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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720  18 GILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTP 97
Cdd:cd23327   41 GILEFISVAVGLVSIRGVDSGLYLGMNDKGELYGSEKLTAECIFREQFEENWYNTYSSNLYKHGDTGRRYFVALNKDGTP 120

                         90       100       110
                 ....*....|....*....|....*....|...
gi 568986720  98 REGTRTKRHQKFTHFLPRPVDPDKVPELYKDIL 130
Cdd:cd23327  121 RDGTRSKRHQKFTHFLPRPVDPEKVPELYKDLL 153

FGF domain, beta-trefoil fold, found in fibroblast growth factor 20 (FGF20) and similar proteins; FGF20 acts as a neurotrophic factor that regulates central nervous development and function. It interacts with fibroblast growth factor receptors, FGFR2 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. FGF20 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 568986720  18 GILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTP 97
Cdd:cd23327   41 GILEFISVAVGLVSIRGVDSGLYLGMNDKGELYGSEKLTAECIFREQFEENWYNTYSSNLYKHGDTGRRYFVALNKDGTP 120

                         90       100       110
                 ....*....|....*....|....*....|...
gi 568986720  98 REGTRTKRHQKFTHFLPRPVDPDKVPELYKDIL 130
Cdd:cd23327  121 RDGTRSKRHQKFTHFLPRPVDPEKVPELYKDLL 153

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720   18 GILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKhvdtGRRYYVALNKDGTP 97
Cdd:pfam00167  33 SILEIESVSVGVVRIKGVESGLYLAMNKKGRLYGSKNFTDECVFKERLLENNYNTYASAKYS----GRGWYVGLNKKGRP 108

                          90
                  ....*....|....*.
gi 568986720   98 REGTRTKRHQKFTHFL 113
Cdd:pfam00167 109 KRGSKTKPGQKAAHFL 124

FGF domain, beta-trefoil fold, found in fibroblast growth factor 20 (FGF20) and similar proteins; FGF20 acts as a neurotrophic factor that regulates central nervous development and function. It interacts with fibroblast growth factor receptors, FGFR2 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. FGF20 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 568986720  18 GILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTP 97
Cdd:cd23327   41 GILEFISVAVGLVSIRGVDSGLYLGMNDKGELYGSEKLTAECIFREQFEENWYNTYSSNLYKHGDTGRRYFVALNKDGTP 120

                         90       100       110
                 ....*....|....*....|....*....|...
gi 568986720  98 REGTRTKRHQKFTHFLPRPVDPDKVPELYKDIL 130
Cdd:cd23327  121 RDGTRSKRHQKFTHFLPRPVDPEKVPELYKDLL 153

FGF domain, beta-trefoil fold, found in fibroblast growth factor 16 (FGF16) and similar proteins; 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 fibroblast growth factor receptors, FGFR1 and FGFR2. FGF16 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 568986720  18 GILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTP 97
Cdd:cd23326   38 GILEFISLAVGLVSIRGVDSGLYLGMNERGELYGSKKLTRECVFREQFEENWYNTYASTLYKHADSGRQYYVALNKDGSP 117

                         90       100       110
                 ....*....|....*....|....*....|..
gi 568986720  98 REGTRTKRHQKFTHFLPRPVDPDKVPELYKDI 129
Cdd:cd23326  118 REGYRTKRHQKFTHFLPRPVDPEKIPAMYRDL 149

FGF domain, beta-trefoil fold, found in the fibroblast growth factor 3 (FGF3)-like family; The FGF3-like family includes FGF3-6. 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. FGF4, also called heparin secretory-transforming protein 1 (HST-1), or HSTF-1, or heparin-binding growth factor 4 (HBGF4), or transforming protein KS3, plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. It is required for normal limb and cardiac valve development during embryogenesis. It interacts with FGFR1, FGFR2, FGFR3, and FGFR4. FGF5, also called heparin-binding growth factor 5 (HBGF5), or Smag-82, plays an important role in the regulation of cell proliferation and cell differentiation. It is required for normal regulation of the hair growth cycle. It functions as an inhibitor of hair elongation by promoting progression from anagen, the growth phase of the hair follicle, into catagen the apoptosis-induced regression phase. FGF5 interacts with FGFR1 and FGFR2. 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 FGFR1, FGFR2, and FGFR4. Affinity between 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720  18 GILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSnlYKHVDTGRRYYVALNKDGTP 97
Cdd:cd23305   32 SWLEIFAVEVGVVGIKGVKSGLYLCMNKKGKLYGSKEFTDECKFKERLEENHYNTYSS--ALYPRRKRGWYVALSKKGRP 109

