FGF1_BOVIN
ID FGF1_BOVIN Reviewed; 155 AA.
AC P03968; Q3ZBL8;
DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Fibroblast growth factor 1;
DE Short=FGF-1;
DE AltName: Full=Acidic eye-derived growth factor II;
DE Short=EDGF II;
DE AltName: Full=Acidic fibroblast growth factor;
DE Short=aFGF;
DE AltName: Full=Endothelial cell growth factor;
DE Short=ECGF;
DE AltName: Full=Heparin-binding growth factor 1;
DE Short=HBGF-1;
DE AltName: Full=Prostatropin;
DE Contains:
DE RecName: Full=Endothelial cell growth factor beta;
DE Contains:
DE RecName: Full=Endothelial cell growth factor alpha;
DE Flags: Precursor;
GN Name=FGF1; Synonyms=AFGF, FGFA, HBGF-1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=3205724; DOI=10.1093/nar/16.22.10913;
RA Halley C., Courtois Y., Laurent M.;
RT "Nucleotide sequence of bovine acidic fibroblast growth factor cDNA.";
RL Nucleic Acids Res. 16:10913-10913(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=2849564; DOI=10.1016/0014-5793(88)80981-5;
RA Alterio J., Halley C., Brou C., Soussi T., Courtois Y., Laurent M.;
RT "Characterization of a bovine acidic FGF cDNA clone and its expression in
RT brain and retina.";
RL FEBS Lett. 242:41-46(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Heart ventricle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 2-155, AND ACETYLATION AT ALA-2.
RX PubMed=3532107; DOI=10.1073/pnas.83.19.7216;
RA Burgess W.H., Mehlman T., Marshak D.R., Fraser B.A., Maciag T.;
RT "Structural evidence that endothelial cell growth factor beta is the
RT precursor of both endothelial cell growth factor alpha and acidic
RT fibroblast growth factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7216-7220(1986).
RN [5]
RP PROTEIN SEQUENCE OF 2-155.
RX PubMed=3768327; DOI=10.1021/bi00366a003;
RA Crabb J.W., Armes L.G., Carr S.A., Johnson C.M., Roberts G.D.,
RA Bordoli R.S., McKeehan W.L.;
RT "Complete primary structure of prostatropin, a prostate epithelial cell
RT growth factor.";
RL Biochemistry 25:4988-4993(1986).
RN [6]
RP PROTEIN SEQUENCE OF 16-155.
RX PubMed=4071057; DOI=10.1126/science.4071057;
RA Gimenez-Gallego G., Rodkey J., Bennett C., Rios-Candelore M., Disalvo J.,
RA Thomas K.;
RT "Brain-derived acidic fibroblast growth factor: complete amino acid
RT sequence and homologies.";
RL Science 230:1385-1388(1985).
RN [7]
RP PROTEIN SEQUENCE OF 16-44, AND AMINO-ACID COMPOSITION.
RX PubMed=4065099; DOI=10.1002/j.1460-2075.1985.tb03876.x;
RA Boehlen P., Esch F., Baird A., Gospodarowicz D.;
RT "Acidic fibroblast growth factor (FGF) from bovine brain: amino-terminal
RT sequence and comparison with basic FGF.";
RL EMBO J. 4:1951-1956(1985).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 16-56.
RX PubMed=2425435; DOI=10.1126/science.2425435;
RA Abraham J.A., Mergia A., Whang J.L., Tumolo A., Friedman J., Hjerrild K.A.,
RA Gospodarowicz D., Fiddes J.C.;
RT "Nucleotide sequence of a bovine clone encoding the angiogenic protein,
RT basic fibroblast growth factor.";
RL Science 233:545-548(1986).
RN [9]
RP PROTEIN SEQUENCE OF 16-45.
