FGF2_MOUSE
ID FGF2_MOUSE Reviewed; 154 AA.
AC P15655;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 198.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2318343; DOI=10.1016/0012-1606(90)90211-z;
RA Hebert J.M., Basilico C., Goldfarb M., Haub O., Martin G.R.;
RT "Isolation of cDNAs encoding four mouse FGF family members and
RT characterization of their expression patterns during embryogenesis.";
RL Dev. Biol. 138:454-463(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=A/J, C57BL/6J, and NOD/LtJ; TISSUE=Spleen;
RA Ma R.Z., Teuscher C.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH FGF2.
RX PubMed=9178765; DOI=10.1038/sj.onc.1201117;
RA Kurtz A., Wang H.-L., Darwiche N., Harris V., Wellstein A.;
RT "Expression of a binding protein for FGF is associated with epithelial
RT development and skin carcinogenesis.";
RL Oncogene 14:2671-2681(1997).
RN [4]
RP INTERACTION WITH FGFBP3.
RX PubMed=20851768; DOI=10.1016/j.mcn.2010.09.003;
RA Yamanaka Y., Kitano A., Takao K., Prasansuklab A., Mushiroda T.,
RA Yamazaki K., Kumada T., Shibata M., Takaoka Y., Awaya T., Kato T., Abe T.,
RA Iwata N., Miyakawa T., Nakamura Y., Nakahata T., Heike T.;
RT "Inactivation of fibroblast growth factor binding protein 3 causes anxiety-
RT related behaviors.";
RL Mol. Cell. Neurosci. 46:200-212(2011).
RN [5]
RP INTERACTION WITH SNORC.
RX PubMed=28323137; DOI=10.1016/j.joca.2017.03.010;
RA Heinonen J., Zhang F.P., Surmann-Schmitt C., Honkala S., Stock M.,
RA Poutanen M., Saeaemaenen A.M.;
RT "Defects in chondrocyte maturation and secondary ossification in mouse knee
RT joint epiphyses due to Snorc deficiency.";
RL Osteoarthritis Cartilage 25:1132-1142(2017).
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 (By similarity). Interacts with
CC FGFBP3 (PubMed:20851768). Interacts with integrin ITGAV:ITGB3; the
CC interaction is required for FGF2 signaling (By similarity). Interacts
CC with SNORC (via the extracellular domain) (PubMed:28323137). Interacts
CC with glypican GPC3 (By similarity). {ECO:0000250|UniProtKB:P09038,
CC ECO:0000250|UniProtKB:P13109, ECO:0000269|PubMed:20851768,
CC ECO:0000269|PubMed:28323137, ECO:0000269|PubMed:9178765}.
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 -!- 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; M30644; AAA37621.1; -; mRNA.
DR EMBL; AF065903; AAC17503.1; -; mRNA.
DR EMBL; AF065904; AAC17504.1; -; mRNA.
DR EMBL; AF065905; AAC17505.1; -; mRNA.
DR CCDS; CCDS17320.1; -.
DR PIR; C37360; C37360.
DR RefSeq; NP_032032.1; NM_008006.2.
DR AlphaFoldDB; P15655; -.
DR SMR; P15655; -.
DR BioGRID; 199647; 6.
DR CORUM; P15655; -.
DR STRING; 10090.ENSMUSP00000037694; -.
DR iPTMnet; P15655; -.
DR PhosphoSitePlus; P15655; -.
DR PaxDb; P15655; -.
DR PeptideAtlas; P15655; -.
DR PRIDE; P15655; -.
DR ProteomicsDB; 266837; -.
DR Antibodypedia; 3433; 1200 antibodies from 47 providers.
DR DNASU; 14173; -.
DR Ensembl; ENSMUST00000138563; ENSMUSP00000122227; ENSMUSG00000037225.
DR Ensembl; ENSMUST00000200585; ENSMUSP00000143094; ENSMUSG00000037225.
DR GeneID; 14173; -.
DR KEGG; mmu:14173; -.
DR UCSC; uc008pap.2; mouse.
DR CTD; 2247; -.
DR MGI; MGI:95516; Fgf2.
DR VEuPathDB; HostDB:ENSMUSG00000037225; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000161583; -.
DR HOGENOM; CLU_081609_5_1_1; -.
DR InParanoid; P15655; -.
DR OMA; KGVCSNR; -.
DR OrthoDB; 1157770at2759; -.
DR PhylomeDB; P15655; -.
DR TreeFam; TF317805; -.
DR Reactome; R-MMU-109704; PI3K Cascade.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-190322; FGFR4 ligand binding and activation.
DR Reactome; R-MMU-190370; FGFR1b ligand binding and activation.
DR Reactome; R-MMU-190372; FGFR3c ligand binding and activation.
DR Reactome; R-MMU-190373; FGFR1c ligand binding and activation.
DR Reactome; R-MMU-190375; FGFR2c ligand binding and activation.
DR Reactome; R-MMU-190377; FGFR2b ligand binding and activation.
DR Reactome; R-MMU-3000170; Syndecan interactions.
DR Reactome; R-MMU-3000171; Non-integrin membrane-ECM interactions.
DR Reactome; R-MMU-5654219; Phospholipase C-mediated cascade: FGFR1.
DR Reactome; R-MMU-5654221; Phospholipase C-mediated cascade, FGFR2.
DR Reactome; R-MMU-5654227; Phospholipase C-mediated cascade, FGFR3.
DR Reactome; R-MMU-5654228; Phospholipase C-mediated cascade, FGFR4.
DR Reactome; R-MMU-5654687; Downstream signaling of activated FGFR1.
