ID   FGF2_RAT                Reviewed;         154 AA.
AC   P13109;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1990, sequence version 1.
DT   04-NOV-2026, entry version 199.
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=Fgf-2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Ovary;
RX   PubMed=3196337; DOI=10.1016/s0006-291x(88)80041-x;
RA   Shimasaki S., Emoto N., Koba A., Mercado M., Shibata F., Cooksey K.,
RA   Baird A., Ling N.;
RT   "Complementary DNA cloning and sequencing of rat ovarian basic fibroblast
RT   growth factor and tissue distribution study of its mRNA.";
RL   Biochem. Biophys. Res. Commun. 157:256-263(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=3387229; DOI=10.1093/nar/16.11.5201;
RA   Kurokawa T., Seno M., Igarashi K.;
RT   "Nucleotide sequence of rat basic fibroblast growth factor cDNA.";
RL   Nucleic Acids Res. 16:5201-5201(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
RC   STRAIN=Sprague-Dawley; TISSUE=Testis;
RX   PubMed=9048734; DOI=10.1046/j.1471-4159.1997.68030898.x;
RA   Pasumarthi K.B.S., Jin Y., Cattini P.A.;
RT   "Cloning of the rat fibroblast growth factor-2 promoter region and its
RT   response to mitogenic stimuli in glioma C6 cells.";
RL   J. Neurochem. 68:898-908(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 35-154.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RX   PubMed=1378302; DOI=10.1016/0167-4781(92)90031-t;
RA   El-Husseini A.E.-D., Paterson J.A., Myal Y., Shiu R.P.C.;
RT   "PCR detection of the rat brain basic fibroblast growth factor (bFGF) mRNA
RT   containing a unique 3' untranslated region.";
RL   Biochim. Biophys. Acta 1131:314-316(1992).
RN   [5]
RP   INTERACTION WITH GPC3.
RX   PubMed=9065409; DOI=10.1074/jbc.272.12.7574;
RA   Song H.H., Shi W., Filmus J.;
RT   "OCI-5/rat glypican-3 binds to fibroblast growth factor-2 but not to
RT   insulin-like growth factor-2.";
RL   J. Biol. Chem. 272:7574-7577(1997).
CC   -!- FUNCTION: Acts as a ligand for FGFR1, FGFR2, FGFR3 and FGFR4 (By
CC       similarity). Also acts as an integrin ligand which is required for FGF2
CC       signaling (By similarity). Binds to integrin ITGAV:ITGB3 (By
CC       similarity). Plays an important role in the regulation of cell
CC       survival, cell division, cell differentiation and cell migration (By
CC       similarity). Functions as a potent mitogen in vitro (By similarity).
CC       Can induce angiogenesis (By similarity). Mediates phosphorylation of
CC       ERK1/2 and thereby promotes retinal lens fiber differentiation (By
CC       similarity). {ECO:0000250|UniProtKB:P09038}.
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. Interacts
CC       with integrin ITGAV:ITGB3; the interaction is required for FGF2
CC       signaling. Interacts with SNORC (via the extracellular domain).
CC       Interacts with GPC3 (PubMed:9065409). {ECO:0000250|UniProtKB:P09038,
CC       ECO:0000250|UniProtKB:P15655, ECO:0000269|PubMed:9065409}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P09038}. Nucleus
CC       {ECO:0000250|UniProtKB:P09038}. Note=Exported from cells by an
CC       endoplasmic reticulum (ER)/Golgi-independent mechanism (By similarity).
CC       Unconventional secretion of FGF2 occurs by direct translocation across
CC       the plasma membrane (By similarity). Binding of exogenous FGF2 to FGFR
CC       facilitates endocytosis followed by translocation of FGF2 across
CC       endosomal membrane into the cytosol (By similarity). Nuclear import
CC       from the cytosol requires the classical nuclear import machinery,
CC       involving proteins KPNA1 and KPNB1, as well as CEP57 (By similarity).
CC       {ECO:0000250|UniProtKB:P09038}.
