FGF

Acidic and basic fibroblast growth factor family.

• SMART accession number: SM00442
• Description: Mitogens that stimulate growth or differentiation of cells of mesodermal or neuroectodermal origin. The family play essential roles in patterning and differentiation during vertebrate embryogenesis, and have neurotrophic activities.
• Interpro abstract (IPR002209):

  Fibroblast growth factors (FGFs) [ (PUBMED:2549857) (PUBMED:3072709) ] are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [ (PUBMED:1705486) (PUBMED:8760337) ]. FGFs are mitogens, which stimulate growth or differentiation of cells of mesodermal or neuroectodermal origin. The function of FGFs in developmental processes include mesoderm induction, anterior-posterior patterning, limb development, and neural induction and development. In mature tissues, they are involved in diverse processes including keratinocyte organisation and wound healing [ (PUBMED:11276432) (PUBMED:23000357) (PUBMED:15689573) (PUBMED:10441498) (PUBMED:23108135) (PUBMED:23016864) ]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [ (PUBMED:1649700) (PUBMED:11746231) (PUBMED:14745970) (PUBMED:8978613) ]. Fibroblast growth factors are heparin-binding proteins and interactions with cell-surface-associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction. FGFs have internal pseudo-threefold symmetry (beta-trefoil topology) [ (PUBMED:10830168) ]. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [ (PUBMED:8652550) (PUBMED:11276432) ]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [ (PUBMED:7583099) ], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [ (PUBMED:7583099) ].

• GO function: growth factor activity (GO:0008083)

There are 6823 FGF domains in 6820 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Wilkie AO, Morriss-Kay GM, Jones EY, Heath JK
• Functions of fibroblast growth factors and their receptors.
• Curr Biol. 1995; 5: 500-7

Fibroblast growth factors were first characterized twenty years ago as mitogens of cultured fibroblasts. Despite a wealth of data from experiments in vitro, insights have begun to emerge only recently on the normal function of these growth factors in mice and humans, as a result of studies of natural and experimental mutations in the factors and their receptors.

• Yamaguchi TP, Rossant J
• Fibroblast growth factors in mammalian development.
• Curr Opin Genet Dev. 1995; 5: 485-91

Polypeptide growth factors are secreted signalling molecules that function as intercellular communicators. Detailed analyses of the expression and function of members of the fibroblast growth factor (FGF) family and their recepotors have demonstrated that the FGF signalling pathways play essential roles in regulating cellular proliferation, differentiation and tissue patterning during vertebrate embryogenesis. Recent studies on the molecular basis of human dysmorphic syndromes have revealed that aberrant FGF signalling during limb and skeletal development can lead to pathogenesis.

• Baird A
• Fibroblast growth factors: activities and significance of non-neurotrophin neurotrophic growth factors.
• Curr Opin Neurobiol. 1994; 4: 78-86

Although first characterized by virtue of their ability to stimulate endothelial cell proliferation in vitro and angiogenesis in vivo, the fibroblast growth factors are now also well recognized for their neurotrophic activities. Understanding the physiological significance of these multifunctional, virtually ubiquitous and pluripotential molecules, however, remains enigmatic. Recent advances describing their molecular, biochemical and biological characteristics has led to a better understanding of their role in the central nervous system.

• Mason IJ
• The ins and outs of fibroblast growth factors.
• Cell. 1994; 78: 547-52

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
33.33	map04810	Regulation of actin cytoskeleton
33.33	map04010	MAPK signaling pathway
33.33	map05218	Melanoma

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with FGF domain which could be assigned to a KEGG orthologous group, and not all proteins containing FGF domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of FGF domains in PDB

