Nucleoside diphosphate kinases (NDP kinases, NDPks): NDP kinases, responsible for the synthesis of nucleoside triphosphates (NTPs), are involved in numerous regulatory processes associated with proliferation, development, and differentiation. They are vital for DNA/RNA synthesis, cell division, macromolecular metabolism and growth. The enzymes generate NTPs or their deoxy derivatives by terminal (gamma) phosphotransfer from an NTP such as ATP or GTP to any nucleoside diphosphate (NDP) or its deoxy derivative. The sequence of NDPk has been highly conserved through evolution. There is a single histidine residue conserved in all known NDK isozymes, which is involved in the catalytic mechanism. The first confirmed metastasis suppressor gene was the NDP kinase protein encoded by the nm23 gene. Unicellular organisms generally possess only one gene encoding NDP kinase, while most multicellular organisms possess not only an ortholog that provides most of the NDP kinase enzymatic activity but also multiple divergent paralogous genes. The human genome codes for at least nine NDP kinases and can be classified into two groups, Groups I and II, according to their genomic architecture and distinct enzymatic activity. Group I isoforms (A-D) are well-conserved, catalytically active, and share 58-88% identity between each other, while Group II are more divergent, with only NDPk6 shown to be active. NDP kinases exist in two different quaternary structures; all known eukaryotic enzymes are hexamers, while some bacterial enzymes are tetramers, as in Myxococcus. The hexamer can be viewed as trimer of dimers, while tetramers are dimers of dimers, with the dimerization interface conserved.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274  38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQ----------------------------------VWEGYNVV 83
Cdd:cd04413     1 ERTLVIIKPDGVQRGLIGEIISRFERKGLKIVALKMLQlteelaeehyaehkgkpffpelvefmtsgpvvamVLEGENAV 80

                          90       100
                  ....*....|....*....|....*...
gi 1622910274  84 RASRAMIGHTDSAEAAPGTIRGDFSVHI 111
Cdd:cd04413    81 KTVRKLMGATNPADAAPGTIRGDFALSI 108

Nucleoside diphosphate kinase Group I (NDPk_I)-like: NDP kinase domains are present in a large family of structurally and functionally conserved proteins from bacteria to humans that generally catalyze the transfer of gamma-phosphates of a nucleoside triphosphate (NTP) donor onto a nucleoside diphosphate (NDP) acceptor through a phosphohistidine intermediate. The mammalian nm23/NDP kinase gene family can be divided into two distinct groups. The group I genes encode proteins that generally have highly homologous counterparts in other organisms and possess the classic enzymatic activity of a kinase. This group includes vertebrate NDP kinases A-D (Nm23- H1 to -H4), and its counterparts in bacteria, archea and other eukaryotes. NDP kinases exist in two different quaternary structures; all known eukaryotic enzymes are hexamers, while some bacterial enzymes are tetramers, as in Myxococcus. They possess the NDP kinase active site motif (NXXH[G/A]SD) and the nine residues that are most essential for catalysis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274  38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQ----------------------------------VWEGYNVV 83
Cdd:cd04413     1 ERTLVIIKPDGVQRGLIGEIISRFERKGLKIVALKMLQlteelaeehyaehkgkpffpelvefmtsgpvvamVLEGENAV 80

                          90       100
                  ....*....|....*....|....*...
gi 1622910274  84 RASRAMIGHTDSAEAAPGTIRGDFSVHI 111
Cdd:cd04413    81 KTVRKLMGATNPADAAPGTIRGDFALSI 108

Nucleoside diphosphate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274  38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQ----------------------------------VWEGYNVV 83
Cdd:pfam00334   1 ERTLAIIKPDAVQRGLIGEIISRFERKGFKIVALKMLQltreqaeehyaehkgkpffpdlvefmtsgpvvamVLEGENAI 80

                          90       100
                  ....*....|....*....|....*....
gi 1622910274  84 RASRAMIGHTDSAEAAPGTIRGDFSVHIS 112
Cdd:pfam00334  81 SKWRELMGATNPAEAAPGTIRGDFAVSIG 109

