NDKA_MOUSE
ID NDKA_MOUSE Reviewed; 152 AA.
AC P15532;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Nucleoside diphosphate kinase A;
DE Short=NDK A;
DE Short=NDP kinase A;
DE EC=2.7.4.6;
DE AltName: Full=Metastasis inhibition factor NM23;
DE AltName: Full=NDPK-A;
DE AltName: Full=Tumor metastatic process-associated protein;
DE AltName: Full=nm23-M1;
GN Name=Nme1; Synonyms=Nm23;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2509941; DOI=10.1038/342177a0;
RA Rosengard A.M., Krutzsch H.C., Shearn A., Biggs J.R., Barker E.,
RA Margulies I.M.K., King C.R., Liotta L.A., Steeg P.S.;
RT "Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila
RT development.";
RL Nature 342:177-180(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3346912; DOI=10.1093/jnci/80.3.200;
RA Steeg P.S., Bevilacqua G., Kopper L., Thorgeirsson U.P., Talmadge J.E.,
RA Liotta L.A., Sobel M.E.;
RT "Evidence for a novel gene associated with low tumor metastatic
RT potential.";
RL J. Natl. Cancer Inst. 80:200-204(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2013093; DOI=10.1016/0092-8674(91)90404-m;
RA Leone A., Flatow U., King C.R., Sandeen M.A., Margulies I.M., Liotta L.A.,
RA Steeg P.S.;
RT "Reduced tumor incidence, metastatic potential, and cytokine responsiveness
RT of nm23-transfected melanoma cells.";
RL Cell 65:25-35(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/Sv;
RA Dabernat S., Masse K., Daniel J.Y.;
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Swiss Webster / NIH;
RA Gervasi F., Fanciulli M., Lombardi D.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 7-26; 67-85; 89-124 AND 129-143, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain, and Hippocampus;
RA Lubec G., Klug S., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-124, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Major role in the synthesis of nucleoside triphosphates other
CC than ATP. The ATP gamma phosphate is transferred to the NDP beta
CC phosphate via a ping-pong mechanism, using a phosphorylated active-site
CC intermediate. Possesses nucleoside-diphosphate kinase,
CC serine/threonine-specific protein kinase, geranyl and farnesyl
CC pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease
CC activities. Involved in cell proliferation, differentiation and
CC development, signal transduction, G protein-coupled receptor
CC endocytosis, and gene expression. Required for neural development
CC including neural patterning and cell fate determination. During GZMA-
CC mediated cell death, works in concert with TREX1. NME1 nicks one strand
CC of DNA and TREX1 removes bases from the free 3' end to enhance DNA
CC damage and prevent DNA end reannealing and rapid repair (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-
CC deoxyribonucleoside 5'-triphosphate + ADP; Xref=Rhea:RHEA:44640,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61560, ChEBI:CHEBI:73316,
CC ChEBI:CHEBI:456216; EC=2.7.4.6;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-diphosphate + ATP = a ribonucleoside 5'-
CC triphosphate + ADP; Xref=Rhea:RHEA:18113, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557, ChEBI:CHEBI:456216; EC=2.7.4.6;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Autophosphorylation at His-118 increases
CC serine/threonine protein kinase activity of the enzyme. Interaction
CC with the SET complex inhibits exonuclease activity (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Hexamer of two different chains: A and B (A6, A5B, A4B2, A3B3,
CC A2B4, AB5, B6). Interacts with PRUNE1. Component of the SET complex,
CC composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1. Within
CC this complex, interacts directly with SET. Also interacts with TREX1,
CC but only following translocation to the nucleus.
CC {ECO:0000250|UniProtKB:P15531}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- DISEASE: Note=This protein is found in reduced amount in tumor cells of
CC high metastatic potential.
CC -!- SIMILARITY: Belongs to the NDK family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA39826.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M35970; AAA39826.1; ALT_INIT; mRNA.
DR EMBL; M65037; AAA63391.1; -; mRNA.
DR EMBL; U85511; AAB42080.1; -; mRNA.
DR EMBL; AF033377; AAB87689.1; -; mRNA.
DR EMBL; BC005629; AAH05629.1; -; mRNA.
DR CCDS; CCDS25247.1; -.
DR PIR; A46557; A46557.
DR RefSeq; NP_032730.1; NM_008704.2.
DR AlphaFoldDB; P15532; -.
DR SMR; P15532; -.
DR BioGRID; 201788; 18.
DR DIP; DIP-34130N; -.
