Fibroblast growth factor; Fibroblast growth factors are a family of proteins involved in growth and differentiation in a wide range of contexts. They are found in a wide range of organizms, from nematodes to humans. Most share an internal core region of high similarity, conserved residues in which are involved in binding with their receptors. On binding, they cause dimerization of their tyrosine kinase receptors leading to intracellular signalling. There are currently four known tyrosine kinase receptors for fibroblast growth factors. These receptors can each bind several different members of this family. Members of this family have a beta trefoil structure. Most have N-terminal signal peptides and are secreted. A few lack signal sequences but are secreted anyway; still others also lack the signal peptide but are found on the cell surface and within the extracellular matrix. A third group remain intracellular. They have central roles in development, regulating cell proliferation, migration and differentiation. On the other hand, they are important in tissue repair following injury in adult organizms.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKhvdtGRRYYVALNKDGTPREGTRTKRHQKFTHFL 71
Cdd:pfam00167  58 MNKKGRLYGSKNFTDECVFKERLLENNYNTYASAKYS----GRGWYVGLNKKGRPKRGSKTKPGQKAAHFL 124

FGF domain, beta-trefoil fold, found in fibroblast growth factor 9 (FGF9) and similar proteins; FGF9, also called glia-activating factor (GAF), or heparin-binding growth factor 9 (HBGF-9), plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation, and cell migration. It acts as a heparin-binding glia-activating factor that may have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors. FGF9 interacts with fibroblast growth factor receptors, FGFR1, FGFR2, FGFR3, and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. FGF9 contains a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPREGTRTKRHQKFTHFLPRPVDPEKV 80
Cdd:cd23325    70 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPREGTRTKRHQKFTHFLPRPVDPDKV 149

                          90
                  ....*....|.
gi 2130840234  81 PELYKDILSQS 91
Cdd:cd23325   150 PELYKDILSQS 160

FGF domain, beta-trefoil fold, found in the fibroblast growth factor 9 (FGF9)-like family; The FGF9-like family includes FGF9, FGF16, and FGF20. FGF9, also called glia-activating factor (GAF), or heparin-binding growth factor 9 (HBGF-9), plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation, and cell migration. It acts as a heparin-binding glia-activating factor that may have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors. FGF9 interacts with fibroblast growth factor receptors, FGFR1, FGFR2, FGFR3, and FGFR4. FGF16 plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. It is required for normal cardiomyocyte proliferation and heart development. FGF16 interacts with FGFR1 and FGFR2. FGF20 acts as a neurotrophic factor that regulates central nervous development and function. It interacts with FGFR2 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Members in this family contain a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPREGTRTKRHQKFTHFLPRP 74
Cdd:cd23308    57 MNEKGELYGSEKLTRECVFREQFEENWYNTYSSNLYKHADTGRRYYVALNKDGTPREGCRTKRHQKFTHFLPRP 130

Fibroblast growth factor; Fibroblast growth factors are a family of proteins involved in growth and differentiation in a wide range of contexts. They are found in a wide range of organizms, from nematodes to humans. Most share an internal core region of high similarity, conserved residues in which are involved in binding with their receptors. On binding, they cause dimerization of their tyrosine kinase receptors leading to intracellular signalling. There are currently four known tyrosine kinase receptors for fibroblast growth factors. These receptors can each bind several different members of this family. Members of this family have a beta trefoil structure. Most have N-terminal signal peptides and are secreted. A few lack signal sequences but are secreted anyway; still others also lack the signal peptide but are found on the cell surface and within the extracellular matrix. A third group remain intracellular. They have central roles in development, regulating cell proliferation, migration and differentiation. On the other hand, they are important in tissue repair following injury in adult organizms.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKhvdtGRRYYVALNKDGTPREGTRTKRHQKFTHFL 71
Cdd:pfam00167  58 MNKKGRLYGSKNFTDECVFKERLLENNYNTYASAKYS----GRGWYVGLNKKGRPKRGSKTKPGQKAAHFL 124

