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MGP002104

UniProt Annotations

Entry Information
Gene NameNME/NM23 nucleoside diphosphate kinase 1
Protein EntryNDKA_HUMAN
UniProt IDP15531
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; Synonyms=NM23-H1A; IsoId=P15531-1; Sequence=Displayed; Name=2; Synonyms=NM23-H1B; IsoId=P15531-2; Sequence=VSP_036707; Name=3; Synonyms=NM23-LV; IsoId=P22392-2; Sequence=External; Note=Based on a naturally occurring readthrough transcript which produces an NME1-NME2 fusion protein.;
Catalytic ActivityATP + nucleoside diphosphate = ADP + nucleoside triphosphate.
CofactorName=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme RegulationAutophosphorylation at His-118 increases serine/threonine protein kinase activity of the enzyme. Interaction with the SET complex inhibits the endonuclease activity. {ECO:0000269|PubMed:12628186}.
FunctionMajor 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. {ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:8810265}.
InteractionSelf; NbExp=4; IntAct=EBI-741141, EBI-741141; Q61097:Ksr1 (xeno); NbExp=7; IntAct=EBI-741141, EBI-1536336; P10911:MCF2; NbExp=4; IntAct=EBI-741141, EBI-1914514; P22392:NME2; NbExp=2; IntAct=EBI-741141, EBI-713693; Q86TP1:PRUNE; NbExp=2; IntAct=EBI-741141, EBI-2127112; Q9Y3F4:STRAP; NbExp=9; IntAct=EBI-741141, EBI-727414; Q96HA8:WDYHV1; NbExp=3; IntAct=EBI-741141, EBI-741158;
MiscellaneousThe role of this protein in tumor development and progression is uncertain. This protein is found in reduced amount in some tumor cells of high metastatic potential. However, increased NME1 levels correlate with aggressive tumor features in neuroblastoma. May have distinct if not opposite roles in different tumors.
Sequence CautionSequence=CAA35621.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the NDK family. {ECO:0000305}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:16442775}. Nucleus {ECO:0000269|PubMed:16442775}. Note=Cell-cycle dependent nuclear localization which can be induced by interaction with Epstein-barr viral proteins or by degradation of the SET complex by GzmA.
SubunitHexamer of two different chains: A and B (A6, A5B, A4B2, A3B3, A2B4, AB5, B6). Interacts with PRUNE. Component of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1. Within this complex, interacts directly with SET. Also interacts with TREX1, but only following translocation to the nucleus. {ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:17906697, ECO:0000269|PubMed:1851158}.
Tissue SpecificityIsoform 1 is expressed in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, spleen and thymus. Expressed in lung carcinoma cell lines but not in normal lung tissues. Isoform 2 is ubiquitously expressed and its expression is also related to tumor differentiation. Isoform 3 is ubiquitously expressed. {ECO:0000269|PubMed:10512675, ECO:0000269|PubMed:12601555, ECO:0000269|PubMed:16442775}.
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