DR IntAct; P15532; 4.
DR STRING; 10090.ENSMUSP00000117022; -.
DR iPTMnet; P15532; -.
DR PhosphoSitePlus; P15532; -.
DR SwissPalm; P15532; -.
DR REPRODUCTION-2DPAGE; P15532; -.
DR SWISS-2DPAGE; P15532; -.
DR EPD; P15532; -.
DR jPOST; P15532; -.
DR PaxDb; P15532; -.
DR PeptideAtlas; P15532; -.
DR PRIDE; P15532; -.
DR ProteomicsDB; 252934; -.
DR Antibodypedia; 35046; 1422 antibodies from 43 providers.
DR DNASU; 18102; -.
DR Ensembl; ENSMUST00000135884; ENSMUSP00000117022; ENSMUSG00000037601.
DR GeneID; 18102; -.
DR KEGG; mmu:18102; -.
DR UCSC; uc007kxu.1; mouse.
DR CTD; 4830; -.
DR MGI; MGI:97355; Nme1.
DR VEuPathDB; HostDB:ENSMUSG00000037601; -.
DR eggNOG; KOG0888; Eukaryota.
DR GeneTree; ENSGT00940000162213; -.
DR InParanoid; P15532; -.
DR OMA; KIVAMKM; -.
DR OrthoDB; 1334716at2759; -.
DR PhylomeDB; P15532; -.
DR TreeFam; TF106373; -.
DR Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates.
DR Reactome; R-MMU-9748787; Azathioprine ADME.
DR BioGRID-ORCS; 18102; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Nme1; mouse.
DR PRO; PR:P15532; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P15532; protein.
DR Bgee; ENSMUSG00000037601; Expressed in right kidney and 172 other tissues.
DR ExpressionAtlas; P15532; baseline and differential.
DR Genevisible; P15532; MM.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005882; C:intermediate filament; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0032587; C:ruffle membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0004536; F:deoxyribonuclease activity; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0043015; F:gamma-tubulin binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019215; F:intermediate filament binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISO:MGI.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0043024; F:ribosomal small subunit binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0003697; F:single-stranded DNA binding; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006241; P:CTP biosynthetic process; IEA:InterPro.
DR GO; GO:0006231; P:dTMP biosynthetic process; NAS:MGI.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006183; P:GTP biosynthetic process; IEA:InterPro.
DR GO; GO:0007595; P:lactation; IMP:MGI.
DR GO; GO:0030879; P:mammary gland development; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0002762; P:negative regulation of myeloid leukocyte differentiation; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0006165; P:nucleoside diphosphate phosphorylation; ISO:MGI.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISO:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0006228; P:UTP biosynthetic process; IEA:InterPro.
DR Gene3D; 3.30.70.141; -; 1.
DR HAMAP; MF_00451; NDP_kinase; 1.
DR InterPro; IPR034907; NDK-like_dom.
DR InterPro; IPR036850; NDK-like_dom_sf.
DR InterPro; IPR001564; Nucleoside_diP_kinase.
DR InterPro; IPR023005; Nucleoside_diP_kinase_AS.
DR Pfam; PF00334; NDK; 1.
DR PRINTS; PR01243; NUCDPKINASE.
DR SMART; SM00562; NDK; 1.
DR SUPFAM; SSF54919; SSF54919; 1.
DR PROSITE; PS00469; NDP_KINASES; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cytoplasm; Differentiation;
KW Direct protein sequencing; Endocytosis; Isopeptide bond; Kinase; Magnesium;
KW Metal-binding; Neurogenesis; Nucleotide metabolism; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase; Ubl conjugation.
FT CHAIN 1..152
FT /note="Nucleoside diphosphate kinase A"
FT /id="PRO_0000137115"
FT ACT_SITE 118
FT /note="Pros-phosphohistidine intermediate"
FT BINDING 12
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 60
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 88
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 115
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15531"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15531"
FT MOD_RES 124
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 125
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15531"
FT CROSSLNK 100
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P15531"
SQ SEQUENCE 152 AA; 17208 MW; EE2E4DB218024686 CRC64;
MANSERTFIA IKPDGVQRGL VGEIIKRFEQ KGFRLVGLKF LQASEDLLKE HYTDLKDRPF
FTGLVKYMHS GPVVAMVWEG LNVVKTGRVM LGETNPADSK PGTIRGDFCI QVGRNIIHGS
DSVKSAEKEI SLWFQPEELV EYKSCAQNWI YE