PDB code	Title
1afc	STRUCTURAL STUDIES OF THE BINDING OF THE ANTI-ULCER DRUG SUCROSE OCTASULFATE TO ACIDIC FIBROBLAST GROWTH FACTOR
1axm	HEPARIN-LINKED BIOLOGICALLY-ACTIVE DIMER OF FIBROBLAST GROWTH FACTOR
1bar	THREE-DIMENSIONAL STRUCTURES OF ACIDIC AND BASIC FIBROBLAST GROWTH FACTORS
1bas	THREE-DIMENSIONAL STRUCTURES OF ACIDIC AND BASIC FIBROBLAST GROWTH FACTORS
1bfb	BASIC FIBROBLAST GROWTH FACTOR COMPLEXED WITH HEPARIN TETRAMER FRAGMENT
1bfc	BASIC FIBROBLAST GROWTH FACTOR COMPLEXED WITH HEPARIN HEXAMER FRAGMENT
1bff	THE 154 AMINO ACID FORM OF HUMAN BASIC FIBROBLAST GROWTH FACTOR
1bfg	CRYSTAL STRUCTURE OF BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION
1bla	BASIC FIBROBLAST GROWTH FACTOR (FGF-2) MUTANT WITH CYS 78 REPLACED BY SER AND CYS 96 REPLACED BY SER, NMR
1bld	BASIC FIBROBLAST GROWTH FACTOR (FGF-2) MUTANT WITH CYS 78 REPLACED BY SER AND CYS 96 REPLACED BY SER, NMR
1cvs	CRYSTAL STRUCTURE OF A DIMERIC FGF2-FGFR1 COMPLEX
1djs	LIGAND-BINDING PORTION OF FIBROBLAST GROWTH FACTOR RECEPTOR 2 IN COMPLEX WITH FGF1
1dzc	High resolution structure of acidic fibroblast growth factor. Mutant FGF-4-ALA-(24-154), 24 NMR structures
1dzd	High resolution structure of acidic fibroblast growth factor (27-154), 24 NMR structures
1e0o	Crystal structure of a ternary FGF1-FGFR2-heparin complex
1ev2	CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)
1evt	CRYSTAL STRUCTURE OF FGF1 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 1 (FGFR1)
1fga	REFINEMENT OF THE STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION AND ANALYSIS OF PRESUMED HEPARIN BINDING SITES BY SELENATE SUBSTITUTION
1fmm	SOLUTION STRUCTURE OF NFGF-1
1fq9	CRYSTAL STRUCTURE OF A TERNARY FGF2-FGFR1-HEPARIN COMPLEX
1g82	STRUCTURE OF FIBROBLAST GROWTH FACTOR 9
1hkn	A complex between acidic fibroblast growth factor and 5-amino-2-naphthalenesulfonate
1ihk	CRYSTAL STRUCTURE OF FIBROBLAST GROWTH FACTOR 9 (FGF9)
1ii4	CRYSTAL STRUCTURE OF SER252TRP APERT MUTANT FGF RECEPTOR 2 (FGFR2) IN COMPLEX WITH FGF2
1iil	CRYSTAL STRUCTURE OF PRO253ARG APERT MUTANT FGF RECEPTOR 2 (FGFR2) IN COMPLEX WITH FGF2
1ijt	Crystal Structure of Fibroblast Growth Factor 4 (FGF4)
1jqz	Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Terminal His Tag.
1jt3	Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Histidine Tag AND LEU 73 REPLACED BY VAL (L73V)
1jt4	Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Terminal His Tag AND VAL 109 REPLACED BY LEU (V109L)
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)
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)
1jtc	Human Acidic Fibroblast Growth Factor. 141 Amino Acid Form with Amino Terminal His Tag AND LEU 44 REPLACED BY PHE (L44F)
1jy0	Human acidic fibroblast growth factor. 141 amino acid form with amino terminal His tag and Cys 117 replaced with Val (C117V).
1k5u	Human acidic fibroblast growth factor. 141 amino acid form with amino terminal His tag with His93 replaced by Gly (H93G).
1k5v	Human acidic fibroblast growth factor. 141 amino acid form with amino terminal His tag with Asn106 replaced by Gly (N106G).
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).
1nun	Crystal Structure Analysis of the FGF10-FGFR2b Complex
1nzk	Crystal Structure of a Multiple Mutant (L44F, L73V, V109L, L111I, C117V) of Human Acidic Fibroblast Growth Factor