Enzymes that catalyze nonsubstrate specific conversions of nucleoside diphosphates to nucleoside triphosphates; These enzymes play important roles in bacterial growth, signal transduction and pathogenicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274   38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQ----------------------------------VWEGYNVV 83
Cdd:smart00562   1 ERTLAIIKPDAVQRGLIGEIISRFERKGFKIVAMKMLQlteeqaeefyaehegkpffndlvefmtsgpvvamVLEGEDAV 80

                           90       100
                   ....*....|....*....|....*...
gi 1622910274   84 RASRAMIGHTDSAEAAPGTIRGDFSVHI 111
Cdd:smart00562  81 KTWRTLMGPTDPREAAPGTIRGDFGLDI 108

Nucleoside diphosphate kinase Group I (NDPk_I)-like: NDP kinase domains are present in a large family of structurally and functionally conserved proteins from bacteria to humans that generally catalyze the transfer of gamma-phosphates of a nucleoside triphosphate (NTP) donor onto a nucleoside diphosphate (NDP) acceptor through a phosphohistidine intermediate. The mammalian nm23/NDP kinase gene family can be divided into two distinct groups. The group I genes encode proteins that generally have highly homologous counterparts in other organisms and possess the classic enzymatic activity of a kinase. This group includes vertebrate NDP kinases A-D (Nm23- H1 to -H4), and its counterparts in bacteria, archea and other eukaryotes. NDP kinases exist in two different quaternary structures; all known eukaryotic enzymes are hexamers, while some bacterial enzymes are tetramers, as in Myxococcus. They possess the NDP kinase active site motif (NXXH[G/A]SD) and the nine residues that are most essential for catalysis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274  38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQ----------------------------------VWEGYNVV 83
Cdd:cd04413     1 ERTLVIIKPDGVQRGLIGEIISRFERKGLKIVALKMLQlteelaeehyaehkgkpffpelvefmtsgpvvamVLEGENAV 80

                          90       100
                  ....*....|....*....|....*...
gi 1622910274  84 RASRAMIGHTDSAEAAPGTIRGDFSVHI 111
Cdd:cd04413    81 KTVRKLMGATNPADAAPGTIRGDFALSI 108

Nucleoside diphosphate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274  38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQ----------------------------------VWEGYNVV 83
Cdd:pfam00334   1 ERTLAIIKPDAVQRGLIGEIISRFERKGFKIVALKMLQltreqaeehyaehkgkpffpdlvefmtsgpvvamVLEGENAI 80

                          90       100
                  ....*....|....*....|....*....
gi 1622910274  84 RASRAMIGHTDSAEAAPGTIRGDFSVHIS 112
Cdd:pfam00334  81 SKWRELMGATNPAEAAPGTIRGDFAVSIG 109

Enzymes that catalyze nonsubstrate specific conversions of nucleoside diphosphates to nucleoside triphosphates; These enzymes play important roles in bacterial growth, signal transduction and pathogenicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274   38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQ----------------------------------VWEGYNVV 83
Cdd:smart00562   1 ERTLAIIKPDAVQRGLIGEIISRFERKGFKIVAMKMLQlteeqaeefyaehegkpffndlvefmtsgpvvamVLEGEDAV 80

                           90       100
                   ....*....|....*....|....*...
gi 1622910274   84 RASRAMIGHTDSAEAAPGTIRGDFSVHI 111
Cdd:smart00562  81 KTWRTLMGPTDPREAAPGTIRGDFGLDI 108

nucleoside diphosphate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274  38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQ----------------------------------VWEGYNVV 83
Cdd:PRK14540    3 ERTFVALKPDAVERKLIGKIIQRFENKGFEIVEMKMLKltremaeeyyeehkgkefyerlinfmtsgrivamVIEGENAI 82

                          90       100
                  ....*....|....*....|....
gi 1622910274  84 RASRAMIGHTDSAEAAPGTIRGDF 107
Cdd:PRK14540   83 STVRKMIGKTNPAEAEPGTIRGDF 106

