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UniProtKB/Swiss-Prot entry P15531


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name NDKA_HUMAN
Primary accession number P15531
Secondary accession numbers None
Integrated into Swiss-Prot on April 1, 1990
Sequence was last modified on April 1, 1990 (Sequence version 1)
Annotations were last modified on    April 29, 2008 (Entry version 101)
Name and origin of the protein
Protein name Nucleoside diphosphate kinase A
Synonyms EC 2.7.4.6
NDK A
NDP kinase A
Tumor metastatic process-associated protein
Metastasis inhibition factor nm23
nm23-H1
Granzyme A-activated DNase
GAAD
Gene name
Name: NME1
Synonyms: NDPKA, NM23
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE.
DOI=10.1038/342177a0; PubMed=2509941 [NCBI, ExPASy, EBI, Israel, Japan]
Rosengard A.M., Krutzsch H.C., Shearn A., Biggs J.R., Barker E., Margulies I.M.K., King C.R., Liotta L.A., Steeg P.S.;
"Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development.";
Nature 342:177-180(1989).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1007/BF00218915; PubMed=8270257 [NCBI, ExPASy, EBI, Israel, Japan]
Dooley S., Seib T., Engel M., Theisinger B., Janz H., Piontek K., Zang K.D., Welter C.;
"Isolation and characterization of the human genomic locus coding for the putative metastasis control gene nm23-H1.";
Hum. Genet. 93:63-66(1994).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=7916650 [NCBI, ExPASy, EBI, Israel, Japan]
Wang L., Patel U., Ghosh L., Chen H.C., Banerjee S.;
"Mutation in the nm23 gene is associated with metastasis in colorectal cancer.";
Cancer Res. 53:717-720(1993).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain, and Lung;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
PROTEIN SEQUENCE, SUBUNIT, AND ACTIVE SITE.
PubMed=1851158 [NCBI, ExPASy, EBI, Israel, Japan]
Gilles A.-M., 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. 266:8784-8789(1991).
[6]
PROTEIN SEQUENCE OF 7-18; 40-49 AND 89-94, AND DISEASE.
PubMed=2056128 [NCBI, ExPASy, EBI, Israel, Japan]
Hailat N., Keim D.R., Melhem R.F., Zhu X.X., Eckerskorn C., Brodeur G.M., Reynolds C.P., Seeger R.C., Lottspeich F., Strahler J.R., Hanash S.J.;
"High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification.";
J. Clin. Invest. 88:341-345(1991).
[7]
PROTEIN SEQUENCE OF 7-18; 57-66 AND 89-105, AND MASS SPECTROMETRY.
TISSUE=Brain, and Cajal-Retzius cell;
Lubec G., Afjehi-Sadat L.;
Submitted (MAR-2007) to UniProtKB.
[8]
TISSUE SPECIFICITY.
DOI=10.1006/geno.1999.5939; PubMed=10512675 [NCBI, ExPASy, EBI, Israel, Japan]
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 61:5-14(1999).
[9]
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
DOI=10.1002/prot.10038; PubMed=11835509 [NCBI, ExPASy, EBI, Israel, Japan]
Min K., Song H.K., Chang C., Kim S.Y., Lee K.J., Suh S.W.;
"Crystal structure of human nucleoside diphosphate kinase A, a metastasis suppressor.";
Proteins 46:340-342(2002).
[10]
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), AND MUTAGENESIS OF PHE-60 AND HIS-118.
DOI=10.1016/j.jmb.2003.07.004; PubMed=12972261 [NCBI, ExPASy, EBI, Israel, Japan]
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. 332:915-926(2003).
[11]
INTERACTION WITH SET.
DOI=10.1016/S0092-8674(03)00150-8; PubMed=12628186 [NCBI, ExPASy, EBI, Israel, Japan]
Fan Z., Beresford P.J., Oh D.Y., 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 112:659-672(2003).
[12]
VARIANT NEUROBLASTOMA GLY-120.
DOI=10.1038/370335a0; PubMed=8047138 [NCBI, ExPASy, EBI, Israel, Japan]
Chang C.L., Zhu X.-X., Thoraval D.H., Ungar D., Rawwas J., Hora N., Strahler J.R., Hanash S.M.;
"Nm23-H1 mutation in neuroblastoma.";
Nature 370:335-336(1994).
Comments
  • FUNCTION: Major role in the synthesis of nucleoside triphosphates other than ATP.
  • CATALYTIC ACTIVITY: ATP + nucleoside diphosphate = ADP + nucleoside triphosphate.
  • COFACTOR: Magnesium.
  • SUBUNIT: Hexamer of two different chains: A and B (A6, A5B, A4B2, A3B3, A2B4, AB5, B6). Interacts with SET.
  • INTERACTION:
    Q61097:Ksr1 (xeno); NbExp=2; IntAct=EBI-741141, EBI-1536336;
  • SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
  • TISSUE SPECIFICITY: Expressed in lung carcinoma cell lines but not in normal lung tissues.
  • PTM: The N-terminus is blocked.
  • DISEASE: This protein is found in reduced amount in tumor cells of high metastatic potential. Somatic mutations of NME1 are found in neuroblastoma. Increased NME1 in neuroblastoma is correlated with features of the disease that are associated with aggressive tumors. May therefore have distinct if not opposite roles in different tumors.
  • SIMILARITY: Belongs to the NDK family.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X17620; CAA35621.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X75598; CAA53270.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X73066; CAA51527.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC000293; AAH00293.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC018994; AAH18994.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A33386; A33386.