1p63	Human Acidic Fibroblast Growth Factor. 140 Amino Acid Form with Amino Terminal His Tag and Leu111 Replaced with Ile (L111I)
1pwa	Crystal structure of Fibroblast Growth Factor 19
1pzz	Crystal structure of FGF-1, V51N mutant
1q03	Crystal structure of FGF-1, S50G/V51G mutant
1q04	Crystal structure of FGF-1, S50E/V51N
1q1u	Crystal structure of human FHF1b (FGF12b)
1qqk	THE CRYSTAL STRUCTURE OF FIBROBLAST GROWTH FACTOR 7 (KERATINOCYTE GROWTH FACTOR)
1qql	THE CRYSTAL STRUCTURE OF FIBROBLAST GROWTH FACTOR 7/1 CHIMERA
1rg8	Human Acidic Fibroblast Growth Factor (haFGF-1) at 1.10 angstrom resolution (140 amino acid form)
1rml	NMR STUDY OF ACID FIBROBLAST GROWTH FACTOR BOUND TO 1,3,6-NAPHTHALENE TRISULPHONATE, 26 STRUCTURES
1ry7	Crystal Structure of the 3 Ig form of FGFR3c in complex with FGF1
1yto	Crystal Structure of Gly19 deletion Mutant of Human Acidic Fibroblast Growth Factor
1z2v	Crystal Structure of Glu60 deletion Mutant of Human Acidic Fibroblast Growth Factor
1z4s	Crystal Structure of Gly19 and Glu60 deletion mutant of Human Acidic Fibroblast Growth Factor
2afg	2.0 ANGSTROM X-RAY STRUCTURE OF HUMAN ACIDIC FIBROBLAST GROWTH FACTOR
2aqz	Crystal structure of FGF-1, S17T/N18T/G19 deletion mutant
2axm	HEPARIN-LINKED BIOLOGICALLY-ACTIVE DIMER OF FIBROBLAST GROWTH FACTOR
2bfh	CRYSTAL STRUCTURE OF BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION
2erm	Solution structure of a biologically active human FGF-1 monomer, complexed to a hexasaccharide heparin-analogue
2fdb	Crystal Structure of Fibroblast growth factor (FGF)8b in complex with FGF Receptor (FGFR) 2c
2fgf	THREE-DIMENSIONAL STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR, A STRUCTURAL HOMOLOG OF INTERLEUKIN 1BETA
2hw9	Crystal structure of Lys12Cys/Cys117Val mutant of human acidic fibroblast Growth factor at 1.60 angstrom resolution.
2hwa	Crystal structure of Lys12Thr/Cys117Val mutant of human acidic fibroblast growth factor at 1.65 angstrom resolution.
2hwm	Crystal structure of Lys12Val/Cys117Val mutant of human acidic fibroblast growth factor at 1.60 angstrom resolution
2hz9	Crystal structure of Lys12Val/Asn95Val/Cys117Val mutant of human acidic fibroblast growth factor at 1.70 angstrom resolution.
2j3p	crystal structure of rat FGF1 at 1.4 A
2k43	Acidic fibroblast growth factor solution structure in the FGF-1-C2A binary complex: key component in the fibroblast growthfactor non-classical pathway
2k4a	FGF-1-C2A binary complex structure: a key component in the fibroblast growthfactor non-classical pathway
2k8r	Solution structure of human acidic fibroblast growth factor in complex with anti-angiogenic drug inositol hexaphosphate (IP6)
2ki4	FGF1-S100A13 complex structure: key component in non-classical path way of FGF1
2ki6	The FGF1-S100A13-C2A hetero-hexameric complex structure: A component in the non-classical pathway for FGF1 secretion
2m49	Structural Insights into Human S100B and Basic Fibroblast Growth Factor (FGF2) Interaction
2ntd	Human fibroblast growth factor-1 (140 amino acid form) with Cys117Val/Pro134Cys mutations
2p23	Crystal structure of human FGF19
2p39	Crystal structure of human FGF23
2q9x	Crystal structure of highly stable mutant Q40P/S47I/H93G of human fibroblast growth factor-1
2rq9	Solution structure of human acidic fibroblast growth factor (aFGF) in the presence of a protein stabilizer NDSB-new
