3
CC (PubMed:28302677). Plays an important role in the regulation of cell
CC survival, cell division, cell differentiation and cell migration
CC (PubMed:8663044, PubMed:28302677). Functions as a potent mitogen in
CC vitro (PubMed:1721615, PubMed:3964259, PubMed:3732516). Can induce
CC angiogenesis (PubMed:23469107, PubMed:28302677). Mediates
CC phosphorylation of ERK1/2 and thereby promotes retinal lens fiber
CC differentiation (PubMed:29501879). {ECO:0000269|PubMed:1721615,
CC ECO:0000269|PubMed:29501879, ECO:0000269|PubMed:3732516,
CC ECO:0000269|PubMed:3964259}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Retains almost half of its activity after treatment at pH 2.0 for 3
CC hours at 20 degrees Celsius. {ECO:0000269|PubMed:1721615};
CC Temperature dependence:
CC Inactivated after 3 minutes at 60 degrees Celsius or 1 minute at 80
CC degrees Celsius. {ECO:0000269|PubMed:1721615};
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. Interacts with CSPG4, FGFBP1 and TEC. Found in
CC a complex with FGFBP1, FGF1 and FGF2. Interacts with FGFBP3
CC (PubMed:18669637). Interacts with integrin ITGAV:ITGB3; the interaction
CC is required for FGF2 signaling (PubMed:28302677). Interacts with SNORC
CC (via the extracellular domain) (By similarity). Interacts with glypican
CC GPC3 (By similarity). {ECO:0000250|UniProtKB:P13109,
CC ECO:0000250|UniProtKB:P15655, ECO:0000269|PubMed:10358027,
CC ECO:0000269|PubMed:11390973, ECO:0000269|PubMed:11509569,
CC ECO:0000269|PubMed:11964394, ECO:0000269|PubMed:16257968,
CC ECO:0000269|PubMed:18669637, ECO:0000269|PubMed:1885605,
CC ECO:0000269|PubMed:20230531, ECO:0000269|PubMed:28302677,
CC ECO:0000269|PubMed:8663044}.
CC -!- INTERACTION:
CC P09038; P29466: CASP1; NbExp=2; IntAct=EBI-977447, EBI-516667;
CC P09038; Q14512: FGFBP1; NbExp=3; IntAct=EBI-977447, EBI-953742;
CC P09038; P11362: FGFR1; NbExp=7; IntAct=EBI-977447, EBI-1028277;
CC P09038; P11362-7: FGFR1; NbExp=2; IntAct=EBI-977447, EBI-15609945;
CC P09038; P11362-14: FGFR1; NbExp=2; IntAct=EBI-977447, EBI-6622185;
CC P09038; P21802: FGFR2; NbExp=3; IntAct=EBI-977447, EBI-1028658;
CC P09038; P21802-1: FGFR2; NbExp=2; IntAct=EBI-977447, EBI-15489960;
CC P09038; P26022: PTX3; NbExp=16; IntAct=EBI-977447, EBI-11574553;
CC P09038-2; P21802: FGFR2; NbExp=2; IntAct=EBI-11122080, EBI-1028658;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20230531}. Nucleus
CC {ECO:0000269|PubMed:22321063}. Note=Exported from cells by an
CC endoplasmic reticulum (ER)/Golgi-independent mechanism. Unconventional
CC secretion of FGF2 occurs by direct translocation across the plasma
CC membrane (PubMed:20230531). Binding of exogenous FGF2 to FGFR
CC facilitates endocytosis followed by translocation of FGF2 across
CC endosomal membrane into the cytosol (PubMed:22321063). Nuclear import
CC from the cytosol requires the classical nuclear import machinery,
CC involving proteins KPNA1 and KPNB1, as well as CEP57 (PubMed:22321063).