CC   -!- TISSUE SPECIFICITY: Found in all tissues examined.
CC   -!- PTM: Phosphorylation at Tyr-81 regulates FGF2 unconventional secretion.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC       {ECO:0000305}.
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DR   EMBL; M22427; AAA41210.1; -; mRNA.
DR   EMBL; X07285; CAA30265.1; -; mRNA.
DR   EMBL; U78079; AAC53225.1; -; Genomic_DNA.
DR   EMBL; X61697; CAA43863.1; -; mRNA.
DR   PIR; A31674; A31674.
DR   RefSeq; NP_062178.1; NM_019305.2.
DR   AlphaFoldDB; P13109; -.
DR   SMR; P13109; -.
DR   BioGRID; 248473; 2.
DR   FunCoup; P13109; 741.
DR   STRING; 10116.ENSRNOP00000023388; -.
DR   PhosphoSitePlus; P13109; -.
DR   PaxDb; 10116-ENSRNOP00000023388; -.
DR   Ensembl; ENSRNOT00000023388.7; ENSRNOP00000023388.4; ENSRNOG00000017392.8.
DR   Ensembl; ENSRNOT00055003524; ENSRNOP00055002630; ENSRNOG00055002219.
DR   Ensembl; ENSRNOT00060011282; ENSRNOP00060008422; ENSRNOG00060006887.
DR   Ensembl; ENSRNOT00065014050; ENSRNOP00065010489; ENSRNOG00065008811.
DR   GeneID; 54250; -.
DR   KEGG; rno:54250; -.
DR   UCSC; RGD:2609; rat.
DR   AGR; RGD:2609; -.
DR   CTD; 2247; -.
DR   RGD; 2609; Fgf2.
DR   eggNOG; KOG3885; Eukaryota.
DR   GeneTree; ENSGT00940000161583; -.
DR   HOGENOM; CLU_081609_5_1_1; -.
DR   InParanoid; P13109; -.
DR   OMA; ANRFLSM; -.
DR   OrthoDB; 5987799at2759; -.
DR   PhylomeDB; P13109; -.
DR   Reactome; R-RNO-109704; PI3K Cascade.
DR   Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-RNO-190322; FGFR4 ligand binding and activation.
DR   Reactome; R-RNO-190370; FGFR1b ligand binding and activation.
DR   Reactome; R-RNO-190372; FGFR3c ligand binding and activation.
DR   Reactome; R-RNO-190373; FGFR1c ligand binding and activation.
DR   Reactome; R-RNO-190375; FGFR2c ligand binding and activation.
DR   Reactome; R-RNO-190377; FGFR2b ligand binding and activation.
DR   Reactome; R-RNO-3000170; Syndecan interactions.
DR   Reactome; R-RNO-5654219; Phospholipase C-mediated cascade: FGFR1.
DR   Reactome; R-RNO-5654221; Phospholipase C-mediated cascade, FGFR2.
DR   Reactome; R-RNO-5654227; Phospholipase C-mediated cascade, FGFR3.
DR   Reactome; R-RNO-5654228; Phospholipase C-mediated cascade, FGFR4.
DR   Reactome; R-RNO-5654687; Downstream signaling of activated FGFR1.
DR   Reactome; R-RNO-5654688; SHC-mediated cascade:FGFR1.
DR   Reactome; R-RNO-5654689; PI-3K cascade:FGFR1.
DR   Reactome; R-RNO-5654693; FRS-mediated FGFR1 signaling.
DR   Reactome; R-RNO-5654695; PI-3K cascade:FGFR2.
DR   Reactome; R-RNO-5654699; SHC-mediated cascade:FGFR2.
DR   Reactome; R-RNO-5654700; FRS-mediated FGFR2 signaling.
DR   Reactome; R-RNO-5654704; SHC-mediated cascade:FGFR3.
DR   Reactome; R-RNO-5654706; FRS-mediated FGFR3 signaling.
DR   Reactome; R-RNO-5654710; PI-3K cascade:FGFR3.
