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 2490654170  69 QLKGIVTRLFSEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFK 148
Cdd:cd23328     2 QLKGIVTRLFSQQGYFLQMHPDGTIDGTKDENSDYTLFNLIPVGLRVVAIQGVKAGLYVAMNGEGYLYSSDVFTPECKFK 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2490654170 149 ESVFENYYVIYSSTLYRQHESGRAWFLGLNKEGIIMKGNRVKKTKACSHFVPRPIQVC 206
Cdd:cd23328    82 ESVFENYYVIYSSTLYRQQESGRAWFLGLNKEGQIMKGNRVKKTKPSSHFVPKPIEVC 139

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 2490654170  69 QLKGIVTRLFSEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFK 148
Cdd:cd23328     2 QLKGIVTRLFSQQGYFLQMHPDGTIDGTKDENSDYTLFNLIPVGLRVVAIQGVKAGLYVAMNGEGYLYSSDVFTPECKFK 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2490654170 149 ESVFENYYVIYSSTLYRQHESGRAWFLGLNKEGIIMKGNRVKKTKACSHFVPRPIQVC 206
Cdd:cd23328    82 ESVFENYYVIYSSTLYRQQESGRAWFLGLNKEGQIMKGNRVKKTKPSSHFVPKPIEVC 139

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 2490654170  74 VTRLFSEQ-GFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKESVF 152
Cdd:pfam00167   2 VRRLYCRTgGFHLQILPDGKVDGTGEDGSPYSILEIESVSVGVVRIKGVESGLYLAMNKKGRLYGSKNFTDECVFKERLL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2490654170 153 ENYYVIYSSTLYrqheSGRAWFLGLNKEGIIMKGNRVKKTKACSHF 198
Cdd:pfam00167  82 ENNYNTYASAKY----SGRGWYVGLNKKGRPKRGSKTKPGQKAAHF 123

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 2490654170  69 QLKGIVTRLFSEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFK 148
Cdd:cd23328     2 QLKGIVTRLFSQQGYFLQMHPDGTIDGTKDENSDYTLFNLIPVGLRVVAIQGVKAGLYVAMNGEGYLYSSDVFTPECKFK 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2490654170 149 ESVFENYYVIYSSTLYRQHESGRAWFLGLNKEGIIMKGNRVKKTKACSHFVPRPIQVC 206
Cdd:cd23328    82 ESVFENYYVIYSSTLYRQQESGRAWFLGLNKEGQIMKGNRVKKTKPSSHFVPKPIEVC 139

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 2490654170  69 QLKGIVTRLFSEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFK 148
Cdd:cd23329     1 QLKGIVTKLYSRQGYHLQLQADGTIDGTKEEDSSYTLFNLIPVGLRVVAIQGVQTKLYLAMNSEGYLYTSEHFTPECKFK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2490654170 149 ESVFENYYVIYSSTLYRQHESGRAWFLGLNKEGIIMKGNRVKKTKACSHFVPRPIQVCMYKEPSLHEL 216
Cdd:cd23329    81 ESVFENYYVTYSSMIYRQQQSGRGWYLGLNKEGEIMKGNHVKKNKPAAHFLPKPLKVAMYREPSLHDL 148

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 2490654170   71 KGIVTRLFSEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKES 150
Cdd:smart00442   1 TKRLRQLYCRNGQHLQILPDGTVDGTRDESSSFTILEIIAVAVGVVAIKGVASCRYLCMNKCGKLYGSKNFTEDCVFREE 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2490654170  151 VFENYYVIYSSTLYRQHesgraWFLGLNKEGIIMKGNRVKKTKACSHFVPR 201
Cdd:smart00442  81 MEENGYNTYASAKYRKR-----WYVALNKKGRPRRGQKTKPLQKASHFLPR 126

