FGF2_SHEEP
ID FGF2_SHEEP Reviewed; 155 AA.
AC P20003;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 140.
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 Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Sutton R., Ward W.G., Raphael K.A., Cam G.R.;
RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 9-155.
RX PubMed=3678486; DOI=10.1016/0014-5793(87)80435-0;
RA Simpson R.J., Moritz R.L., Lloyd C.J., Fabri L.J., Nice E.C., Rubira M.R.,
RA Burgess A.W.;
RT "Primary structure of ovine pituitary basic fibroblast growth factor.";
RL FEBS Lett. 224:128-132(1987).
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 glypican GPC3 (By similarity).
CC {ECO:0000250|UniProtKB:P09038, ECO:0000250|UniProtKB:P13109,
CC 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-82 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; L36136; AAA31519.1; -; mRNA.
DR PIR; S00185; S00185.
DR RefSeq; NP_001009769.1; NM_001009769.1.
DR AlphaFoldDB; P20003; -.
DR SMR; P20003; -.
DR Ensembl; ENSOART00000018748; ENSOARP00000018486; ENSOARG00000017222.
DR Ensembl; ENSOART00020016015; ENSOARP00020013252; ENSOARG00020010451.
DR GeneID; 443306; -.
DR KEGG; oas:443306; -.
DR CTD; 2247; -.
DR HOGENOM; CLU_081609_5_1_1; -.
DR OMA; KGVCSNR; -.
DR OrthoDB; 1157770at2759; -.
DR Proteomes; UP000002356; Chromosome 17.
DR Bgee; ENSOARG00000017222; Expressed in aortic valve and 51 other tissues.
DR ExpressionAtlas; P20003; baseline.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; IEA:Ensembl.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
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:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
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: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: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; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
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: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; IEA:Ensembl.
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;
KW Direct protein sequencing; Growth factor; Heparin-binding; Isopeptide bond;
KW Mitogen; Nucleus; Phosphoprotein; Reference proteome; Secreted;
KW Ubl conjugation.
FT PROPEP 1..9
FT /id="PRO_0000008940"
FT CHAIN 10..155
FT /note="Fibroblast growth factor 2"
FT /id="PRO_0000008941"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 128..144
FT /note="Heparin-binding"
FT /evidence="ECO:0000250"
FT MOTIF 46..48
FT /note="Cell attachment site; atypical"
FT /evidence="ECO:0000255"
FT MOTIF 88..90
FT /note="Cell attachment site; atypical"
FT /evidence="ECO:0000255"
FT BINDING 36
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT SITE 128
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000250|UniProtKB:P09038"
FT SITE 129
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000250|UniProtKB:P09038"
FT SITE 134
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000250|UniProtKB:P09038"
FT MOD_RES 82
FT /note="Phosphotyrosine; by TEC"
FT /evidence="ECO:0000250|UniProtKB:P09038"
FT CROSSLNK 95
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:P09038"
SQ SEQUENCE 155 AA; 17280 MW; B5F2364BA610606D CRC64;
MAAGSITTLP ALPEDGGSSA FPPGHFKDPK RLYCKNGGFF LRIHPDGRVD GVREKSDPHI
KLQLQAEERG VVSIKGVCAN RYLAMKEDGR LLASKCVTDE CFFFERLESN NYNTYRSRKY
SSWYVALKRT GQYKLGPKTG PGQKAILFLP MSAKS
