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 4503693     53 REYQLYSRTSGKHVQVTG-RRISATAEDGNKFAKLIVETDTFGsRVRIKGAESEKYICMNKRGKLIGKPSGKSkDCVFTE 131
Cdd:pfam00167   1 RVRRLYCRTGGFHLQILPdGKVDGTGEDGSPYSILEIESVSVG-VVRIKGVESGLYLAMNKKGRLYGSKNFTD-ECVFKE 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 4503693    132 IVLENNYTAFQNARH--EGWFMAFTRQGRPRQASRSRQNQREAHFI 175
Cdd:pfam00167  79 RLLENNYNTYASAKYsgRGWYVGLNKKGRPKRGSKTKPGQKAAHFL 124

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 4503693   33 FNQYVRDQGAMTDQLSRRQIREYQLYSRTSGKHVQVTG-RRISATAEDGNKFAKLIVETDTFGSRVRIKGAESEKYICMN 111
Cdd:cd23322   1 FTQHVREQSLVTDQLSRRLIRTYQLYSRTSGKHVQVLAnKKINAMAEDGDPHAKLIVETDTFGSRVRIKGAETGYYICMN 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4503693  112 KRGKLIGKPSGKSKDCVFTEIVLENNYTAFQNARHEGWFMAFTRQGRPRQASRSRQNQREAHFIKRL 178
Cdd:cd23322  81 KKGKLIGKSNGKGKDCVFTEIVLENNYTALQNAKYEGWYMAFTRKGRPRKGSKTRQHQREVHFMKRL 147

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 4503693     53 REYQLYSRTSGKHVQVTG-RRISATAEDGNKFAKLIVETDTFGsRVRIKGAESEKYICMNKRGKLIGKPSGKSkDCVFTE 131
Cdd:pfam00167   1 RVRRLYCRTGGFHLQILPdGKVDGTGEDGSPYSILEIESVSVG-VVRIKGVESGLYLAMNKKGRLYGSKNFTD-ECVFKE 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 4503693    132 IVLENNYTAFQNARH--EGWFMAFTRQGRPRQASRSRQNQREAHFI 175
Cdd:pfam00167  79 RLLENNYNTYASAKYsgRGWYVGLNKKGRPKRGSKTKPGQKAAHFL 124

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 4503693      52 IREYQLYSRTsGKHVQVTGR-RISATAEDGNKFakLIVETDTFG-SRVRIKGAESEKYICMNKRGKLIGKPSgKSKDCVF 129
Cdd:smart00442   2 KRLRQLYCRN-GQHLQILPDgTVDGTRDESSSF--TILEIIAVAvGVVAIKGVASCRYLCMNKCGKLYGSKN-FTEDCVF 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 4503693     130 TEIVLENNYTAFQNARHEG-WFMAFTRQGRPRQASRSRQNQREAHFIKR 177
Cdd:smart00442  78 REEMEENGYNTYASAKYRKrWYVALNKKGRPRRGQKTKPLQKASHFLPR 126

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 4503693   53 REYQLYSRTSGKHVQV--TGRrISATAEDGNkFAKLIVETDTFGSrVRIKGAESEKYICMNKRGKLIGKPSgKSKDCVFT 130
Cdd:cd23305   1 RYRLLYCRVIGFHLQIlpDGS-VNGTHEDTE-YSWLEIFAVEVGV-VGIKGVKSGLYLCMNKKGKLYGSKE-FTDECKFK 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 4503693  131 EIVLENNYTAFQNARHE----GWFMAFTRQGRPRQASRSRQNQREAHFIKR 177
Cdd:cd23305  77 ERLEENHYNTYSSALYPrrkrGWYVALSKKGRPRRGSRVRRTQKSTHFLPR 127

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 4503693   56 QLYSRTSGKHVQVTGR-RISATAEDGNKFAKLIVETDTFGSrVRIKGAESEKYICMNKRGKLIGKpSGKSKDCVFTEIVL 134
Cdd:cd23304   4 KLYCSNGGYHLRILPDgTVDGTREESDPYIILQLKAESPGV-VVIKGTETGQYLAMNEDGRLYGS-QTVNDECLFLERLE 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 4503693  135 ENNYTAFQNARH--EGWFMAFTRQGRPRQASRSRQNQREAHFIKR 177
Cdd:cd23304  82 ENHYNTYRSQKYaeKNWYVGLKKNGRCKLGPRTHYGQKAILFLPR 126

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 4503693   52 IREYQLYSRTS-----GKHVQVTGrrisaTAEDGNKFAKLIVETDTFGSrVRIKGAESEKYICMNKRGKLIGKPSgKSKD 126
Cdd:cd23306   3 VRWRRLFSRTKfflriDKNGKVNG-----TKSENNPYSILEIRSVDVGV-VAIKGVKSNYYLAMNKKGKLYGKKD-YNDD 75

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 4503693  127 CVFTEIVLENNYTAFQNAR--HEG--WFMAFTRQGRPRQASRSRQNQREAHFIKRL 178
Cdd:cd23306  76 CRFKERIEENGYNTYASAKwtHNGreMFVALSQKGRPLRGKKTRRKNTAAHFLPMV 131

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 4503693   53 REYQLYSRTS-GKHVQV-TGRRISATAEDgNKFAKLIVETDTFGSrVRIKGAESEKYICMNKRGKLIGKPSGKSkDCVFT 130
Cdd:cd23318   1 RLRRLYCNVGiGFHLQIlPDGRINGVHNE-NQYSLLEISTVERGV-VSLYGVKSGLFVAMNSKGRLYGTPNFQD-ECKFK 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 4503693  131 EIVLENNYTAFQNARHEGWFMAFTRQGRPRQASRSRQNQREAHFIKRL 178
Cdd:cd23318  78 ETLLPNNYNAYESSLYKGAYIALSKHGRVKRGNKVSPAMTVTHFLPRI 125

