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Protein

Nucleoside diphosphate kinase, mitochondrial

Gene

NME4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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. Through the catalyzed exchange of gamma-phosphate between di- and triphosphonucleosides participates in regulation of intracellular nucleotide homeostasis (PubMed:10799505). Binds to anionic phospholipids, predominantly to cardiolipin; the binding inhibits its phosphotransfer activity (PubMed:18635542, PubMed:23150663). Acts as mitochondria-specific NDK; its association with cardiolipin-containing mitochondrial inner membrane is coupled to respiration suggesting that ADP locally regenerated in the mitochondrion innermembrane space by its activity is directly taken up via ANT ADP/ATP translocase into the matrix space to stimulate respiratory ATP regeneration (PubMed:18635542). Proposed to increase GTP-loading on dynamin-related GTPase OPA1 in mitochondria (PubMed:24970086). In vitro can induce liposome cross-linking suggesting that it can cross-link inner and outer membranes to form contact sites, and promotes intermembrane migration of anionic phosphoplipids. Promotes the redistribution of cardiolipin between the mitochondrial inner membrane and outer membrane which is implicated in pro-apoptotic signaling (PubMed:18635542, PubMed:17028143, PubMed:23150663).Curated4 Publications

Catalytic activityi

ATP + nucleoside diphosphate = ADP + nucleoside triphosphate.

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei45ATPBy similarity1
Binding sitei93ATPBy similarity1
Binding sitei121ATPBy similarity1
Binding sitei127ATPBy similarity1
Binding sitei138ATPBy similarity1
Binding sitei148ATPBy similarity1
Active sitei151Pros-phosphohistidine intermediateBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
Biological processLipid transport, Nucleotide metabolism, Transport
LigandATP-binding, Lipid-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.4.6 2681
ReactomeiR-HSA-499943 Interconversion of nucleotide di- and triphosphates

Chemistry databases

SwissLipidsiSLP:000000360

Names & Taxonomyi

Protein namesi
Recommended name:
Nucleoside diphosphate kinase, mitochondrial (EC:2.7.4.6)
Short name:
NDK
Short name:
NDP kinase, mitochondrial
Alternative name(s):
Nucleoside diphosphate kinase D
Short name:
NDPKD
nm23-H4
Gene namesi
Name:NME4
Synonyms:NM23D
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000103202.12
HGNCiHGNC:7852 NME4
MIMi601818 gene
neXtProtiNX_O00746

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi90R → D: Abolishes cardiolipin-containing membrane binding; decreases lipid transfer and pro-apoptotic activity; does not change phosphotransfer activity. 2 Publications1

Organism-specific databases

DisGeNETi4833
OpenTargetsiENSG00000103202
PharmGKBiPA31657

Polymorphism and mutation databases

BioMutaiNME4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 28MitochondrionSequence analysisAdd BLAST28
ChainiPRO_000001943229 – 187Nucleoside diphosphate kinase, mitochondrialAdd BLAST159

Proteomic databases

EPDiO00746
MaxQBiO00746
PaxDbiO00746
PeptideAtlasiO00746
PRIDEiO00746
ProteomicsDBi48013

PTM databases

iPTMnetiO00746
PhosphoSitePlusiO00746

Expressioni

Tissue specificityi

Widely distributed. Found at very high levels in prostate, heart, liver, small intestine, and skeletal muscle tissues, and in low amounts in the brain and in blood leukocytes.

Gene expression databases

BgeeiENSG00000103202 Expressed in 232 organ(s), highest expression level in fundus of stomach
CleanExiHS_NME4
ExpressionAtlasiO00746 baseline and differential
GenevisibleiO00746 HS

Organism-specific databases

HPAiCAB045997
HPA072588

Interactioni

Subunit structurei

Homohexamer (PubMed:10799505). Interacts with OPA1 (PubMed:23150663). Interacts with CAPN8 (By similarity).By similarity2 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi110897, 64 interactors
IntActiO00746, 62 interactors
MINTiO00746
STRINGi9606.ENSP00000219479

Structurei

Secondary structure

1187
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO00746
SMRiO00746
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00746

