Nucleoside diphosphate kinase A

Details

Name
Nucleoside diphosphate kinase A
Synonyms
  • 2.7.4.6
  • GAAD
  • Granzyme A-activated DNase
  • Metastasis inhibition factor nm23
  • NDK A
  • NDP kinase A
  • NDPKA
  • NM23
  • NM23-H1
  • Tumor metastatic process-associated protein
Gene Name
NME1
UniProtKB Entry
P15531Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0006062|Nucleoside diphosphate kinase A
MANCERTFIAIKPDGVQRGLVGEIIKRFEQKGFRLVGLKFMQASEDLLKEHYVDLKDRPF
FAGLVKYMHSGPVVAMVWEGLNVVKTGRVMLGETNPADSKPGTIRGDFCIQVGRNIIHGS
DSVESAEKEIGLWFHPEELVDYTSCAQNWIYE
Number of residues
152
Molecular Weight
17148.635
Theoretical pI
6.11
GO Classification
Functions
3'-5' exonuclease activity / DNA nuclease activity / RNA binding
Processes
lactation / negative regulation of cell population proliferation
Components
early endosome
General Function
Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. During GZMA-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair
Specific Function
3'-5' exonuclease activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021353|Nucleoside diphosphate kinase A (NME1)
ATGGCCAACTGTGAGCGTACCTTCATTGCGATCAAACCAGATGGGGTCCAGCGGGGTCTT
GTGGGAGAGATTATCAAGCGTTTTGAGCAGAAAGGATTCCGCCTTGTTGGTCTGAAATTC
ATGCAAGCTTCCGAAGATCTTCTCAAGGAACACTACGTTGACCTGAAGGACCGTCCATTC
TTTGCCGGCCTGGTGAAATACATGCACTCAGGGCCGGTAGTTGCCATGGTCTGGGAGGGG
CTGAATGTGGTGAAGACGGGCCGAGTCATGCTCGGGGAGACCAACCCTGCAGACTCCAAG
CCTGGGACCATCCGTGGAGACTTCTGCATACAAGTTGGCAGGAACATTATACATGGCAGT
GATTCTGTGGAGAGTGCAGAGAAGGAGATCGGCTTGTGGTTTCACCCTGAGGAACTGGTA
GATTACACGAGCTGTGCTCAGAACTGGATCTATGAATGA
Chromosome Location
17
Locus
17q21.33
External Identifiers
ResourceLink
UniProtKB IDP15531
UniProtKB Entry NameNDKA_HUMAN
GenBank Gene IDX75598
GeneCard IDNME1
GenAtlas IDNME1
HGNC IDHGNC:7849
PDB ID(s)1JXV, 1UCN, 2HVD, 2HVE, 3L7U, 4ENO, 5UI4, 8OOV
KEGG IDhsa:4830
NCBI Gene ID4830
General References
  1. Rosengard AM, Krutzsch HC, Shearn A, Biggs JR, Barker E, Margulies IM, King CR, Liotta LA, Steeg PS: Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development. Nature. 1989 Nov 9;342(6246):177-80. [Article]
  2. Gilles AM, Presecan E, Vonica A, Lascu I: Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J Biol Chem. 1991 May 15;266(14):8784-9. [Article]
  3. Wang L, Patel U, Ghosh L, Chen HC, Banerjee S: Mutation in the nm23 gene is associated with metastasis in colorectal cancer. Cancer Res. 1993 Feb 15;53(4):717-20. [Article]
  4. Dooley S, Seib T, Engel M, Theisinger B, Janz H, Piontek K, Zang KD, Welter C: Isolation and characterization of the human genomic locus coding for the putative metastasis control gene nm23-H1. Hum Genet. 1994 Jan;93(1):63-6. [Article]
  5. Ni X, Gu S, Dai J, Cheng H, Guo L, Li L, Ji C, Xie Y, Ying K, Mao Y: Isolation and characterization of a novel human NM23-H1B gene, a different transcript of NM23-H1. J Hum Genet. 2003;48(2):96-100. [Article]
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  7. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [Article]
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  9. Hailat N, Keim DR, Melhem RF, Zhu XX, Eckerskorn C, Brodeur GM, Reynolds CP, Seeger RC, Lottspeich F, Strahler JR, et al.: High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification. J Clin Invest. 1991 Jul;88(1):341-5. [Article]
  10. MacDonald NJ, Freije JM, Stracke ML, Manrow RE, Steeg PS: Site-directed mutagenesis of nm23-H1. Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells. J Biol Chem. 1996 Oct 11;271(41):25107-16. [Article]
  11. Manda R, Kohno T, Matsuno Y, Takenoshita S, Kuwano H, Yokota J: Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display. Genomics. 1999 Oct 1;61(1):5-14. [Article]