RX PubMed=2714282; DOI=10.1111/j.1432-1033.1989.tb14694.x;
RA Quinkler W., Maasberg M., Bernotat-Danielowski S., Luethe N., Sharma H.S.,
RA Schaper W.;
RT "Isolation of heparin-binding growth factors from bovine, porcine and
RT canine hearts.";
RL Eur. J. Biochem. 181:67-73(1989).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-18.
RX PubMed=1280126; DOI=10.1016/0006-291x(92)91133-b;
RA Philippe J.-M., Renaud F., Desset S., Laurent M., Mallet J., Courtois Y.,
RA Edwards J.B.;
RT "Cloning of two different 5' untranslated exons of bovine acidic fibroblast
RT growth factor by the single strand ligation to single-stranded cDNA
RT methodology.";
RL Biochem. Biophys. Res. Commun. 188:843-850(1992).
RN [11]
RP INTERACTION WITH SYT1, FUNCTION, HEPARIN BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=9712834; DOI=10.1074/jbc.273.35.22209;
RA Tarantini F., LaVallee T., Jackson A., Gamble S., Mouta Carreira C.,
RA Garfinkel S., Burgess W.H., Maciag T.;
RT "The extravesicular domain of synaptotagmin-1 is released with the latent
RT fibroblast growth factor-1 homodimer in response to heat shock.";
RL J. Biol. Chem. 273:22209-22216(1998).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11039909; DOI=10.1038/sj.onc.1203872;
RA Bryckaert M., Guillonneau X., Hecquet C., Perani P., Courtois Y.,
RA Mascarelli F.;
RT "Regulation of proliferation-survival decisions is controlled by FGF1
RT secretion in retinal pigmented epithelial cells.";
RL Oncogene 19:4917-4929(2000).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
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).
CC -!- FUNCTION: Plays an important role in the regulation of cell survival,
CC cell division, angiogenesis, cell differentiation and cell migration.
CC Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and
CC integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1
CC dimerization and activation via sequential autophosphorylation on
CC tyrosine residues which act as docking sites for interacting proteins,
CC leading to the activation of several signaling cascades. Binds to
CC integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary
CC complex formation with integrin and FGFR1, and the recruitment of
CC PTPN11 to the complex are essential for FGF1 signaling. Induces the
CC phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2
CC and AKT1. Can induce angiogenesis (By similarity).
CC {ECO:0000250|UniProtKB:P05230, ECO:0000269|PubMed:11039909,
CC ECO:0000269|PubMed:9712834}.
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. Found in a complex with FGFBP1, FGF1 and FGF2.
CC Interacts with FGFBP1. Part of a Cu(2+)-dependent multiprotein
CC aggregate containing FGF1, S100A13 and SYT1. Interacts with S100A13.
CC Interacts with FGFBP1 (By similarity). Interacts with LRRC59 (By
CC similarity). Interacts with CSNKA, CSNKB and FIBP (By similarity).
CC While binding with LRRC59, CSNKA and FIBP seem mutually exclusive,
CC CSNKB and FIBP may cooperatively interact with FGF1 (By similarity).
CC Interacts with SYT1 (PubMed:9712834). Forms a ternary complex with
CC FGFR1 and ITGAV:ITGB3 and induces the recruitment of PTPN11 to the
CC complex (By similarity). {ECO:0000250|UniProtKB:P05230,
CC ECO:0000269|PubMed:9712834}.
CC -!- INTERACTION:
CC P03968; P21802: FGFR2; Xeno; NbExp=2; IntAct=EBI-6358090, EBI-1028658;
CC P03968; P21802-3: FGFR2; Xeno; NbExp=2; IntAct=EBI-6358090, EBI-6354683;
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasm {ECO:0000250}. Cytoplasm,
CC cell cortex {ECO:0000250}. Cytoplasm, cytosol. Nucleus. Note=Lacks a
CC cleavable signal sequence. Within the cytoplasm, it is transported to
CC the cell membrane and then secreted by a non-classical pathway that
CC requires Cu(2+) ions and S100A13. Secreted in a complex with SYT1.
