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 4885233   44 RRRKLYCATKYHLQLHPSGRVNGSLE-NSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERIH 122
Cdd:cd23315   1 RRRKLYCATKYHLQIHPNGKIDGTLEkNSVFSILEITAVDVGVVAIKGLFSGRYLAMNKRGRLYASEVYNAECEFVERIH 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4885233  123 ELGYNTYASRLYRTVSSTPGARRQPSAERLWYVSVNGKGRPRRGFKTRRTQKSSLFLPRV 182
Cdd:cd23315  81 ELGYNTYASRLYRTVPSGAGTKRKASAERLWYVSINGKGRPRRGFKTRRTQKSSLFLPRV 140

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 4885233   44 RRRKLYCATKYHLQLHPSGRVNGSLE-NSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERIH 122
Cdd:cd23315   1 RRRKLYCATKYHLQIHPNGKIDGTLEkNSVFSILEITAVDVGVVAIKGLFSGRYLAMNKRGRLYASEVYNAECEFVERIH 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4885233  123 ELGYNTYASRLYRTVSSTPGARRQPSAERLWYVSVNGKGRPRRGFKTRRTQKSSLFLPRV 182
Cdd:cd23315  81 ELGYNTYASRLYRTVPSGAGTKRKASAERLWYVSINGKGRPRRGFKTRRTQKSSLFLPRV 140

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 4885233      44 RRRKLYCATKYHLQLHPSGRVNGSLE-NSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERIH 122
Cdd:smart00442   3 RLRQLYCRNGQHLQILPDGTVDGTRDeSSSFTILEIIAVAVGVVAIKGVASCRYLCMNKCGKLYGSKNFTEDCVFREEME 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 4885233     123 ELGYNTYASRLYRTvsstpgarrqpsaerLWYVSVNGKGRPRRGFKTRRTQKSSLFLPR 181
Cdd:smart00442  83 ENGYNTYASAKYRK---------------RWYVALNKKGRPRRGQKTKPLQKASHFLPR 126

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 4885233   44 RRRKLYCATKYHLQLHPSGRVNGSLE-NSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERIH 122
Cdd:cd23315   1 RRRKLYCATKYHLQIHPNGKIDGTLEkNSVFSILEITAVDVGVVAIKGLFSGRYLAMNKRGRLYASEVYNAECEFVERIH 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4885233  123 ELGYNTYASRLYRTVSSTPGARRQPSAERLWYVSVNGKGRPRRGFKTRRTQKSSLFLPRV 182
Cdd:cd23315  81 ELGYNTYASRLYRTVPSGAGTKRKASAERLWYVSINGKGRPRRGFKTRRTQKSSLFLPRV 140

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 4885233     44 RRRKLYCAT-KYHLQLHPSGRVNGSLE-NSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERI 121
Cdd:pfam00167   1 RVRRLYCRTgGFHLQILPDGKVDGTGEdGSPYSILEIESVSVGVVRIKGVESGLYLAMNKKGRLYGSKNFTDECVFKERL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 4885233    122 HELGYNTYASRLYRtvsstpgarrqpsaERLWYVSVNGKGRPRRGFKTRRTQKSSLFL 179
Cdd:pfam00167  81 LENNYNTYASAKYS--------------GRGWYVGLNKKGRPKRGSKTKPGQKAAHFL 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 4885233   44 RRRKLYCATKYHLQLHPSGRVNGSL-ENSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERIH 122
Cdd:cd00058   1 RLVRLYSRTGYFLQILPDGTVNGTKdENSPYAILELQSVGTGLVRIKGVKTGRYLAMDKNGKLYGTKKPTEDCVFKETLE 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 4885233  123 ELGYNTYASRLYrtvsstpgarrqPSAERLWYVSVNGKGRPRRGFKTRRTQKSSLFLPR 181
Cdd:cd00058  81 ENGYNTYSSYKY------------YHTRKGWYLAIKKNGKPKRGKKTKPGQKSTQFLPL 127

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 4885233   38 HLGGAPRRRKLYCATKYHLQLHPSGRVNGS-LENSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECE 116
Cdd:cd23320   1 HLQGDVRWRKLFSFTKYFLKIDKNGKVSGTkKENCPYSILEITSVEVGVVAVKAINSNYYLAMNKKGKIYGSKEFNIDCK 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4885233  117 FVERIHELGYNTYASRLYRtvsstpgarrqpSAERLWYVSVNGKGRPRRGFKTRRTQKSSLFLPRV 182
Cdd:cd23320  81 LKERIEENGYNTYASLNWK------------HNGRQMFVALNGKGAPKRGQKTRRKNTSAHFLPMV 134