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 2490654170  76 RLFSEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKESVFENY 155
Cdd:cd00058     4 RLYSRTGYFLQILPDGTVNGTKDENSPYAILELQSVGTGLVRIKGVKTGRYLAMDKNGKLYGTKKPTEDCVFKETLEENG 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2490654170 156 YVIYSSTLYRQHesGRAWFLGLNKEGIIMKGNRVKKTKACSHFVPR 201
Cdd:cd00058    84 YNTYSSYKYYHT--RKGWYLAIKKNGKPKRGKKTKPGQKSTQFLPL 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 2490654170  82 GFYLQMLSDGTISGCKdENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKESVFENYYVIYSS 161
Cdd:cd23305    11 GFHLQILPDGSVNGTH-EDTEYSWLEIFAVEVGVVGIKGVKSGLYLCMNKKGKLYGSKEFTDECKFKERLEENHYNTYSS 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2490654170 162 TLYRQheSGRAWFLGLNKEGIIMKGNRVKKTKACSHFVPR 201
Cdd:cd23305    90 ALYPR--RKRGWYVALSKKGRPRRGSRVRRTQKSTHFLPR 127

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 2490654170  68 EQLKGIVTR--LFSEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPEC 145
Cdd:cd23325     7 DHLKGILRRrqLYCRTGFHLEIFPNGTIQGTRKDHSRFGILEFISIAVGLVSIRGVDSGLYLGMNEKGELYGSEKLTQEC 86

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2490654170 146 KFKESVFENYYVIYSSTLYRQHESGRAWFLGLNKEGIIMKGNRVKKTKACSHFVPRPIQVCmyKEPSLHE 215
Cdd:cd23325    87 VFREQFEENWYNTYSSNLYKHVDTGRRYYVALNKDGTPREGTRTKRHQKFTHFLPRPVDPD--KVPELYK 154

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 2490654170  76 RLFSEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKESVFENY 155
Cdd:cd23306     7 RLFSRTKFFLRIDKNGKVNGTKSENNPYSILEIRSVDVGVVAIKGVKSNYYLAMNKKGKLYGKKDYNDDCRFKERIEENG 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2490654170 156 YVIYSSTLYRQheSGRAWFLGLNKEGIIMKGNRVKKTKACSHFVPRP 202
Cdd:cd23306    87 YNTYASAKWTH--NGREMFVALSQKGRPLRGKKTRRKNTAAHFLPMV 131

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 2490654170  82 GFYLQMLSDGTISGCKDENSdYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKESVFENYYVIYSS 161
Cdd:cd23316    12 GFHIQVLPDGRINGVHNENR-YSLLEISPVERGVVSIFGVKSGLFVAMNSKGKLYGSPFFNDECKFKEILLPNNYNAYES 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2490654170 162 TLYrqhesgRAWFLGLNKEGIIMKGNRVKKTKACSHFVPR 201
Cdd:cd23316    91 RKY------PGMYIALSKNGKTKKGNRVSPTMTVTHFLPR 124

FGF domain, beta-trefoil fold, found in fibroblast growth factor 5 (FGF5) and similar proteins; 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 fibroblast growth factor receptors, FGFR1 and FGFR2. Affinity between FGFs and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. FGF-5 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 2490654170  82 GFYLQMLSDGTISGCKDENSdYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKESVFENYYVIYSS 161
Cdd:cd23317    12 GFHLQIHPDGRVNGSHEANL-LSVLEIFAVSQGIVGIRGVFSNRFLAMSKKGKLHASAKFTDDCKFRERFQENSYNTYAS 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2490654170 162 TLYRQHESGRAWFLGLNKEGIIMKGN--RVKKTKACSHFVPR 201
Cdd:cd23317    91 ATHRNHRTGREWYVALNKRGKAKRGCspRVKPQHISTHFLPR 132

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 2490654170  76 RLFSEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKESVFENY 155
Cdd:cd23320    10 KLFSFTKYFLKIDKNGKVSGTKKENCPYSILEITSVEVGVVAVKAINSNYYLAMNKKGKIYGSKEFNIDCKLKERIEENG 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2490654170 156 YVIYSSTLYRQheSGRAWFLGLNKEGIIMKGNRVKKTKACSHFVP 200
Cdd:cd23320    90 YNTYASLNWKH--NGRQMFVALNGKGAPKRGQKTRRKNTSAHFLP 132