2uus	Crystal structure of the rat FGF1-sucrose octasulfate (SOS) complex.
3b9u	Crystal structure of L26N/D28N/H93G mutant of Human acidic fibroblast growth factor
3ba4	Crystal structure of L26D mutant of Human acidic fibroblast growth factor
3ba5	Crystal structure of D28A mutant of Human acidic fibroblast growth factor
3ba7	Crystal structure of L26N/D28A mutant of Human acidic fibroblast growth factor
3bad	Crystal structure of D70A/H93G mutant of Human acidic fibroblast growth factor
3bag	Crystal structure of K112N/N114A mutant of Human acidic fibroblast growth factor
3bah	Crystal structure of K112N mutant of Human acidic fibroblast growth factor
3bao	Crystal structure of L26N mutant of Human acidic fibroblast growth factor
3baq	Crystal structure of L26A mutant of Human acidic fibroblast growth factor
3bau	Crystal structure of K12V/L26D/D28A mutant of Human acidic fibroblast growth factor
3bav	Crystal structure of L26A/D28N mutant of Human acidic fibroblast growth factor
3bb2	Crystal structure of L26D/D28N mutant of Human acidic fibroblast growth factor
3cqa	Crystal structure of human fibroblast growth factor-1 with mutations Glu81Ala and Lys101Ala
3crg	Crystal structure of human fibroblast growth factor-1 with mutations Glu81Ala, Glu82Asn and Lys101Ala
3crh	Crystal structure of human fibroblast growth factor-1 with mutations Glu81Ser and Lys101Ala
3cri	Crystal structure of human fibroblast growth factor-1 with mutations Glu81Ser, Glu82Asn and Lys101Ala
3cu1	Crystal Structure of 2:2:2 FGFR2D2:FGF1:SOS complex
3f1r	Crystal structure of FGF20 dimer
3fgm	Crystal structure of L44F/C83T/C117V/F132W mutant of Human acidic fibroblast growth factor
3fj8	Crystal structure of C117I mutant of Human acidic fibroblast growth factor
3fj9	Crystal structure of F85W mutant of Human acidic fibroblast growth factor
3fja	Crystal structure of F132W mutant of Human acidic fibroblast growth factor
3fjb	Crystal structure of V31I mutant of Human acidic fibroblast growth factor
3fjc	Crystal structure of L44W mutant of Human acidic fibroblast growth factor
3fjd	Crystal structure of L44F/F132W mutant of Human acidic fibroblast growth factor
3fje	Crystal structure of C83S mutant of Human acidic fibroblast growth factor
3fjf	Crystal structure of C83T mutant of Human acidic fibroblast growth factor
3fjh	Crystal structure of C83A mutant of Human acidic fibroblast growth factor
3fji	Crystal structure of K12V/C83I/C117V mutant of Human acidic fibroblast growth factor
3fjj	Crystal structure of C83V mutant of Human acidic fibroblast growth factor
3fjk	Crystal structure of A66C mutant of Human acidic fibroblast growth factor
3hal	Crystal structure of Rabbit acidic fibroblast growth factor
3hbw	Crystal Structure of Human Fibroblast Growth Factor Homologous Factor 2A (FHF2A), also referred to as Fibroblast Growth Factor 13A (FGF13A)
3hom	Crystal structure of oxidized A66C mutant of Human acidic fibroblast growth factor
3jut	Acidic Fibroblast Growth Factor (FGF-1) complexed with gentisic acid
3k1x	Acidic Fibroblast Growth Factor (FGF-1) complexed with dobesilate
3o3q	Crystal structure of "L44F/M67I/L73V/A103G/deletion 104-106/F108Y/V109L/L111I/C117V/R119G/deletion 120-122" mutant form of Human acidic fibroblast growth factor