FGF domain, beta-trefoil fold, found in acidic and basic fibroblast growth factor (FGF) superfamily; The FGF superfamily includes FGF1-23 and similar proteins. FGFs are mitogens, which stimulate growth or differentiation of cells of mesodermal or neuroectodermal origin. They play essential roles in patterning and differentiation during vertebrate embryogenesis and have neurotrophic activities. FGFs have a high affinity for heparan sulfate proteoglycans and require heparan sulfate to activate one of four cell surface FGF receptors. Upon binding to FGF, the receptors dimerize, and their intracellular tyrosine kinase domains become active. The structure of FGFs is typical of the beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSnlYKHVDTGRRYYVALNKDGTPREGTRTKRHQKFTHFLPR 73
Cdd:cd00058    57 MDKNGKLYGTKKPTEDCVFKETLEENGYNTYSS--YKYYHTRKGWYLAIKKNGKPKRGKKTKPGQKSTQFLPL 127

FGF domain, beta-trefoil fold, found in the fibroblast growth factor 7 (FGF7)-like family; The FGF7-like family includes FGF7, FGF10 and FGF22. FGF7, also called heparin-binding growth factor 7 (HBGF7), or keratinocyte growth factor (KGF), and FGF10 play important roles in the regulation of embryonic development, cell proliferation, and cell differentiation. They are required for normal branching morphogenesis. FGF7 is a growth factor active on keratinocytes. It may act as major paracrine effector of normal epithelial cell proliferation. FGF10 may play a role in wound healing. FGF22 plays a role in the fasting response, glucose homeostasis, lipolysis, and lipogenesis. It can stimulate cell proliferation (in vitro). It may be involved in hair development. FGF7 interacts with fibroblast growth factor receptor FGFR2 and fibroblast growth factor-binding protein 1 (FGFBP1). FGF10 and FGF22 interact with FGFR1, FGFR2 and FGFBP1. Members in this family contain a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHvdTGRRYYVALNKDGTPREGTRTKRHQKFTHFLPRP 74
Cdd:cd23306    60 MNKKGKLYGKKDYNDDCRFKERIEENGYNTYASAKWTH--NGREMFVALSQKGRPLRGKKTRRKNTAAHFLPMV 131

FGF domain, beta-trefoil fold, found in the fibroblast growth factor 11 (FGF11)-like family; The FGF11-like family includes FGF11-14. FGF11, also called fibroblast growth factor homologous factor 3 (FHF3), may be involved in nervous system development and function. It plays roles in angiogenesis, tumorigenesis, adipogenesis, or liver regeneration. FGF12, also called fibroblast growth factor homologous factor 1 (FHF1), or myocyte-activating factor, is involved in nervous system development and function. It plays a role in the positive regulation of voltage-gated sodium channel activity. It promotes neuronal excitability by elevating the voltage dependence of neuronal sodium channel SCN8A fast inactivation. FGF12 interacts with the C-terminal region of SCN9A. FGF13, also called Fibroblast growth factor homologous factor 2 (FHF2), is a microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules. Through its action on microtubules, it may participate in the refinement of axons by negatively regulating axonal and leading processes branching. FGF13 plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus. It may regulate voltage-gated sodium channels transport and function. It may also play a role in MAPK signaling. It is required for the development of axonal initial segment-targeting inhibitory GABAergic synapses made by chandelier neurons. FGF13 interacts with SCN1A, SCN5A, and SCN8A. It may also interact with SCN2A and SCN11A. FGF14, also called fibroblast growth factor homologous factor 4 (FH-4), may be involved in nervous system development and function. It interacts with SCN8A. Members in this family contain a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPREGTRTKRHQKFTHFLPR 73
Cdd:cd23309    58 MNSEGYLYTSEHFTPECKFKESVFENYYVIYSSMLYRQQQSGRAWYLGLNKEGQIMKGNRVKKTKPAAHFLPK 130