RefSeq NP_000260.1; -.
UniGene Hs.463456
3D structure databases
PDB
1JXV; X-ray; 2.20 A; A/B/C/D/E/F=1-152.[ExPASy / RCSB / EBI]
1UCN; X-ray; 2.00 A; A/B/C=1-152.[ExPASy / RCSB / EBI]
2HVD; X-ray; 2.15 A; A/B/C=1-152.[ExPASy / RCSB / EBI]
2HVE; X-ray; 2.40 A; A/B/C=1-152.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1JXV; -.
1UCN; -.
2HVD; -.
2HVE; -.
ModBase P15531.
Protein-protein interaction databases
IntAct P15531; -.
PTM databases
PhosphoSite P15531; -.
Enzyme and pathway databases
Reactome REACT_1698; Nucleotide metabolism.
2D gel databases
Aarhus/Ghent-2DPAGE 4115; IEF.
5112; IEF.
DOSAC-COBS-2DPAGE P15531; -.
OGP P15531; -.
PMMA-2DPAGE P15531; -.
Organism-specific databases
HGNC HGNC:7849; NME1.
GeneLynx NME1; Homo sapiens.
GenAtlas NME1.
HPA CAB002169; -.
HPA008467; -.
MIM 156490; gene. [NCBI / EBI]
Orphanet 635; Neuroblastoma.
PharmGKB PA249; -.
GeneCards P15531.
Gene expression databases
ArrayExpress P15531; -.
CleanEx HS_NME1; -.
GermOnline ENSG00000011052; Homo sapiens.
Ontologies
GO
GO:0005737; Cellular component: cytoplasm (traceable author statement from UniProtKB).
GO:0005634; Cellular component: nucleus (traceable author statement from UniProtKB).
GO:0005524; Molecular function: ATP binding (inferred from direct assay from UniProtKB).
GO:0004536; Molecular function: deoxyribonuclease activity (inferred from direct assay from UniProtKB).
GO:0003677; Molecular function: DNA binding (inferred by curator from UniProtKB).
GO:0005525; Molecular function: GTP binding (inferred from direct assay from UniProtKB).
GO:0000287; Molecular function: magnesium ion binding (inferred from direct assay from UniProtKB).
GO:0004550; Molecular function: nucleoside diphosphate kinase activity (inferred from direct assay from UniProtKB).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0008285; Biological process: negative regulation of cell proliferation (traceable author statement from UniProtKB).
GO:0043388; Biological process: positive regulation of DNA binding (inferred from direct assay from UniProtKB).
GO:0050679; Biological process: positive regulation of epithelial cell proliferation (inferred from mutant phenotype from HGNC).
GO:0042981; Biological process: regulation of apoptosis (traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR001564; Nuc_diP_kinase_core.
Graphical view of domain structure.
Gene3D G3DSA:3.30.70.141; NDK; 1.
PANTHER PTHR11349; Nuc_diP_kinase_core; 1.
Pfam PF00334; NDK; 1.
Pfam graphical view of domain structure.
PRINTS PR01243; NUCDPKINASE.
ProDom PD001018; NDK; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00562; NDK; 1.
SMART graphical view of domain structure.
PROSITE PS00469; NDP_KINASES; 1.
BLOCKS P15531.
Genome annotation databases
Ensembl ENSG00000011052; Homo sapiens. [Contig view]
GeneID 4830; -.
KEGG hsa:4830; -.
Other
DrugBank DB00441; Gemcitabine.
DB00396; Progesterone.
LinkHub P15531; -.
SOURCE NME1; Homo sapiens.
ProtoNet P15531.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Anti-oncogene; ATP-binding; Cell cycle; Cytoplasm; Direct protein sequencing; Disease mutation; Kinase; Magnesium; Metal-binding; Nucleotide metabolism; Nucleotide-binding; Nucleus; Phosphoprotein; Transferase.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
CHAIN   1   152  152     Nucleoside diphosphate kinase A. PRO_0000137114
ACT_SITE   118   118        Pros-phosphohistidine intermediate. 
BINDING   12    12        ATP. 
BINDING   60    60        ATP. 
BINDING   88    88        ATP. 
BINDING   94    94        ATP. 
BINDING   105   105        ATP. 
BINDING   115   115        ATP. 
VARIANT   120   120  1     S -> G (in neuroblastoma). VAR_004625 [3D]
MUTAGEN   60    60        F->W: No loss of activity or substrate binding. 
MUTAGEN   118   118        H->G: Loss of activity. 
STRAND   6    11  6      
HELIX   13    17  5      
HELIX   21    31  11      
STRAND   34    41  8      
HELIX   45    51  7      
HELIX   53    55  3      
HELIX   61    69  9      
STRAND   73    80  8      
HELIX   83    91  9      
HELIX   96    98  3      
HELIX   104   108  5      
STRAND   117   119  3      
HELIX   123   133  11      
HELIX   136   138  3      
HELIX   147   150  4      
Sequence information
Length: 152 AA [This is the length of the unprocessed precursor] Molecular weight: 17149 Da [This is the MW of the unprocessed precursor] CRC64: AAE9C0DF63CB70A1 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MANCERTFIA IKPDGVQRGL VGEIIKRFEQ KGFRLVGLKF MQASEDLLKE HYVDLKDRPF 

        70         80         90        100        110        120 
FAGLVKYMHS GPVVAMVWEG LNVVKTGRVM LGETNPADSK PGTIRGDFCI QVGRNIIHGS 

       130        140        150 
DSVESAEKEI GLWFHPEELV DYTSCAQNWI YE 

P15531 in FASTA format

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