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P15532

- NDKA_MOUSE

UniProt

P15532 - NDKA_MOUSE

Protein

Nucleoside diphosphate kinase A

Gene

Nme1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    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 By similarity.By similarity

    Catalytic activityi

    ATP + nucleoside diphosphate = ADP + nucleoside triphosphate.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Autophosphorylation at His-118 increases serine/threonine protein kinase activity of the enzyme. Interaction with the SET complex inhibits exonuclease activity By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei12 – 121ATPBy similarity
    Binding sitei60 – 601ATPBy similarity
    Binding sitei88 – 881ATPBy similarity
    Binding sitei94 – 941ATPBy similarity
    Binding sitei105 – 1051ATPBy similarity
    Binding sitei115 – 1151ATPBy similarity
    Active sitei118 – 1181Pros-phosphohistidine intermediate

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. deoxyribonuclease activity Source: Ensembl
    3. GTP binding Source: Ensembl
    4. magnesium ion binding Source: Ensembl
    5. nucleoside diphosphate kinase activity Source: UniProtKB-EC
    6. ribosomal small subunit binding Source: Ensembl
    7. RNA polymerase II regulatory region sequence-specific DNA binding Source: Ensembl
    8. single-stranded DNA binding Source: Ensembl

    GO - Biological processi

    1. cellular response to drug Source: Ensembl
    2. cellular response to fatty acid Source: Ensembl
    3. cellular response to glucose stimulus Source: Ensembl
    4. CTP biosynthetic process Source: InterPro
    5. endocytosis Source: UniProtKB-KW
    6. GTP biosynthetic process Source: InterPro
    7. hippocampus development Source: Ensembl
    8. lactation Source: MGI
    9. mammary gland development Source: MGI
    10. negative regulation of gene expression Source: Ensembl
    11. negative regulation of myeloid leukocyte differentiation Source: Ensembl
    12. positive regulation of DNA binding Source: Ensembl
    13. positive regulation of epithelial cell proliferation Source: Ensembl
    14. positive regulation of neuron projection development Source: Ensembl
    15. response to amine Source: Ensembl
    16. response to cAMP Source: Ensembl
    17. response to testosterone Source: Ensembl
    18. UTP biosynthetic process Source: InterPro

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Differentiation, Endocytosis, Neurogenesis, Nucleotide metabolism

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Nucleoside diphosphate kinase A (EC:2.7.4.6)
    Short name:
    NDK A
    Short name:
    NDP kinase A
    Alternative name(s):
    Metastasis inhibition factor NM23
    NDPK-A
    Tumor metastatic process-associated protein
    nm23-M1
    Gene namesi
    Name:Nme1
    Synonyms:Nm23
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:97355. Nme1.

    Subcellular locationi

    GO - Cellular componenti

    1. centrosome Source: Ensembl
    2. cytosol Source: Ensembl
    3. mitochondrion Source: MGI
    4. nucleus Source: UniProtKB-SubCell
    5. perinuclear region of cytoplasm Source: Ensembl
    6. ruffle membrane Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    This protein is found in reduced amount in tumor cells of high metastatic potential.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 152151Nucleoside diphosphate kinase APRO_0000137115Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Cross-linki100 – 100Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei124 – 1241N6-acetyllysine1 Publication

    Keywords - PTMi

    Acetylation, Isopeptide bond, Ubl conjugation

    Proteomic databases

    MaxQBiP15532.
    PaxDbiP15532.
    PRIDEiP15532.

    2D gel databases

    REPRODUCTION-2DPAGEP15532.
    SWISS-2DPAGEP15532.

    PTM databases

    PhosphoSiteiP15532.

    Expressioni

    Gene expression databases

    ArrayExpressiP15532.
    BgeeiP15532.
    GenevestigatoriP15532.

    Interactioni

    Subunit structurei

    Hexamer 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 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi201788. 2 interactions.
    IntActiP15532. 5 interactions.
    MINTiMINT-1868955.

    Structurei

    3D structure databases

    ProteinModelPortaliP15532.
    SMRiP15532. Positions 5-152.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the NDK family.Curated

    Phylogenomic databases

    eggNOGiCOG0105.
    HOGENOMiHOG000224564.
    HOVERGENiHBG000423.
    InParanoidiP15532.
    KOiK00940.
    OMAiVWEGDNI.
    OrthoDBiEOG7GJ6FG.
    PhylomeDBiP15532.
    TreeFamiTF106373.

