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 189230264 159 SYTVAIIKPDAVAHGKTDEIIMKIQESGFEILANEESTMTESEAREFYQHREGEEKFQELIQFMSSGPCHVLIISKsded 238
Cdd:cd00595    1 ERTLALIKPDAVAEGLLGEIIMRIEDAGFEIVAMKELHLTEEQAEEFYVEHKGRPFFPDLVQFMSSGPVVAMILEK---- 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 189230264 239 EDVIPAWREFIGPTDVEIAKKEKPESLRAQYGTEVLYNAVHGSNDREQASRELAFFF 295
Cdd:cd00595   77 DNAVGEWREMLGPTNPEIARHLAPGSLRADFGTDVLRNAVHGSDSVESAAREIAFFF 133

TRX domain, TRX and NDP-kinase (NDPK) fusion protein family; most members of this group are fusion proteins which contain one redox active TRX domain containing a CXXC motif and three NDPK domains, and are characterized as intermediate chains (ICs) of axonemal outer arm dynein. Dyneins are molecular motors that generate force against microtubules to produce cellular movement, and are divided into two classes: axonemal and cytoplasmic. They are supramolecular complexes consisting of three protein groups classified according to size: dynein heavy, intermediate and light chains. Axonemal dyneins form two structures, the inner and outer arms, which are attached to doublet microtubules throughout the cilia and flagella. The human homolog is the sperm-specific Sptrx-2, presumed to be a component of the human sperm axoneme architecture. Included in this group is another human protein, TRX-like protein 2, a smaller fusion protein containing one TRX and one NDPK domain, which is also associated with microtubular structures. The other members of this group are hypothetical insect proteins containing a TRX domain and outer arm dynein light chains (14 and 16kDa) of Chlamydomonas reinhardtii. Using standard assays, the fusion proteins have shown no TRX enzymatic activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264  11 QIALSNQEQWEEALSTKGLLVVDVYQAWCGPCKPTVSLFRKIKNELGDDLLHFAVAESDTIDSLMKYRGKCEPTFLLLAG 90
Cdd:cd02948    1 QVEINNQEEWEELLSNKGLTVVDVYQEWCGPCKAVVSLFKKIKNELGDDLLHFATAEADTIDTLKRYRGKCEPTFLFYKN 80

                         90       100
                 ....*....|....*....|..
gi 189230264  91 GELVAVVRGANGPLLQKTIIEQ 112
Cdd:cd02948   81 GELVAVIRGANAPLLNKTITEL 102

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 189230264 159 SYTVAIIKPDAVAHGKTDEIIMKIQESGFEILANEESTMTESEAREFYQHREGEEKFQELIQFMSSGPCHVLIISKsded 238
Cdd:cd00595    1 ERTLALIKPDAVAEGLLGEIIMRIEDAGFEIVAMKELHLTEEQAEEFYVEHKGRPFFPDLVQFMSSGPVVAMILEK---- 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 189230264 239 EDVIPAWREFIGPTDVEIAKKEKPESLRAQYGTEVLYNAVHGSNDREQASRELAFFF 295
Cdd:cd00595   77 DNAVGEWREMLGPTNPEIARHLAPGSLRADFGTDVLRNAVHGSDSVESAAREIAFFF 133