3o49	Crystal structure of Symfoil-1: de novo designed beta-trefoil architecture with symmetric primary structure
3o4a	Crystal structure of Symfoil-2: de novo designed beta-trefoil architecture with symmetric primary structure
3o4b	Crystal structure of Symfoil-4T: de novo designed beta-trefoil architecture with symmetric primary structure
3o4c	Crystal structure of Symfoil-4V: de novo designed beta-trefoil architecture with symmetric primary structure
3o4d	Crystal structure of Symfoil-4P: de novo designed beta-trefoil architecture with symmetric primary structure
3ogf	Crystal structure of Difoil-4P homo-trimer: de novo designed dimeric trefoil-fold sub-domain which forms homo-trimer assembly
3oj2	Crystal structure of FGF1 complexed with the ectodomain of FGFR2b harboring the A172F Pfeiffer syndrome mutation
3ojm	Crystal Structure of FGF1 complexed with the ectodomain of FGFR2b harboring P253R Apert mutation
3ojv	Crystal Structure of FGF1 complexed with the ectodomain of FGFR1c exhibiting an ordered ligand specificity-determining betaC'-betaE loop
3p6i	Crystal structure of Symfoil-4T Permutation #2: de novo designed beta-trefoil architecture with symmetric primary structure
3p6j	Crystal structure of Symfoil-4T Permutation #3: de novo designed beta-trefoil architecture with symmetric primary structure
3q7w	Crystal structure of Symfoil-4P/PV1: de novo designed beta-trefoil architecture with symmetric primary structure, primitive version 1
3q7x	Crystal structure of Symfoil-4P/PV1: de novo designed beta-trefoil architecture with symmetric primary structure, primitive version 1
3q7y	Crystal structure of K15R/E18D/Y22W/H41G/F44W/E51D/E53P/K57R/E60D/Y64W/H82G/F85W/E90D/E94P/K98R/E101D/Y108W/H129G/F132W/E137D Symfoil-4P: de novo designed beta-trefoil architecture with symmetric primary structure
3snv	Crystal structure of Symfoil-4T Permutation #1: de novo designed beta-trefoil architecture with symmetric primary structure
3ud7	Crystal Structure Analysis of FGF1-Disaccharide(NI21) complexes
3ud8	Crystal Structure Analysis of FGF1-Disaccharide(NI22) complex
3ud9	Crystal Structure Analysis of FGF1-Disaccharide(NI23) complex
3uda	Crystal Structure Analysis of FGF1-Disaccharide(NI24) complex
4cjm	Crystal structure of human FGF18
4d8h	Crystal structure of Symfoil-4P/PV2: de novo designed beta-trefoil architecture with symmetric primary structure, primitive version 2 (6xLeu / PV1)
4dck	Crystal structure of the C-terminus of voltage-gated sodium channel in complex with FGF13 and CaM
4f34	Symfoil-4V synthetic protein with T30E/T72E/T116E mutations, and delta His tag
4fgf	REFINEMENT OF THE STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION AND ANALYSIS OF PRESUMED HEPARIN BINDING SITES BY SELENATE SUBSTITUTION
4j23	Low resolution crystal structure of the FGFR2D2D3/FGF1/SR128545 complex
4jpz	Voltage-gated sodium channel 1.2 C-terminal domain in complex with FGF13U and Ca2+/calmodulin
4jq0	Voltage-gated sodium channel 1.5 C-terminal domain in complex with FGF12B and Ca2+/calmodulin
4oee	4OEE
4oef	4OEF
4oeg	4OEG
4ow4	4OW4
4q91	4Q91
4q9g	4Q9G
4q9p	4Q9P
4qal	4QAL
4qbc	4QBC
4qbv	4QBV
4qc4	4QC4
4qkr	4QKR
4qks	4QKS
4qo3	4QO3
4xki	4XKI
4yol	4YOL

Links (links to other resources describing this domain)

• PFAM: FGF
• INTERPRO: IPR002209
• PROSITE: HBGF_FGF