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.

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gi 817477401  20 QLTLALIKPDAVAHPLILEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHE 72
Cdd:cd04414    1 QLTLALIKPDAVAHPLALEAVRQLILSNGFTIVRKKELRWTTEDAERFYAEHK 53

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.

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gi 817477401  20 QLTLALIKPDAVAHPLILEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHE 72
Cdd:cd04414    1 QLTLALIKPDAVAHPLALEAVRQLILSNGFTIVRKKELRWTTEDAERFYAEHK 53

Nucleoside diphosphate kinase;

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gi 817477401   22 TLALIKPDAVAHPLIlEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHE 72
Cdd:pfam00334   3 TLAIIKPDAVQRGLI-GEIISRFERKGFKIVALKMLQLTREQAEEHYAEHK 52

nucleoside diphosphate kinase; Provisional

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gi 817477401  19 LQLTLALIKPDAVAHPLILEAVhQQILSNKFLIVRMRELLWRKEDCQRFYREHE 72
Cdd:PRK14540   2 KERTFVALKPDAVERKLIGKII-QRFENKGFEIVEMKMLKLTREMAEEYYEEHK 54

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.

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gi 817477401  20 QLTLALIKPDAVAHPLILEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHE 72
Cdd:cd04414    1 QLTLALIKPDAVAHPLALEAVRQLILSNGFTIVRKKELRWTTEDAERFYAEHK 53

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

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gi 817477401    20 QLTLALIKPDAVAHPLILEAVHQqILSNKFLIVRMRELLWRKEDCQRFYREHE 72
Cdd:smart00562   1 ERTLAIIKPDAVQRGLIGEIISR-FERKGFKIVAMKMLQLTEEQAEEFYAEHE 52

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).

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gi 817477401  22 TLALIKPDAVAHPlilEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHeAGQSEPTSLPTRMpsSSG 90
Cdd:cd04418    3 TLAIIKPDAVHKA---EEIEDIILESGFTIVQKRKLQLSPEQCSDFYAEH-YGKMFFPHLVAYM--SSG 65

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.

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gi 817477401  20 QLTLALIKPDAVAHPliLEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHEAG 74
Cdd:cd04416    1 EYTLALIKPDAVAEK--KDEILEKIKEAGFEILAQKEMVLTEEQAREFYKEHEEE 53

nucleoside diphosphate kinase; Provisional

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gi 817477401  19 LQLTLALIKPDAVAHPLILEAVhQQILSNKFLIVRMRELLWRKEDCQRFYREHE 72
Cdd:PRK14540   2 KERTFVALKPDAVERKLIGKII-QRFENKGFEIVEMKMLKLTREMAEEYYEEHK 54

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.

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gi 817477401  22 TLALIKPDAVAHPLILEAVhQQILSNKFLIVRMRELLWRKEDCQRFYREHE 72
Cdd:cd04413    3 TLVIIKPDGVQRGLIGEII-SRFERKGLKIVALKMLQLTEELAEEHYAEHK 52