CC {ECO:0000269|PubMed:20230531, ECO:0000269|PubMed:22321063}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=4;
CC Name=1;
CC IsoId=P09038-4; Sequence=Displayed;
CC Name=2;
CC IsoId=P09038-1; Sequence=VSP_038236, VSP_038237;
CC Name=3;
CC IsoId=P09038-2; Sequence=VSP_037383;
CC Name=4;
CC IsoId=P09038-3; Sequence=VSP_037384, VSP_037385;
CC -!- TISSUE SPECIFICITY: Expressed in granulosa and cumulus cells. Expressed
CC in hepatocellular carcinoma cells, but not in non-cancerous liver
CC tissue. {ECO:0000269|PubMed:1417798, ECO:0000269|PubMed:1721615}.
CC -!- PTM: Phosphorylation at Tyr-215 regulates FGF2 unconventional
CC secretion. {ECO:0000269|PubMed:20230531}.
CC -!- PTM: Several N-termini starting at positions 94, 125, 126, 132, 143 and
CC 162 have been identified by direct sequencing.
CC -!- MISCELLANEOUS: This protein binds heparin more strongly than does aFGF.
CC -!- MISCELLANEOUS: [Isoform 1]: Starts at an alternative CUG codon.
CC -!- MISCELLANEOUS: [Isoform 2]: Starts at an alternative CUG codon.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Starts at an alternative CUG codon.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA52448.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAB21432.2; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAB21432.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=ABO43041.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=ABO43041.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=CAA28027.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA28027.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=CAA73868.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA73868.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=EAX05222.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAX05222.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fgf2/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FGF2ID511ch4q27.html";
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DR EMBL; X04431; CAA28027.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X04432; CAA28028.1; -; Genomic_DNA.
DR EMBL; X04433; CAA28029.1; -; Genomic_DNA.
DR EMBL; J04513; AAA52531.1; -; mRNA.
DR EMBL; J04513; AAA52532.1; -; mRNA.
DR EMBL; J04513; AAA52533.1; -; mRNA.
DR EMBL; AB451321; BAG70135.1; -; mRNA.
DR EMBL; AB451450; BAG70264.1; -; mRNA.
DR EMBL; EF506888; ABO43041.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC021205; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX05222.1; ALT_SEQ; Genomic_DNA.
DR EMBL; S81809; AAB21432.2; ALT_SEQ; Genomic_DNA.
DR EMBL; Y13468; CAA73868.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M27968; AAA52448.1; ALT_FRAME; mRNA.
DR EMBL; M17599; AAA52534.1; -; mRNA.
DR EMBL; AY820133; AAV70487.1; -; mRNA.
DR EMBL; S47380; AAD13853.1; -; mRNA.
DR CCDS; CCDS34059.1; -. [P09038-4]
DR PIR; A32398; A32398.
DR RefSeq; NP_001997.5; NM_002006.4. [P09038-4]
DR PDB; 1BAS; X-ray; 1.90 A; A=135-288.
DR PDB; 1BFB; X-ray; 1.90 A; A=142-288.
DR PDB; 1BFC; X-ray; 2.20 A; A=142-288.
DR PDB; 1BFF; X-ray; 2.00 A; A=160-288.
DR PDB; 1BFG; X-ray; 1.60 A; A=143-288.
DR PDB; 1BLA; NMR; -; A=134-288.
DR PDB; 1BLD; NMR; -; A=134-288.
DR PDB; 1CVS; X-ray; 2.80 A; A/B=157-288.
DR PDB; 1EV2; X-ray; 2.20 A; A/B/C/D=157-288.
DR PDB; 1FGA; X-ray; 2.20 A; A=143-288.
DR PDB; 1FQ9; X-ray; 3.00 A; A/B=157-288.
DR PDB; 1II4; X-ray; 2.70 A; A/B/C/D=134-288.
DR PDB; 1IIL; X-ray; 2.30 A; A/B/C/D=134-288.
DR PDB; 2BFH; X-ray; 2.50 A; A=161-288.
DR PDB; 2FGF; X-ray; 1.77 A; A=143-288.