DR Reactome; R-MMU-5654688; SHC-mediated cascade:FGFR1.
DR Reactome; R-MMU-5654689; PI-3K cascade:FGFR1.
DR Reactome; R-MMU-5654693; FRS-mediated FGFR1 signaling.
DR Reactome; R-MMU-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-MMU-5654699; SHC-mediated cascade:FGFR2.
DR Reactome; R-MMU-5654700; FRS-mediated FGFR2 signaling.
DR Reactome; R-MMU-5654704; SHC-mediated cascade:FGFR3.
DR Reactome; R-MMU-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-MMU-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-MMU-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-MMU-5654719; SHC-mediated cascade:FGFR4.
DR Reactome; R-MMU-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-MMU-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-MMU-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-MMU-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-MMU-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-MMU-5658623; FGFRL1 modulation of FGFR1 signaling.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR BioGRID-ORCS; 14173; 0 hits in 59 CRISPR screens.
DR PRO; PR:P15655; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P15655; protein.
DR Bgee; ENSMUSG00000037225; Expressed in mesenchyme of tongue and 149 other tissues.
DR ExpressionAtlas; P15655; baseline and differential.
DR Genevisible; P15655; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0042056; F:chemoattractant activity; ISO:MGI.
DR GO; GO:0019956; F:chemokine binding; ISO:MGI.
DR GO; GO:0005125; F:cytokine activity; ISO:MGI.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; ISO:MGI.
DR GO; GO:0008083; F:growth factor activity; IDA:MGI.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; ISO:MGI.
DR GO; GO:0090722; F:receptor-receptor interaction; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IGI:MGI.
DR GO; GO:0060978; P:angiogenesis involved in coronary vascular morphogenesis; ISO:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; TAS:DFLAT.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:MGI.
DR GO; GO:0008283; P:cell population proliferation; IDA:MGI.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0021930; P:cerebellar granule cell precursor proliferation; IDA:MGI.
DR GO; GO:0060591; P:chondroblast differentiation; ISO:MGI.
DR GO; GO:0060128; P:corticotropin hormone secreting cell differentiation; IDA:MGI.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; ISO:MGI.
DR GO; GO:0043542; P:endothelial cell migration; IDA:MGI.
DR GO; GO:0001935; P:endothelial cell proliferation; IDA:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IDA:MGI.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IDA:MGI.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0010001; P:glial cell differentiation; IMP:MGI.
DR GO; GO:0014843; P:growth factor dependent regulation of skeletal muscle satellite cell proliferation; ISO:MGI.
DR GO; GO:0030214; P:hyaluronan catabolic process; ISO:MGI.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IDA:MGI.
DR GO; GO:0032958; P:inositol phosphate biosynthetic process; ISO:MGI.
DR GO; GO:0030324; P:lung development; IDA:MGI.
DR GO; GO:1904977; P:lymphatic endothelial cell migration; IDA:MGI.
DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; IDA:MGI.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; ISO:MGI.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IGI:MGI.
DR GO; GO:0061045; P:negative regulation of wound healing; ISO:MGI.
DR GO; GO:0007405; P:neuroblast proliferation; IGI:MGI.
DR GO; GO:0060563; P:neuroepithelial cell differentiation; IDA:MGI.
DR GO; GO:0001759; P:organ induction; IDA:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IGI:MGI.
DR GO; GO:0038001; P:paracrine signaling; ISO:MGI.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; ISO:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:MGI.
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; IDA:MGI.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISO:MGI.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0042660; P:positive regulation of cell fate specification; ISO:MGI.
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:MGI.
DR GO; GO:0021940; P:positive regulation of cerebellar granule cell precursor proliferation; IDA:MGI.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:MGI.
DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISO:MGI.
DR GO; GO:2000546; P:positive regulation of endothelial cell chemotaxis to fibroblast growth factor; ISO:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:MGI.
DR GO; GO:1905278; P:positive regulation of epithelial tube formation; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR GO; GO:0045609; P:positive regulation of inner ear auditory receptor cell differentiation; IDA:MGI.
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:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IGI:MGI.
DR GO; GO:1902913; P:positive regulation of neuroepithelial cell differentiation; IDA:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IGI:MGI.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0010863; P:positive regulation of phospholipase C activity; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:2000738; P:positive regulation of stem cell differentiation; IDA:MGI.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; IDA:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:MGI.
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:MGI.
DR GO; GO:0046668; P:regulation of retinal cell programmed cell death; IDA:MGI.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:MGI.
DR GO; GO:0048678; P:response to axon injury; IMP:MGI.
DR GO; GO:0048864; P:stem cell development; IMP:BHF-UCL.
DR GO; GO:0048863; P:stem cell differentiation; IDA:MGI.
DR GO; GO:0072089; P:stem cell proliferation; IDA:MGI.
DR GO; GO:0021762; P:substantia nigra development; IMP:MGI.
DR GO; GO:0060129; P:thyroid-stimulating hormone-secreting cell differentiation; IDA:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0042060; P:wound healing; ISO:MGI.
DR CDD; cd00058; FGF; 1.
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 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_0000008936"
FT CHAIN 10..154
FT /note="Fibroblast growth factor 2"
FT /id="PRO_0000008937"
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; 17153 MW; 689F677416274388 CRC64;
MAASGITSLP ALPEDGGAAF PPGHFKDPKR LYCKNGGFFL RIHPDGRVDG VREKSDPHVK
LQLQAEERGV VSIKGVCANR YLAMKEDGRL LASKCVTEEC FFFERLESNN YNTYRSRKYS
SWYVALKRTG QYKLGSKTGP GQKAILFLPM SAKS