DR   Reactome; R-RNO-5654712; FRS-mediated FGFR4 signaling.
DR   Reactome; R-RNO-5654719; SHC-mediated cascade:FGFR4.
DR   Reactome; R-RNO-5654720; PI-3K cascade:FGFR4.
DR   Reactome; R-RNO-5654726; Negative regulation of FGFR1 signaling.
DR   Reactome; R-RNO-5654727; Negative regulation of FGFR2 signaling.
DR   Reactome; R-RNO-5654732; Negative regulation of FGFR3 signaling.
DR   Reactome; R-RNO-5654733; Negative regulation of FGFR4 signaling.
DR   Reactome; R-RNO-5658623; FGFRL1 modulation of FGFR1 signaling.
DR   Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-RNO-9839397; TGFBR3 regulates FGF2 signaling.
DR   PRO; PR:P13109; -.
DR   Proteomes; UP000002494; Chromosome 2.
DR   Bgee; ENSRNOG00000017392; Expressed in quadriceps femoris and 12 other cell types or tissues.
DR   ExpressionAtlas; P13109; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; IDA:RGD.
DR   GO; GO:0016604; C:nuclear body; ISO:RGD.
DR   GO; GO:0005654; C:nucleoplasm; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0042056; F:chemoattractant activity; ISO:RGD.
DR   GO; GO:0019956; F:chemokine binding; ISO:RGD.
DR   GO; GO:0005125; F:cytokine activity; ISO:RGD.
DR   GO; GO:0005104; F:fibroblast growth factor receptor binding; IPI:MGI.
DR   GO; GO:0008083; F:growth factor activity; ISO:RGD.
DR   GO; GO:0062072; F:histone H3K9me2/3 reader activity; IDA:RGD.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR   GO; GO:0090722; F:receptor-receptor interaction; ISO:RGD.
DR   GO; GO:0060978; P:angiogenesis involved in coronary vascular morphogenesis; IMP:RGD.
DR   GO; GO:0048149; P:behavioral response to ethanol; IMP:RGD.
DR   GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR   GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:RGD.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR   GO; GO:0060591; P:chondroblast differentiation; ISO:RGD.
DR   GO; GO:0060128; P:corticotropin hormone secreting cell differentiation; ISO:RGD.
DR   GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:RGD.
DR   GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IPI:MGI.
DR   GO; GO:0010001; P:glial cell differentiation; ISO:RGD.
DR   GO; GO:0014843; P:growth factor dependent regulation of skeletal muscle satellite cell proliferation; ISO:RGD.
DR   GO; GO:0030214; P:hyaluronan catabolic process; ISO:RGD.
DR   GO; GO:0030324; P:lung development; ISO:RGD.
DR   GO; GO:0060644; P:mammary gland epithelial cell differentiation; ISO:RGD.
DR   GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:RGD.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:0010764; P:negative regulation of fibroblast migration; ISO:RGD.
DR   GO; GO:1903377; P:negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IMP:RGD.
DR   GO; GO:0061045; P:negative regulation of wound healing; ISO:RGD.
DR   GO; GO:0022008; P:neurogenesis; IBA:GO_Central.
DR   GO; GO:0001759; P:organ induction; ISO:RGD.
DR   GO; GO:0038001; P:paracrine signaling; IDA:ARUK-UCL.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR   GO; GO:1905555; P:positive regulation of blood vessel branching; ISO:RGD.
DR   GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISS:UniProtKB.
DR   GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:RGD.
DR   GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IDA:RGD.
DR   GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD.
DR   GO; GO:0042660; P:positive regulation of cell fate specification; ISO:RGD.
DR   GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISS:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR   GO; GO:0021940; P:positive regulation of cerebellar granule cell precursor proliferation; ISO:RGD.
DR   GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:RGD.
DR   GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISO:RGD.
DR   GO; GO:2000546; P:positive regulation of endothelial cell chemotaxis to fibroblast growth factor; ISO:RGD.