    Family and domain databases

    Gene3Di3.30.70.141. 1 hit.
    HAMAPiMF_00451. NDP_kinase.
    InterProiIPR001564. Nucleoside_diP_kinase.
    IPR023005. Nucleoside_diP_kinase_AS.
    [Graphical view]
    PfamiPF00334. NDK. 1 hit.
    [Graphical view]
    PRINTSiPR01243. NUCDPKINASE.
    SMARTiSM00562. NDK. 1 hit.
    [Graphical view]
    SUPFAMiSSF54919. SSF54919. 1 hit.
    PROSITEiPS00469. NDP_KINASES. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P15532-1 [UniParc]FASTAAdd to Basket

    « Hide

    MANSERTFIA IKPDGVQRGL VGEIIKRFEQ KGFRLVGLKF LQASEDLLKE    50
    HYTDLKDRPF FTGLVKYMHS GPVVAMVWEG LNVVKTGRVM LGETNPADSK 100
    PGTIRGDFCI QVGRNIIHGS DSVKSAEKEI SLWFQPEELV EYKSCAQNWI 150
    YE 152
    Length:152
    Mass (Da):17,208
    Last modified:April 1, 1990 - v1
    Checksum:iEE2E4DB218024686
    GO

    Sequence cautioni

    The sequence AAA39826.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M35970 mRNA. Translation: AAA39826.1. Different initiation.
    M65037 mRNA. Translation: AAA63391.1.
    U85511 mRNA. Translation: AAB42080.1.
    AF033377 mRNA. Translation: AAB87689.1.
    BC005629 mRNA. Translation: AAH05629.1.
    CCDSiCCDS25247.1.
    PIRiA46557.
    RefSeqiNP_032730.1. NM_008704.2.
    UniGeneiMm.439702.

    Genome annotation databases

    EnsembliENSMUST00000135884; ENSMUSP00000117022; ENSMUSG00000037601.
    GeneIDi18102.
    KEGGimmu:18102.
    UCSCiuc007kxu.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M35970 mRNA. Translation: AAA39826.1 . Different initiation.
    M65037 mRNA. Translation: AAA63391.1 .
    U85511 mRNA. Translation: AAB42080.1 .
    AF033377 mRNA. Translation: AAB87689.1 .
    BC005629 mRNA. Translation: AAH05629.1 .
    CCDSi CCDS25247.1.
    PIRi A46557.
    RefSeqi NP_032730.1. NM_008704.2.
    UniGenei Mm.439702.

    3D structure databases

    ProteinModelPortali P15532.
    SMRi P15532. Positions 5-152.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201788. 2 interactions.
    IntActi P15532. 5 interactions.
    MINTi MINT-1868955.

    PTM databases

    PhosphoSitei P15532.

    2D gel databases

    REPRODUCTION-2DPAGE P15532.
    SWISS-2DPAGE P15532.

    Proteomic databases

    MaxQBi P15532.
    PaxDbi P15532.
    PRIDEi P15532.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000135884 ; ENSMUSP00000117022 ; ENSMUSG00000037601 .
    GeneIDi 18102.
    KEGGi mmu:18102.
    UCSCi uc007kxu.1. mouse.

    Organism-specific databases

    CTDi 4830.
    MGIi MGI:97355. Nme1.

    Phylogenomic databases

    eggNOGi COG0105.
    HOGENOMi HOG000224564.
    HOVERGENi HBG000423.
    InParanoidi P15532.
    KOi K00940.
    OMAi VWEGDNI.
    OrthoDBi EOG7GJ6FG.
    PhylomeDBi P15532.
    TreeFami TF106373.

    Miscellaneous databases

    ChiTaRSi NME1. mouse.
    NextBioi 293271.
    PROi P15532.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P15532.
    Bgeei P15532.
    Genevestigatori P15532.

    Family and domain databases

    Gene3Di 3.30.70.141. 1 hit.
    HAMAPi MF_00451. NDP_kinase.
    InterProi IPR001564. Nucleoside_diP_kinase.
    IPR023005. Nucleoside_diP_kinase_AS.
    [Graphical view ]
    Pfami PF00334. NDK. 1 hit.
    [Graphical view ]
    PRINTSi PR01243. NUCDPKINASE.
    SMARTi SM00562. NDK. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54919. SSF54919. 1 hit.
    PROSITEi PS00469. NDP_KINASES. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development."
      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.
      Nature 342:177-180(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells."
      Leone A., Flatow U., King C.R., Sandeen M.A., Margulies I.M., Liotta L.A., Steeg P.S.
      Cell 65:25-35(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. Dabernat S., Masse K., Daniel J.Y.
      Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: 129/Sv.
    5. Gervasi F., Fanciulli M., Lombardi D.
      Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Swiss Webster / NIH.
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Mammary gland.
    7. Lubec G., Klug S., Kang S.U.
      Submitted (APR-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 7-26; 67-85; 89-124 AND 129-143, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: C57BL/6.
      Tissue: Brain and Hippocampus.
    8. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-124, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast.

    Entry informationi

    Entry nameiNDKA_MOUSE
    AccessioniPrimary (citable) accession number: P15532
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: April 1, 1990
    Last modified: October 1, 2014
    This is version 137 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3