FGF1 (fibroblast growth factor 1)

Gene

• Entrez ID: 2246
• Gene name: Fibroblast growth factor 1
• Gene symbol: FGF1
• Synonyms: AFGF, ECGF, ECGF-beta, ECGFA, ECGFB, FGF-1, FGF-alpha, FGFA, GLIO703, HBGF-1, HBGF1
• Chromosome: 5
• Chromosome location: 5q31.3
• Summary: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. 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. Multiple alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022188	hsa-miR-124-3p	Microarray	18668037
MIRT025666	hsa-miR-7-5p	Microarray	17612493
MIRT446182	hsa-miR-943	PAR-CLIP	22100165
MIRT446183	hsa-miR-4439	PAR-CLIP	22100165
MIRT446184	hsa-miR-3136-5p	PAR-CLIP	22100165
MIRT446185	hsa-miR-526b-5p	PAR-CLIP	22100165
MIRT446186	hsa-miR-6857-3p	PAR-CLIP	22100165
MIRT446187	hsa-miR-6855-3p	PAR-CLIP	22100165
MIRT446188	hsa-miR-4513	PAR-CLIP	22100165
MIRT710277	hsa-miR-6069	HITS-CLIP	19536157
MIRT710278	hsa-miR-6728-3p	HITS-CLIP	19536157
MIRT710279	hsa-miR-186-3p	HITS-CLIP	19536157
MIRT710280	hsa-miR-6877-3p	HITS-CLIP	19536157
MIRT710281	hsa-miR-6819-3p	HITS-CLIP	19536157
MIRT710282	hsa-miR-7109-3p	HITS-CLIP	19536157
MIRT717728	hsa-miR-4753-3p	HITS-CLIP	19536157
MIRT717729	hsa-miR-302d-5p	HITS-CLIP	19536157
MIRT717730	hsa-miR-302b-5p	HITS-CLIP	19536157
MIRT717731	hsa-miR-130b-5p	HITS-CLIP	19536157
MIRT717732	hsa-miR-589-3p	HITS-CLIP	19536157
MIRT717733	hsa-miR-500b-3p	HITS-CLIP	19536157
MIRT717734	hsa-miR-4773	HITS-CLIP	19536157
MIRT717735	hsa-miR-1912	HITS-CLIP	19536157
MIRT717736	hsa-miR-1295b-5p	HITS-CLIP	19536157
MIRT731763	hsa-miR-326	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	26183397

Transcription factors

Transcription factor	Regulation	Reference
PPARG	Unknown	22522926
RFX1	Unknown	20189986;22415835
RFX2	Unknown	22415835
RFX3	Unknown	22415835
STAT3	Repression	14673954

