UniProt functional annotation for P03968



	UniProt functional annotation for P03968

UniProt code: P03968.

Organism: Bos taurus (Bovine).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos.

Function: Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1. Can induce angiogenesis (By similarity). {ECO:0000250|UniProtKB:P05230, ECO:0000269|PubMed:11039909, ECO:0000269|PubMed:9712834}.

Subunit: Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Found in a complex with FGFBP1, FGF1 and FGF2. Interacts with FGFBP1. Part of a Cu(2+)-dependent multiprotein aggregate containing FGF1, S100A13 and SYT1. Interacts with S100A13. Interacts with FGFBP1 (By similarity). Interacts with LRRC59 (By similarity). Interacts with CSNKA, CSNKB and FIBP (By similarity). While binding with LRRC59, CSNKA and FIBP seem mutually exclusive, CSNKB and FIBP may cooperatively interact with FGF1 (By similarity). Interacts with SYT1 (PubMed:9712834). Forms a ternary complex with FGFR1 and ITGAV:ITGB3 and induces the recruitment of PTPN11 to the complex (By similarity). {ECO:0000250|UniProtKB:P05230, ECO:0000269|PubMed:9712834}.

Subcellular location: Secreted. Cytoplasm {ECO:0000250}. Cytoplasm, cell cortex {ECO:0000250}. Cytoplasm, cytosol. Nucleus. Note=Lacks a cleavable signal sequence. Within the cytoplasm, it is transported to the cell membrane and then secreted by a non-classical pathway that requires Cu(2+) ions and S100A13. Secreted in a complex with SYT1. Binding of exogenous FGF1 to FGFR facilitates endocytosis followed by translocation of FGF1 across endosomal membrane into the cytosol. Nuclear import from the cytosol requires the classical nuclear import machinery, involving proteins KPNA1 and KPNB1, as well as LRRC59 (By similarity). {ECO:0000250}.

Ptm: In the nucleus, phosphorylated by PKC/PRKCD. {ECO:0000250}.

Similarity: Belongs to the heparin-binding growth factors family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Bos taurus (Bovine).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos.



Function:		Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1. Can induce angiogenesis (By similarity). {ECO:0000250\|UniProtKB:P05230, ECO:0000269\|PubMed:11039909, ECO:0000269\|PubMed:9712834}.


Subunit:		Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Found in a complex with FGFBP1, FGF1 and FGF2. Interacts with FGFBP1. Part of a Cu(2+)-dependent multiprotein aggregate containing FGF1, S100A13 and SYT1. Interacts with S100A13. Interacts with FGFBP1 (By similarity). Interacts with LRRC59 (By similarity). Interacts with CSNKA, CSNKB and FIBP (By similarity). While binding with LRRC59, CSNKA and FIBP seem mutually exclusive, CSNKB and FIBP may cooperatively interact with FGF1 (By similarity). Interacts with SYT1 (PubMed:9712834). Forms a ternary complex with FGFR1 and ITGAV:ITGB3 and induces the recruitment of PTPN11 to the complex (By similarity). {ECO:0000250\|UniProtKB:P05230, ECO:0000269\|PubMed:9712834}.
Subcellular location:		Secreted. Cytoplasm {ECO:0000250}. Cytoplasm, cell cortex {ECO:0000250}. Cytoplasm, cytosol. Nucleus. Note=Lacks a cleavable signal sequence. Within the cytoplasm, it is transported to the cell membrane and then secreted by a non-classical pathway that requires Cu(2+) ions and S100A13. Secreted in a complex with SYT1. Binding of exogenous FGF1 to FGFR facilitates endocytosis followed by translocation of FGF1 across endosomal membrane into the cytosol. Nuclear import from the cytosol requires the classical nuclear import machinery, involving proteins KPNA1 and KPNB1, as well as LRRC59 (By similarity). {ECO:0000250}.
Ptm:		In the nucleus, phosphorylated by PKC/PRKCD. {ECO:0000250}.
Similarity:		Belongs to the heparin-binding growth factors family. {ECO:0000305}.