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 73486655    87 RTGSLYCRVGiGFHLQIYPDGKVNGSHEA-NMLSVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRER 165
Cdd:pfam00167   1 RVRRLYCRTG-GFHLQILPDGKVDGTGEDgSPYSILEIESVSVGVVRIKGVESGLYLAMNKKGRLYGSKNFTDECVFKER 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 73486655   166 FQENSYNTYASAIHRtektGREWYVALNKRGKAKRGcsPRVKPQHISTHFL 216
Cdd:pfam00167  80 LLENNYNTYASAKYS----GRGWYVGLNKKGRPKRG--SKTKPGQKAAHFL 124

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 73486655  87 RTGSLYCRVgIGFHLQIYPDGKVNGSHEANMLSVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRERF 166
Cdd:cd23305   1 RYRLLYCRV-IGFHLQILPDGSVNGTHEDTEYSWLEIFAVEVGVVGIKGVKSGLYLCMNKKGKLYGSKEFTDECKFKERL 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 73486655 167 QENSYNTYASAIHRTekTGREWYVALNKRGKAKRGCspRVKPQHISTHFLPR 218
Cdd:cd23305  80 EENHYNTYSSALYPR--RKRGWYVALSKKGRPRRGS--RVRRTQKSTHFLPR 127

Acidic and basic fibroblast growth factor family; 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 73486655     85 GRRTGSLYCRVGigFHLQIYPDGKVNGSHEA-NMLSVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFR 163
Cdd:smart00442   1 TKRLRQLYCRNG--QHLQILPDGTVDGTRDEsSSFTILEIIAVAVGVVAIKGVASCRYLCMNKCGKLYGSKNFTEDCVFR 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 73486655    164 ERFQENSYNTYASAIHRTektgrEWYVALNKRGKAKRGcsPRVKPQHISTHFLPR 218
Cdd:smart00442  79 EEMEENGYNTYASAKYRK-----RWYVALNKKGRPRRG--QKTKPLQKASHFLPR 126

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 73486655  87 RTGSLYCRVGigFHLQIYPDGKVNGSHEA-NMLSVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRER 165
Cdd:cd23308   1 RRRQLYCRTG--FHLEILPNGTVQGTRQDhSRFGILEFISVAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTRECVFREQ 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 73486655 166 FQENSYNTYASAIHRTEKTGREWYVALNKRGKAKRGCspRVKPQHISTHFLPR 218
Cdd:cd23308  79 FEENWYNTYSSNLYKHADTGRRYYVALNKDGTPREGC--RTKRHQKFTHFLPR 129

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 73486655  87 RTGSLYCRVGIGFHLQIYPDGKVNGSHEANMLSVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRERF 166
Cdd:cd23316   1 RLRRLYCNVGIGFHIQVLPDGRINGVHNENRYSLLEISPVERGVVSIFGVKSGLFVAMNSKGKLYGSPFFNDECKFKEIL 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 73486655 167 QENSYNTYASAIHRTektgreWYVALNKRGKAKRGcsPRVKPQHISTHFLPR 218
Cdd:cd23316  81 LPNNYNAYESRKYPG------MYIALSKNGKTKKG--NRVSPTMTVTHFLPR 124

FGF domain, beta-trefoil fold, found in the fibroblast growth factor 1 (FGF1)-like family; The FGF1-like family includes FGF1 and FGF2. FGF1, also called acidic fibroblast growth factor (aFGF), or endothelial cell growth factor (ECGF), or heparin-binding growth factor 1 (HBGF-1), plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation, and cell migration. It functions as a potent mitogen in vitro. FGF1 acts as a ligand for fibroblast growth factor receptor 1 (FGFR1) and integrin. It interacts with FGFR1, FGFR2, FGFR3, and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. FGF1 also interacts with fibroblast growth factor-binding protein 1 (FGFBP1), FGF1, and FGF2. FGF2, also called basic fibroblast growth factor (bFGF), or heparin-binding growth factor 2 (HBGF2), acts as a ligand for FGFR1, FGFR2, FGFR3, and FGFR4. It also acts as an integrin ligand which is required for FGF2 signaling. FGF2 plays an important role in the regulation of cell survival, cell division, cell differentiation and cell migration. Both FGF1 and FGF2 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 73486655  91 LYCRVGiGFHLQIYPDGKVNGSHEAN-MLSVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRERFQEN 169
Cdd:cd23304   5 LYCSNG-GYHLRILPDGTVDGTREESdPYIILQLKAESPGVVVIKGTETGQYLAMNEDGRLYGSQTVNDECLFLERLEEN 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 73486655 170 SYNTYASAIHrtekTGREWYVALNKRGKAKRGcsPRVKPQHISTHFLPR 218
Cdd:cd23304  84 HYNTYRSQKY----AEKNWYVGLKKNGRCKLG--PRTHYGQKAILFLPR 126