DR PDB; 2M49; NMR; -; A/C=161-286.
DR PDB; 4FGF; X-ray; 1.60 A; A=143-288.
DR PDB; 4OEE; X-ray; 1.50 A; A=134-288.
DR PDB; 4OEF; X-ray; 1.80 A; A=134-288.
DR PDB; 4OEG; X-ray; 1.60 A; A=134-288.
DR PDB; 5X1O; X-ray; 1.90 A; A/B=143-288.
DR PDB; 6L4O; X-ray; 2.60 A; B=135-288.
DR PDBsum; 1BAS; -.
DR PDBsum; 1BFB; -.
DR PDBsum; 1BFC; -.
DR PDBsum; 1BFF; -.
DR PDBsum; 1BFG; -.
DR PDBsum; 1BLA; -.
DR PDBsum; 1BLD; -.
DR PDBsum; 1CVS; -.
DR PDBsum; 1EV2; -.
DR PDBsum; 1FGA; -.
DR PDBsum; 1FQ9; -.
DR PDBsum; 1II4; -.
DR PDBsum; 1IIL; -.
DR PDBsum; 2BFH; -.
DR PDBsum; 2FGF; -.
DR PDBsum; 2M49; -.
DR PDBsum; 4FGF; -.
DR PDBsum; 4OEE; -.
DR PDBsum; 4OEF; -.
DR PDBsum; 4OEG; -.
DR PDBsum; 5X1O; -.
DR PDBsum; 6L4O; -.
DR AlphaFoldDB; P09038; -.
DR BMRB; P09038; -.
DR SMR; P09038; -.
DR BioGRID; 108538; 41.
DR CORUM; P09038; -.
DR DIP; DIP-4012N; -.
DR IntAct; P09038; 19.
DR MINT; P09038; -.
DR STRING; 9606.ENSP00000264498; -.
DR BindingDB; P09038; -.
DR ChEMBL; CHEMBL3107; -.
DR DrugBank; DB03981; 1,4-Dideoxy-5-Dehydro-O2-Sulfo-Glucuronic Acid.
DR DrugBank; DB03935; 1,4-Dideoxy-O2-Sulfo-Glucuronic Acid.
DR DrugBank; DB05434; ABT-510.
DR DrugBank; DB01109; Heparin.
DR DrugBank; DB03959; N,O6-Disulfo-Glucosamine.
DR DrugBank; DB00686; Pentosan polysulfate.
DR DrugBank; DB00364; Sucralfate.
DR TCDB; 1.A.108.1.1; the fibroblast growth factor 2 (fgf2) family.
DR iPTMnet; P09038; -.
DR PhosphoSitePlus; P09038; -.
DR BioMuta; FGF2; -.
DR DMDM; 261260095; -.
DR EPD; P09038; -.
DR jPOST; P09038; -.
DR MassIVE; P09038; -.
DR MaxQB; P09038; -.
DR PaxDb; P09038; -.
DR PeptideAtlas; P09038; -.
DR PRIDE; P09038; -.
DR ProteomicsDB; 52187; -. [P09038-4]
DR ProteomicsDB; 52188; -. [P09038-1]
DR ProteomicsDB; 52189; -. [P09038-2]
DR ProteomicsDB; 52190; -. [P09038-3]
DR ABCD; P09038; 1 sequenced antibody.
DR Antibodypedia; 3433; 1200 antibodies from 47 providers.
DR DNASU; 2247; -.
DR Ensembl; ENST00000264498.8; ENSP00000264498.4; ENSG00000138685.17. [P09038-4]
DR Ensembl; ENST00000608478.1; ENSP00000477134.1; ENSG00000138685.17. [P09038-2]
DR Ensembl; ENST00000644866.2; ENSP00000494222.1; ENSG00000138685.17. [P09038-2]
DR GeneID; 2247; -.
DR KEGG; hsa:2247; -.
