C-terminal putative kinase domain of FAM20 (family with sequence similarity 20), Drosophila Four-jointed (Fj), and related proteins; Drosophila Fj is a Golgi kinase that phosphorylates Ser or Thr residues within extracellular cadherin domains of a transmembrane receptor Fat and its ligand, Dachsous (Ds). The Fat signaling pathway regulates growth, gene expression, and planar cell polarity (PCP). Defects from mutation in the Drosophila fj gene include loss of the intermediate leg joint, and a PCP defect in the eye. Fjx1, the murine homologue of Fj, has been shown to be involved in both the Fat and Hippo signaling pathways, these two pathways intersect at multiple points. The Hippo pathway is important in organ size control and in cancer. FAM20B is a xylose kinase that may regulate the number of glycosaminoglycan chains by phosphorylating the xylose residue in the glycosaminoglycan-protein linkage region of proteoglycans. This domain has homology to a kinase-active site, mutation of three conserved Asp residues at the Drosophila Fj putative active site abolished its ability to phosphorylate Ft and Ds cadherin domains. FAM20A may participate in enamel development and gingival homeostasis, FAM20B in proteoglycan production, and FAM20C in bone development. FAM20C, also called Dentin Matrix Protein 4, is abundant in the dentin matrix, and may participate in the differentiation of mesenchymal precursor cells into functional odontoblast-like cells. Mutations in FAM20C are associated with lethal Osteosclerotic Bone Dysplasia (Raine Syndrome), and mutations in FAM20A with Amelogenesis imperfecta (AI) and Gingival Hyperplasia Syndrome. This model includes the FAM20_C domain family, previously known as DUF1193; FAM20_C appears to be homologous to the catalytic domain of the phosphoinositide 3-kinase (PI3K)-like family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668590 349 FVSPANNICFYGECSYYCSTEHALCGKPDQIEGSLAAFLPDLSLAKRKTWRNPWRRSYHKRKKAEWEVDPDYCEEVKQTP 428
Cdd:cd10471     1 FISPANNICFYGECSYYCSTEHALCGKPDQIEGSLAAFLPDLSLAKRKTWRNPWRRSYHKRKKAEWEVDPDYCEEVKQTP 80

                          90       100
                  ....*....|....*....|..
gi 1958668590 429 PYDSGHRILDIMDMTVFDFLMG 450
Cdd:cd10471    81 PYDSGTRILDIMDMTVFDFLMG 102

C-terminal putative kinase domain of FAM20C (also known as Dentin Matrix Protein 4, DMP4); Mouse DMP4 is abundant in the dentin matrix, and is expressed in high levels in odontoblasts. These latter cells synthesize various nucleators or inhibitors of mineralization. The in vivo role of DMP4 in dentinogenesis is unclear. However, gain- and loss-of-function experiments suggest that it participates in the differentiation of mesenchymal precursor cells into functional odontoblast-like cells. In addition to this domain, DMP4 contains a Greek key calcium-binding domain. Human FAM20C participates in bone development; mutations in FAM20C are associated with lethal Osteosclerotic Bone Dysplasia (Raine Syndrome), an autosomal recessive disorder in which affected individuals die within days or weeks of birth, usually due to thoratic malformation resulting in respiratory failure. The C-terminal domain of FAM20C is a putative kinase domain, based on mutagenesis of the C-terminal domain of Drosophila Four-Jointed, a related Golgi kinase. This subfamily belongs to the FAM20_C (also known as DUF1193) domain family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668590 349 FVSPANNICFYGECSYYCSTEHALCGKPDQIEGSLAAFLPDLSLAKRKTWRNPWRRSYHKRKKAEWEVDPDYCEEVKQTP 428
Cdd:cd10471     1 FISPANNICFYGECSYYCSTEHALCGKPDQIEGSLAAFLPDLSLAKRKTWRNPWRRSYHKRKKAEWEVDPDYCEEVKQTP 80

                          90       100
                  ....*....|....*....|..
gi 1958668590 429 PYDSGHRILDIMDMTVFDFLMG 450
Cdd:cd10471    81 PYDSGTRILDIMDMTVFDFLMG 102