FGF domain, beta-trefoil fold, found in fibroblast growth factor 12 (FGF12) and similar proteins; FGF12, also called fibroblast growth factor homologous factor 1 (FHF1), or myocyte-activating factor, is involved in nervous system development and function. It plays a role in the positive regulation of voltage-gated sodium channel activity. It promotes neuronal excitability by elevating the voltage dependence of neuronal sodium channel SCN8A fast inactivation. FGF12 interacts with the C-terminal region of SCN9A. FGF12 contains a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPREGTRTKRHQKFTHFLPRPVD 76
Cdd:cd23328    62 MNGEGYLYSSDVFTPECKFKESVFENYYVIYSSTLYRQQESGRAWFLGLNKEGQIMKGNRVKKTKPSSHFVPKPIE 137

FGF domain, beta-trefoil fold, found in fibroblast growth factor 13 (FGF13) and similar proteins; FGF13, also called fibroblast growth factor homologous factor 2 (FHF2), is a microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules. Through its action on microtubules, it may participate in the refinement of axons by negatively regulating axonal and leading processes branching. FGF13 plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus. It may regulate voltage-gated sodium channels transport and function. It may also play a role in MAPK signaling. It is required for the development of axonal initial segment-targeting inhibitory GABAergic synapses made by chandelier neurons. FGF13 interacts with SCN1A, SCN5A, and SCN8A. It may also interact with SCN2A and SCN11A. FGF-13 contains a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPREGTRTKRHQKFTHFLPRPV 75
Cdd:cd23329    61 MNSEGYLYTSEHFTPECKFKESVFENYYVTYSSMIYRQQQSGRGWYLGLNKEGEIMKGNHVKKNKPAAHFLPKPL 135

FGF domain, beta-trefoil fold, found in fibroblast growth factor 7 (FGF7) and similar proteins; FGF7, also called heparin-binding growth factor 7 (HBGF7), or keratinocyte growth factor (KGF), plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. It is required for normal branching morphogenesis. It is a growth factor active on keratinocytes. It may act as major paracrine effector of normal epithelial cell proliferation. FGF7 interacts with fibroblast growth factor receptor FGFR2 and fibroblast growth factor-binding protein 1 (FGFBP1). Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. FGF7 contains a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNlyKHVDTGRRYYVALNKDGTPREGTRTKRHQKFTHFLP 72
Cdd:cd23319    65 MNKEGKLYGKKVCNEDCNFKELIEENHYNTYASA--KWTHKGKEMFVALNQKGKPMKGKKTKKEHKTSHFLP 134

FGF domain, beta-trefoil fold, found in fibroblast growth factor 3 (FGF3) and similar proteins; FGF3, also called heparin-binding growth factor 3 (HBGF3), or proto-oncogene Int-2, plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. It is required for normal ear development. FGF3 interacts with fibroblast growth factor receptors, FGFR1 and FGFR2. Affinity between FGFs and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. FGF3 contains a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTG----------RRYYVALNKDGTPREGTRTKRHQKFTHF 70
Cdd:cd23315    57 MNKRGRLYASEVYNAECEFVERIHELGYNTYASRLYRTVPSGagtkrkasaeRLWYVSINGKGRPRRGFKTRRTQKSSLF 136

                  ...
gi 2130840234  71 LPR 73
Cdd:cd23315   137 LPR 139

FGF domain, beta-trefoil fold, found in Drosophila melanogaster protein branchless (Bnl) and similar proteins; Protein Bnl is a homolog of mammalian fibroblast growth factors. It is a dosage-sensitive regulator of terminal branching. It functions as a chemoattractant that can guide terminal branches to new tissues and even to individual cells within a tissue. Bnl contains a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKhvdtgRRYYVALNKDGTPR 56
Cdd:cd23311    59 INECGYVYSSKVPNKDCLFNESYEENNYNYYYKKFNR-----RRAYLALNKEGKTR 109

