FGF1_RAT
ID FGF1_RAT Reviewed; 155 AA.
AC P61149; P10935;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Fibroblast growth factor 1;
DE Short=FGF-1;
DE AltName: Full=Acidic fibroblast growth factor;
DE Short=aFGF;
DE AltName: Full=Heparin-binding growth factor 1;
DE Short=HBGF-1;
DE Flags: Precursor;
GN Name=Fgf1; Synonyms=Fgf-1, Fgfa;
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].
RX PubMed=2470029; DOI=10.1093/nar/17.7.2867;
RA Goodrich S., Yan G.C., Bahrenburg K., Mansson P.E.;
RT "The nucleotide sequence of rat heparin binding growth factor 1 (HBGF-1).";
RL Nucleic Acids Res. 17:2867-2867(1989).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=15627653; DOI=10.1194/jlr.m400313-jlr200;
RA Ito J., Nagayasu Y., Lu R., Kheirollah A., Hayashi M., Yokoyama S.;
RT "Astrocytes produce and secrete FGF-1, which promotes the production of
RT apoE-HDL in a manner of autocrine action.";
RL J. Lipid Res. 46:679-686(2005).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 22-155.
RX PubMed=17277441; DOI=10.1107/s1744309107003144;
RA Kulahin N., Kiselyov V., Kochoyan A., Kristensen O., Kastrup J.S.,
RA Berezin V., Bock E., Gajhede M.;
RT "Structure of rat acidic fibroblast growth factor at 1.4 A resolution.";
RL Acta Crystallogr. F 63:65-68(2007).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 22-153.
RX PubMed=18540049; DOI=10.1107/s174430910801066x;
RA Kulahin N., Kiselyov V., Kochoyan A., Kristensen O., Kastrup J.S.,
RA Berezin V., Bock E., Gajhede M.;
RT "Dimerization effect of sucrose octasulfate on rat FGF1.";
RL Acta Crystallogr. F 64:448-452(2008).
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. {ECO:0000250|UniProtKB:P05230}.
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 SYT1.
CC Interacts with S100A13 (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. Forms a ternary
CC complex with FGFR1 and ITGAV:ITGB3 and induces the recruitment of
CC PTPN11 to the complex (By similarity). {ECO:0000250|UniProtKB:P05230}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15627653}. Cytoplasm
CC {ECO:0000250}. Cytoplasm, cell cortex {ECO:0000250}. Cytoplasm, cytosol
CC {ECO:0000250}. Nucleus {ECO:0000250}. Note=Lacks a cleavable signal
CC sequence. Within the cytoplasm, it is transported to the cell membrane
CC and then secreted by a non-classical pathway that requires Cu(2+) ions
CC and S100A13. Secreted in a complex with SYT1 (By similarity). Binding
CC 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}.
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DR EMBL; X14232; CAA32448.1; -; mRNA.
DR PIR; S04147; S04147.
DR RefSeq; NP_036978.1; NM_012846.1.
DR RefSeq; XP_006254712.1; XM_006254650.3.
DR RefSeq; XP_006254713.1; XM_006254651.3.
DR RefSeq; XP_006254714.1; XM_006254652.3.
DR PDB; 2J3P; X-ray; 1.40 A; A/B=22-155.
DR PDB; 2UUS; X-ray; 2.20 A; A/B=22-153.
DR PDBsum; 2J3P; -.
DR PDBsum; 2UUS; -.
DR AlphaFoldDB; P61149; -.
DR BMRB; P61149; -.
DR SMR; P61149; -.
DR BioGRID; 247356; 1.
DR IntAct; P61149; 2.
DR MINT; P61149; -.
DR STRING; 10116.ENSRNOP00000018577; -.
DR PhosphoSitePlus; P61149; -.
DR PaxDb; P61149; -.
DR Ensembl; ENSRNOT00000087408; ENSRNOP00000070685; ENSRNOG00000013867.
DR GeneID; 25317; -.
DR KEGG; rno:25317; -.
DR UCSC; RGD:2605; rat.
DR CTD; 2246; -.
DR RGD; 2605; Fgf1.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000160557; -.
DR InParanoid; P61149; -.
DR OMA; MHADKNW; -.
DR OrthoDB; 1157770at2759; -.
DR PhylomeDB; P61149; -.
DR TreeFam; TF317805; -.
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-190371; FGFR3b 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-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-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR EvolutionaryTrace; P61149; -.
DR PRO; PR:P61149; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000013867; Expressed in heart and 17 other tissues.
DR Genevisible; P61149; RN.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IDA:RGD.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IPI:RGD.
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; ISO:RGD.
DR GO; GO:0072163; P:mesonephric epithelium development; ISS:UniProtKB.
DR GO; GO:0001759; P:organ induction; ISO:RGD.
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; ISO:RGD.
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:2000347; P:positive regulation of hepatocyte proliferation; IDA:UniProtKB.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO: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; 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; ISO:RGD.
DR GO; GO:1901509; P:regulation of endothelial tube morphogenesis; ISS:UniProtKB.
DR GO; GO:0042060; P:wound healing; ISO:RGD.
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; Growth factor; Heparin-binding; Mitogen; Nucleus;
KW Phosphoprotein; Reference proteome; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P03968"
FT PROPEP 2..15
FT /evidence="ECO:0000250"
FT /id="PRO_0000008916"
FT CHAIN 16..155
FT /note="Fibroblast growth factor 1"
FT /id="PRO_0000008917"
FT REGION 127..143
FT /note="Heparin-binding"
FT /evidence="ECO:0000250"
FT BINDING 33
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P03968"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:2J3P"
FT TURN 32..35
FT /evidence="ECO:0007829|PDB:2J3P"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:2J3P"
FT STRAND 44..50
FT /evidence="ECO:0007829|PDB:2J3P"
FT HELIX 55..57
FT /evidence="ECO:0007829|PDB:2UUS"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:2J3P"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:2J3P"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:2J3P"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:2J3P"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:2J3P"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:2J3P"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:2J3P"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:2J3P"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:2J3P"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:2J3P"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:2J3P"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:2J3P"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:2J3P"
SQ SEQUENCE 155 AA; 17418 MW; 8880E4FF0FBA4161 CRC64;
MAEGEITTFA ALTERFNLPL GNYKKPKLLY CSNGGHFLRI LPDGTVDGTR DRSDQHIQLQ
LSAESAGEVY IKGTETGQYL AMDTEGLLYG SQTPNEECLF LERLEENHYN TYTSKKHAEK
NWFVGLKKNG SCKRGPRTHY GQKAILFLPL PVSSD