DR MANE-Select; ENST00000644866.2; ENSP00000494222.1; NM_001361665.2; NP_001348594.1. [P09038-2]
DR UCSC; uc062zki.1; human. [P09038-4]
DR CTD; 2247; -.
DR DisGeNET; 2247; -.
DR GeneCards; FGF2; -.
DR HGNC; HGNC:3676; FGF2.
DR HPA; ENSG00000138685; Low tissue specificity.
DR MIM; 134920; gene.
DR neXtProt; NX_P09038; -.
DR OpenTargets; ENSG00000138685; -.
DR PharmGKB; PA28115; -.
DR VEuPathDB; HostDB:ENSG00000138685; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000161583; -.
DR HOGENOM; CLU_081609_5_1_1; -.
DR InParanoid; P09038; -.
DR PhylomeDB; P09038; -.
DR TreeFam; TF317805; -.
DR PathwayCommons; P09038; -.
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-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-2892247; POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
DR Reactome; R-HSA-3000170; Syndecan interactions.
DR Reactome; R-HSA-3000171; Non-integrin membrane-ECM interactions.
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-5658623; FGFRL1 modulation of FGFR1 signaling.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
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; P09038; -.
DR SIGNOR; P09038; -.
DR BioGRID-ORCS; 2247; 7 hits in 1048 CRISPR screens.
DR EvolutionaryTrace; P09038; -.
DR GeneWiki; Basic_fibroblast_growth_factor; -.
DR GenomeRNAi; 2247; -.
DR Pharos; P09038; Tchem.
DR PRO; PR:P09038; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P09038; protein.
DR Bgee; ENSG00000138685; Expressed in cartilage tissue and 151 other tissues.
DR ExpressionAtlas; P09038; baseline and differential.
DR Genevisible; P09038; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0042056; F:chemoattractant activity; IDA:BHF-UCL.
DR GO; GO:0019956; F:chemokine binding; IPI:BHF-UCL.
DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IPI:MGI.
DR GO; GO:0008083; F:growth factor activity; IDA:BHF-UCL.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL.
DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:UniProtKB.
DR GO; GO:0090722; F:receptor-receptor interaction; IDA:ParkinsonsUK-UCL.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0060978; P:angiogenesis involved in coronary vascular morphogenesis; IEA:Ensembl.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IDA:UniProtKB.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; IDA:BHF-UCL.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0021930; P:cerebellar granule cell precursor proliferation; IEA:Ensembl.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0060591; P:chondroblast differentiation; IDA:UniProtKB.
DR GO; GO:0060128; P:corticotropin hormone secreting cell differentiation; IEA:Ensembl.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IEA:Ensembl.
DR GO; GO:0048598; P:embryonic morphogenesis; TAS:DFLAT.
DR GO; GO:0001935; P:endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0010001; P:glial cell differentiation; IEA:Ensembl.
DR GO; GO:0014843; P:growth factor dependent regulation of skeletal muscle satellite cell proliferation; IMP:AgBase.
DR GO; GO:0030214; P:hyaluronan catabolic process; IDA:UniProtKB.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl.
DR GO; GO:0032958; P:inositol phosphate biosynthetic process; IDA:DFLAT.
DR GO; GO:0030324; P:lung development; IBA:GO_Central.
DR GO; GO:1904977; P:lymphatic endothelial cell migration; IEA:Ensembl.
DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:BHF-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; IDA:UniProtKB.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; NAS:BHF-UCL.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; NAS:BHF-UCL.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0061045; P:negative regulation of wound healing; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0001759; P:organ induction; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0038001; P:paracrine signaling; ISS:ARUK-UCL.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IDA:DFLAT.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0042660; P:positive regulation of cell fate specification; IDA:MGI.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0021940; P:positive regulation of cerebellar granule cell precursor proliferation; IEA:Ensembl.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IDA:UniProtKB.
DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; IGI:UniProtKB.