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 4885233   45 RRKLYCATK-YHLQLHPSGRVNGSLENS-AYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERIH 122
Cdd:cd23304   2 PKKLYCSNGgYHLRILPDGTVDGTREESdPYIILQLKAESPGVVVIKGTETGQYLAMNEDGRLYGSQTVNDECLFLERLE 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 4885233  123 ELGYNTYasrlyrtvsstpgaRRQPSAERLWYVSVNGKGRPRRGFKTRRTQKSSLFLPR 181
Cdd:cd23304  82 ENHYNTY--------------RSQKYAEKNWYVGLKKNGRCKLGPRTHYGQKAILFLPR 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 4885233   38 HLGGAPRRRKLYCATKYHLQLHPSGRVNGSLEN-SAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECE 116
Cdd:cd23327   4 HLQGILRRRQLYCRTGFHLEILPDGSVQGTRKDhSRFGILEFISVAVGLVSIRGVDSGLYLGMNDKGELYGSEKLTAECI 83

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4885233  117 FVERIHELGYNTYASRLYRTVSStpGARrqpsaerlWYVSVNGKGRPRRGFKTRRTQKSSLFLPRVLD 184
Cdd:cd23327  84 FREQFEENWYNTYSSNLYKHGDT--GRR--------YFVALNKDGTPRDGTRSKRHQKFTHFLPRPVD 141

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 4885233   44 RRRKLYC--ATKYHLQLHPSGRVNGSLENSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERI 121
Cdd:cd23317   1 RTGRLYCrvGIGFHLQIHPDGRVNGSHEANLLSVLEIFAVSQGIVGIRGVFSNRFLAMSKKGKLHASAKFTDDCKFRERF 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4885233  122 HELGYNTYASRLYRTVSSTpgarrqpsaeRLWYVSVNGKGRPRRGFKTR-RTQK-SSLFLPR 181
Cdd:cd23317  81 QENSYNTYASATHRNHRTG----------REWYVALNKRGKAKRGCSPRvKPQHiSTHFLPR 132

FGF domain, beta-trefoil fold, found in fibroblast growth factor 7 (FGF7) and similar proteins; FGF7, also called heparin-binding growth factor 7 (HBGF7), or keratinocyte growth factor (KGF), plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. It is required for normal branching morphogenesis. It is a growth factor active on keratinocytes. It may act as major paracrine effector of normal epithelial cell proliferation. FGF7 interacts with fibroblast growth factor receptor FGFR2 and fibroblast growth factor-binding protein 1 (FGFBP1). Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. FGF7 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 4885233   40 GGAPRRRKLYCATKYHLQLHPSGRVNGSLE-NSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFV 118
Cdd:cd23319   5 GGDVRVRRLFCRTQWYLRIDKRGKVKGTQEmNNSYNILEIRTVAVGIVAIKGVESEYFLAMNKEGKLYGKKVCNEDCNFK 84

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4885233  119 ERIHELGYNTYASRLYrtvsstpgarrqpsAERLW--YVSVNGKGRPRRGFKTRRTQKSSLFLP 180
Cdd:cd23319  85 ELIEENHYNTYASAKW--------------THKGKemFVALNQKGKPMKGKKTKKEHKTSHFLP 134

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 4885233   47 KLYCATKYHLQLHPSGRVNGSL-ENSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERIHELG 125
Cdd:cd23329   8 KLYSRQGYHLQLQADGTIDGTKeEDSSYTLFNLIPVGLRVVAIQGVQTKLYLAMNSEGYLYTSEHFTPECKFKESVFENY 87

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4885233  126 YNTYASRLYrtvsstpgarRQPSAERLWYVSVNGKGRPRRGFKTRRTQKSSLFLPRVL 183
Cdd:cd23329  88 YVTYSSMIY----------RQQQSGRGWYLGLNKEGEIMKGNHVKKNKPAAHFLPKPL 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 4885233   44 RRRKLYC--ATKYHLQLHPSGRVNGSLENSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERI 121
Cdd:cd23316   1 RLRRLYCnvGIGFHIQVLPDGRINGVHNENRYSLLEISPVERGVVSIFGVKSGLFVAMNSKGKLYGSPFFNDECKFKEIL 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4885233  122 HELGYNTYASRLYrtvsstPGArrqpsaerlwYVSVNGKGRPRRGFKTRRTQKSSLFLPRV 182
Cdd:cd23316  81 LPNNYNAYESRKY------PGM----------YIALSKNGKTKKGNRVSPTMTVTHFLPRI 125

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 4885233   47 KLYCATKYHLQLHPSGRVNGSL-ENSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERIHELG 125
Cdd:cd23328   9 RLFSQQGYFLQMHPDGTIDGTKdENSDYTLFNLIPVGLRVVAIQGVKAGLYVAMNGEGYLYSSDVFTPECKFKESVFENY 88

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 4885233  126 YNTYASRLYrtvsstpgarRQPSAERLWYVSVNGKGRPRRGFKTRRTQKSSLFLPRVLD 184
Cdd:cd23328  89 YVIYSSTLY----------RQQESGRAWFLGLNKEGQIMKGNRVKKTKPSSHFVPKPIE 137

