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 1238280281  25 KPKLLYCSNGGHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERL 104
Cdd:pfam00167   1 RVRRLYCRTGGFHLQILPDGKVDGTGEDGSPYSILEIESVSVGVVRIKGVESGLYLAMNKKGRLYGSKNFTDECVFKERL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1238280281 105 EENHYNTYISKKHAEKNWFVGLKKNGSCKRGPRTHYGQKAILFL 148
Cdd:pfam00167  81 LENNYNTYASAKYSGRGWYVGLNKKGRPKRGSKTKPGQKAAHFL 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 1238280281  25 KPKLLYCSNGGHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERL 104
Cdd:cd23304     1 KPKKLYCSNGGYHLRILPDGTVDGTREESDPYIILQLKAESPGVVVIKGTETGQYLAMNEDGRLYGSQTVNDECLFLERL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1238280281 105 EENHYNTYISKKHAEKNWFVGLKKNGSCKRGPRTHYGQKAILFLPLP 151
Cdd:cd23304    81 EENHYNTYRSQKYAEKNWYVGLKKNGRCKLGPRTHYGQKAILFLPRP 127

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 1238280281  26 PKLLYCSNGGHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLE 105
Cdd:cd23314     2 PKRLYCKNGGFFLRIHPDGRVDGVREKSDPHIKLQLQAEERGVVSIKGVCANRYLAMKEDGRLLASKSVTDECFFFERLE 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1238280281 106 ENHYNTYISKKHAekNWFVGLKKNGSCKRGPRTHYGQKAILFLPL 150
Cdd:cd23314    82 SNNYNTYRSRKYT--SWYVALKRTGQYKLGSKTGPGQKAILFLPM 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1238280281  25 KPKLLYCSNGgHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERL 104
Cdd:cd00058     1 RLVRLYSRTG-YFLQILPDGTVNGTKDENSPYAILELQSVGTGLVRIKGVKTGRYLAMDKNGKLYGTKKPTEDCVFKETL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1238280281 105 EENHYNTYISKKH--AEKNWFVGLKKNGSCKRGPRTHYGQKAILFLPL 150
Cdd:cd00058    80 EENGYNTYSSYKYyhTRKGWYLAIKKNGKPKRGKKTKPGQKSTQFLPL 127

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 1238280281  27 KLLYCSNGGHFLRILPDGTVDGTRDRSDqHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEE 106
Cdd:cd23305     3 RLLYCRVIGFHLQILPDGSVNGTHEDTE-YSWLEIFAVEVGVVGIKGVKSGLYLCMNKKGKLYGSKEFTDECKFKERLEE 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1238280281 107 NHYNTYISKKH--AEKNWFVGLKKNGSCKRGPRTHYGQKAILFLPL 150
Cdd:cd23305    82 NHYNTYSSALYprRKRGWYVALSKKGRPRRGSRVRRTQKSTHFLPR 127

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 1238280281  29 LYCSNGGHfLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENH 108
Cdd:cd23327    14 LYCRTGFH-LEILPDGSVQGTRKDHSRFGILEFISVAVGLVSIRGVDSGLYLGMNDKGELYGSEKLTAECIFREQFEENW 92

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1238280281 109 YNTYISK--KHAE--KNWFVGLKKNGSCKRGPRTHYGQKAILFLPLPVSSD 155
Cdd:cd23327    93 YNTYSSNlyKHGDtgRRYFVALNKDGTPRDGTRSKRHQKFTHFLPRPVDPE 143

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 1238280281  29 LYCSNGGHfLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENH 108
Cdd:cd23326    11 LYCRTGFH-LEIFPNGTVHGTRQDHSRFGILEFISLAVGLVSIRGVDSGLYLGMNERGELYGSKKLTRECVFREQFEENW 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1238280281 109 YNTYISK--KHA--EKNWFVGLKKNGSCKRGPRTHYGQKAILFLPLPVSSD 155
Cdd:cd23326    90 YNTYASTlyKHAdsGRQYYVALNKDGSPREGYRTKRHQKFTHFLPRPVDPE 140

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 1238280281  29 LYCSNGgHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENH 108
Cdd:cd23321    11 LYSATK-FFLRIDKGGRVEGTRWKNCPDSILEIRSVSVGVVAIKSVSTGFYLAMNKKGKLYGSKLYSPNCKFKERIEENG 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1238280281 109 YNTYISK--KHAEKNWFVGLKKNGSCKRGPRTHYGQKAILFLPL 150
Cdd:cd23321    90 YNTYASLrwRHRGRPMFLSLNSRGRPRRGGKTRRKHLSTHFLPM 133

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1238280281  35 GHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENHYNTYiS 114
Cdd:cd23311    12 NRYLQVNADGTVNGTTDSNSNDTVWQRIAVNNGKILIRSVATCMYLCINECGYVYSSKVPNKDCLFNESYEENNYNYY-Y 90

                          90       100
                  ....*....|....*....|
gi 1238280281 115 KKHAEKNWFVGLKKNGSCKR 134
Cdd:cd23311    91 KKFNRRRAYLALNKEGKTRR 110