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	TAS
GO:0000187	Process	Activation of MAPK activity	IMP	18441324
GO:0001525	Process	Angiogenesis	IEA
GO:0001759	Process	Organ induction	IEA
GO:0001934	Process	Positive regulation of protein phosphorylation	IBA	21873635
GO:0005104	Function	Fibroblast growth factor receptor binding	IBA	21873635
GO:0005104	Function	Fibroblast growth factor receptor binding	IMP	18441324
GO:0005104	Function	Fibroblast growth factor receptor binding	IPI	10830168, 12815063
GO:0005178	Function	Integrin binding	IDA	18441324
GO:0005515	Function	Protein binding	IPI	10618369, 10830168, 14613973, 14732692, 18441324, 25241761, 32296183
GO:0005576	Component	Extracellular region	IDA	12746488
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	18400376
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005654	Component	Nucleoplasm	IDA
GO:0005730	Component	Nucleolus	IEA
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	IDA	12746488
GO:0005938	Component	Cell cortex	IEA
GO:0007165	Process	Signal transduction	NAS	3778488
GO:0007275	Process	Multicellular organism development	TAS	10903182
GO:0008083	Function	Growth factor activity	IBA	21873635
GO:0008083	Function	Growth factor activity	IDA	20145243
GO:0008201	Function	Heparin binding	IDA	20145243
GO:0008201	Function	Heparin binding	IMP	18441324
GO:0008284	Process	Positive regulation of cell population proliferation	IBA	21873635
GO:0008284	Process	Positive regulation of cell population proliferation	IGI	8663044, 18187602
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	18441324, 23469107
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IBA	21873635
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IDA	20145243
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IGI	8663044, 18187602
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IMP	18441324
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IPI	10830168
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	TAS
GO:0009653	Process	Anatomical structure morphogenesis	TAS	1693186
GO:0009887	Process	Animal organ morphogenesis	IBA	21873635
GO:0010595	Process	Positive regulation of endothelial cell migration	IBA	21873635
GO:0010595	Process	Positive regulation of endothelial cell migration	IMP	23469107
GO:0010628	Process	Positive regulation of gene expression	IBA	21873635
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0030324	Process	Lung development	IBA	21873635
GO:0030334	Process	Regulation of cell migration	IBA	21873635
GO:0030335	Process	Positive regulation of cell migration	IDA	20145243
GO:0030335	Process	Positive regulation of cell migration	IMP	18441324
GO:0030544	Function	Hsp70 protein binding	IEA
GO:0031012	Component	Extracellular matrix	IEA
GO:0032148	Process	Activation of protein kinase B activity	IMP	18441324
GO:0034605	Process	Cellular response to heat	IDA	12746488
GO:0042060	Process	Wound healing	IBA	21873635
GO:0042060	Process	Wound healing	IDA	16756958
GO:0043406	Process	Positive regulation of MAP kinase activity	IBA	21873635
GO:0043406	Process	Positive regulation of MAP kinase activity	IDA	16756958
GO:0044548	Function	S100 protein binding	IPI	11432880
GO:0045542	Process	Positive regulation of cholesterol biosynthetic process	IDA	19229075
GO:0045766	Process	Positive regulation of angiogenesis	IDA	20145243
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	19229075
GO:0050679	Process	Positive regulation of epithelial cell proliferation	IBA	21873635
GO:0051781	Process	Positive regulation of cell division	IDA	20145243
GO:0051897	Process	Positive regulation of protein kinase B signaling	TAS
GO:0060681	Process	Branch elongation involved in ureteric bud branching	IDA	11731227
GO:0072163	Process	Mesonephric epithelium development	IDA	11731227
GO:1901509	Process	Regulation of endothelial tube morphogenesis	IMP	23469107
GO:1902533	Process	Positive regulation of intracellular signal transduction	IDA	19229075
GO:1903672	Process	Positive regulation of sprouting angiogenesis	IMP	23469107
GO:2000347	Process	Positive regulation of hepatocyte proliferation	IEA
GO:2000544	Process	Regulation of endothelial cell chemotaxis to fibroblast growth factor	IDA	16756958

Other IDs

• MIM: 131220
• HGNC: 3665
• e!Ensembl: ENSG00000113578

Protein

• UniProt ID: P05230
• Protein name: Fibroblast growth factor 1 (FGF-1) (Acidic fibroblast growth factor) (aFGF) (Endothelial cell growth factor) (ECGF) (Heparin-binding growth factor 1) (HBGF-1)
• Protein 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 (PubMed:18441324, PubMed:20422052). Can induce angiogenesis (PubMed:23469107).
• PDB: 1AXM, 1DJS, 1DZC, 1DZD, 1E0O, 1EVT, 1HKN, 1JQZ, 1JT3, 1JT4, 1JT5, 1JT7, 1JTC, 1JY0, 1K5U, 1K5V, 1M16, 1NZK, 1P63, 1PZZ, 1Q03, 1Q04, 1QCT, 1RG8, 1RML, 1RY7, 1YTO, 1Z2V, 1Z4S, 2AFG, 2AQZ, 2AXM, 2ERM, 2HW9, 2HWA, 2HWM, 2HZ9, 2K43, 2K4A, 2K8R, 2KI4, 2KI6, 2NTD, 2Q9X, 2RQ9, 3B9U, 3BA4, 3BA5, 3BA7, 3BAD, 3BAG
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00167	FGF	25 → 148	Fibroblast growth factor	Domain