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 73486655  87 RTGSLYCRVGigFHLQIYPDGKVNGS-HEANMLSVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRER 165
Cdd:cd23326   7 RRRQLYCRTG--FHLEIFPNGTVHGTrQDHSRFGILEFISLAVGLVSIRGVDSGLYLGMNERGELYGSKKLTRECVFREQ 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 73486655 166 FQENSYNTYASAIHRTEKTGREWYVALNKRGKAKRGCspRVKPQHISTHFLPR 218
Cdd:cd23326  85 FEENWYNTYASTLYKHADSGRQYYVALNKDGSPREGY--RTKRHQKFTHFLPR 135

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 73486655  87 RTGSLYCRVGigFHLQIYPDGKVNGSH-EANMLSVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRER 165
Cdd:cd23325  14 RRRQLYCRTG--FHLEIFPNGTIQGTRkDHSRFGILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFREQ 91

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 73486655 166 FQENSYNTYASAIHRTEKTGREWYVALNKRGKAKRGCspRVKPQHISTHFLPR-FKQSEQPEL 227
Cdd:cd23325  92 FEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPREGT--RTKRHQKFTHFLPRpVDPDKVPEL 152

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 73486655  99 FHLQIYPDGKVNGSHEANML-SVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRERFQENSYNTYASA 177
Cdd:cd23321  17 FFLRIDKGGRVEGTRWKNCPdSILEIRSVSVGVVAIKSVSTGFYLAMNKKGKLYGSKLYSPNCKFKERIEENGYNTYASL 96

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 73486655 178 ihRTEKTGREWYVALNKRGKAKRGcsPRVKPQHISTHFLP 217
Cdd:cd23321  97 --RWRHRGRPMFLSLNSRGRPRRG--GKTRRKHLSTHFLP 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 73486655  91 LYCRVGigFHLQIYPDGKVNGSHEANMLSVL-EIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRERFQEN 169
Cdd:cd23309   6 LYSRQG--YYLQMQPDGTIDGTKDENSSYTLfNLIPVGLRVVAIQGVKTGLYIAMNSEGYLYTSEHFTPECKFKESVFEN 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 73486655 170 SYNTYASAIHRTEKTGREWYVALNKRGKAKRGcsPRVKPQHISTHFLPR 218
Cdd:cd23309  84 YYVIYSSMLYRQQQSGRAWYLGLNKEGQIMKG--NRVKKTKPAAHFLPK 130

FGF domain, beta-trefoil fold, found in fibroblast growth factor 2 (FGF2) and similar proteins; FGF2, also called basic fibroblast growth factor (bFGF), or heparin-binding growth factor 2 (HBGF2), acts as a ligand for fibroblast growth factor receptors, FGFR1, FGFR2, FGFR3, and FGFR4. It also acts as an integrin ligand which is required for FGF2 signaling. FGF2 plays an important role in the regulation of cell survival, cell division, cell differentiation, and cell migration. It functions as a potent mitogen in vitro. It can induce angiogenesis. FGF2 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 73486655  91 LYCRVGiGFHLQIYPDGKVNGSHEANMLSV-LEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRERFQEN 169
Cdd:cd23314   5 LYCKNG-GFFLRIHPDGRVDGVREKSDPHIkLQLQAEERGVVSIKGVCANRYLAMKEDGRLLASKSVTDECFFFERLESN 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 73486655 170 SYNTYASaihrteKTGREWYVALNKRGKAKRGcsPRVKPQHISTHFLP 217
Cdd:cd23314  84 NYNTYRS------RKYTSWYVALKRTGQYKLG--SKTGPGQKAILFLP 123