C-terminal putative kinase domain of FAM20C (also known as Dentin Matrix Protein 4, DMP4); Mouse DMP4 is abundant in the dentin matrix, and is expressed in high levels in odontoblasts. These latter cells synthesize various nucleators or inhibitors of mineralization. The in vivo role of DMP4 in dentinogenesis is unclear. However, gain- and loss-of-function experiments suggest that it participates in the differentiation of mesenchymal precursor cells into functional odontoblast-like cells. In addition to this domain, DMP4 contains a Greek key calcium-binding domain. Human FAM20C participates in bone development; mutations in FAM20C are associated with lethal Osteosclerotic Bone Dysplasia (Raine Syndrome), an autosomal recessive disorder in which affected individuals die within days or weeks of birth, usually due to thoratic malformation resulting in respiratory failure. The C-terminal domain of FAM20C is a putative kinase domain, based on mutagenesis of the C-terminal domain of Drosophila Four-Jointed, a related Golgi kinase. This subfamily belongs to the FAM20_C (also known as DUF1193) domain family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668590 349 FVSPANNICFYGECSYYCSTEHALCGKPDQIEGSLAAFLPDLSLAKRKTWRNPWRRSYHKRKKAEWEVDPDYCEEVKQTP 428
Cdd:cd10471     1 FISPANNICFYGECSYYCSTEHALCGKPDQIEGSLAAFLPDLSLAKRKTWRNPWRRSYHKRKKAEWEVDPDYCEEVKQTP 80

                          90       100
                  ....*....|....*....|..
gi 1958668590 429 PYDSGHRILDIMDMTVFDFLMG 450
Cdd:cd10471    81 PYDSGTRILDIMDMTVFDFLMG 102

C-terminal putative kinase domain of FAM20 (family with sequence similarity 20) proteins; This family contains the C-terminal domain of FAM20A, -B, -C and related proteins. FAM20A may participate in enamel development and gingival homeostasis, FAM20B in proteoglycan production, and FAM20C in bone development. FAM20B is a xylose kinase that may regulate the number of glycosaminoglycan chains by phosphorylating the xylose residue in the glycosaminoglycan-protein linkage region of proteoglycans. FAM20C, also called Dentin Matrix Protein 4, is abundant in the dentin matrix, and may participate in the differentiation of mesenchymal precursor cells into functional odontoblast-like cells. Mutations in FAM20C are associated with lethal Osteosclerotic Bone Dysplasia (Raine Syndrome), and mutations in FAM20A with Amelogenesis imperfecta (AI) and Gingival Hyperplasia Syndrome. The C-terminal domains of members of this family are putative kinase domains, based on mutagenesis of the C-terminal domain of Drosophila Four-Jointed, a related Golgi kinase. This domain family is also known as DUF1193.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668590 349 FVSPANNICFYGECsYYCSTEHALCGKPDQIEGSLAAFLPDLSLAKrkTWRNPWRRSYHKRKKAEWEVDPDYCEEVKQTP 428
Cdd:cd10314     1 FISPANNTCFYGKC-YYCKTEEAVCGNPDLLEGSLTAFLPDLSLLK--KWRHPWRRTYHKRKKAEWEVDPDYCDKVKKTP 77

                          90       100
                  ....*....|....*....|....*..
gi 1958668590 429 PYDSGHRILDIMDMTVFDFLMGLGSTH 455
Cdd:cd10314    78 PYDSGRRLLDLIDMAIFDFLIGNMDRH 104

C-terminal putative kinase domain of FAM20A; Human FAM20A may play a fundamental role in enamel development and gingival homeostasis as mutations in FAM20A may underlie the pathogenesis of the autosomal recessive Amelogenesis imperfecta (AI) and Gingival Hyperplasia Syndrome. It is expressed in ameloblasts and gingivae. AI refers to a heterogeneous group of disorders of biomineralization caused by a lack of normal enamel formation. Mouse FAM20A is a secreted protein and the gene encoding it is differentially expressed in hematopoietic cells undergoing myeloid differentiation. This protein has also been associated with growth disorder in mice. The C-terminal domain of FAM20A is a putative kinase domain, based on mutagenesis of the C-terminal domain of Drosophila Four-Jointed, a related Golgi kinase. This subfamily belongs to the FAM20_C (also known as DUF1193) domain family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668590 349 FVSPANNICFYGECSYYCSTEHALCGKPDQIEGSLAAFLPDLSLAKRKTWRNPWRRSYHKRKKAEWEVDPDYCEEVKQTP 428
Cdd:cd10469     1 FNSPASNVCFFAKCPYMCKTEYAVCGNPHLLEGSLSAFLPSLNLAPRLSIPNPWIRSYTFAGKEEWEVNPLYCDTVKEIY 80

                          90       100
                  ....*....|....*....|..
gi 1958668590 429 PYDSGHRILDIMDMTVFDFLMG 450
Cdd:cd10469    81 PYNSGNRLLNIIDMAIFDFLIG 102