TRX domain, TRX and NDP-kinase (NDPK) fusion protein family; most members of this group are fusion proteins which contain one redox active TRX domain containing a CXXC motif and three NDPK domains, and are characterized as intermediate chains (ICs) of axonemal outer arm dynein. Dyneins are molecular motors that generate force against microtubules to produce cellular movement, and are divided into two classes: axonemal and cytoplasmic. They are supramolecular complexes consisting of three protein groups classified according to size: dynein heavy, intermediate and light chains. Axonemal dyneins form two structures, the inner and outer arms, which are attached to doublet microtubules throughout the cilia and flagella. The human homolog is the sperm-specific Sptrx-2, presumed to be a component of the human sperm axoneme architecture. Included in this group is another human protein, TRX-like protein 2, a smaller fusion protein containing one TRX and one NDPK domain, which is also associated with microtubular structures. The other members of this group are hypothetical insect proteins containing a TRX domain and outer arm dynein light chains (14 and 16kDa) of Chlamydomonas reinhardtii. Using standard assays, the fusion proteins have shown no TRX enzymatic activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264  11 QIALSNQEQWEEALSTKGLLVVDVYQAWCGPCKPTVSLFRKIKNELGDDLLHFAVAESDTIDSLMKYRGKCEPTFLLLAG 90
Cdd:cd02948    1 QVEINNQEEWEELLSNKGLTVVDVYQEWCGPCKAVVSLFKKIKNELGDDLLHFATAEADTIDTLKRYRGKCEPTFLFYKN 80

                         90       100
                 ....*....|....*....|..
gi 189230264  91 GELVAVVRGANGPLLQKTIIEQ 112
Cdd:cd02948   81 GELVAVIRGANAPLLNKTITEL 102

Nucleoside diphosphate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264  449 EHTLATIKPDALEEHR-DEILEQIQGTGFTISQIKEANLSREMAEEFYKEHKGKPFFEQLVNYMCRGPCLMMILSKENAV 527
Cdd:pfam00334   1 ERTLAIIKPDAVQRGLiGEIISRFERKGFKIVALKMLQLTREQAEEHYAEHKGKPFFPDLVEFMTSGPVVAMVLEGENAI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 189230264  528 QEWRSLMGPTDPTEAQkvsPDSLRAKFAKSILQNAVHGSSNGEHAMEKMKFIFGDIDL 585
Cdd:pfam00334  81 SKWRELMGATNPAEAA---PGTIRGDFAVSIGRNAVHGSDSPESAEREIALFFPEEEI 135

Nucleoside diphosphate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264  161 TVAIIKPDAVAHGKTDEIIMKIQESGFEILANEESTMTESEAREFYQHREGEEKFQELIQFMSSGPCHVLIISKsdedED 240
Cdd:pfam00334   3 TLAIIKPDAVQRGLIGEIISRFERKGFKIVALKMLQLTREQAEEHYAEHKGKPFFPDLVEFMTSGPVVAMVLEG----EN 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264  241 VIPAWREFIGPTDVEIAkkeKPESLRAQYGTEVLYNAVHGSNDREQASRELAFFFPNFKI 300
Cdd:pfam00334  79 AISKWRELMGATNPAEA---APGTIRGDFAVSIGRNAVHGSDSPESAEREIALFFPEEEI 135

Nucleoside diphosphate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264  314 ERTLALIRPD-ILKDKKDEILQSIRDAGFSIAMQKEVMLTEQQVQEFYIEHIDKDYYPALLKQMTSGPVLALALVKDHAV 392
Cdd:pfam00334   1 ERTLAIIKPDaVQRGLIGEIISRFERKGFKIVALKMLQLTREQAEEHYAEHKGKPFFPDLVEFMTSGPVVAMVLEGENAI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 189230264  393 DHWRNMLGPASLRQAlseAPDSLRAQFApNDSDINQLHGSSTPEEAKKELNFFFP 447
Cdd:pfam00334  81 SKWRELMGATNPAEA---APGTIRGDFA-VSIGRNAVHGSDSPESAEREIALFFP 131

mulitfunctional nucleoside diphosphate kinase/apyrimidinic endonuclease/3'-; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264 448 VEHTLATIKPDALEehRD---EILEQIQGTGFTISQIKEANLSREMAEEFYKEHKGKPFFEQLVNYMCRGPCLMMILSKE 524
Cdd:PRK00668   1 MERTFSIIKPDAVQ--RGligEIISRFEKKGLKIVALKMMQLSRELAEGHYAEHKEKPFFGELVEFMTSGPVVVMVLEGE 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 189230264 525 NAVQEWRSLMGPTDPTEAQkvsPDSLRAKFAKSILQNAVHGSSNGEHAMEKMKFIFGD 582
Cdd:PRK00668  79 NAIAKVRELMGATNPAEAA---PGTIRGDFALSIGENVVHGSDSPESAAREIALFFSE 133