FGF domain, beta-trefoil fold, found in fibroblast growth factor 14 (FGF14) and similar proteins; FGF14, also called fibroblast growth factor homologous factor 4 (FH-4), may be involved in nervous system development and function. It interacts with SCN8A. FGF14 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 73486655  91 LYCRVGigFHLQIYPDGKVNGSHEANMLSVL-EIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDDCKFRERFQEN 169
Cdd:cd23330  11 LYCRQG--YYLQMHPDGSLDGTKDDSSNSTLfNLIPVGLRVVAIQGVKTGLYIAMNGEGYLYTSELFTPECKFKESVFEN 88

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 73486655 170 SYNTYASAIHRTEKTGREWYVALNKRGKAKRGcsPRVKPQHISTHFLPR 218
Cdd:cd23330  89 YYVIYSSMLYRQQESGRAWFLGLNKEGQAMKG--NRVKKTKPAAHFLPK 135

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 73486655  97 IGFHLQIYPDGKVNGSHEANMLSVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFT-DDCKFRERFQENSYNTYA 175
Cdd:cd23331  15 SSCFLRIRADGVVDGSRGQSAHSLLEIKAVALGTVAIKGVASSRYLCMEADGKLYGSLSYSeEDCSFEEEILPDGYNVYR 94

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 73486655 176 SAIHRTektgrewYVALNkRGKAKRGCSPRVKPQHisTHFLPRF 219
Cdd:cd23331  95 SKKHGL-------PVSLS-SAKQRQQYKDKGFLPL--SQFLPMI 128

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 73486655  98 GFHLQIYPDGKVNGSHEANMLSVLEIFAVSQGIVGIRGVFSNKFLAMSKKGKLHASAKFT-DDCKFRERFQENSYNTYAS 176
Cdd:cd23310  13 SCFLEIRPDGTVDGAPHQTAYSLLELKSVKPGETVIKGVASSLYLCVDSDGKLKGQHHYDeEDCSFQELLLEDGYTVFLS 92

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 73486655 177 AIHRTEktgrewyVALNKRGKAKRGCSPrvkpqhiSTHFLPR 218
Cdd:cd23310  93 PHHGLP-------VSLLSKKQPFRHPLP-------LSRFLPL 120

FGF domain, beta-trefoil fold, found in the fibroblast growth factor 8 (FGF8)-like family; The FGF8-like family includes FGF8, FGF17 and FGF18. 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. FGF17 plays an important role in the regulation of embryonic development and as signaling molecule in the induction and patterning of the embryonic brain. It is required for normal brain development. FGF17 interacts with FGFR3 and FGFR4. 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 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 73486655 127 SQGIVGIRGVFSNKFLAMSKKGKLHASAKFTDD--CKFRERFQENSYNTYASAIHRTektgreWYVALNKRGKAKRGcSP 204
Cdd:cd23307  41 FSGKVRIRGAKSGRYLCFNKKGKLVAKKNGKKDkrCVFEEELTDGYYTRYRSVKNPS------WYLGFNRNGRPLKG-SK 113

                        90
                ....*....|....
gi 73486655 205 RVKPQHISTHFLPR 218
Cdd:cd23307 114 TRKKKQKCFHFLKR 127

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 73486655 131 VGIRGVFSNKFLAMSKKGKLHAS-AKFTDDCKFRERFQENSYNTYASAIHrtekTGreWYVALNKRGKAKRGcsPRVKPQ 209
Cdd:cd23324  45 VRIKGKETDFYLCMNRKGKLVGKpDGTSKECVFIEKVLENNYTALMSAKY----SG--WYVGFTKKGRPRKG--PKTREN 116

                        90
                ....*....|
gi 73486655 210 HISTHFLPRF 219
Cdd:cd23324 117 QQDVHFMKRY 126

FGF domain, beta-trefoil fold, found in fibroblast growth factor 17 (FGF17) and similar proteins; FGF17 plays an important role in the regulation of embryonic development and as signaling molecule in the induction and patterning of the embryonic brain. It is required for normal brain development. FGF17 interacts with fibroblast growth factor receptors, FGFR3 and FGFR4. FGF17 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 73486655 131 VGIRGVFSNKFLAMSKKGKLHASAK-FTDDCKFRERFQENSYNTYASAIHRTektgreWYVALNKRGKAKRGCSPRVKPQ 209
Cdd:cd23323  45 VRIKGAESGKYICMNKRGKLVGKPNgKSKDCIFTEIVLENNYTAFQNARHEG------WFMAFTRKGRPRKASKTRQNQR 118

                        90
                ....*....|
gi 73486655 210 HIstHFLPRF 219
Cdd:cd23323 119 EV--HFIKRL 126