Nucleoside diphosphate kinases (NDP kinases, NDPks): NDP kinases, responsible for the synthesis of nucleoside triphosphates (NTPs), are involved in numerous regulatory processes associated with proliferation, development, and differentiation. They are vital for DNA/RNA synthesis, cell division, macromolecular metabolism and growth. The enzymes generate NTPs or their deoxy derivatives by terminal (gamma) phosphotransfer from an NTP such as ATP or GTP to any nucleoside diphosphate (NDP) or its deoxy derivative. The sequence of NDPk has been highly conserved through evolution. There is a single histidine residue conserved in all known NDK isozymes, which is involved in the catalytic mechanism. The first confirmed metastasis suppressor gene was the NDP kinase protein encoded by the nm23 gene. Unicellular organisms generally possess only one gene encoding NDP kinase, while most multicellular organisms possess not only an ortholog that provides most of the NDP kinase enzymatic activity but also multiple divergent paralogous genes. The human genome codes for at least nine NDP kinases and can be classified into two groups, Groups I and II, according to their genomic architecture and distinct enzymatic activity. Group I isoforms (A-D) are well-conserved, catalytically active, and share 58-88% identity between each other, while Group II are more divergent, with only NDPk6 shown to be active. NDP kinases exist in two different quaternary structures; all known eukaryotic enzymes are hexamers, while some bacterial enzymes are tetramers, as in Myxococcus. The hexamer can be viewed as trimer of dimers, while tetramers are dimers of dimers, with the dimerization interface conserved.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274  38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQ----------------------------------VWEGYNVV 83
Cdd:cd00595     1 ERTLALIKPDAVAEGLLGEIIMRIEDAGFEIVAMKELHlteeqaeefyvehkgrpffpdlvqfmssgpvvamILEKDNAV 80

                          90       100
                  ....*....|....*....|....*..
gi 1622910274  84 RASRAMIGHTDSAEA---APGTIRGDF 107
Cdd:cd00595    81 GEWREMLGPTNPEIArhlAPGSLRADF 107

nucleoside diphosphate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274  38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQ------------------------------------------ 75
Cdd:PRK14544    4 ERTLVILKPDAVKRGLVGEIISRFEKAGLKIVAMKMVKatpeqierfypsseewyrsvgnkllkayqelgidprarlgtd 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622910274  76 -------------------------VWEGYNVVRASRAMIGHTDSAEAAPGTIRGDFSV 109
Cdd:PRK14544   84 dpvevgkkvkeslvkymtsgpivamVLKGNRAVEVVRKLVGPTSPHKAPPGTIRGDYSI 142

nucleoside diphosphate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274  38 ERTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKMLQV----------------------------------WEGYNVV 83
Cdd:PRK14542    2 SRTFIMIKPDGVKNKHVGNILQRIEKEGFKILGLKYLKLsledakqfykvhsarpfyndlcnymssgpivaaaLERDNAV 81

                          90       100
                  ....*....|....*....|....*
gi 1622910274  84 RASRAMIGHTDSAEAAPGTIRGDFS 108
Cdd:PRK14542   82 LHWREVIGATDPKEAAAGTIRALYA 106

Nucleoside diphosphate kinase 7 domain B (NDPk7B): The nm23-H7 class of nucleoside diphosphate kinase (NDPk7) consists of an N-terminal DM10 domain and two functional catalytic NDPk modules, NDPk7A and NDPk7B. The function of the DM10 domain, which also occurs in multiple copies in other proteins, is unknown. NDPk7 is predominantly expressed in testes, although appreciable amount are also found in liver, heart, brain, ovary, small intestine and spleen. The nm23-H7 gene is located in or near the hereditary prostrate cancer susceptibility locus. Nm23-H7 may be involved in the development of colon and gastric carcinoma, the latter possibly in a type-specific manner.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622910274  39 RTLVAVKPDGVQRRLVGDVIQRFERRGFTLVGMKM-----------LQVWEGY------------------------NVV 83
Cdd:cd04412     2 CTVCIIKPHAVSHGLLGEILQQILDEGFEITALQMfnltranaeefLEVYKGVvpelpamvdeltsgpcialeiageNAV 81

                          90       100
                  ....*....|....*....|....*....
gi 1622910274  84 RASRAMIGHTDSAEA---APGTIRGDFSV 109
Cdd:cd04412    82 KTFREFCGPFDPEIAkqlRPNTLRARYGK 110