ID   NDKD_COLLI              Reviewed;         181 AA.
AC   P87355; O42206;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 3.
DT   02-SEP-2026, entry version 113.
DE   RecName: Full=Nucleoside diphosphate kinase D, mitochondrial {ECO:0000250|UniProtKB:O00746};
DE            Short=NDPK-D {ECO:0000250|UniProtKB:O00746};
DE            EC=2.7.4.6 {ECO:0000269|PubMed:9305928};
DE   AltName: Full=Nucleoside diphosphate kinase 4 {ECO:0000250|UniProtKB:O00746};
DE            Short=NDK4 {ECO:0000250|UniProtKB:O00746};
DE   Flags: Precursor;
GN   Name=NME4 {ECO:0000250|UniProtKB:O00746};
OS   Columba livia (Rock dove).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Neoaves; Columbimorphae; Columbiformes;
OC   Columbidae; Columba.
OX   NCBI_TaxID=8932;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-45, FUNCTION, CATALYTIC
RP   ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX   PubMed=9305928; DOI=10.1074/jbc.272.39.24604;
RA   Lambeth D.O., Mehus J.G., Ivey M.A., Milavetz B.I.;
RT   "Characterization and cloning of a nucleoside-diphosphate kinase targeted
RT   to matrix of mitochondria in pigeon.";
RL   J. Biol. Chem. 272:24604-24611(1997).
CC   -!- FUNCTION: Mitochondria-specific nucleoside diphosphate kinase that
CC       catalyzes the transfer of a gamma-phosphoryl group from ATP to a
CC       nucleoside diphosphate via a ping-pong mechanism involving a
CC       phosphohistidine intermediate, participating in nucleoside triphosphate
CC       homeostasis (PubMed:9305928). In vitro, purine nucleoside triphosphates
CC       are much more effective as donors and acceptors than pyrimidine
CC       nucleoside triphosphates, and ribonucleosides derivatives are superior
CC       to their deoxyribonucleosides counterparts (PubMed:9305928). Associates
CC       with cardiolipin-containing mitochondrial inner membrane and locally
CC       produces ADP in the mitochondrial intermembrane space, which is
CC       directly taken up via the ADP/ATP translocase (ANT) into the matrix to
CC       stimulate respiratory ATP regeneration. Also directly provides GTP for
CC       mitochondrial GTPases, such as the dynamin-related GTPase OPA1.
CC       Additionally, catalyzes the anionic phospholipid transfer, namely
CC       cardiolipin, from the mitochondrial inner membrane (IM) to the outer
CC       membrane (OM) through the formation of contact sites between IM and OM,
CC       in a nucleoside diphosphate kinase-independent manner. The switch
CC       between the nucleoside diphosphate kinase and the phospholipid transfer
CC       activity may depend on the availability and accessibility of
CC       cardiolipin and other anionic phospholipids in the IM outer leaflet and
CC       OM inner leaflet (By similarity). {ECO:0000250|UniProtKB:O00746,
CC       ECO:0000269|PubMed:9305928}.
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         Evidence={ECO:0000269|PubMed:9305928};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44641;
CC         Evidence={ECO:0000269|PubMed:9305928};
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         Evidence={ECO:0000269|PubMed:9305928};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18114;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=CDP + ATP = CTP + ADP; Xref=Rhea:RHEA:25237,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:37563, ChEBI:CHEBI:58069,
CC         ChEBI:CHEBI:456216; EC=2.7.4.6;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25238;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=GDP + ATP = GTP + ADP; Xref=Rhea:RHEA:27686,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:37565, ChEBI:CHEBI:58189,
CC         ChEBI:CHEBI:456216; EC=2.7.4.6;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27687;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=UDP + ATP = UTP + ADP; Xref=Rhea:RHEA:25098,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:46398, ChEBI:CHEBI:58223,
CC         ChEBI:CHEBI:456216; EC=2.7.4.6;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25099;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dCDP + ATP = dCTP + ADP; Xref=Rhea:RHEA:27678,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:58593, ChEBI:CHEBI:61481,
CC         ChEBI:CHEBI:456216; EC=2.7.4.6;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27680;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dGDP + ATP = dGTP + ADP; Xref=Rhea:RHEA:27690,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:58595, ChEBI:CHEBI:61429,
CC         ChEBI:CHEBI:456216; EC=2.7.4.6;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27691;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dTDP + ATP = dTTP + ADP; Xref=Rhea:RHEA:27682,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:37568, ChEBI:CHEBI:58369,
CC         ChEBI:CHEBI:456216; EC=2.7.4.6;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27683;
CC         Evidence={ECO:0000269|PubMed:9305928};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a cardiolipin(in) = a cardiolipin(out); Xref=Rhea:RHEA:38695,
CC         ChEBI:CHEBI:62237; Evidence={ECO:0000250|UniProtKB:O00746};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q13232};
CC   -!- ACTIVITY REGULATION: Binding to anionic phospholipids, predominantly to
CC       cardiolipin inhibits its phosphotransfer activity (By similarity).
CC       Feedback inhibition by ADP (PubMed:9305928). Inhibition of nucleoside
CC       diphosphate kinase activity at higher concentrations (>100uM) of GDP
CC       (PubMed:9305928). {ECO:0000250|UniProtKB:O00746,
CC       ECO:0000269|PubMed:9305928}.
