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 1958760279  65 RVRRLFCRT-QWYLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKELI 143
Cdd:pfam00167   1 RVRRLYCRTgGFHLQILPDGKVDGTGEDGSPYSILEIESVSVGVVRIKGVESGLYLAMNKKGRLYGSKNFTDECVFKERL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1958760279 144 LENHYNTYASAKwtHSGGEMFVALNQKGLPVKGKKTKKEQKTAHFL 189
Cdd:pfam00167  81 LENNYNTYASAK--YSGRGWYVGLNKKGRPKRGSKTKPGQKAAHFL 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 1958760279  62 GDIRVRRLFCRTQWYLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKE 141
Cdd:cd23306     1 GDVRWRRLFSRTKFFLRIDKNGKVNGTKSENNPYSILEIRSVDVGVVAIKGVKSNYYLAMNKKGKLYGKKDYNDDCRFKE 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958760279 142 LILENHYNTYASAKWTHSGGEMFVALNQKGLPVKGKKTKKEQKTAHFLPMA 192
Cdd:cd23306    81 RIEENGYNTYASAKWTHNGREMFVALSQKGRPLRGKKTRRKNTAAHFLPMV 131

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 1958760279   63 DIRVRRLFCRTQWYLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKEL 142
Cdd:smart00442   1 TKRLRQLYCRNGQHLQILPDGTVDGTRDESSSFTILEIIAVAVGVVAIKGVASCRYLCMNKCGKLYGSKNFTEDCVFREE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1958760279  143 ILENHYNTYASAKWTHsggEMFVALNQKGLPVKGKKTKKEQKTAHFLPM 191
Cdd:smart00442  81 MEENGYNTYASAKYRK---RWYVALNKKGRPRRGQKTKPLQKASHFLPR 126

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 1958760279  62 GDIRVRRLFCRTQWYLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKE 141
Cdd:cd23321     4 GDVRWRRLYSATKFFLRIDKGGRVEGTRWKNCPDSILEIRSVSVGVVAIKSVSTGFYLAMNKKGKLYGSKLYSPNCKFKE 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958760279 142 LILENHYNTYASAKWTHSGGEMFVALNQKGLPVKGKKTKKEQKTAHFLPM 191
Cdd:cd23321    84 RIEENGYNTYASLRWRHRGRPMFLSLNSRGRPRRGGKTRRKHLSTHFLPM 133

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 1958760279  65 RVRRLFCR-TQWYLRIDKRGKVKGTQEmRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKELI 143
Cdd:cd23305     1 RYRLLYCRvIGFHLQILPDGSVNGTHE-DTEYSWLEIFAVEVGVVGIKGVKSGLYLCMNKKGKLYGSKEFTDECKFKERL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1958760279 144 LENHYNTYASAKWTHSGGEMFVALNQKGLPVKGKKTKKEQKTAHFLP 190
Cdd:cd23305    80 EENHYNTYSSALYPRRKRGWYVALSKKGRPRRGSRVRRTQKSTHFLP 126

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 1958760279  62 GDIRVRRLFCRTQWYLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKE 141
Cdd:cd23327     7 GILRRRQLYCRTGFHLEILPDGSVQGTRKDHSRFGILEFISVAVGLVSIRGVDSGLYLGMNDKGELYGSEKLTAECIFRE 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958760279 142 LILENHYNTYASAKWTH--SGGEMFVALNQKGLPVKGKKTKKEQKTAHFLP 190
Cdd:cd23327    87 QFEENWYNTYSSNLYKHgdTGRRYFVALNKDGTPRDGTRSKRHQKFTHFLP 137

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 1958760279  62 GDIRVRRLFCRTQWYLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKE 141
Cdd:cd23325    11 GILRRRQLYCRTGFHLEIFPNGTIQGTRKDHSRFGILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQECVFRE 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958760279 142 LILENHYNTYASAKWTH--SGGEMFVALNQKGLPVKGKKTKKEQKTAHFLPMAI 193
Cdd:cd23325    91 QFEENWYNTYSSNLYKHvdTGRRYYVALNKDGTPREGTRTKRHQKFTHFLPRPV 144

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 1958760279  65 RVRRLFCRTQWYLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKELIL 144
Cdd:cd23315     1 RRRKLYCATKYHLQIHPNGKIDGTLEKNSVFSILEITAVDVGVVAIKGLFSGRYLAMNKRGRLYASEVYNAECEFVERIH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958760279 145 ENHYNTYAS-----------AKWTHSGGEM-FVALNQKGLPVKGKKTKKEQKTAHFLP 190
Cdd:cd23315    81 ELGYNTYASrlyrtvpsgagTKRKASAERLwYVSINGKGRPRRGFKTRRTQKSSLFLP 138

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 1958760279  66 VRRLFCRTQWYLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKELILE 145
Cdd:cd23309     3 VTRLYSRQGYYLQMQPDGTIDGTKDENSSYTLFNLIPVGLRVVAIQGVKTGLYIAMNSEGYLYTSEHFTPECKFKESVFE 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1958760279 146 NHYNTYASA--KWTHSGGEMFVALNQKGLPVKGKKTKKEQKTAHFLP 190
Cdd:cd23309    83 NYYVIYSSMlyRQQQSGRAWYLGLNKEGQIMKGNRVKKTKPAAHFLP 129