  12. Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J: Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell. 2003 Mar 7;112(5):659-72. [Article]
  13. Valentijn LJ, Koster J, Versteeg R: Read-through transcript from NM23-H1 into the neighboring NM23-H2 gene encodes a novel protein, NM23-LV. Genomics. 2006 Apr;87(4):483-9. Epub 2006 Jan 25. [Article]
  14. Chowdhury D, Beresford PJ, Zhu P, Zhang D, Sung JS, Demple B, Perrino FW, Lieberman J: The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Mol Cell. 2006 Jul 7;23(1):133-42. [Article]
  15. Garzia L, D'Angelo A, Amoresano A, Knauer SK, Cirulli C, Campanella C, Stauber RH, Steegborn C, Iolascon A, Zollo M: Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility. Oncogene. 2008 Mar 20;27(13):1853-64. Epub 2007 Oct 1. [Article]
  16. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  17. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  18. Rosenow A, Noben JP, Jocken J, Kallendrusch S, Fischer-Posovszky P, Mariman EC, Renes J: Resveratrol-induced changes of the human adipocyte secretion profile. J Proteome Res. 2012 Sep 7;11(9):4733-43. doi: 10.1021/pr300539b. Epub 2012 Aug 27. [Article]
  19. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  20. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  21. Min K, Song HK, Chang C, Kim SY, Lee KJ, Suh SW: Crystal structure of human nucleoside diphosphate kinase A, a metastasis suppressor. Proteins. 2002 Feb 15;46(3):340-2. [Article]
  22. Chen Y, Gallois-Montbrun S, Schneider B, Veron M, Morera S, Deville-Bonne D, Janin J: Nucleotide binding to nucleoside diphosphate kinases: X-ray structure of human NDPK-A in complex with ADP and comparison to protein kinases. J Mol Biol. 2003 Sep 26;332(4):915-26. [Article]
  23. Chang CL, Zhu XX, Thoraval DH, Ungar D, Rawwas J, Hora N, Strahler JR, Hanash SM, Radany E: Nm23-H1 mutation in neuroblastoma. Nature. 1994 Aug 4;370(6488):335-6. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Nucleoside diphosphate kinase A (Humans)protein
primary
Nucleoside diphosphokinase (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
2'-Deoxyguanosine-5'-TriphosphateexperimentalunknowntargetDetails
SelenocysteineexperimentalunknowntargetDetails
2',3'-Dehydro-2',3'-Deoxy-Thymidine 5'-DiphosphateexperimentalunknowntargetDetails
Adenosine Phosphonoacetic AcidexperimentalunknowntargetDetails
Stavudine triphosphateexperimentalunknowntargetDetails
Thymidine-5'- DiphosphateexperimentalunknowntargetDetails
2'-Deoxyguanosine-5'-DiphosphateexperimentalunknowntargetDetails
2',3'-dideoxy-3'-fluoro-urididine-5'-diphosphateexperimentalunknowntargetDetails
3'-Deoxy 3'-Amino Adenosine-5'-DiphosphateexperimentalunknowntargetDetails
Zidovudine diphosphateexperimentalunknowntargetDetails
Guanosine-5'-DiphosphateexperimentalunknowntargetDetails
Lamivudineapproved, investigationalunknownenzymesubstrateDetails
Adefovir dipivoxilapproved, investigationalunknownenzymesubstrateDetails
SofosbuvirapprovedunknownenzymesubstrateDetails
Copperapproved, investigationalunknowntargetDetails
Zincapproved, investigationalunknowntargetDetails
Zinc acetateapproved, investigationalunknowntargetDetails
Zinc chlorideapproved, investigationalunknowntargetinhibitorDetails
Tenofovir alafenamideapprovednoenzymesubstrateDetails
Tenofovirexperimental, investigationalnoenzymesubstrateDetails
Zinc sulfate, unspecified formapproved, experimentalunknowntargetinhibitorDetails
Adenosineapproved, investigationalunknownenzymesubstrateDetails
GemcitabineapprovednoenzymesubstrateDetails
Tenofovir disoproxilapproved, investigationalunknownenzymesubstrateDetails
AcyclovirapprovedunknownenzymesubstrateDetails
Decitabineapproved, investigationalyesenzymesubstrateDetails