nucleoside diphosphate kinase family protein

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264 310 SVRPERTLALIRPD-ILKDKKDEILQSIRDAGFSIAMQKEVMLTEQQVQEFYIEHIDKDYYPALLKQMTSGPVLALALVK 388
Cdd:PLN02931  26 ASEEERTLAMIKPDgLSGNYTERIKEVILESGFSIVKEMTTQLDEDRASLFYAEHSSRSFFPSLVKYMTSGPVLVMVLEK 105

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 189230264 389 DHAVDHWRNMLGPASLRQALSEAPDSLRAqFAPNDSDINQLHGSSTPEEAKKELNFFF-PVEHTLATIKPDAL 460
Cdd:PLN02931 106 ENAVSDWRTLIGPTDARKAKISHPNSIRA-MCGLDSEKNCVHGSDSPESAEREISFFFgDVSSGDVASQHDEL 177

Nucleoside diphosphate kinase [Nucleotide transport and metabolism]; Nucleoside diphosphate kinase is part of the Pathway/BioSystem: Pyrimidine biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264 314 ERTLALIRPDILKDKK-DEILQSIRDAGFSIAMQKEVMLTEQQVQEFYIEHIDKDYYPALLKQMTSGPVLALALVKDHAV 392
Cdd:COG0105    3 ERTLVIIKPDAVQRGLiGEIISRFERKGLKIVALKMLQLTREQAEEHYAEHKGKPFFGELVEFMTSGPVVAMVLEGENAV 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 189230264 393 DHWRNMLGPASLRQAlseAPDSLRAQFApNDSDINQLHGSSTPEEAKKELNFFFP 447
Cdd:COG0105   83 AVVRKLMGATNPAEA---APGTIRGDFA-LSIGENAVHGSDSPESAEREIALFFS 133

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264   12 IALSNQEQWEEAL-STKGLLVVDVYQAWCGPCKPTVSLFRKIKNELGDDLLhFAVAESDTIDSL-MKYRGKCEPTFLLLA 89
Cdd:pfam00085   2 VVVLTDANFDEVVqKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVV-FAKVDVDENPDLaSKYGVRGYPTLIFFK 80

                          90
                  ....*....|...
gi 189230264   90 GGELVAVVRGANG 102
Cdd:pfam00085  81 NGQPVDDYVGARP 93

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264  14 LSNQEQWEEALSTKGLLVVDVYQAWCGPCKPTVSLFRKIKNELGDdlLHFAVAESDTIDSLM-KYRGKCEPTFLLLAGGE 92
Cdd:PTZ00051   5 VTSQAEFESTLSQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTK--MVFVKVDVDELSEVAeKENITSMPTFKVFKNGS 82

                         90
                 ....*....|....*.
gi 189230264  93 LVAVVRGANGPLLQKT 108
Cdd:PTZ00051  83 VVDTLLGANDEALKQL 98

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 189230264 159 SYTVAIIKPDAVAHGKTDEIIMKIQESGFEILANEESTMTESEAREFYQHREGEEKFQELIQFMSSGPCHVLIISKsded 238
Cdd:cd00595    1 ERTLALIKPDAVAEGLLGEIIMRIEDAGFEIVAMKELHLTEEQAEEFYVEHKGRPFFPDLVQFMSSGPVVAMILEK---- 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 189230264 239 EDVIPAWREFIGPTDVEIAKKEKPESLRAQYGTEVLYNAVHGSNDREQASRELAFFF 295
Cdd:cd00595   77 DNAVGEWREMLGPTNPEIARHLAPGSLRADFGTDVLRNAVHGSDSVESAAREIAFFF 133