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958760279  66 VRRLFCRTQWYLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKELILE 145
Cdd:cd23329     6 VTKLYSRQGYHLQLQADGTIDGTKEEDSSYTLFNLIPVGLRVVAIQGVQTKLYLAMNSEGYLYTSEHFTPECKFKESVFE 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1958760279 146 NHYNTYASA--KWTHSGGEMFVALNQKGLPVKGKKTKKEQKTAHFLP 190
Cdd:cd23329    86 NYYVTYSSMiyRQQQSGRGWYLGLNKEGEIMKGNHVKKNKPAAHFLP 132

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 1958760279  65 RVRRLFCRTQ--WYLRIDKRGKVKGTQEmRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKEL 142
Cdd:cd23318     1 RLRRLYCNVGigFHLQILPDGRINGVHN-ENQYSLLEISTVERGVVSLYGVKSGLFVAMNSKGRLYGTPNFQDECKFKET 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958760279 143 ILENHYNTYASAkwTHSGgeMFVALNQKGLPVKGKKTKKEQKTAHFLP 190
Cdd:cd23318    80 LLPNNYNAYESS--LYKG--AYIALSKHGRVKRGNKVSPAMTVTHFLP 123

FGF domain, beta-trefoil fold, found in fibroblast growth factor 1 (FGF1) and similar proteins; FGF1, also called acidic fibroblast growth factor (aFGF), or endothelial cell growth factor (ECGF), or heparin-binding growth factor 1 (HBGF1), plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation, and cell migration. It functions as potent mitogen in vitro. FGF-1 acts as a ligand for fibroblast growth factor receptor 1 (FGFR1) and integrins. 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. It also interacts with fibroblast growth factor-binding protein 1 (FGFBP1), FGF1, and FGF2. It can induce angiogenesis. FGF1 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 1958760279  69 LFCRTQWY-LRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKELILENH 147
Cdd:cd23313     5 LYCSNGGHfLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENH 84

                          90       100
                  ....*....|....*....|....
gi 1958760279 148 YNTYASAKwtHSGGEMFVALNQKG 171
Cdd:cd23313    85 YNTYISKK--HAEKNWFVGLKKNG 106

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 1958760279  66 VRRLFCRTQWYLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECNEDCNFKELILE 145
Cdd:cd23330     8 VTRLYCRQGYYLQMHPDGSLDGTKDDSSNSTLFNLIPVGLRVVAIQGVKTGLYIAMNGEGYLYTSELFTPECKFKESVFE 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1958760279 146 NHYNTYASA--KWTHSGGEMFVALNQKGLPVKGKKTKKEQKTAHFLP 190
Cdd:cd23330    88 NYYVIYSSMlyRQQESGRAWFLGLNKEGQAMKGNRVKKTKPAAHFLP 134

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 1958760279  65 RVRRLFC---RTQWYLRIDKRGKVKGTQEMrNSYNIMEIRTVAVGIVAIKGVESEYYLAMNKEGKLYAKKECN-EDCNFK 140
Cdd:cd23310     1 RQRHLYTetpRSSCFLEIRPDGTVDGAPHQ-TAYSLLELKSVKPGETVIKGVASSLYLCVDSDGKLKGQHHYDeEDCSFQ 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958760279 141 ELILENHYNTYASAkwtHSGgeMFVALNQKGLPvkgkkTKKEQKTAHFLPMA 192
Cdd:cd23310    80 ELLLEDGYTVFLSP---HHG--LPVSLLSKKQP-----FRHPLPLSRFLPLR 121

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958760279  65 RVRRLFCRTQW-YLRIDKRgKVKGTQEMRNSYNIMEIRTVAVGI-VAIKGVESEYYLAMNKEGKLYAKKEC-NEDCNFKE 141
Cdd:cd23323     1 RVYQLYSRTSGkHVQVTGR-RVSATAEDGNKFAKLIVETDTFGSrVRIKGAESGKYICMNKRGKLVGKPNGkSKDCIFTE 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958760279 142 LILENHYNTYASAKwtHSGgeMFVALNQKGLPVKGKKTKKEQKTAHFL 189
Cdd:cd23323    80 IVLENNYTAFQNAR--HEG--WFMAFTRKGRPRKASKTRQNQREVHFI 123

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 1958760279  65 RVRRLFCR-TQWYLRIdKRGKVKGTQEMRNSYNIMEIRTVA-VGIVAIKGVESEYYLAMNKEGKLYAKKECNED--CNFK 140
Cdd:cd23307     1 RSVRLYSRcSKKFVRI-TGGRVDARGEKGSPYAKLTIESVGfSGKVRIRGAKSGRYLCFNKKGKLVAKKNGKKDkrCVFE 79

                          90
                  ....*....|....*
gi 1958760279 141 ELILENHYNTYASAK 155
Cdd:cd23307    80 EELTDGYYTRYRSVK 94

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 1958760279  64 IRVRRLFCRTQW-YLRIDKRGKVKGTQEMRNSYNIMEIRTVAVGI-VAIKGVESEYYLAMNKEGKLYAKKEC-NEDCNFK 140
Cdd:cd23322    20 IRTYQLYSRTSGkHVQVLANKKINAMAEDGDPHAKLIVETDTFGSrVRIKGAETGYYICMNKKGKLIGKSNGkGKDCVFT 99

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1958760279 141 ELILENHYNTYASAKWTHsggeMFVALNQKGLPVKGKKTKKEQKTAHFL 189
Cdd:cd23322   100 EIVLENNYTALQNAKYEG----WYMAFTRKGRPRKGSKTRQHQREVHFM 144