Family & Domainsi

Sequence similaritiesi

Belongs to the NDK family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0888 Eukaryota
COG0105 LUCA
GeneTreeiENSGT00760000119146
HOGENOMiHOG000224564
HOVERGENiHBG000423
InParanoidiO00746
KOiK00940
PhylomeDBiO00746
TreeFamiTF106373

Family and domain databases

Gene3Di3.30.70.141, 1 hit
HAMAPiMF_00451 NDP_kinase, 1 hit
InterProiView protein in InterPro
IPR034907 NDK-like_dom
IPR036850 NDK-like_dom_sf
IPR001564 Nucleoside_diP_kinase
IPR023005 Nucleoside_diP_kinase_AS
PfamiView protein in Pfam
PF00334 NDK, 1 hit
PRINTSiPR01243 NUCDPKINASE
SMARTiView protein in SMART
SM00562 NDK, 1 hit
SUPFAMiSSF54919 SSF54919, 1 hit
PROSITEiView protein in PROSITE
PS00469 NDP_KINASES, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O00746-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGGLFWRSAL RGLRCGPRAP GPSLLVRHGS GGPSWTRERT LVAVKPDGVQ
60 70 80 90 100
RRLVGDVIQR FERRGFTLVG MKMLQAPESV LAEHYQDLRR KPFYPALIRY
110 120 130 140 150
MSSGPVVAMV WEGYNVVRAS RAMIGHTDSA EAAPGTIRGD FSVHISRNVI
160 170 180
HASDSVEGAQ REIQLWFQSS ELVSWADGGQ HSSIHPA
Length:187
Mass (Da):20,659
Last modified:July 1, 1997 - v1
Checksum:iA56FEF18A7D712D4
GO
Isoform 2 (identifier: O00746-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:117
Mass (Da):12,979
Checksum:i3B885B828E3C1042
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q4TT34Q4TT34_HUMAN
Nucleoside diphosphate kinase
NME4
195Annotation score:
F2Z2X0F2Z2X0_HUMAN
Nucleoside diphosphate kinase
NME4
233Annotation score:
A0A087WVT9A0A087WVT9_HUMAN
Nucleoside diphosphate kinase
NME4
153Annotation score:
H0Y6J0H0Y6J0_HUMAN
Nucleoside diphosphate kinase, mito...
NME4
169Annotation score:
A2IDC9A2IDC9_HUMAN
Nucleoside diphosphate kinase, mito...
NME4
37Annotation score:
F2Z297F2Z297_HUMAN
Nucleoside diphosphate kinase, mito...
NME4
44Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0547431 – 70Missing in isoform 2. CuratedAdd BLAST70

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y07604 mRNA Translation: CAA68877.1
BT019438 mRNA Translation: AAV38245.1
AE006463 Genomic DNA Translation: AAK61230.1
Z97634 Genomic DNA No translation available.
CH471112 Genomic DNA Translation: EAW85818.1
CH471112 Genomic DNA Translation: EAW85819.1
CH471112 Genomic DNA Translation: EAW85820.1
BC004880 mRNA Translation: AAH04880.1
BC017067 mRNA Translation: AAH17067.1
CCDSiCCDS10408.1 [O00746-1]
CCDS66886.1 [O00746-2]
RefSeqiNP_001273362.1, NM_001286433.1
NP_001273364.1, NM_001286435.1
NP_001273365.1, NM_001286436.1 [O00746-2]
NP_001273367.1, NM_001286438.1 [O00746-2]
NP_001273368.1, NM_001286439.1 [O00746-2]
NP_001273369.1, NM_001286440.1 [O00746-2]
NP_005000.1, NM_005009.2 [O00746-1]
UniGeneiHs.9235