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 4503693   52 IREYQLYSRTsGKHVQV-TGRRISATAEDGNKFAKLIVETDTFGsRVRIKGAESEKYICMNKRGKLIGKPSgKSKDCVFT 130
Cdd:cd23325  13 LRRRQLYCRT-GFHLEIfPNGTIQGTRKDHSRFGILEFISIAVG-LVSIRGVDSGLYLGMNEKGELYGSEK-LTQECVFR 89

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 4503693  131 EIVLENNYTAFQNARHEG------WFMAFTRQGRPRQASRSRQNQREAHFIKR 177
Cdd:cd23325  90 EQFEENWYNTYSSNLYKHvdtgrrYYVALNKDGTPREGTRTKRHQKFTHFLPR 142

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 4503693   97 VRIKGAESEKYICMNKRGKLIGKPSgKSKDCVFTEIVLENNYTAF--QNARHEG--WFMAFTRQGRPRQASRSRQNQREA 172
Cdd:cd23321  50 VAIKSVSTGFYLAMNKKGKLYGSKL-YSPNCKFKERIEENGYNTYasLRWRHRGrpMFLSLNSRGRPRRGGKTRRKHLST 128

                ....*.
gi 4503693  173 HFIKRL 178
Cdd:cd23321 129 HFLPML 134

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 4503693   72 RISATAEDGNKFAKLIVETDTFGSrVRIKGAESEKYICMNKRGKLIGKPSgKSKDCVFTEIVLENNYTAFQNARH--EGW 149
Cdd:cd23313  21 TVDGTRDRSDQHIQLQLSAESVGE-VYIKSTETGQYLAMDTDGLLYGSQT-PNEECLFLERLEENHYNTYISKKHaeKNW 98

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 4503693  150 FMAFTRQGRPRQASRSRQNQREAHFikrlyqgqLPFP 186
Cdd:cd23313  99 FVGLKKNGSCKRGPRTHYGQKAILF--------LPLP 127

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 4503693   53 REYQLYSRTSGkHVQVTGRRISATAedgnkfakLIVETDTFGsRVRIKGAESEKYICMNKRGKLIGKPSGKSKDCVFTEI 132
Cdd:cd23333  28 NSYHLQINPDG-HVDGTPHQTIYSA--------LLIKSEDAG-RVVITGVKSNRYLCMDFRGNIFGSHYFNKEDCLFQHE 97

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 4503693  133 VLENNYTAFQNARH------EGWFMAFTRQGRPRQASR--SRQNQ 169
Cdd:cd23333  98 TLENGYDVYHSPKYnilvslGGAKQAFIPGMNLPPYSQflSRRNE 142

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 4503693   72 RISATAEDGNKFAKLIVETDTFGSrVRIKGAESEKYICMNKRGKLIGKPSGKSkDCVFTEIVLENNYTAFQ--NARHEG- 148
Cdd:cd23320  26 KVSGTKKENCPYSILEITSVEVGV-VAVKAINSNYYLAMNKKGKIYGSKEFNI-DCKLKERIEENGYNTYAslNWKHNGr 103

                        90       100
                ....*....|....*....|....*...
gi 4503693  149 -WFMAFTRQGRPRQASRSRQNQREAHFI 175
Cdd:cd23320 104 qMFVALNGKGAPKRGQKTRRKNTSAHFL 131

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
                ....*....|....*....|....*....|....*....|....*....|
gi 4503693   97 VRIKGAESEKYICMNKRGKLIGKPSGKSKDCVFTEIVLENNYTAFQNARH 146
Cdd:cd23310  46 TVIKGVASSLYLCVDSDGKLKGQHHYDEEDCSFQELLLEDGYTVFLSPHH 95

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 4503693   56 QLYSRtSGKHVQVTGR-RISATAEDGNKFA--KLIvetdTFGSR-VRIKGAESEKYICMNKRGKLIGKPSgKSKDCVFTE 131
Cdd:cd23309   5 RLYSR-QGYYLQMQPDgTIDGTKDENSSYTlfNLI----PVGLRvVAIQGVKTGLYIAMNSEGYLYTSEH-FTPECKFKE 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 4503693  132 IVLENNYTAF------QNARHEGWFMAFTRQGRPRQASRSRQNQREAHFIKR 177
Cdd:cd23309  79 SVFENYYVIYssmlyrQQQSGRAWYLGLNKEGQIMKGNRVKKTKPAAHFLPK 130

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503693   97 VRIKGAESEKYICMNKRGKLIGKPSgKSKDCVFTEIVLENNYTAF------QNARHEGWFMAFTRQGRPRQASRSRQNQR 170
Cdd:cd23328  49 VAIQGVKAGLYVAMNGEGYLYSSDV-FTPECKFKESVFENYYVIYsstlyrQQESGRAWFLGLNKEGQIMKGNRVKKTKP 127

                ....*..
gi 4503693  171 EAHFIKR 177
Cdd:cd23328 128 SSHFVPK 134

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 4503693   56 QLYSRTSGKHVQVTGR-RISATAEDGNKFAKLIVetdtfgsrVRIKG--------AESEKYICMnKRGKLIGKPSGkSKD 126
Cdd:cd23312   7 QLYSKLTGQALRVKPDgSVDATGDKKDKFAYFRV--------HKVKGnirifqsvANPGYFLAI-DDGKVDGNGKG-GED 76

                        90       100       110
                ....*....|....*....|....*....|....
gi 4503693  127 CVFTEIVLENNYTAFQNARHEGWFMAFTRQGRPR 160
Cdd:cd23312  77 CEFRVRVQPDRSVTLESVKNPGQFVGFNPDGKPR 110