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 2490654170  76 RLFSEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKESVFENY 155
Cdd:cd23321    10 RLYSATKFFLRIDKGGRVEGTRWKNCPDSILEIRSVSVGVVAIKSVSTGFYLAMNKKGKLYGSKLYSPNCKFKERIEENG 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2490654170 156 YVIYSSTLYRQHesGRAWFLGLNKEGIIMKGNRVKKTKACSHFVP 200
Cdd:cd23321    90 YNTYASLRWRHR--GRPMFLSLNSRGRPRRGGKTRRKHLSTHFLP 132

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 2490654170  79 SEQGFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKESVFENYYVI 158
Cdd:cd23313     8 SNGGHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENHYNT 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2490654170 159 YSSTLYRQhesgRAWFLGLNKEGIIMKGNRVKKTKACSHFVPRPI 203
Cdd:cd23313    88 YISKKHAE----KNWFVGLKKNGSCKRGPRTHYGQKAILFLPLPV 128

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 2490654170  76 RLFSEQG-FYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPECKFKESVFEN 154
Cdd:cd23314     4 RLYCKNGgFFLRIHPDGRVDGVREKSDPHIKLQLQAEERGVVSIKGVCANRYLAMKEDGRLLASKSVTDECFFFERLESN 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2490654170 155 YYVIYSSTLYRQhesgraWFLGLNKEGIIMKGNRVKKTKACSHFVP 200
Cdd:cd23314    84 NYNTYRSRKYTS------WYVALKRTGQYKLGSKTGPGQKAILFLP 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 2490654170  81 QGFYLQMLSDGTIsGCKDENSDYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPE-CKFKESVFENYYVIY 159
Cdd:cd23310    12 SSCFLEIRPDGTV-DGAPHQTAYSLLELKSVKPGETVIKGVASSLYLCVDSDGKLKGQHHYDEEdCSFQELLLEDGYTVF 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2490654170 160 SSTLYRQHESGRAwflglnkegiimKGNRVKKTKACSHFVPRP 202
Cdd:cd23310    91 LSPHHGLPVSLLS------------KKQPFRHPLPLSRFLPLR 121

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 2490654170  83 FYLQMLSDGTISGCKDENSdYTLFNLIPVGLRVVAIQGVKVGLYVAMNAEGFLYTSDVFTPE-CKFKESVFENYYVIYSS 161
Cdd:cd23333    30 YHLQINPDGHVDGTPHQTI-YSALLIKSEDAGRVVITGVKSNRYLCMDFRGNIFGSHYFNKEdCLFQHETLENGYDVYHS 108

                  ...
gi 2490654170 162 TLY 164
Cdd:cd23333   109 PKY 111

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 2490654170 116 VAIQGVKVGLYVAMNAEGFLY-TSDVFTPECKFKESVFENYYVIYSSTLYRqhesgrAWFLGLNKEGIIMKGNRVKKTKA 194
Cdd:cd23324    45 VRIKGKETDFYLCMNRKGKLVgKPDGTSKECVFIEKVLENNYTALMSAKYS------GWYVGFTKKGRPRKGPKTRENQQ 118

                  ....*..
gi 2490654170 195 CSHFVPR 201
Cdd:cd23324   119 DVHFMKR 125

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 2490654170  71 KGIVTRLFSEQ-GFYLQMLSDGTISGCKDENSDYTLFNLIPVGLRVVAIQGVKV-GLYVAM-------NAEGFLYtsdvf 141
Cdd:cd23312     2 DGNVVQLYSKLtGQALRVKPDGSVDATGDKKDKFAYFRVHKVKGNIRIFQSVANpGYFLAIddgkvdgNGKGGED----- 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2490654170 142 tpeCKFKESVFENYYVIYSSTLYRQHesgrawFLGLNKEGIIMKGNRVKKTKAcSHFVPR 201
Cdd:cd23312    77 ---CEFRVRVQPDRSVTLESVKNPGQ------FVGFNPDGKPRDPRGTGDGPN-AQFYVY 126