Genome annotation databases

EnsembliENST00000219479; ENSP00000219479; ENSG00000103202 [O00746-1]
ENST00000397722; ENSP00000380834; ENSG00000103202 [O00746-2]
ENST00000450036; ENSP00000389048; ENSG00000103202 [O00746-2]
ENST00000620944; ENSP00000479996; ENSG00000103202 [O00746-2]
GeneIDi4833
KEGGihsa:4833
UCSCiuc002cgz.4 human [O00746-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y07604 mRNA Translation: CAA68877.1
BT019438 mRNA Translation: AAV38245.1
AE006463 Genomic DNA Translation: AAK61230.1
Z97634 Genomic DNA No translation available.
CH471112 Genomic DNA Translation: EAW85818.1
CH471112 Genomic DNA Translation: EAW85819.1
CH471112 Genomic DNA Translation: EAW85820.1
BC004880 mRNA Translation: AAH04880.1
BC017067 mRNA Translation: AAH17067.1
CCDSiCCDS10408.1 [O00746-1]
CCDS66886.1 [O00746-2]
RefSeqiNP_001273362.1, NM_001286433.1
NP_001273364.1, NM_001286435.1
NP_001273365.1, NM_001286436.1 [O00746-2]
NP_001273367.1, NM_001286438.1 [O00746-2]
NP_001273368.1, NM_001286439.1 [O00746-2]
NP_001273369.1, NM_001286440.1 [O00746-2]
NP_005000.1, NM_005009.2 [O00746-1]
UniGeneiHs.9235

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EHWX-ray2.40A/B33-175[»]
ProteinModelPortaliO00746
SMRiO00746
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110897, 64 interactors
IntActiO00746, 62 interactors
MINTiO00746
STRINGi9606.ENSP00000219479

Chemistry databases

SwissLipidsiSLP:000000360

PTM databases

iPTMnetiO00746
PhosphoSitePlusiO00746

Polymorphism and mutation databases

BioMutaiNME4

Proteomic databases

EPDiO00746
MaxQBiO00746
PaxDbiO00746
PeptideAtlasiO00746
PRIDEiO00746
ProteomicsDBi48013

Protocols and materials databases

DNASUi4833
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000219479; ENSP00000219479; ENSG00000103202 [O00746-1]
ENST00000397722; ENSP00000380834; ENSG00000103202 [O00746-2]
ENST00000450036; ENSP00000389048; ENSG00000103202 [O00746-2]
ENST00000620944; ENSP00000479996; ENSG00000103202 [O00746-2]
GeneIDi4833
KEGGihsa:4833
UCSCiuc002cgz.4 human [O00746-1]

Organism-specific databases

CTDi4833
DisGeNETi4833
EuPathDBiHostDB:ENSG00000103202.12
GeneCardsiNME4
H-InvDBiHIX0012647
HGNCiHGNC:7852 NME4
HPAiCAB045997
HPA072588
MIMi601818 gene
neXtProtiNX_O00746
OpenTargetsiENSG00000103202
PharmGKBiPA31657
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0888 Eukaryota
COG0105 LUCA
GeneTreeiENSGT00760000119146
HOGENOMiHOG000224564
HOVERGENiHBG000423
InParanoidiO00746
KOiK00940
PhylomeDBiO00746
TreeFamiTF106373

Enzyme and pathway databases

BRENDAi2.7.4.6 2681
ReactomeiR-HSA-499943 Interconversion of nucleotide di- and triphosphates

Miscellaneous databases

ChiTaRSiNME4 human
EvolutionaryTraceiO00746
GeneWikiiNME4
GenomeRNAii4833
PROiPR:O00746
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000103202 Expressed in 232 organ(s), highest expression level in fundus of stomach
CleanExiHS_NME4
ExpressionAtlasiO00746 baseline and differential
GenevisibleiO00746 HS

Family and domain databases

Gene3Di3.30.70.141, 1 hit
HAMAPiMF_00451 NDP_kinase, 1 hit
InterProiView protein in InterPro
IPR034907 NDK-like_dom
IPR036850 NDK-like_dom_sf
IPR001564 Nucleoside_diP_kinase
IPR023005 Nucleoside_diP_kinase_AS
PfamiView protein in Pfam
PF00334 NDK, 1 hit
PRINTSiPR01243 NUCDPKINASE
SMARTiView protein in SMART
SM00562 NDK, 1 hit
SUPFAMiSSF54919 SSF54919, 1 hit
PROSITEiView protein in PROSITE
PS00469 NDP_KINASES, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNDKM_HUMAN
AccessioniPrimary (citable) accession number: O00746
Secondary accession number(s): A2IDD0, Q5U0M9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: November 7, 2018
This is version 179 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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