                         90
                 ....*....|....*...
gi 568986720  98 REGTRTKRHQKFTHFLPR 115
Cdd:cd23305  110 RRGSRVRRTQKSTHFLPR 127

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720   18 GILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKhvdtGRRYYVALNKDGTP 97
Cdd:pfam00167  33 SILEIESVSVGVVRIKGVESGLYLAMNKKGRLYGSKNFTDECVFKERLLENNYNTYASAKYS----GRGWYVGLNKKGRP 108

                          90
                  ....*....|....*.
gi 568986720   98 REGTRTKRHQKFTHFL 113
Cdd:pfam00167 109 KRGSKTKPGQKAAHFL 124

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720  19 ILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHvdTGRRYYVALNKDGTPR 98
Cdd:cd23306   36 ILEIRSVDVGVVAIKGVKSNYYLAMNKKGKLYGKKDYNDDCRFKERIEENGYNTYASAKWTH--NGREMFVALSQKGRPL 113

                         90
                 ....*....|....*...
gi 568986720  99 EGTRTKRHQKFTHFLPRP 116
Cdd:cd23306  114 RGKKTRRKNTAAHFLPMV 131

FGF domain, beta-trefoil fold, found in fibroblast growth factor 22 (FGF22) and similar proteins; 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. FGF22 interacts with fibroblast growth factor receptors, FGFR1 and FGFR2, as well as fibroblast growth factor-binding protein 1 (FGFBP1). FGF22 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 568986720  11 GQRRRTA--GILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHvdTGRRYY 88
Cdd:cd23321   29 GTRWKNCpdSILEIRSVSVGVVAIKSVSTGFYLAMNKKGKLYGSKLYSPNCKFKERIEENGYNTYASLRWRH--RGRPMF 106

                         90       100
                 ....*....|....*....|....*.
gi 568986720  89 VALNKDGTPREGTRTKRHQKFTHFLP 114
Cdd:cd23321  107 LSLNSRGRPRRGGKTRRKHLSTHFLP 132

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720  22 FISIAVGL--VSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPRE 99
Cdd:cd23309   35 FNLIPVGLrvVAIQGVKTGLYIAMNSEGYLYTSEHFTPECKFKESVFENYYVIYSSMLYRQQQSGRAWYLGLNKEGQIMK 114

                         90
                 ....*....|....*.
gi 568986720 100 GTRTKRHQKFTHFLPR 115
Cdd:cd23309  115 GNRVKKTKPAAHFLPK 130

FGF domain, beta-trefoil fold, found in fibroblast growth factor 10 (FGF10) and similar proteins; FGF10 plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. It is required for normal branching morphogenesis. It may play a role in wound healing. FGF10 interacts with fibroblast growth factor receptors FGFR1 and FGFR2, as well as fibroblast growth factor-binding protein 1 (FGFBP1). FGF10 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 568986720  19 ILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHvdTGRRYYVALNKDGTPR 98
Cdd:cd23320   39 ILEITSVEVGVVAVKAINSNYYLAMNKKGKIYGSKEFNIDCKLKERIEENGYNTYASLNWKH--NGRQMFVALNGKGAPK 116

                         90
                 ....*....|....*.
gi 568986720  99 EGTRTKRHQKFTHFLP 114
Cdd:cd23320  117 RGQKTRRKNTSAHFLP 132

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720  19 ILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPR 98
Cdd:cd23328   38 LFNLIPVGLRVVAIQGVKAGLYVAMNGEGYLYSSDVFTPECKFKESVFENYYVIYSSTLYRQQESGRAWFLGLNKEGQIM 117

                         90       100
                 ....*....|....*....|
gi 568986720  99 EGTRTKRHQKFTHFLPRPVD 118
Cdd:cd23328  118 KGNRVKKTKPSSHFVPKPIE 137

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720  19 ILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVDTG----------RRYY 88
Cdd:cd23315   33 ILEITAVDVGVVAIKGLFSGRYLAMNKRGRLYASEVYNAECEFVERIHELGYNTYASRLYRTVPSGagtkrkasaeRLWY 112

