FGF2_MONDO
ID FGF2_MONDO Reviewed; 156 AA.
AC P48798;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 143.
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;
OS Monodelphis domestica (Gray short-tailed opossum).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Metatheria; Didelphimorphia; Didelphidae; Monodelphis.
OX NCBI_TaxID=13616;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Eye;
RX PubMed=8024698; DOI=10.1089/dna.1994.13.549;
RA Kusewitt D.F., Sabourin C.L.K., Sherburn T.E., Ley R.D.;
RT "Characterization of cDNA encoding basic fibroblast growth factor of the
RT marsupial Monodelphis domestica.";
RL DNA Cell Biol. 13:549-554(1994).
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. Can induce
CC angiogenesis (By similarity). Mediates phosphorylation of ERK1/2 and
CC thereby promotes retinal lens fiber differentiation (By similarity).
CC {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 glypican GPC3. {ECO:0000250|UniProtKB:P09038,
CC ECO:0000250|UniProtKB:P13109, ECO:0000250|UniProtKB:P15655}.
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-83 regulates FGF2 unconventional secretion.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA78854.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; Z15154; CAA78854.1; ALT_INIT; mRNA.
DR RefSeq; NP_001029148.1; NM_001033976.2.
DR AlphaFoldDB; P48798; -.
DR SMR; P48798; -.
DR STRING; 13616.ENSMODP00000023577; -.
DR Ensembl; ENSMODT00000023996; ENSMODP00000023577; ENSMODG00000018899.
DR GeneID; 619384; -.
DR KEGG; mdo:619384; -.
DR CTD; 2247; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000161583; -.
DR HOGENOM; CLU_081609_5_1_1; -.
DR InParanoid; P48798; -.
DR OMA; KGVCSNR; -.
DR OrthoDB; 1157770at2759; -.
DR TreeFam; TF317805; -.
DR Proteomes; UP000002280; Chromosome 5.
DR Bgee; ENSMODG00000018899; Expressed in skeletal muscle tissue and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0042056; F:chemoattractant activity; IEA:Ensembl.
DR GO; GO:0019956; F:chemokine binding; IEA:Ensembl.
DR GO; GO:0005125; F:cytokine activity; IEA:Ensembl.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IEA:Ensembl.
DR GO; GO:0090722; F:receptor-receptor interaction; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; IEA:Ensembl.
DR GO; GO:0021930; P:cerebellar granule cell precursor proliferation; IEA:Ensembl.
DR GO; GO:0060591; P:chondroblast differentiation; IEA:Ensembl.
DR GO; GO:0060128; P:corticotropin hormone secreting cell differentiation; IEA:Ensembl.
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; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0030214; P:hyaluronan catabolic process; IEA:Ensembl.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl.
DR GO; GO:0032958; P:inositol phosphate biosynthetic process; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0060548; P:negative regulation of cell death; ISS:UniProtKB.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; IEA:Ensembl.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0061045; P:negative regulation of wound healing; IEA:Ensembl.
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:0006661; P:phosphatidylinositol biosynthetic process; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0042660; P:positive regulation of cell fate specification; IEA:Ensembl.
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; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:2000546; P:positive regulation of endothelial cell chemotaxis to fibroblast growth factor; IEA:Ensembl.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS: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; ISS:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0010863; P:positive regulation of phospholipase C activity; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISS: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; IBA:GO_Central.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
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:0046668; P:regulation of retinal cell programmed cell death; IEA:Ensembl.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0048864; P:stem cell development; IEA:Ensembl.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
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; IBA:GO_Central.
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 2: Evidence at transcript 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 /evidence="ECO:0000250"
FT /id="PRO_0000008934"
FT CHAIN 10..156
FT /note="Fibroblast growth factor 2"
FT /id="PRO_0000008935"
FT REGION 129..145
FT /note="Heparin-binding"
FT /evidence="ECO:0000250"
FT BINDING 37
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT SITE 129
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000250|UniProtKB:P09038"
FT SITE 130
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000250|UniProtKB:P09038"
FT SITE 135
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000250|UniProtKB:P09038"
FT MOD_RES 83
FT /note="Phosphotyrosine; by TEC"
FT /evidence="ECO:0000250|UniProtKB:P09038"
FT CROSSLNK 96
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:P09038"
SQ SEQUENCE 156 AA; 17303 MW; 7E655FCC49BF1209 CRC64;
MAAGSITTLP ALSGDGGGGG AFPPGHFKDP KRLYCKNGGF FLRIHPDGRV DGIREKSDPN
IKLQLQAEER GVVSIKGVCA NRYLAMKEDG RLLALKYVTE ECFFFERLES NNYNTYRSRK
YSNWYVALKR TGQYKLGSKT GPGQKAILFL PMSAKS