NDP kinase domain of thioredoxin domain-containing proteins (TXNDC3 and TXNDC6): Txl-2 (TXNDC6) and Sptrx-2 (TXNDC3) are fusion proteins of Group II N-terminal thioredoxin domains followed by one or three NDP kinase domains, respectively. Sptrx-2, which has a tissue specific distribution in human testis, has been considered as a member of the nm23 family (nm23-H8) and exhibits a high homology with sea urchin IC1 (intermediate chain-1) protein, a component of the sperm axonemal outer dynein arm complex. Txl-2 is mainly represented in close association with microtubules within tissues with cilia and flagella such as seminiferous epithelium (spermatids) and lung airway epithelium, suggesting possible role in control of microtubule stability and maintenance.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264 314 ERTLALIRPDILKDKKDEILQSIRDAGFSIAMQKEVMLTEQQVQEFYIEHIDKDYYPALLKQMTSGPVLALALVKDHAVD 393
Cdd:cd04416    1 EYTLALIKPDAVAEKKDEILEKIKEAGFEILAQKEMVLTEEQAREFYKEHEEEDYFEDLVEFMTSGPSLILVLSKENAVE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 189230264 394 HWRNMLGPASLRQALSEAPDSLRAQFApNDSDINQLHGSSTPEEAKKELNFFF 446
Cdd:cd04416   81 EWRELMGPTDPEEAKEEKPDSLRAQFA-RDHLSNAVHGSSSAEEAEKEIDFFF 132

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 189230264 314 ERTLALIRPDIL-KDKKDEILQSIRDAGFSIAMQKEVMLTEQQVQEFYIEHIDKDYYPALLKQMTSGPVLALALVKDHAV 392
Cdd:cd00595    1 ERTLALIKPDAVaEGLLGEIIMRIEDAGFEIVAMKELHLTEEQAEEFYVEHKGRPFFPDLVQFMSSGPVVAMILEKDNAV 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 189230264 393 DHWRNMLGPASLRQALSEAPDSLRAQFAPNDsDINQLHGSSTPEEAKKELNFFF 446
Cdd:cd00595   81 GEWREMLGPTNPEIARHLAPGSLRADFGTDV-LRNAVHGSDSVESAAREIAFFF 133

Nucleoside diphosphate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264  449 EHTLATIKPDALEEHR-DEILEQIQGTGFTISQIKEANLSREMAEEFYKEHKGKPFFEQLVNYMCRGPCLMMILSKENAV 527
Cdd:pfam00334   1 ERTLAIIKPDAVQRGLiGEIISRFERKGFKIVALKMLQLTREQAEEHYAEHKGKPFFPDLVEFMTSGPVVAMVLEGENAI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 189230264  528 QEWRSLMGPTDPTEAQkvsPDSLRAKFAKSILQNAVHGSSNGEHAMEKMKFIFGDIDL 585
Cdd:pfam00334  81 SKWRELMGATNPAEAA---PGTIRGDFAVSIGRNAVHGSDSPESAEREIALFFPEEEI 135

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 189230264 449 EHTLATIKPDALEEHR-DEILEQIQGTGFTISQIKEANLSREMAEEFYKEHKGKPFFEQLVNYMCRGPCLMMILSKENAV 527
Cdd:cd00595    1 ERTLALIKPDAVAEGLlGEIIMRIEDAGFEIVAMKELHLTEEQAEEFYVEHKGRPFFPDLVQFMSSGPVVAMILEKDNAV 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 189230264 528 QEWRSLMGPTDPTEAQKVSPDSLRAKFAKSILQNAVHGSSNGEHAMEKMKFIF 580
Cdd:cd00595   81 GEWREMLGPTNPEIARHLAPGSLRADFGTDVLRNAVHGSDSVESAAREIAFFF 133