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 4885233   46 RKLYCATK-YHLQLHPSGRVNGSLENSAYSI-LEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAECEFVERIHE 123
Cdd:cd23314   3 KRLYCKNGgFFLRIHPDGRVDGVREKSDPHIkLQLQAEERGVVSIKGVCANRYLAMKEDGRLLASKSVTDECFFFERLES 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 4885233  124 LGYNTYASRLYRTvsstpgarrqpsaerlWYVSVNGKGRPRRGFKTRRTQKSSLFLP 180
Cdd:cd23314  83 NNYNTYRSRKYTS----------------WYVALKRTGQYKLGSKTGPGQKAILFLP 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 4885233   44 RRRKLYCA---TKYHLQLHPSGRVNGSLENSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAE-CEFVE 119
Cdd:cd23332   3 RLRHLYTAdeqTQLHLEIREDGTVGGAADQSPYSLLELKAVKPGVVQILGKKTLRFLCMDPDGRLYGSLHYSPEaCSFRE 82

                        90       100       110
                ....*....|....*....|....*....|....*
gi 4885233  120 RIHELGYNTYASRLYRTVSSTPGAR---RQPSAER 151
Cdd:cd23332  83 VVLEDGYNLYQSEAHGLPLTLSPNRaphRDGGAPP 117

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 4885233   44 RRRKLYC-ATKYHLQLHPsGRVNG-SLENSAYSILEITAV-EVGIVAIRGLFSGRYLAMNKRGRLYASEHYSA--ECEFV 118
Cdd:cd23307   1 RSVRLYSrCSKKFVRITG-GRVDArGEKGSPYAKLTIESVgFSGKVRIRGAKSGRYLCFNKKGKLVAKKNGKKdkRCVFE 79

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4885233  119 ERIHELGYNTYASRLYRTvsstpgarrqpsaerlWYVSVNGKGRPRRGFKTRR-TQKSSLFLPR 181
Cdd:cd23307  80 EELTDGYYTRYRSVKNPS----------------WYLGFNRNGRPLKGSKTRKkKQKCFHFLKR 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 4885233   41 GAPRRR-KLYCATK---YHLQLHPSGRVNGSLENSAYSILEITAVEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSAE-C 115
Cdd:cd23333  13 GNPRRLiHLYTSTDrnsYHLQINPDGHVDGTPHQTIYSALLIKSEDAGRVVITGVKSNRYLCMDFRGNIFGSHYFNKEdC 92

                        90       100       110
                ....*....|....*....|....*....|
gi 4885233  116 EFVERIHELGYNTYASRLYRTVSSTPGARR 145
Cdd:cd23333  93 LFQHETLENGYDVYHSPKYNILVSLGGAKQ 122

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 4885233   44 RRRKLYCATK-YHLQLHPSGRVNGSLENS---AYSILEiTAVEVGIVAIRGLFSGRYLAMNKRGRLYA-SEHYSAECEFV 118
Cdd:cd23322  21 RTYQLYSRTSgKHVQVLANKKINAMAEDGdphAKLIVE-TDTFGSRVRIKGAETGYYICMNKKGKLIGkSNGKGKDCVFT 99

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4885233  119 ERIHELGYNTYASRLYRTvsstpgarrqpsaerlWYVSVNGKGRPRRGFKTRRTQKSSLFLPRV 182
Cdd:cd23322 100 EIVLENNYTALQNAKYEG----------------WYMAFTRKGRPRKGSKTRQHQREVHFMKRL 147

ricin B-type lectin domain, beta-trefoil fold, found in Lysinibacillus sphaericus BinA, BinB, and similar proteins; This subfamily includes Lysinibacillus sphaericus binary larvicide subunit BinA (also called 41.9 kDa insecticidal toxin, or larvicidal toxin protein P42) and subunit BinB (including 51.4 kDa insecticidal toxin and 63 kDa toxin crystal protein). They are components of a binary toxin active against Culex and some Aedes mosquito larvae. The individual subunits are not toxic. BinA forms a heterodimer with BinB. BinAB binds to the gastric caecum and posterior midgut of C. quinquefasciatus larvae. Binary toxin internalization into host gut cells requires both proteins. Both BinA and BinB have an N-terminal ricin B-type lectin domain and a C-terminal pore-forming domain. The ricin B-type lectin domain shows a beta-trefoil fold that has barrel and cap subdomains. The cap has 3 carbohydrate-binding modules while the barrel is involved in host cell receptor binding. At neutral pH, the carbohydrate-binding modules are accessible on the toxin surface, but the barrel subdomain is not.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4885233   65 NGSLENSAYSILEITavEVGIVAIRGLFSGRYLAMNKRGRLYASEHYSA-ECEFVERIHELGYNTYASrLYRTVSSTPGA 143
Cdd:cd23429  49 NKSRDNNQQLIFFLL--DDGRVIIADRDNGEVFTVAATYHPIISRVYTGeERQLFRQVGSGDYITSEA-TNYLATQNKDT 125

                        90
                ....*....|....*...
gi 4885233  144 R------RQPSAERLWYV 155
Cdd:cd23429 126 RalapcrAQDSAWRLLYT 143