CC Binding of exogenous FGF1 to FGFR facilitates endocytosis followed by
CC translocation of FGF1 across endosomal membrane into the cytosol.
CC Nuclear import from the cytosol requires the classical nuclear import
CC machinery, involving proteins KPNA1 and KPNB1, as well as LRRC59 (By
CC similarity). {ECO:0000250}.
CC -!- PTM: In the nucleus, phosphorylated by PKC/PRKCD. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X13221; CAA31610.1; -; mRNA.
DR EMBL; X14032; CAA32192.1; -; mRNA.
DR EMBL; M35608; AAA30517.1; -; mRNA.
DR EMBL; BC103225; AAI03226.1; -; mRNA.
DR EMBL; M13439; AAA30516.1; -; Genomic_DNA.
DR EMBL; X66446; CAA47063.1; -; mRNA.
DR EMBL; M97660; AAA30563.1; -; mRNA.
DR EMBL; M97661; AAA30564.1; -; mRNA.
DR PIR; JH0613; GKBOA.
DR RefSeq; NP_001300935.1; NM_001314006.1.
DR RefSeq; NP_776480.1; NM_174055.3.
DR RefSeq; XP_015327761.1; XM_015472275.1.
DR RefSeq; XP_015327762.1; XM_015472276.1.
DR RefSeq; XP_015327763.1; XM_015472277.1.
DR PDB; 1AFC; X-ray; 2.70 A; A/B/C/D/E/F/G/H=16-155.
DR PDB; 1BAR; X-ray; 2.70 A; A/B=16-155.
DR PDBsum; 1AFC; -.
DR PDBsum; 1BAR; -.
DR AlphaFoldDB; P03968; -.
DR SMR; P03968; -.
DR BioGRID; 158520; 1.
DR IntAct; P03968; 3.
DR STRING; 9913.ENSBTAP00000040651; -.
DR iPTMnet; P03968; -.
DR PaxDb; P03968; -.
DR Ensembl; ENSBTAT00000043056; ENSBTAP00000040651; ENSBTAG00000005198.
DR Ensembl; ENSBTAT00000068787; ENSBTAP00000073018; ENSBTAG00000005198.
DR Ensembl; ENSBTAT00000072959; ENSBTAP00000058186; ENSBTAG00000005198.
DR Ensembl; ENSBTAT00000078959; ENSBTAP00000065580; ENSBTAG00000005198.
DR GeneID; 281160; -.
DR KEGG; bta:281160; -.
DR CTD; 2246; -.
DR VEuPathDB; HostDB:ENSBTAG00000005198; -.
DR VGNC; VGNC:28970; FGF1.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000160557; -.
DR HOGENOM; CLU_081609_5_1_1; -.
DR InParanoid; P03968; -.
DR OMA; MHADKNW; -.
DR OrthoDB; 1157770at2759; -.
DR TreeFam; TF317805; -.
DR Reactome; R-BTA-109704; PI3K Cascade.
DR Reactome; R-BTA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-BTA-190322; FGFR4 ligand binding and activation.
DR Reactome; R-BTA-190370; FGFR1b ligand binding and activation.
DR Reactome; R-BTA-190371; FGFR3b ligand binding and activation.
DR Reactome; R-BTA-190372; FGFR3c ligand binding and activation.
DR Reactome; R-BTA-190373; FGFR1c ligand binding and activation.
DR Reactome; R-BTA-190375; FGFR2c ligand binding and activation.
DR Reactome; R-BTA-190377; FGFR2b ligand binding and activation.
DR Reactome; R-BTA-5654219; Phospholipase C-mediated cascade: FGFR1.
DR Reactome; R-BTA-5654221; Phospholipase C-mediated cascade, FGFR2.
DR Reactome; R-BTA-5654227; Phospholipase C-mediated cascade, FGFR3.
DR Reactome; R-BTA-5654228; Phospholipase C-mediated cascade, FGFR4.