                         90       100
                 ....*....|....*....|....*..
gi 568986720  89 VALNKDGTPREGTRTKRHQKFTHFLPR 115
Cdd:cd23315  113 VSINGKGRPRRGFKTRRTQKSSLFLPR 139

FGF domain, beta-trefoil fold, found in fibroblast growth factor 4 (FGF4) and similar proteins; FGF4, also called heparin secretory-transforming protein 1 (HST-1), or HSTF-1, or heparin-binding growth factor 4 (HBGF4), or transforming protein KS3, plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. It is required for normal limb and cardiac valve development during embryogenesis. It 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. FGF4 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 568986720  19 ILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHVdtgrryYVALNKDGTPR 98
Cdd:cd23316   34 LLEISPVERGVVSIFGVKSGLFVAMNSKGKLYGSPFFNDECKFKEILLPNNYNAYESRKYPGM------YIALSKNGKTK 107

                         90
                 ....*....|....*..
gi 568986720  99 EGTRTKRHQKFTHFLPR 115
Cdd:cd23316  108 KGNRVSPTMTVTHFLPR 124

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720  19 ILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQFEENWYNTYSSNLYKHvdtgrrYYVALNKDGTPR 98
Cdd:cd23318   34 LLEISTVERGVVSLYGVKSGLFVAMNSKGRLYGTPNFQDECKFKETLLPNNYNAYESSLYKG------AYIALSKHGRVK 107

                         90
                 ....*....|....*..
gi 568986720  99 EGTRTKRHQKFTHFLPR 115
Cdd:cd23318  108 RGNKVSPAMTVTHFLPR 124

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720  19 ILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQE-CVFREQFEENWYNTYSSNlyKHvdtgrRYYVALNKdGTP 97
Cdd:cd23331   38 LLEIKAVALGTVAIKGVASSRYLCMEADGKLYGSLSYSEEdCSFEEEILPDGYNVYRSK--KH-----GLPVSLSS-AKQ 109

                         90
                 ....*....|....*..
gi 568986720  98 REGTRTKRHQKFTHFLP 114
Cdd:cd23331  110 RQQYKDKGFLPLSQFLP 126

FGF domain, beta-trefoil fold, found in fibroblast growth factor 8 (FGF8) and similar proteins; FGF8, also called androgen-induced growth factor (AIGF), or heparin-binding growth factor 8 (HBGF8), plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation, and cell migration. It is required for normal brain, eye, ear, and limb development during embryogenesis. It is also required for normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. It plays a role in neurite outgrowth in hippocampal cells. FGF8 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. FGF8 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 568986720  30 VSIRGVDSGLYLGMNEKGELYGSEK-LTQECVFREQFEENWYNTYSSNLYKHvdtgrrYYVALNKDGTPREGTRTKRHQK 108
Cdd:cd23322   66 VRIKGAETGYYICMNKKGKLIGKSNgKGKDCVFTEIVLENNYTALQNAKYEG------WYMAFTRKGRPRKGSKTRQHQR 139

                 ....*..
gi 568986720 109 FTHFLPR 115
Cdd:cd23322  140 EVHFMKR 146

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568986720  30 VSIRGVDSGLYLGMNEKGELYGSEKLT-QECVFREQFEENWYNTYSSNLYkhvdTGrrYYVALNKDGTPREGTRTKRHQK 108
Cdd:cd23324   45 VRIKGKETDFYLCMNRKGKLVGKPDGTsKECVFIEKVLENNYTALMSAKY----SG--WYVGFTKKGRPRKGPKTRENQQ 118

                 ....*..
gi 568986720 109 FTHFLPR 115
Cdd:cd23324  119 DVHFMKR 125

FGF domain, beta-trefoil fold, found in fibroblast growth factor 21 (FGF21) and similar proteins; 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 beta-Klotho (KLB). It interacts (via C-terminus) with KLB and fibroblast growth factor receptor FGFR4. FGF21 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 568986720  19 ILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQE-CVFREQFEENWYNTYSSNlyKHvdtgrRYYVALNKDGTP 97
Cdd:cd23332   37 LLELKAVKPGVVQILGKKTLRFLCMDPDGRLYGSLHYSPEaCSFREVVLEDGYNLYQSE--AH-----GLPLTLSPNRAP 109

                         90
                 ....*....|....*....
gi 568986720  98 REGTRTKRhqKFTHFLPRP 116
Cdd:cd23332  110 HRDGGAPP--PLAHFLPLV 126