NDKM_MOUSE
ID NDKM_MOUSE Reviewed; 186 AA.
AC Q9WV84;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Nucleoside diphosphate kinase, mitochondrial;
DE Short=NDK;
DE Short=NDP kinase, mitochondrial;
DE EC=2.7.4.6;
DE AltName: Full=Nucleoside diphosphate kinase D;
DE Short=NDPKD;
DE AltName: Full=nm23-M4;
DE Flags: Precursor;
GN Name=Nme4;
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].
RA Mehus J.G., Lambeth D.O.;
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=12383506; DOI=10.1016/s0378-1119(02)00836-3;
RA Masse K., Dabernat S., Bourbon P.-M., Larou M., Amrein L., Barraud P.,
RA Perel Y., Camara M., Landry M., Lacombe M.L., Daniel J.-Y.;
RT "Characterization of the nm23-M2, nm23-M3 and nm23-M4 mouse genes:
RT comparison with their human orthologs.";
RL Gene 296:87-97(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; 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 [4]
RP INTERACTION WITH CAPN8, AND TISSUE SPECIFICITY.
RX PubMed=16476741; DOI=10.1074/jbc.m509244200;
RA Hata S., Koyama S., Kawahara H., Doi N., Maeda T., Toyama-Sorimachi N.,
RA Abe K., Suzuki K., Sorimachi H.;
RT "Stomach-specific calpain, nCL-2, localizes in mucus cells and proteolyzes
RT the beta-subunit of coatomer complex, beta-COP.";
RL J. Biol. Chem. 281:11214-11224(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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).
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. Through the catalyzed exchange of gamma-phosphate between
CC di- and triphosphonucleosides participates in regulation of
CC intracellular nucleotide homeostasis. Binds to anionic phospholipids,
CC predominantly to cardiolipin; the binding inhibits its phosphotransfer
CC activity. Acts as mitochondria-specific NDK; its association with
CC cardiolipin-containing mitochondrial inner membrane is coupled to
CC respiration suggesting that ADP locally regenerated in the
CC mitochondrion innermembrane space by its activity is directly taken up
CC via ANT ADP/ATP translocase into the matrix space to stimulate
CC respiratory ATP regeneration. Proposed to increase GTP-loading on
CC dynamin-related GTPase OPA1 in mitochondria. In vitro can induce
CC liposome cross-linking suggesting that it can cross-link inner and
CC outer membranes to form contact sites, and promotes intermembrane
CC migration of anionic phosphoplipids. Promotes the redistribution of
CC cardiolipin between the mitochondrial inner membrane and outer membrane
CC which is implicated in pro-apoptotic signaling (By similarity).
CC {ECO:0000250|UniProtKB:O00746}.
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 -!- SUBUNIT: Homohexamer (By similarity). Interacts with OPA1 (By
CC similarity). Interacts with CAPN8 (PubMed:16476741).
CC {ECO:0000250|UniProtKB:O00746, ECO:0000269|PubMed:16476741}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:O00746}; Peripheral membrane protein.
CC Mitochondrion matrix {ECO:0000250|UniProtKB:O00746}. Note=Predominantly
CC localized in the mitochondrion intermembrane space. Colocalizes with
CC OPA1 in mitochondria (By similarity). {ECO:0000250|UniProtKB:O00746}.
CC -!- TISSUE SPECIFICITY: Expressed in the base region of the oxyntic and
CC pyloric mucosae. {ECO:0000269|PubMed:16476741}.
CC -!- SIMILARITY: Belongs to the NDK family. {ECO:0000305}.
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DR EMBL; AF153451; AAD38977.1; -; mRNA.
DR EMBL; AF288690; AAG02200.1; -; mRNA.
DR EMBL; AF288692; AAG02202.1; -; Genomic_DNA.
DR EMBL; BC027277; AAH27277.1; -; mRNA.
DR CCDS; CCDS28544.1; -.
DR RefSeq; NP_062705.1; NM_019731.1.
DR AlphaFoldDB; Q9WV84; -.
DR SMR; Q9WV84; -.
DR BioGRID; 208032; 2.
DR STRING; 10090.ENSMUSP00000025007; -.
DR PhosphoSitePlus; Q9WV84; -.
DR EPD; Q9WV84; -.
DR MaxQB; Q9WV84; -.
DR PaxDb; Q9WV84; -.
DR PRIDE; Q9WV84; -.
DR ProteomicsDB; 252820; -.
DR Antibodypedia; 34896; 405 antibodies from 26 providers.
DR DNASU; 56520; -.
DR Ensembl; ENSMUST00000025007; ENSMUSP00000025007; ENSMUSG00000024177.
DR GeneID; 56520; -.
DR KEGG; mmu:56520; -.
DR UCSC; uc008bdh.1; mouse.
DR CTD; 4833; -.
DR MGI; MGI:1931148; Nme4.
DR VEuPathDB; HostDB:ENSMUSG00000024177; -.
DR eggNOG; KOG0888; Eukaryota.
DR GeneTree; ENSGT00940000160286; -.
DR HOGENOM; CLU_060216_6_0_1; -.
DR InParanoid; Q9WV84; -.
DR OrthoDB; 1334716at2759; -.
DR PhylomeDB; Q9WV84; -.
DR TreeFam; TF106373; -.
DR BRENDA; 2.7.4.6; 3474.
DR Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates.
DR BioGRID-ORCS; 56520; 2 hits in 75 CRISPR screens.
DR PRO; PR:Q9WV84; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9WV84; protein.
DR Bgee; ENSMUSG00000024177; Expressed in hindlimb bud and 161 other tissues.
DR ExpressionAtlas; Q9WV84; baseline and differential.
DR Genevisible; Q9WV84; MM.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:1901612; F:cardiolipin binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IBA:GO_Central.
DR GO; GO:0006241; P:CTP biosynthetic process; IEA:InterPro.
DR GO; GO:0006183; P:GTP biosynthetic process; IEA:InterPro.
DR GO; GO:0006869; P:lipid transport; ISO:MGI.
DR GO; GO:0006165; P:nucleoside diphosphate phosphorylation; IEA:InterPro.
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 ATP-binding; Kinase; Lipid transport; Lipid-binding; Magnesium; Membrane;
KW Metal-binding; Mitochondrion; Nucleotide metabolism; Nucleotide-binding;
KW Reference proteome; Transferase; Transit peptide; Transport.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:O00746"
FT CHAIN 33..186
FT /note="Nucleoside diphosphate kinase, mitochondrial"
FT /id="PRO_0000019433"
FT ACT_SITE 150
FT /note="Pros-phosphohistidine intermediate"
FT /evidence="ECO:0000250"
FT BINDING 44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 92
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 120
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 126
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 137
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 147
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 186 AA; 20549 MW; 472A32D65C0B25A0 CRC64;
MGSLFGRVAA LRALLCGPRF QCLLVRPSSG GPPWPQERTL VAVKPDGVQR RLVGTVIQRF
ERRGFKLVGM KMLQAPESIL AEHYRDLQRK PFYPALISYM SSGPVVAMVW EGPNVVHISR
AMIGHTDSTE AAPGTIRGDF SVHISRNVIH ASDSVDGAQR EIELWFQSSE LLNWADGGHH
SSCYPA
