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Conserved domains on  [gi|817476079|ref|NP_001295362|]
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nucleoside diphosphate kinase 6 isoform 4 [Homo sapiens]

Protein Classification

nucleoside-diphosphate kinase( domain architecture ID 1539)

nucleoside-diphosphate kinase catalyzes the exchange of phosphate groups between different nucleoside diphosphates

CATH:  3.30.70.141
EC:  2.7.4.6
Gene Ontology:  GO:0006165|GO:0006241|GO:0004550|GO:0046872|GO:0005524|GO:0006228|GO:0006183

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
NDPk super family cl00335
Nucleoside diphosphate kinases (NDP kinases, NDPks): NDP kinases, responsible for the ...
 12-64 2.44e-26

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.


The actual alignment was detected with superfamily member cd04414:

Pssm-ID: 469726  Cd Length: 135  Bit Score: 96.70  E-value: 2.44e-26
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 817476079  12 QLTLALIKPDAVAHPLILEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:cd04414    1 QLTLALIKPDAVAHPLALEAVRQLILSNGFTIVRKKELRWTTEDAERFYAEHK 53
 
Name Accession Description Interval E-value
NDPk6 cd04414
Nucleoside diphosphate kinase 6 (NDP kinase 6, NDPk6, NM23-H6; NME6; Inhibitor of p53-induced ...
 12-64 2.44e-26

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.


Pssm-ID: 239877  Cd Length: 135  Bit Score: 96.70  E-value: 2.44e-26
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 817476079  12 QLTLALIKPDAVAHPLILEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:cd04414    1 QLTLALIKPDAVAHPLALEAVRQLILSNGFTIVRKKELRWTTEDAERFYAEHK 53
NDK smart00562
Enzymes that catalyze nonsubstrate specific conversions of nucleoside diphosphates to ...
 12-64 1.27e-15

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


Pssm-ID: 197791  Cd Length: 135  Bit Score: 69.12  E-value: 1.27e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 817476079    12 QLTLALIKPDAVAHPLILEAVHQqILSNKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:smart00562   1 ERTLAIIKPDAVQRGLIGEIISR-FERKGFKIVAMKMLQLTEEQAEEFYAEHE 52
NDK pfam00334
Nucleoside diphosphate kinase;
14-64 1.06e-08

Nucleoside diphosphate kinase;


Pssm-ID: 459766  Cd Length: 135  Bit Score: 50.95  E-value: 1.06e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 817476079   14 TLALIKPDAVAHPLIlEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:pfam00334   3 TLAIIKPDAVQRGLI-GEIISRFERKGFKIVALKMLQLTREQAEEHYAEHK 52
Ndk COG0105
Nucleoside diphosphate kinase [Nucleotide transport and metabolism]; Nucleoside diphosphate ...
 10-64 7.14e-05

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


Pssm-ID: 439875  Cd Length: 140  Bit Score: 40.44  E-value: 7.14e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 817476079  10 ALQLTLALIKPDAVAHPLILEavhqqILS----NKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:COG0105    1 AMERTLVIIKPDAVQRGLIGE-----IISrferKGLKIVALKMLQLTREQAEEHYAEHK 54
PRK14540 PRK14540
nucleoside diphosphate kinase; Provisional
 11-64 3.89e-04

nucleoside diphosphate kinase; Provisional


Pssm-ID: 184733  Cd Length: 134  Bit Score: 38.26  E-value: 3.89e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 817476079  11 LQLTLALIKPDAVAHPLILEAVhQQILSNKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:PRK14540   2 KERTFVALKPDAVERKLIGKII-QRFENKGFEIVEMKMLKLTREMAEEYYEEHK 54
 
Name Accession Description Interval E-value
NDPk6 cd04414
Nucleoside diphosphate kinase 6 (NDP kinase 6, NDPk6, NM23-H6; NME6; Inhibitor of p53-induced ...
 12-64 2.44e-26

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.


Pssm-ID: 239877  Cd Length: 135  Bit Score: 96.70  E-value: 2.44e-26
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 817476079  12 QLTLALIKPDAVAHPLILEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:cd04414    1 QLTLALIKPDAVAHPLALEAVRQLILSNGFTIVRKKELRWTTEDAERFYAEHK 53
NDPk cd00595
Nucleoside diphosphate kinases (NDP kinases, NDPks): NDP kinases, responsible for the ...
 12-65 8.91e-19

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.