Nucleoside diphosphate kinase [Nucleotide transport and metabolism]; Nucleoside diphosphate kinase is part of the Pathway/BioSystem: Pyrimidine biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264 448 VEHTLATIKPDALEEHR-DEILEQIQGTGFTISQIKEANLSREMAEEFYKEHKGKPFFEQLVNYMCRGPCLMMILSKENA 526
Cdd:COG0105    2 MERTLVIIKPDAVQRGLiGEIISRFERKGLKIVALKMLQLTREQAEEHYAEHKGKPFFGELVEFMTSGPVVAMVLEGENA 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 189230264 527 VQEWRSLMGPTDPTEAQkvsPDSLRAKFAKSILQNAVHGSSNGEHAMEKMKFIFGDIDL 585
Cdd:COG0105   82 VAVVRKLMGATNPAEAA---PGTIRGDFALSIGENAVHGSDSPESAEREIALFFSEEEI 137

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 189230264   314 ERTLALIRPDILKD-KKDEILQSIRDAGFSIAMQKEVMLTEQQVQEFYIEHIDKDYYPALLKQMTSGPVLALALVKDHAV 392
Cdd:smart00562   1 ERTLAIIKPDAVQRgLIGEIISRFERKGFKIVAMKMLQLTEEQAEEFYAEHEGKPFFNDLVEFMTSGPVVAMVLEGEDAV 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 189230264   393 DHWRNMLGPaslRQALSEAPDSLRAQFApNDSDINQLHGSSTPEEAKKELNFFFP 447
Cdd:smart00562  81 KTWRTLMGP---TDPREAAPGTIRGDFG-LDIGRNAVHGSDSPESAEREIALFFP 131

Nucleoside diphosphate kinase homolog 5 (NDP kinase homolog 5, NDPk5, NM23-H5; Inhibitor of p53-induced apoptosis-beta, IPIA-beta): In human, mRNA for NDPk5 is almost exclusively found in testis, especially in the flagella of spermatids and spermatozoa, in association with axoneme microtubules, and may play a role in spermatogenesis by increasing the ability of late-stage spermatids to eliminate reactive oxygen species. It belongs to the nm23 Group II genes and appears to differ from the other human NDPks in that it lacks two important catalytic site residues, and thus does not appear to possess NDP kinase activity. NDPk5 confers protection from cell death by Bax and alters the cellular levels of several antioxidant enzymes, including glutathione peroxidase 5 (Gpx5).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264 449 EHTLATIKPDALEeHRDEILEQIQGTGFTISQIKEANLSREMAEEFYKEHKGKPFFEQLVNYMCRGPCLMMILSKENAVQ 528
Cdd:cd04418    1 ERTLAIIKPDAVH-KAEEIEDIILESGFTIVQKRKLQLSPEQCSDFYAEHYGKMFFPHLVAYMSSGPIVAMVLARHNAIS 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 189230264 529 EWRSLMGPTDPTEAQKVSPDSLRAKFAKSILQNAVHGSSNGEHAMEKMKFIF 580
Cdd:cd04418   80 YWKELLGPTNSLKAKETHPDSLRAIYGTDDLRNAVHGSDSFSSAEREIRFMF 131

Nucleoside diphosphate kinase homolog 5 (NDP kinase homolog 5, NDPk5, NM23-H5; Inhibitor of p53-induced apoptosis-beta, IPIA-beta): In human, mRNA for NDPk5 is almost exclusively found in testis, especially in the flagella of spermatids and spermatozoa, in association with axoneme microtubules, and may play a role in spermatogenesis by increasing the ability of late-stage spermatids to eliminate reactive oxygen species. It belongs to the nm23 Group II genes and appears to differ from the other human NDPks in that it lacks two important catalytic site residues, and thus does not appear to possess NDP kinase activity. NDPk5 confers protection from cell death by Bax and alters the cellular levels of several antioxidant enzymes, including glutathione peroxidase 5 (Gpx5).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264 314 ERTLALIRPDILkDKKDEILQSIRDAGFSIAMQKEVMLTEQQVQEFYIEHIDKDYYPALLKQMTSGPVLALALVKDHAVD 393
Cdd:cd04418    1 ERTLAIIKPDAV-HKAEEIEDIILESGFTIVQKRKLQLSPEQCSDFYAEHYGKMFFPHLVAYMSSGPIVAMVLARHNAIS 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 189230264 394 HWRNMLGPASLRQALSEAPDSLRAQFAPNDSDiNQLHGSSTPEEAKKELNFFFP 447
Cdd:cd04418   80 YWKELLGPTNSLKAKETHPDSLRAIYGTDDLR-NAVHGSDSFSSAEREIRFMFP 132