DR   GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
DR   GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
DR   GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:RGD.
DR   GO; GO:1905278; P:positive regulation of epithelial tube formation; ISO:RGD.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:RGD.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR   GO; GO:1902748; P:positive regulation of lens fiber cell differentiation; ISS:UniProtKB.
DR   GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:RGD.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR   GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:RGD.
DR   GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:RGD.
DR   GO; GO:0051726; P:regulation of cell cycle; ISO:RGD.
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; ISO:RGD.
DR   GO; GO:0046668; P:regulation of retinal cell programmed cell death; ISO:RGD.
DR   GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:RGD.
DR   GO; GO:0048678; P:response to axon injury; ISO:RGD.
DR   GO; GO:0045471; P:response to ethanol; IMP:RGD.
DR   GO; GO:1904567; P:response to wortmannin; IMP:RGD.
DR   GO; GO:0048864; P:stem cell development; ISO:RGD.
DR   GO; GO:0021762; P:substantia nigra development; ISO:RGD.
DR   GO; GO:0060129; P:thyroid-stimulating hormone-secreting cell differentiation; ISO:RGD.
DR   GO; GO:0042060; P:wound healing; ISO:RGD.
DR   CDD; cd23314; beta-trefoil_FGF2; 1.
DR   FunFam; 2.80.10.50:FF:000020; Fibroblast growth factor 1; 1.
DR   Gene3D; 2.80.10.50; -; 1.
DR   InterPro; IPR002209; Fibroblast_GF_fam.
DR   InterPro; IPR008996; IL1/FGF.
DR   PANTHER; PTHR11486; FIBROBLAST GROWTH FACTOR; 1.
DR   Pfam; PF00167; FGF; 1.
DR   PRINTS; PR00263; HBGFFGF.
DR   PRINTS; PR00262; IL1HBGF.
DR   SMART; SM00442; FGF; 1.
DR   SUPFAM; SSF50353; Cytokine; 1.
DR   PROSITE; PS00247; HBGF_FGF; 1.
PE   1: Evidence at protein level;
KW   Angiogenesis; Developmental protein; Differentiation; Growth factor;
KW   Heparin-binding; Isopeptide bond; Mitogen; Nucleus; Phosphoprotein;
KW   Reference proteome; Secreted; Ubl conjugation.
FT   PROPEP          1..9
FT                   /id="PRO_0000008938"
FT   CHAIN           10..154
FT                   /note="Fibroblast growth factor 2"
FT                   /id="PRO_0000008939"
FT   REGION          1..20
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          127..143
FT                   /note="Heparin-binding"
FT                   /evidence="ECO:0000250"
FT   BINDING         35
FT                   /ligand="heparin"
FT                   /ligand_id="ChEBI:CHEBI:28304"
FT                   /evidence="ECO:0000250"
FT   SITE            127
FT                   /note="Important for interaction with integrin"
FT                   /evidence="ECO:0000250|UniProtKB:P09038"
FT   SITE            128
FT                   /note="Important for interaction with integrin"
FT                   /evidence="ECO:0000250|UniProtKB:P09038"
FT   SITE            133
FT                   /note="Important for interaction with integrin"
FT                   /evidence="ECO:0000250|UniProtKB:P09038"
FT   MOD_RES         81
FT                   /note="Phosphotyrosine; by TEC"
FT                   /evidence="ECO:0000250|UniProtKB:P09038"
FT   CROSSLNK        94
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO1)"
FT                   /evidence="ECO:0000250|UniProtKB:P09038"
SQ   SEQUENCE   154 AA;  17139 MW;  1A0F14FF423D8403 CRC64;
     MAAGSITSLP ALPEDGGGAF PPGHFKDPKR LYCKNGGFFL RIHPDGRVDG VREKSDPHVK
     LQLQAEERGV VSIKGVCANR YLAMKEDGRL LASKCVTEEC FFFERLESNN YNTYRSRKYS
     SWYVALKRTG QYKLGSKTGP GQKAILFLPM SAKS
//