Pssm-ID: 238335  Cd Length: 133  Bit Score: 77.39  E-value: 8.91e-19
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 817476079  12 QLTLALIKPDAVAHpLILEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHEA 65
Cdd:cd00595    1 ERTLALIKPDAVAE-GLLGEIIMRIEDAGFEIVAMKELHLTEEQAEEFYVEHKG 53
NDK smart00562
Enzymes that catalyze nonsubstrate specific conversions of nucleoside diphosphates to ...
 12-64 1.27e-15

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


Pssm-ID: 197791  Cd Length: 135  Bit Score: 69.12  E-value: 1.27e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 817476079    12 QLTLALIKPDAVAHPLILEAVHQqILSNKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:smart00562   1 ERTLAIIKPDAVQRGLIGEIISR-FERKGFKIVAMKMLQLTEEQAEEFYAEHE 52
NDK pfam00334
Nucleoside diphosphate kinase;
14-64 1.06e-08

Nucleoside diphosphate kinase;


Pssm-ID: 459766  Cd Length: 135  Bit Score: 50.95  E-value: 1.06e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 817476079   14 TLALIKPDAVAHPLIlEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:pfam00334   3 TLAIIKPDAVQRGLI-GEIISRFERKGFKIVALKMLQLTREQAEEHYAEHK 52
NDPk5 cd04418
Nucleoside diphosphate kinase homolog 5 (NDP kinase homolog 5, NDPk5, NM23-H5; Inhibitor of ...
 14-82 4.30e-06

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).


Pssm-ID: 239880  Cd Length: 132  Bit Score: 43.97  E-value: 4.30e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 817476079  14 TLALIKPDAVAHPlilEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHeAGQSEPTSLPTRMpsSSG 82
Cdd:cd04418    3 TLAIIKPDAVHKA---EEIEDIILESGFTIVQKRKLQLSPEQCSDFYAEH-YGKMFFPHLVAYM--SSG 65
NDPk_TX cd04416
NDP kinase domain of thioredoxin domain-containing proteins (TXNDC3 and TXNDC6): Txl-2 ...
 12-66 4.40e-05

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.


Pssm-ID: 239879  Cd Length: 132  Bit Score: 41.04  E-value: 4.40e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 817476079  12 QLTLALIKPDAVAHPliLEAVHQQILSNKFLIVRMRELLWRKEDCQRFYREHEAG 66
Cdd:cd04416    1 EYTLALIKPDAVAEK--KDEILEKIKEAGFEILAQKEMVLTEEQAREFYKEHEEE 53
NDPk7A cd04415
Nucleoside diphosphate kinase 7 domain A (NDPk7A): The nm23-H7 class of nucleoside diphosphate ...
 14-70 4.42e-05

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.


Pssm-ID: 239878  Cd Length: 131  Bit Score: 40.89  E-value: 4.42e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 817476079  14 TLALIKPDAVAH--PLIleavhQQILSNKFLIVRMRELLWRKEDCQRFYREHeagQSEP 70
Cdd:cd04415    3 TLALIKPDAYSKigKII-----QIIEDAGFTITKAKMTKLSRKEAQDFYAEH---QSKP 53
Ndk COG0105
Nucleoside diphosphate kinase [Nucleotide transport and metabolism]; Nucleoside diphosphate ...
 10-64 7.14e-05

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


Pssm-ID: 439875  Cd Length: 140  Bit Score: 40.44  E-value: 7.14e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 817476079  10 ALQLTLALIKPDAVAHPLILEavhqqILS----NKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:COG0105    1 AMERTLVIIKPDAVQRGLIGE-----IISrferKGLKIVALKMLQLTREQAEEHYAEHK 54
PRK14540 PRK14540
nucleoside diphosphate kinase; Provisional
 11-64 3.89e-04

nucleoside diphosphate kinase; Provisional


Pssm-ID: 184733  Cd Length: 134  Bit Score: 38.26  E-value: 3.89e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 817476079  11 LQLTLALIKPDAVAHPLILEAVhQQILSNKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:PRK14540   2 KERTFVALKPDAVERKLIGKII-QRFENKGFEIVEMKMLKLTREMAEEYYEEHK 54
ndk PRK00668
mulitfunctional nucleoside diphosphate kinase/apyrimidinic endonuclease/3'-; Validated
 14-65 2.00e-03

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


Pssm-ID: 179085  Cd Length: 134  Bit Score: 36.24  E-value: 2.00e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 817476079  14 TLALIKPDAVAHPLILEavhqqILS---NK-FLIVRMRELLWRKEDCQRFYREHEA 65
Cdd:PRK00668   4 TFSIIKPDAVQRGLIGE-----IISrfeKKgLKIVALKMMQLSRELAEGHYAEHKE 54
NDPk_I cd04413
Nucleoside diphosphate kinase Group I (NDPk_I)-like: NDP kinase domains are present in a large ...
 14-64 3.20e-03

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.


Pssm-ID: 239876  Cd Length: 130  Bit Score: 35.91  E-value: 3.20e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 817476079  14 TLALIKPDAVAHPLILEAVhQQILSNKFLIVRMRELLWRKEDCQRFYREHE 64
Cdd:cd04413    3 TLVIIKPDGVQRGLIGEII-SRFERKGLKIVALKMLQLTEELAEEHYAEHK 52
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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