FGF1_MESAU
ID FGF1_MESAU Reviewed; 155 AA.
AC P34004;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 121.
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;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1693366; DOI=10.1002/jcb.240430103;
RA Hall J.A., Harris M.A., Malark M., Mansson P.E., Zhou H., Harris S.E.;
RT "Characterization of the hamster DDT-1 cell aFGF/HGBF-I gene and cDNA and
RT its modulation by steroids.";
RL J. Cell. Biochem. 43:17-26(1990).
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. Cytoplasm {ECO:0000250}. Cytoplasm,
CC cell cortex {ECO:0000250}. Cytoplasm, cytosol {ECO:0000250}. Nucleus
CC {ECO:0000250}. Note=Lacks a cleavable signal sequence. Within the
CC cytoplasm, it is transported to the cell membrane and then secreted by
CC a non-classical pathway that requires Cu(2+) ions and S100A13. Secreted
CC in a complex with SYT1. Binding of exogenous FGF1 to FGFR facilitates
CC endocytosis followed by translocation of FGF1 across endosomal membrane
CC into the cytosol. Nuclear import from the cytosol requires the
CC classical nuclear import machinery, involving proteins KPNA1 and KPNB1,
CC as well as LRRC59 (By 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 PIR; A60721; A60721.
DR RefSeq; XP_005069250.1; XM_005069193.2.
DR RefSeq; XP_012968217.1; XM_013112763.1.
DR RefSeq; XP_012968218.1; XM_013112764.1.
DR AlphaFoldDB; P34004; -.
DR BMRB; P34004; -.
DR SMR; P34004; -.
DR STRING; 10036.XP_005069250.1; -.
DR GeneID; 101823630; -.
DR CTD; 2246; -.
DR eggNOG; KOG3885; Eukaryota.
DR OrthoDB; 1157770at2759; -.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
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: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:0060681; P:branch elongation involved in ureteric bud branching; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
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; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS: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; IEA:Ensembl.
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: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; IEA:Ensembl.
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 2: Evidence at transcript level;
KW 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_0000008909"
FT CHAIN 16..155
FT /note="Fibroblast growth factor 1"
FT /id="PRO_0000008910"
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"
SQ SEQUENCE 155 AA; 17404 MW; 41E5EC760E412CC5 CRC64;
MAEGEITTFS ALTERFNLPP GNYKKPKLLY CSNGGHFLRI LPDGTVDGTR DRSDQHIQLQ
LSAESAGEVY IKGTETGQYL AMDTDGLLYG SQTPNEECLF LERLEENHYN TYTSKKHAEK
NWFVGLKKNG SCKRGPRTHY GQKAILFLPL PVSSD
