UniProtKB - O00746 (NDKM_HUMAN)
Nucleoside diphosphate kinase, mitochondrial
NME4
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 PublicationsCatalytic activityi
- a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-deoxyribonucleoside 5'-triphosphate + ADP1 PublicationEC:2.7.4.61 Publication
- EC:2.7.4.61 Publication
- This reaction proceeds in the forward1 Publication direction.
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 45 | ATPBy similarity | 1 | |
Binding sitei | 93 | ATPBy similarity | 1 | |
Binding sitei | 121 | ATPBy similarity | 1 | |
Binding sitei | 127 | ATPBy similarity | 1 | |
Binding sitei | 138 | ATPBy similarity | 1 | |
Binding sitei | 148 | ATPBy similarity | 1 | |
Active sitei | 151 | Pros-phosphohistidine intermediateBy similarity | 1 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- cardiolipin binding Source: BHF-UCL
- metal ion binding Source: UniProtKB-KW
- nucleoside diphosphate kinase activity Source: GO_Central
GO - Biological processi
- CTP biosynthetic process Source: InterPro
- GTP biosynthetic process Source: InterPro
- lipid transport Source: BHF-UCL
- nucleoside metabolic process Source: ProtInc
- UTP biosynthetic process Source: InterPro
Keywordsi
Molecular function | Kinase, Transferase |
Biological process | Lipid transport, Nucleotide metabolism, Transport |
Ligand | ATP-binding, Lipid-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.4.6, 2681 |
PathwayCommonsi | O00746 |
Reactomei | R-HSA-499943, Interconversion of nucleotide di- and triphosphates |
SignaLinki | O00746 |
Chemistry databases
SwissLipidsi | SLP:000000360 |
Names & Taxonomyi
Protein namesi | Recommended name: Nucleoside diphosphate kinase, mitochondrialCurated (EC:2.7.4.61 Publication)Short name: NDK Short name: NDP kinase, mitochondrial Alternative name(s): Nucleoside diphosphate kinase D Short name: NDPKD nm23-H4 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7852, NME4 |
MIMi | 601818, gene |
neXtProti | NX_O00746 |
VEuPathDBi | HostDB:ENSG00000103202 |
Subcellular locationi
Mitochondrion
- Mitochondrion intermembrane space 1 Publication; Peripheral membrane protein
- Mitochondrion matrix 1 Publication
Note: Predominantly localized in the mitochondrion intermembrane space (PubMed:18635542). Colocalizes with OPA1 in mitochondria (PubMed:24970086).2 Publications
Mitochondrion
- mitochondrial inner membrane Source: Reactome
- mitochondrial intermembrane space Source: BHF-UCL
- mitochondrial matrix Source: UniProtKB-SubCell
- mitochondrion Source: HPA
Keywords - Cellular componenti
Membrane, MitochondrionPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 90 | R → D: Abolishes cardiolipin-containing membrane binding; decreases lipid transfer and pro-apoptotic activity; does not change phosphotransfer activity. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 4833 |
OpenTargetsi | ENSG00000103202 |
PharmGKBi | PA31657 |
Miscellaneous databases
Pharosi | O00746, Tbio |
Genetic variation databases
BioMutai | NME4 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 28 | MitochondrionSequence analysisAdd BLAST | 28 | |
ChainiPRO_0000019432 | 29 – 187 | Nucleoside diphosphate kinase, mitochondrialAdd BLAST | 159 |
Proteomic databases
EPDi | O00746 |
jPOSTi | O00746 |
MassIVEi | O00746 |
MaxQBi | O00746 |
PaxDbi | O00746 |
PeptideAtlasi | O00746 |
PRIDEi | O00746 |
ProteomicsDBi | 449 48013 [O00746-1] |
PTM databases
iPTMneti | O00746 |
PhosphoSitePlusi | O00746 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000103202, Expressed in fundus of stomach and 245 other tissues |
ExpressionAtlasi | O00746, baseline and differential |
Genevisiblei | O00746, HS |
Organism-specific databases
HPAi | ENSG00000103202, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
O00746
Protein-protein interaction databases
BioGRIDi | 110897, 181 interactors |
IntActi | O00746, 120 interactors |
MINTi | O00746 |
STRINGi | 9606.ENSP00000219479 |
Miscellaneous databases
RNActi | O00746, protein |
Structurei
Secondary structure
3D structure databases
SMRi | O00746 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O00746 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG0888, Eukaryota |
GeneTreei | ENSGT00940000160286 |
HOGENOMi | CLU_060216_6_3_1 |
InParanoidi | O00746 |
OMAi | WADEGHH |
OrthoDBi | 1334716at2759 |
PhylomeDBi | O00746 |
TreeFami | TF106373 |
Family and domain databases
Gene3Di | 3.30.70.141, 1 hit |
HAMAPi | MF_00451, NDP_kinase, 1 hit |
InterProi | View protein in InterPro IPR034907, NDK-like_dom IPR036850, NDK-like_dom_sf IPR001564, Nucleoside_diP_kinase IPR023005, Nucleoside_diP_kinase_AS |
Pfami | View protein in Pfam PF00334, NDK, 1 hit |
PRINTSi | PR01243, NUCDPKINASE |