• Sequence:

  MAEGEITTFTALTEKFNLPPGNYKKPKLLYCSNGGHFLRILPDGTVDGTRDRSDQHIQLQ
  LSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENHYNTYISKKHAEK
  NWFVGLKKNGSCKRGPRTHYGQKAILFLPLPVSSD

• Sequence length: 155

Pathways

KEGG:

MAPK signaling pathway
Ras signaling pathway
Rap1 signaling pathway
Calcium signaling pathway
PI3K-Akt signaling pathway
Hippo signaling pathway
Regulation of actin cytoskeleton
Pathways in cancer
Melanoma
Breast cancer
Gastric cancer

Reactome:

PI3K Cascade
PIP3 activates AKT signaling
Signaling by activated point mutants of FGFR1
Signaling by activated point mutants of FGFR3
FGFR4 ligand binding and activation
FGFR1b ligand binding and activation
FGFR3b ligand binding and activation
FGFR3c ligand binding and activation
FGFR1c ligand binding and activation
FGFR2c ligand binding and activation
FGFR2b ligand binding and activation
FGFR3 mutant receptor activation
Activated point mutants of FGFR2
Constitutive Signaling by Aberrant PI3K in Cancer
Phospholipase C-mediated cascade: FGFR1
Phospholipase C-mediated cascade; FGFR2
Phospholipase C-mediated cascade; FGFR3
Phospholipase C-mediated cascade; FGFR4
Downstream signaling of activated FGFR1
SHC-mediated cascade:FGFR1
PI-3K cascade:FGFR1
FRS-mediated FGFR1 signaling
PI-3K cascade:FGFR2
SHC-mediated cascade:FGFR2
FRS-mediated FGFR2 signaling
SHC-mediated cascade:FGFR3
FRS-mediated FGFR3 signaling
PI-3K cascade:FGFR3
FRS-mediated FGFR4 signaling
SHC-mediated cascade:FGFR4
PI-3K cascade:FGFR4
Negative regulation of FGFR1 signaling
Negative regulation of FGFR2 signaling
Negative regulation of FGFR3 signaling
Negative regulation of FGFR4 signaling
Signaling by FGFR2 in disease
Signaling by FGFR1 in disease
RAF/MAP kinase cascade
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
Signaling by FGFR3 point mutants in cancer

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Mesothelioma	Mesothelioma	rs121907908, rs387906350, rs387906351	15878867
Leukemia	leukemia	rs-1, rs121909646, rs121913488, rs587776834, rs752746786, rs869312821, rs767454740, rs1554564297	17219402
Ovarian cancer	Malignant neoplasm of ovary	rs34424986, rs137853060, rs28934575, rs79658334, rs121913021, rs62625308, rs80356898, rs80357579, rs41293497, rs80356904, rs80357471, rs80357522, rs80357234, rs80357912, rs80357828, rs80357208, rs55770810, rs80358165, rs80358010, rs587780226, rs536907995, rs139414606, rs371638537, rs574552037, rs730881647, rs747993448, rs786202125, rs786202962, rs121913321, rs189261858, rs869320800, rs753023295, rs779466229, rs752411477, rs80357438, rs191486604, rs760874290, rs752780954, rs760782298, rs1555591361, rs1555578360, rs1555588460, rs1555587401, rs747427602, rs112675807, rs80357393	25174399
Pulmonary fibrosis	Pulmonary Fibrosis	rs121918666, rs199422300, rs121917737, rs121917834, rs199422294, rs201159197, rs199422297, rs199422305, rs751381953, rs876661305, rs878853260, rs863223336, rs786205702, rs1555811762, rs1060502990, rs1555903332, rs1554038539, rs1554042899, rs938938578	16324872

Unknown
Disease name	Disease term	dbSNP ID	References
Alveolitis	Alveolitis, Fibrosing		16324872
Myocardial ischemia	Myocardial Ischemia		16214533
Ovarian neoplasm	ovarian neoplasm		25174399