FGF-1 has no definitive signal sequence and thus is not secreted through classical pathways, but it does appear to form a disulfide linked dimer inside cells that associate with a complex of proteins at the cell membrane (including S100A13 and Syt1) which then help flip it through the membrane to the exterior of the cell. Once in the reducing conditions of the surrounding tissue, the dimer dissociates into monomeric FGF1 that can enter systemic circulation or be sequestered in tissues binding to heparan sulfate proteoglycans of the extracellular matrix. FGF1 can then bind to and exert its effects via specific fibroblast growth factor receptor (FGFR) proteins which themselves constitute a family of closely related molecules.
In addition to its extracellular activity, FGF1 can also function intracellularly. The protein has a nuclear localization sequence (NLS) but the route that FGF1 takes to get to the nucleus is unclear and it appears that some sort of cell surface receptor binding is necessary, followed by its internalization and translocation to the nucleus whereupon it can interact with nuclear isoforms of FGFRs. This is different from FGF2 which also can activate nuclear FGFRs but has splicing variants of the protein that never leave the cell and go directly to the nucleus.
FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Three alternatively spliced variants encoding different isoforms have been described.
FGF1 is multifunctional with many reported effects. For one example, in mice with diet-induced diabetes that is an experimental equivalent of type 2 diabetes in humans, a single injection of the FGF1 protein is enough to restore blood sugar levels to a healthy range for > 2 days.
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1afc: STRUCTURAL STUDIES OF THE BINDING OF THE ANTI-ULCER DRUG SUCROSE OCTASULFATE TO ACIDIC FIBROBLAST GROWTH FACTOR
PDB 1axm EBI.jpg
1axm: HEPARIN-LINKED BIOLOGICALLY-ACTIVE DIMER OF FIBROBLAST GROWTH FACTOR
PDB 1bar EBI.jpg
1bar: THREE-DIMENSIONAL STRUCTURES OF ACIDIC AND BASIC FIBROBLAST GROWTH FACTORS
PDB 1djs EBI.jpg
1djs: LIGAND-BINDING PORTION OF FIBROBLAST GROWTH FACTOR RECEPTOR 2 IN COMPLEX WITH FGF1
PDB 1dzc EBI.jpg
1dzc: HIGH RESOLUTION STRUCTURE OF ACIDIC FIBROBLAST GROWTH FACTOR. MUTANT FGF-4-ALA-(23-154), 24 NMR STRUCTURES
PDB 1dzd EBI.jpg
1dzd: HIGH RESOLUTION STRUCTURE OF ACIDIC FIBROBLAST GROWTH FACTOR (27-154), 24 NMR STRUCTURES
PDB 1e0o EBI.jpg
1e0o: CRYSTAL STRUCTURE OF A TERNARY FGF1-FGFR2-HEPARIN COMPLEX
PDB 1evt EBI.jpg
1evt: CRYSTAL STRUCTURE OF FGF1 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 1 (FGFR1)
PDB 1hkn EBI.jpg
1hkn: A COMPLEX BETWEEN ACIDIC FIBROBLAST GROWTH FACTOR AND 5-AMINO-2-NAPHTHALENESULFONATE
PDB 1jqz EBI.jpg
1jqz: Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Terminal His Tag.
PDB 1jt3 EBI.jpg
1jt3: Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Histidine Tag AND LEU 73 REPLACED BY VAL (L73V)
PDB 1jt4 EBI.jpg
1jt4: Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Terminal His Tag AND VAL 109 REPLACED BY LEU (V109L)
PDB 1jt5 EBI.jpg
1jt5: Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Terminal His Tag AND LEU 73 REPLACED BY VAL AND VAL 109 REPLACED BY LEU (L73V/V109L)
PDB 1jt7 EBI.jpg
1jt7: Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Terminal His Tag AND LEU 44 REPLACED BY PHE AND LEU 73 REPLACED BY VAL AND VAL 109 REPLACED BY LEU (L44F/L73V/V109L)
PDB 1jtc EBI.jpg
1jtc: Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Terminal His Tag AND LEU 44 REPLACED BY PHE (L44F)
PDB 1jy0 EBI.jpg
1jy0: Human acidic fibroblast growth factor. 141 amino acid form with amino terminal His tag and Cys 117 replaced with Val (C117V).
PDB 1k5u EBI.jpg
1k5u: Human acidic fibroblast growth factor. 141 amino acid form with amino terminal His tag with His93 replaced by Gly (H93G).
PDB 1k5v EBI.jpg
1k5v: Human acidic fibroblast growth factor. 141 amino acid form with amino terminal His tag with Asn106 replaced by Gly (N106G).
PDB 1m16 EBI.jpg
1m16: Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Terminal His Tag and Leu 44 Replaced with Phe (L44F), Leu 73 Replaced with Val (L73V), Val 109 Replaced with Leu (V109L) and Cys 117 Replaced with Val (C117V).
PDB 1nzk EBI.jpg
1nzk: Crystal Structure of a Multiple Mutant (L44F, L73V, V109L, L111I, C117V) of Human Acidic Fibroblast Growth Factor
PDB 1p63 EBI.jpg
1p63: Human Acidic Fibroblast Growth Factor. 140 Amino Acid Form with Amino Terminal His Tag and Leu111 Replaced with Ile (L111I)
PDB 1pzz EBI.jpg
1pzz: Crystal structure of FGF-1, V51N mutant
PDB 1q03 EBI.jpg
1q03: Crystal structure of FGF-1, S50G/V51G mutant
PDB 1q04 EBI.jpg
1q04: Crystal structure of FGF-1, S50E/V51N
PDB 1rg8 EBI.jpg
1rg8: Human Acidic Fibroblast Growth Factor (haFGF-1) at 1.10 angstrom resolution (140 amino acid form)
PDB 1rml EBI.jpg
1rml: NMR STUDY OF ACID FIBROBLAST GROWTH FACTOR BOUND TO 1,3,6-NAPHTHALENE TRISULPHONATE, 26 STRUCTURES
PDB 1ry7 EBI.jpg
1ry7: Crystal Structure of the 3 Ig form of FGFR3c in complex with FGF1
PDB 1yto EBI.png
1yto: Crystal Structure of Gly19 deletion Mutant of Human Acidic Fibroblast Growth Factor
PDB 1z2v EBI.png
1z2v: Crystal Structure of Glu60 deletion Mutant of Human Acidic Fibroblast Growth Factor
PDB 1z4s EBI.png
1z4s: Crystal Structure of Gly19 and Glu60 deletion mutant of Human Acidic Fibroblast Growth Factor
PDB 2afg EBI.jpg
2afg: 2.0 ANGSTROM X-RAY STRUCTURE OF HUMAN ACIDIC FIBROBLAST GROWTH FACTOR
PDB 2aqz EBI.png
2aqz: Crystal structure of FGF-1, S17T/N18T/G19 deletion mutant
PDB 2axm EBI.jpg
2axm: HEPARIN-LINKED BIOLOGICALLY-ACTIVE DIMER OF FIBROBLAST GROWTH FACTOR
PDB 2erm EBI.jpg
2erm: Solution structure of a biologically active human FGF-1 monomer, complexed to a hexasaccharide heparin-analogue