DR GO; GO:2000546; P:positive regulation of endothelial cell chemotaxis to fibroblast growth factor; IDA:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:BHF-UCL.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IBA:GO_Central.
DR GO; GO:1905278; P:positive regulation of epithelial tube formation; IDA:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR GO; GO:0045609; P:positive regulation of inner ear auditory receptor cell differentiation; IEA:Ensembl.
DR GO; GO:1902748; P:positive regulation of lens fiber cell differentiation; IDA:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; NAS:BHF-UCL.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl.
DR GO; GO:1902913; P:positive regulation of neuroepithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IDA:DFLAT.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IGI:BHF-UCL.
DR GO; GO:0010863; P:positive regulation of phospholipase C activity; IDA:DFLAT.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IDA:UniProtKB.
DR GO; GO:2000738; P:positive regulation of stem cell differentiation; IEA:Ensembl.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IGI:BHF-UCL.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IGI:BHF-UCL.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; TAS:ProtInc.
DR GO; GO:0045765; P:regulation of angiogenesis; TAS:DFLAT.
DR GO; GO:1903587; P:regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; NAS:BHF-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR GO; GO:0090049; P:regulation of cell migration involved in sprouting angiogenesis; NAS:BHF-UCL.
DR GO; GO:2000544; P:regulation of endothelial cell chemotaxis to fibroblast growth factor; IDA:UniProtKB.
DR GO; GO:0046668; P:regulation of retinal cell programmed cell death; IEA:Ensembl.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:DFLAT.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0048864; P:stem cell development; IEA:Ensembl.
DR GO; GO:0072089; P:stem cell proliferation; NAS:ParkinsonsUK-UCL.
DR GO; GO:0021762; P:substantia nigra development; IEA:Ensembl.
DR GO; GO:0060129; P:thyroid-stimulating hormone-secreting cell differentiation; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; IDA:UniProtKB.
DR CDD; cd00058; FGF; 1.
DR DisProt; DP01644; -.
DR IDEAL; IID00438; -.
DR InterPro; IPR028223; FGF2.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; PTHR11486; 1.
DR PANTHER; PTHR11486:SF83; PTHR11486:SF83; 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; Alternative initiation; Angiogenesis; Developmental protein;
KW Differentiation; Direct protein sequencing; Growth factor; Heparin-binding;
KW Isopeptide bond; Methylation; Mitogen; Nucleus; Phosphoprotein;
KW Reference proteome; Secreted; Ubl conjugation.
FT PROPEP 1..142
FT /note="Or 93, or 124, or 125, or 131, or 161"
FT /id="PRO_0000008932"
FT CHAIN 143..288
FT /note="Fibroblast growth factor 2"
FT /id="PRO_0000008933"
FT REGION 1..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 261..277
FT /note="Heparin-binding"
FT /evidence="ECO:0000250"
FT MOTIF 179..181
FT /note="Cell attachment site; atypical"
FT /evidence="ECO:0000255"
FT MOTIF 221..223
FT /note="Cell attachment site; atypical"
FT /evidence="ECO:0000255"
FT COMPBIAS 64..80
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 169
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT SITE 261
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000269|PubMed:28302677"
FT SITE 262
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000269|PubMed:28302677"
FT SITE 267
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000269|PubMed:28302677"
FT MOD_RES 108
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q60487"
FT MOD_RES 108
FT /note="Symmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q60487"
FT MOD_RES 110
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q60487"
FT MOD_RES 110
FT /note="Symmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q60487"
FT MOD_RES 112
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q60487"
FT MOD_RES 112
FT /note="Symmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q60487"
FT MOD_RES 215
FT /note="Phosphotyrosine; by TEC"
FT /evidence="ECO:0000269|PubMed:20230531"
FT CROSSLNK 228
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0007744|PubMed:25114211"
FT VAR_SEQ 1..133
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:19054851,
FT ECO:0000303|PubMed:2538817"
FT /id="VSP_037383"
FT VAR_SEQ 1..92
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:2538817"
FT /id="VSP_037384"
FT VAR_SEQ 1..78
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2538817"
FT /id="VSP_038236"
FT VAR_SEQ 79
FT /note="L -> M (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2538817"
FT /id="VSP_038237"
FT VAR_SEQ 93
FT /note="L -> M (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:2538817"
FT /id="VSP_037385"
FT MUTAGEN 181
FT /note="R->E: No effect on integrin binding."