FGF domain, beta-trefoil fold, found in fibroblast growth factor 6 (FGF6) and similar proteins; FGF6, also called heparin secretory-transforming protein 2 (HST-2), or HSTF-2, or heparin-binding growth factor 6 (HBGF6), plays an important role in the regulation of cell proliferation, cell differentiation, angiogenesis, and myogenesis, and is required for normal muscle regeneration. FGF6 interacts with fibroblast growth factor receptors, FGFR1, FGFR2, and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. FGF6 contains a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2130840234   1 MNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHvdtgrrYYVALNKDGTPREGTRTKRHQKFTHFLPR 73
Cdd:cd23318    58 MNSKGRLYGTPNFQDECKFKETLLPNNYNAYESSLYKG------AYIALSKHGRVKRGNKVSPAMTVTHFLPR 124

FGF domain, beta-trefoil fold, found in fibroblast growth factor 18 (FGF18) and similar proteins; FGF18, also called zFGF5, plays an important role in the regulation of cell proliferation, cell differentiation, and cell migration. It is required for normal ossification and bone development. It stimulates hepatic and intestinal proliferation. FGF18 interacts with fibroblast growth factor receptors, FGFR3 and FGFR4. FGF18 contains a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2130840234   1 MNEKGELYGSEKLT-QECVFREQFEENWYNTYSSNLYkhvdTGrrYYVALNKDGTPREGTRTKRHQKFTHFLPR 73
Cdd:cd23324    58 MNRKGKLVGKPDGTsKECVFIEKVLENNYTALMSAKY----SG--WYVGFTKKGRPRKGPKTRENQQDVHFMKR 125

FGF domain, beta-trefoil fold, found in fibroblast growth factor 19 (FGF19) and similar proteins; FGF19 is involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. It stimulates glucose uptake in adipocytes. Its activity requires the presence of beta-Klotho (KLB) and FGFR4. FGF-19 interacts with fibroblast growth factor receptors, FGFR1, FGFR2, FGFR3, and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by alpha-Klotho (KL), KLB and heparan sulfate glycosaminoglycans that function as coreceptors. FGF19 contains a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2130840234   1 MNEKGELYGSEKLTQE-CVFREQFEENWYNTYSSNlyKHvdtgrRYYVALNKdGTPREGTRTKRHQKFTHFLP 72
Cdd:cd23331    62 MEADGKLYGSLSYSEEdCSFEEEILPDGYNVYRSK--KH-----GLPVSLSS-AKQRQQYKDKGFLPLSQFLP 126

FGF domain, beta-trefoil fold, found in the fibroblast growth factor 19 (FGF19)-like family; The FGF19-like family includes FGF19, FGF21, and FGF23. FGF19 is involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. It stimulates glucose uptake in adipocytes. Its activity requires the presence of beta-Klotho (KLB) and FGFR4. FGF-19 interacts with fibroblast growth factor receptors, FGFR1, FGFR2, FGFR3, and FGFR4. FGF21 stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Its activity requires the presence of KLB. It interacts (via C-terminus) with KLB and fibroblast growth factor receptor FGFR4. FGF23, also called phosphatonin, or tumor-derived hypophosphatemia-inducing factor (HYPF), is a regulator of phosphate homeostasis. It inhibits renal tubular phosphate transport by reducing SLC34A1 levels. It upregulates EGR1 expression in the presence of alpha-Klotho (KL). It acts directly on the parathyroid to decrease PTH secretion. FGF23 acts as a regulator of vitamin-D metabolism. It negatively regulates osteoblast differentiation and matrix mineralization. FGF23 interacts with FGFR1, FGFR2, FGFR3, and FGFR4. Members in this family contain a FGF domain with beta-trefoil fold, which is characterized by 12 beta strands folded into three similar trefoil subdomains (alpha, beta, and gamma) associated to give an overall structure with pseudo-3-fold symmetry.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2130840234   1 MNEKGELYGSEKLTQE-CVFREQFEENWYNTYSSNLYkhvdtgrRYYVALnkdgtPREGTRTKRHQKFTHFLPRP 74
Cdd:cd23310    59 VDSDGKLKGQHHYDEEdCSFQELLLEDGYTVFLSPHH-------GLPVSL-----LSKKQPFRHPLPLSRFLPLR 121