SMARTi | View protein in SMART SM00562, NDK, 1 hit |
SUPFAMi | SSF54919, SSF54919, 1 hit |
PROSITEi | View protein in PROSITE PS00469, NDP_KINASES, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ4TT34 | Q4TT34_HUMAN | Nucleoside diphosphate kinase | NME4 | 195 | Annotation score: | ||
F2Z2X0 | F2Z2X0_HUMAN | Nucleoside diphosphate kinase | NME4 | 233 | Annotation score: | ||
A0A087WVT9 | A0A087WVT9_HUMAN | Nucleoside diphosphate kinase | NME4 | 153 | Annotation score: | ||
A2IDC9 | A2IDC9_HUMAN | Nucleoside diphosphate kinase, mito... | NME4 | 37 | Annotation score: | ||
H0Y6J0 | H0Y6J0_HUMAN | Nucleoside diphosphate kinase, mito... | NME4 | 169 | Annotation score: | ||
F2Z297 | F2Z297_HUMAN | Nucleoside diphosphate kinase, mito... | NME4 | 44 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054743 | 1 – 70 | Missing in isoform 2. CuratedAdd BLAST | 70 |
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 |
CCDSi | CCDS10408.1 [O00746-1] CCDS66886.1 [O00746-2] |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000219479; ENSP00000219479; ENSG00000103202 ENST00000397722; ENSP00000380834; ENSG00000103202 [O00746-2] ENST00000450036; ENSP00000389048; ENSG00000103202 [O00746-2] ENST00000620944; ENSP00000479996; ENSG00000103202 [O00746-2] |
GeneIDi | 4833 |
KEGGi | hsa:4833 |
MANE-Selecti | ENST00000219479.7; ENSP00000219479.2; NM_005009.3; NP_005000.1 |
UCSCi | uc002cgz.4, human [O00746-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS10408.1 [O00746-1] CCDS66886.1 [O00746-2] |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1EHW | X-ray | 2.40 | A/B | 33-175 | [»] | |
SMRi | O00746 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110897, 181 interactors |
IntActi | O00746, 120 interactors |
MINTi | O00746 |
STRINGi | 9606.ENSP00000219479 |
Chemistry databases
SwissLipidsi | SLP:000000360 |
PTM databases
iPTMneti | O00746 |
PhosphoSitePlusi | O00746 |
Genetic variation databases
BioMutai | NME4 |
Proteomic databases
EPDi | O00746 |
jPOSTi | O00746 |
MassIVEi | O00746 |
MaxQBi | O00746 |
PaxDbi | O00746 |
PeptideAtlasi | O00746 |
PRIDEi | O00746 |
ProteomicsDBi | 449 48013 [O00746-1] |
Protocols and materials databases
Antibodypediai | 34896, 380 antibodies from 25 providers |
DNASUi | 4833 |
Genome annotation databases
Ensembli | ENST00000219479; ENSP00000219479; ENSG00000103202 ENST00000397722; ENSP00000380834; ENSG00000103202 [O00746-2] ENST00000450036; ENSP00000389048; ENSG00000103202 [O00746-2] ENST00000620944; ENSP00000479996; ENSG00000103202 [O00746-2] |
GeneIDi | 4833 |
KEGGi | hsa:4833 |
MANE-Selecti | ENST00000219479.7; ENSP00000219479.2; NM_005009.3; NP_005000.1 |
UCSCi | uc002cgz.4, human [O00746-1] |
Organism-specific databases
CTDi | 4833 |
DisGeNETi | 4833 |
GeneCardsi | NME4 |
HGNCi | HGNC:7852, NME4 |
HPAi | ENSG00000103202, Low tissue specificity |
MIMi | 601818, gene |
neXtProti | NX_O00746 |
OpenTargetsi | ENSG00000103202 |
PharmGKBi | PA31657 |
VEuPathDBi | HostDB:ENSG00000103202 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0888, Eukaryota |
GeneTreei | ENSGT00940000160286 |
HOGENOMi | CLU_060216_6_3_1 |
InParanoidi | O00746 |
OMAi | WADEGHH |
OrthoDBi | 1334716at2759 |
PhylomeDBi | O00746 |
TreeFami | TF106373 |
Enzyme and pathway databases
BRENDAi | 2.7.4.6, 2681 |
PathwayCommonsi | O00746 |
Reactomei | R-HSA-499943, Interconversion of nucleotide di- and triphosphates |
SignaLinki | O00746 |
Miscellaneous databases
BioGRID-ORCSi | 4833, 5 hits in 1045 CRISPR screens |
ChiTaRSi | NME4, human |
EvolutionaryTracei | O00746 |
GeneWikii | NME4 |
GenomeRNAii | 4833 |
Pharosi | O00746, Tbio |
PROi | PR:O00746 |
RNActi | O00746, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000103202, Expressed in fundus of stomach and 245 other tissues |
ExpressionAtlasi | O00746, baseline and differential |
Genevisiblei | O00746, HS |
Family and domain databases
Gene3Di | 3.30.70.141, 1 hit |
HAMAPi | MF_00451, NDP_kinase, 1 hit |
InterProi | View protein in InterPro IPR034907, NDK-like_dom IPR036850, NDK-like_dom_sf IPR001564, Nucleoside_diP_kinase IPR023005, Nucleoside_diP_kinase_AS |
Pfami | View protein in Pfam PF00334, NDK, 1 hit |
PRINTSi | PR01243, NUCDPKINASE |
SMARTi | View protein in SMART SM00562, NDK, 1 hit |
SUPFAMi | SSF54919, SSF54919, 1 hit |
PROSITEi | View protein in PROSITE PS00469, NDP_KINASES, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NDKM_HUMAN | |
Accessioni | O00746Primary (citable) accession number: O00746 Secondary accession number(s): A2IDD0, Q5U0M9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | July 1, 1997 | |
Last modified: | February 23, 2022 | |
This is version 198 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families