Nucleoside diphosphate kinase 6 (NDP kinase 6, NDPk6, NM23-H6; NME6; Inhibitor of p53-induced apoptosis-alpha, IPIA-alpha): The nm23-H6 gene encoding NDPk6 is expressed mainly in mitochondria, but also found at a lower level in most tissues. NDPk6 has all nine residues considered crucial for enzyme structure and activity, and has been found to have NDP kinase activity. It may play a role in cell growth and cell cycle progression. The nm23-H6 gene locus has been implicated in a variety of malignant tumors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264 161 TVAIIKPDAVAHGKTDEIIM-KIQESGFEILANEESTMTESEAREFYQHREGEEKFQELIQFMSSGPCHVLIISKsdedE 239
Cdd:cd04414    3 TLALIKPDAVAHPLALEAVRqLILSNGFTIVRKKELRWTTEDAERFYAEHKGKFFYDRLVSFMTSGPSWALILAH----E 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 189230264 240 DVIPAWREFIGPTDVEIAKKEKPESLRAQYGTEVLYNAVHGSNDREQASRELAFFFP 296
Cdd:cd04414   79 NAIKTWRALMGPTKVFRARASAPDSIRGLYGLTDTRNATHGSDSPASAQREIALFFP 135

Nucleoside diphosphate kinase 7 domain A (NDPk7A): 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 189230264 314 ERTLALIRPDILKdKKDEILQSIRDAGFSIAMQKEVMLTEQQVQEFYIEHIDKDYYPALLKQMTSGPVLALALVKDHAVD 393
Cdd:cd04415    1 EKTLALIKPDAYS-KIGKIIQIIEDAGFTITKAKMTKLSRKEAQDFYAEHQSKPFYNELVQFMTSGPIVAMELVGDDAIS 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 189230264 394 HWRNMLGPASLRQALSEAPDSLRAQFApNDSDINQLHGSSTPEEAKKELNFFF 446
Cdd:cd04415   80 EWRKLLGPTNSSVARSDAPNSIRALFG-TDGTRNAAHGSDSVASAARELEFFF 131

Nucleoside diphosphate kinase 6 (NDP kinase 6, NDPk6, NM23-H6; NME6; Inhibitor of p53-induced apoptosis-alpha, IPIA-alpha): The nm23-H6 gene encoding NDPk6 is expressed mainly in mitochondria, but also found at a lower level in most tissues. NDPk6 has all nine residues considered crucial for enzyme structure and activity, and has been found to have NDP kinase activity. It may play a role in cell growth and cell cycle progression. The nm23-H6 gene locus has been implicated in a variety of malignant tumors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 189230264 314 ERTLALIRPDILK--DKKDEILQSIRDAGFSIAMQKEVMLTEQQVQEFYIEHIDKDYYPALLKQMTSGPVLALALVKDHA 391
Cdd:cd04414    1 QLTLALIKPDAVAhpLALEAVRQLILSNGFTIVRKKELRWTTEDAERFYAEHKGKFFYDRLVSFMTSGPSWALILAHENA 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 189230264 392 VDHWRNMLGPASLRQALSEAPDSLRAQFAPNDSDiNQLHGSSTPEEAKKELNFFFP 447
Cdd:cd04414   81 IKTWRALMGPTKVFRARASAPDSIRGLYGLTDTR-NATHGSDSPASAQREIALFFP 135