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 1238280281  29 LYCSNGgHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENH 108
Cdd:cd23309     6 LYSRQG-YYLQMQPDGTIDGTKDENSSYTLFNLIPVGLRVVAIQGVKTGLYIAMNSEGYLYTSEHFTPECKFKESVFENY 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1238280281 109 YNTYIS----KKHAEKNWFVGLKKNGSCKRGPRTHYGQKAILFLP 149
Cdd:cd23309    85 YVIYSSmlyrQQQSGRAWYLGLNKEGQIMKGNRVKKTKPAAHFLP 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 1238280281  29 LYCSNGGHfLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENH 108
Cdd:cd23329     9 LYSRQGYH-LQLQADGTIDGTKEEDSSYTLFNLIPVGLRVVAIQGVQTKLYLAMNSEGYLYTSEHFTPECKFKESVFENY 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1238280281 109 YNTYIS----KKHAEKNWFVGLKKNGSCKRGPRTHYGQKAILFLPLPV 152
Cdd:cd23329    88 YVTYSSmiyrQQQSGRGWYLGLNKEGEIMKGNHVKKNKPAAHFLPKPL 135

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 1238280281  29 LYCSNG-GHFLRILPDGTVDGTRDrSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEEN 107
Cdd:cd23316     5 LYCNVGiGFHIQVLPDGRINGVHN-ENRYSLLEISPVERGVVSIFGVKSGLFVAMNSKGKLYGSPFFNDECKFKEILLPN 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1238280281 108 HYNTYISKKHAekNWFVGLKKNGSCKRGPRTHYGQKAILFLP 149
Cdd:cd23316    84 NYNAYESRKYP--GMYIALSKNGKTKKGNRVSPTMTVTHFLP 123

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 1238280281  28 LLYCSN--GGHFLRILPDGTVDGTRDRSdQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEE-CLFLERL 104
Cdd:cd23310     4 HLYTETprSSCFLEIRPDGTVDGAPHQT-AYSLLELKSVKPGETVIKGVASSLYLCVDSDGKLKGQHHYDEEdCSFQELL 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1238280281 105 EENHYNTYISKKHaekNWFVGLKKNGSCKRGPRThYGQkailFLPLP 151
Cdd:cd23310    83 LEDGYTVFLSPHH---GLPVSLLSKKQPFRHPLP-LSR----FLPLR 121

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 1238280281  29 LYCSNG-GHFLRILPDGTVDGTRDRSdQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEEN 107
Cdd:cd23318     5 LYCNVGiGFHLQILPDGRINGVHNEN-QYSLLEISTVERGVVSLYGVKSGLFVAMNSKGRLYGTPNFQDECKFKETLLPN 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1238280281 108 HYNTYISKKHaeKNWFVGLKKNGSCKRGPRTHYGQKAILFLP 149
Cdd:cd23318    84 NYNAYESSLY--KGAYIALSKHGRVKRGNKVSPAMTVTHFLP 123

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 1238280281  38 LRILPDGTVDGTRDRSDQHIqLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEE-CLFLERLEENHYNTYISKK 116
Cdd:cd23332    18 LEIREDGTVGGAADQSPYSL-LELKAVKPGVVQILGKKTLRFLCMDPDGRLYGSLHYSPEaCSFREVVLEDGYNLYQSEA 96

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1238280281 117 HaekNWFVGLKKNGSCKRGPRTHYGqkAILFLPLP 151
Cdd:cd23332    97 H---GLPLTLSPNRAPHRDGGAPPP--LAHFLPLV 126

FGF domain, beta-trefoil fold, found in fibroblast growth factor 23 (FGF23) and similar proteins; 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 fibroblast growth factor receptors, FGFR1, FGFR2, FGFR3, and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by KL and heparan sulfate glycosaminoglycans that function as coreceptors. FGF23 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 1238280281  37 FLRILPDGTVDGTRDRSDQHIQLqLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPN-EECLFLERLEENHYNTYISK 115
Cdd:cd23333    31 HLQINPDGHVDGTPHQTIYSALL-IKSEDAGRVVITGVKSNRYLCMDFRGNIFGSHYFNkEDCLFQHETLENGYDVYHSP 109

                  ..
gi 1238280281 116 KH 117
Cdd:cd23333   110 KY 111

FGF domain, beta-trefoil fold, found in oxygen-regulated protein 1 (ORP1) and similar proteins; ORP1, also called retinitis pigmentosa 1 protein, or retinitis pigmentosa RP1 protein, is a microtubule-associated protein that regulates the stability and length of the microtubule-based axoneme of photoreceptors. It is required for the differentiation of photoreceptor cells. It plays a role in the organization of the outer segment of rod and cone photoreceptors ensuring the correct orientation and higher-order stacking of outer segment disks along the photoreceptor axoneme. Members in this family may contain one or two fibroblast growth factor (FGF) domain(s) in the middle region. The FGF domain shows a 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 1238280281  28 LLYCSNGGHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTET-GQYLAMDtDGLLYGSQTPNEECLFLERLEE 106
Cdd:cd23312     7 QLYSKLTGQALRVKPDGSVDATGDKKDKFAYFRVHKVKGNIRIFQSVANpGYFLAID-DGKVDGNGKGGEDCEFRVRVQP 85

                          90       100
                  ....*....|....*....|....*
gi 1238280281 107 NHYNTYISKKHAekNWFVGLKKNGS 131
Cdd:cd23312    86 DRSVTLESVKNP--GQFVGFNPDGK 108