DR Reactome; R-BTA-5654687; Downstream signaling of activated FGFR1.
DR Reactome; R-BTA-5654688; SHC-mediated cascade:FGFR1.
DR Reactome; R-BTA-5654689; PI-3K cascade:FGFR1.
DR Reactome; R-BTA-5654693; FRS-mediated FGFR1 signaling.
DR Reactome; R-BTA-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-BTA-5654699; SHC-mediated cascade:FGFR2.
DR Reactome; R-BTA-5654700; FRS-mediated FGFR2 signaling.
DR Reactome; R-BTA-5654704; SHC-mediated cascade:FGFR3.
DR Reactome; R-BTA-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-BTA-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-BTA-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-BTA-5654719; SHC-mediated cascade:FGFR4.
DR Reactome; R-BTA-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-BTA-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-BTA-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-BTA-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-BTA-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-BTA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-BTA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR EvolutionaryTrace; P03968; -.
DR Proteomes; UP000009136; Chromosome 7.
DR Bgee; ENSBTAG00000005198; Expressed in cardiac ventricle and 97 other tissues.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR GO; GO:0044548; F:S100 protein binding; ISS:UniProtKB.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0060681; P:branch elongation involved in ureteric bud branching; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030324; P:lung development; IBA:GO_Central.
DR GO; GO:0072163; P:mesonephric epithelium development; ISS:UniProtKB.
DR GO; GO:0001759; P:organ induction; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IBA:GO_Central.
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:1902533; P:positive regulation of intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IBA:GO_Central.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
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; ISS:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:1901509; P:regulation of endothelial tube morphogenesis; ISS:UniProtKB.
DR GO; GO:0042060; P:wound healing; IBA:GO_Central.
DR CDD; cd00058; FGF; 1.
DR InterPro; IPR028210; FGF1.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; PTHR11486; 1.
DR PANTHER; PTHR11486:SF86; PTHR11486:SF86; 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; Acetylation; Angiogenesis; Cytoplasm; Developmental protein;
KW Differentiation; Direct protein sequencing; Growth factor; Heparin-binding;
KW Mitogen; Nucleus; Phosphoprotein; Reference proteome; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:3532107,
FT ECO:0000269|PubMed:3768327"
FT CHAIN 2..155
FT /note="Endothelial cell growth factor beta"
FT /id="PRO_0000008904"
FT CHAIN 16..155
FT /note="Fibroblast growth factor 1"
FT /id="PRO_0000008905"
FT CHAIN 22..155
FT /note="Endothelial cell growth factor alpha"
FT /id="PRO_0000008906"
FT MOTIF 24..27
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT BINDING 24..28
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000255"
FT BINDING 113..116
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:3532107"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:1AFC"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:1AFC"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:1AFC"
FT STRAND 46..50
FT /evidence="ECO:0007829|PDB:1AFC"
FT HELIX 55..57
FT /evidence="ECO:0007829|PDB:1AFC"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:1AFC"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:1AFC"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:1AFC"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:1AFC"
FT STRAND 86..93
FT /evidence="ECO:0007829|PDB:1AFC"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:1AFC"
FT STRAND 99..104
FT /evidence="ECO:0007829|PDB:1BAR"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:1BAR"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:1AFC"
FT TURN 116..121
FT /evidence="ECO:0007829|PDB:1AFC"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:1BAR"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:1AFC"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:1BAR"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:1AFC"
SQ SEQUENCE 155 AA; 17493 MW; F636641F189F9BFD CRC64;
MAEGETTTFT ALTEKFNLPL GNYKKPKLLY CSNGGYFLRI LPDGTVDGTK DRSDQHIQLQ
LCAESIGEVY IKSTETGQFL AMDTDGLLYG SQTPNEECLF LERLEENHYN TYISKKHAEK
HWFVGLKKNG RSKLGPRTHF GQKAILFLPL PVSSD