CC   -!- SUBUNIT: Homohexamer. {ECO:0000250|UniProtKB:O00746}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC       {ECO:0000250|UniProtKB:O00746}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:O00746}. Mitochondrion matrix
CC       {ECO:0000269|PubMed:9305928}. Mitochondrion outer membrane
CC       {ECO:0000250|UniProtKB:O00746}. Note=Predominantly localized in the
CC       mitochondrion intermembrane space. Phospholipid binding mediates
CC       mitochondrial inner membrane binding. Fully membrane-bound, when
CC       attached simultaneously to inner membrane (IM) and outer membrane (OM)
CC       through the formation of contact sites between IM and OM. The
CC       additional binding to OM may depend on the availability or
CC       accessibility of cardiolipin and/or other anionic phospholipids in the
CC       IM outer leaflet and the OM inner leaflet.
CC       {ECO:0000250|UniProtKB:O00746}.
CC   -!- TISSUE SPECIFICITY: Highest levels in the liver and kidney with lower
CC       levels in the heart, brain and breast muscle.
CC   -!- SIMILARITY: Belongs to the NDK family. {ECO:0000305}.
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DR   EMBL; U89605; AAC78439.1; -; mRNA.
DR   EMBL; AF018267; AAC78438.1; -; Genomic_DNA.
DR   AlphaFoldDB; P87355; -.
DR   SMR; P87355; -.
DR   eggNOG; KOG0888; Eukaryota.
DR   BRENDA; 2.7.4.6; 1579.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; EXP:UniProtKB.
DR   GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR   GO; GO:0004550; F:nucleoside diphosphate kinase activity; ISS:UniProtKB.
DR   GO; GO:0140339; F:phosphatidylglycerol transfer activity; ISS:UniProtKB.
DR   GO; GO:0005543; F:phospholipid binding; ISS:UniProtKB.
DR   GO; GO:0006241; P:CTP biosynthetic process; IEA:InterPro.
DR   GO; GO:0006183; P:GTP biosynthetic process; IEA:InterPro.
DR   GO; GO:0120010; P:intermembrane phospholipid transfer; ISS:UniProtKB.
DR   GO; GO:0006228; P:UTP biosynthetic process; IEA:InterPro.
DR   CDD; cd04413; NDPk_I; 1.
DR   FunFam; 3.30.70.141:FF:000017; Nucleoside diphosphate kinase; 1.
DR   Gene3D; 3.30.70.141; Nucleoside diphosphate kinase-like domain; 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   NCBIfam; NF001908; PRK00668.1; 1.
DR   PANTHER; PTHR11349; NUCLEOSIDE DIPHOSPHATE KINASE; 1.
DR   Pfam; PF00334; NDK; 1.
DR   PRINTS; PR01243; NUCDPKINASE.
DR   SMART; SM00562; NDK; 1.
DR   SUPFAM; SSF54919; Nucleoside diphosphate kinase, NDK; 1.
DR   PROSITE; PS00469; NDPK; 1.
DR   PROSITE; PS51374; NDPK_LIKE; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Direct protein sequencing; Kinase; Lipid-binding; Magnesium;
KW   Membrane; Metal-binding; Mitochondrion; Mitochondrion outer membrane;
KW   Nucleotide metabolism; Nucleotide-binding; Phosphoprotein; Transferase;
KW   Transit peptide.
FT   TRANSIT         1..24
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:9305928"
FT   CHAIN           25..181
FT                   /note="Nucleoside diphosphate kinase D, mitochondrial"
FT                   /id="PRO_0000019431"
FT   REGION          1..22
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..10
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        146
FT                   /note="Pros-phosphohistidine intermediate"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        146
FT                   /note="Pros-phosphohistidine intermediatee"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         40
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         40
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         40
FT                   /ligand="UDP"
FT                   /ligand_id="ChEBI:CHEBI:58223"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         86
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         116
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         116
FT                   /ligand="UDP"
FT                   /ligand_id="ChEBI:CHEBI:58223"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         122
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         122
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         122
FT                   /ligand="UDP"
FT                   /ligand_id="ChEBI:CHEBI:58223"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         133
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         133
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         140
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         140
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         140
FT                   /ligand="UDP"
FT                   /ligand_id="ChEBI:CHEBI:58223"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         143
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         143
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
FT   BINDING         143
FT                   /ligand="UDP"
FT                   /ligand_id="ChEBI:CHEBI:58223"
FT                   /evidence="ECO:0000250|UniProtKB:Q13232"
SQ   SEQUENCE   181 AA;  20342 MW;  B892F7C44C001D2C CRC64;
     MFRGGTHRLR GQPGLSLPHG PRCYGSAPPE LQEKTLVLVK PDAVQRRLVG NVIQRFERRG
     FKLVAMKLLQ ADQGLLDKHY QQLRQKPFYP ALLAYMTSGP LVAMVWEGYN VVRSTRAMVG
     DTDSAVAAAG TIRGDFSMHV SRNVVHASDS VETAQREIGF WFQRNELVAW ESGDRDYTWG
     P
//