FT /evidence="ECO:0000269|PubMed:28302677"
FT MUTAGEN 186
FT /note="R->E: No effect on integrin binding."
FT /evidence="ECO:0000269|PubMed:28302677"
FT MUTAGEN 188
FT /note="K->E: No effect on integrin binding."
FT /evidence="ECO:0000269|PubMed:28302677"
FT MUTAGEN 261..262
FT /note="KR->EE: Abolishes binding to integrin ITGAV:ITGB3
FT and suppresses FGF2 signaling with loss of ERK1/2
FT activation and reduced ability to induce DNA synthesis,
FT cell migration and angiogenesis. Acts as a potent
FT antagonist of FGF2-mediated angiogenesis."
FT /evidence="ECO:0000269|PubMed:28302677"
FT MUTAGEN 267
FT /note="K->E: Reduces binding to integrin ITGAV:ITGB3 and
FT suppresses FGF2 signaling with reduced ERK1/2 activation
FT and reduced ability to induce DNA synthesis, cell migration
FT and angiogenesis. Acts as a potent antagonist of FGF2-
FT mediated angiogenesis."
FT /evidence="ECO:0000269|PubMed:28302677"
FT CONFLICT 25
FT /note="G -> R (in Ref. 10; AAA52448)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="H -> Q (in Ref. 10; AAA52448)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="A -> R (in Ref. 10; AAA52448)"
FT /evidence="ECO:0000305"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:1BLA"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:1BLA"
FT HELIX 156..160
FT /evidence="ECO:0007829|PDB:4OEE"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:4OEE"
FT TURN 168..170
FT /evidence="ECO:0007829|PDB:4OEE"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:4OEE"
FT STRAND 182..186
FT /evidence="ECO:0007829|PDB:4OEE"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:1BFG"
FT STRAND 195..201
FT /evidence="ECO:0007829|PDB:4OEE"
FT STRAND 204..209
FT /evidence="ECO:0007829|PDB:4OEE"
FT TURN 210..213
FT /evidence="ECO:0007829|PDB:4OEE"
FT STRAND 214..218
FT /evidence="ECO:0007829|PDB:4OEE"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:1BLA"
FT STRAND 224..229
FT /evidence="ECO:0007829|PDB:4OEE"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:4OEE"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:4OEE"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:2FGF"
FT STRAND 246..253
FT /evidence="ECO:0007829|PDB:4OEE"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:4OEE"
FT HELIX 269..271
FT /evidence="ECO:0007829|PDB:4OEE"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:4OEE"
FT STRAND 281..284
FT /evidence="ECO:0007829|PDB:4OEE"
SQ SEQUENCE 288 AA; 30770 MW; EAE98552A39D5E19 CRC64;
MVGVGGGDVE DVTPRPGGCQ ISGRGARGCN GIPGAAAWEA ALPRRRPRRH PSVNPRSRAA
GSPRTRGRRT EERPSGSRLG DRGRGRALPG GRLGGRGRGR APERVGGRGR GRGTAAPRAA
PAARGSRPGP AGTMAAGSIT TLPALPEDGG SGAFPPGHFK DPKRLYCKNG GFFLRIHPDG
RVDGVREKSD PHIKLQLQAE ERGVVSIKGV CANRYLAMKE DGRLLASKCV TDECFFFERL
ESNNYNTYRS RKYTSWYVAL KRTGQYKLGS KTGPGQKAIL FLPMSAKS
