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Aliases for NME4 Gene

Aliases for NME4 Gene

  • NME/NM23 Nucleoside Diphosphate Kinase 4 2 3
  • Non-Metastatic Cells 4, Protein Expressed In 2 3
  • Nucleoside Diphosphate Kinase D 3 4
  • NDP Kinase, Mitochondrial 3 4
  • EC 2.7.4.6 4 63
  • Nm23-H4 3 4
  • NDPKD 3 4
  • NDK 3 4
  • Nucleoside Diphosphate Kinase, Mitochondrial 3
  • NDP Kinase D 3
  • NDPK-D 3
  • NM23H4 3
  • NM23D 4

External Ids for NME4 Gene

Previous GeneCards Identifiers for NME4 Gene

  • GC16P000466
  • GC16P000387
  • GC16P000446
  • GC16P000368

Summaries for NME4 Gene

Entrez Gene Summary for NME4 Gene

  • The nucleoside diphosphate (NDP) kinases (EC 2.7.4.6) are ubiquitous enzymes that catalyze transfer of gamma-phosphates, via a phosphohistidine intermediate, between nucleoside and dioxynucleoside tri- and diphosphates. The enzymes are products of the nm23 gene family, which includes NME4 (Milon et al., 1997 [PubMed 9099850]).[supplied by OMIM, May 2008]

GeneCards Summary for NME4 Gene

NME4 (NME/NM23 Nucleoside Diphosphate Kinase 4) is a Protein Coding gene. Diseases associated with NME4 include fatal infantile lactic acidosis and cystic fibrosis. Among its related pathways are Metabolism and Metabolism. An important paralog of this gene is NME7.

UniProtKB/Swiss-Prot for NME4 Gene

  • 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).

Gene Wiki entry for NME4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NME4 Gene

Genomics for NME4 Gene

Regulatory Elements for NME4 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for NME4 Gene

Start:
396,725 bp from pter
End:
410,367 bp from pter
Size:
13,643 bases
Orientation:
Plus strand

Genomic View for NME4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NME4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NME4 Gene

Proteins for NME4 Gene

  • Protein details for NME4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O00746-NDKM_HUMAN
    Recommended name:
    Nucleoside diphosphate kinase, mitochondrial
    Protein Accession:
    O00746
    Secondary Accessions:
    • A2IDD0
    • Q5U0M9

    Protein attributes for NME4 Gene

    Size:
    187 amino acids
    Molecular mass:
    20659 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Homohexamer (PubMed:10799505). Interacts with OPA1 (PubMed:23150663). Interacts with CAPN8 (By similarity).

    Three dimensional structures from OCA and Proteopedia for NME4 Gene

    Alternative splice isoforms for NME4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NME4 Gene

Proteomics data for NME4 Gene at MOPED

Selected DME Specific Peptides for NME4 Gene

Post-translational modifications for NME4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains for NME4 Gene

Protein Domains for NME4 Gene

Graphical View of Domain Structure for InterPro Entry

O00746

UniProtKB/Swiss-Prot:

NDKM_HUMAN :
  • O00746
Family:
  • Belongs to the NDK family.
genes like me logo Genes that share domains with NME4: view

No data available for Gene Families for NME4 Gene

Function for NME4 Gene

Molecular function for NME4 Gene

GENATLAS Biochemistry: non-metastatic cells 4,protein,nm23 nucleoside diphosphate kinase gene family,involved in the phosphorylation of nucleoside diphosphates and putatively involved int intramitochondrial GTP metabolism
UniProtKB/Swiss-Prot CatalyticActivity: ATP + nucleoside diphosphate = ADP + nucleoside triphosphate
UniProtKB/Swiss-Prot Function: 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).

Enzyme Numbers (IUBMB) for NME4 Gene

Gene Ontology (GO) - Molecular Function for NME4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004550 nucleoside diphosphate kinase activity EXP --
GO:0005515 protein binding IPI 16189514
GO:0005524 ATP binding IEA --
GO:0032403 protein complex binding IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with NME4: view

Animal Model Products

CRISPR Products

No data available for Phenotypes , Animal Models , Transcription Factor Targeting and HOMER Transcription for NME4 Gene

Localization for NME4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NME4 Gene

Mitochondrion intermembrane space; Peripheral membrane protein. Mitochondrion matrix. Note=Predominantly localized in the mitochondrion intermembrane space (PubMed:18635542). Colocalizes with OPA1 in mitochondria (PubMed:24970086). {ECO:0000269 PubMed:18635542, ECO:0000269 PubMed:24970086}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NME4 Gene COMPARTMENTS Subcellular localization image for NME4 gene
Compartment Confidence
mitochondrion 5
chloroplast 2
cytoskeleton 2
cytosol 2
plasma membrane 2
nucleus 1

Gene Ontology (GO) - Cellular Components for NME4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion TAS 9099850
GO:0005743 mitochondrial inner membrane TAS --
GO:0005758 mitochondrial intermembrane space IEA --
GO:0005829 cytosol IBA --
genes like me logo Genes that share ontologies with NME4: view

Pathways for NME4 Gene

genes like me logo Genes that share pathways with NME4: view

Pathways by source for NME4 Gene

1 GeneGo (Thomson Reuters) pathway for NME4 Gene

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

Gene Ontology (GO) - Biological Process for NME4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006163 purine nucleotide metabolic process IBA --
GO:0006165 nucleoside diphosphate phosphorylation IEA --
GO:0006183 GTP biosynthetic process IEA --
GO:0006220 pyrimidine nucleotide metabolic process IBA --
GO:0006228 UTP biosynthetic process IEA --
genes like me logo Genes that share ontologies with NME4: view

Compounds for NME4 Gene

(21) HMDB Compounds for NME4 Gene

Compound Synonyms Cas Number PubMed IDs
2'-Deoxyinosine triphosphate
  • 2'-Deoxyinosine-5'-triphosphate
16595-02-1
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
CDP
  • CDP
63-38-7
Cytidine triphosphate
  • cytidine 5'-(tetrahydrogen triphosphate)
65-47-4

(8) Novoseek inferred chemical compound relationships for NME4 Gene

Compound -log(P) Hits PubMed IDs
gtp 57.7 9
alginate 54.4 3
gdp 44.5 4
atp 44.3 1
adp 34.4 1
genes like me logo Genes that share compounds with NME4: view

Transcripts for NME4 Gene

Unigene Clusters for NME4 Gene

NME/NM23 nucleoside diphosphate kinase 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for NME4

Primer Products

  • OriGene qSTAR qPCR primer pairs in human,mouse,rat for NME4

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for NME4 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b · 4c · 4d · 4e ^ 5a · 5b · 5c · 5d · 5e ^ 6a · 6b ^ 7a · 7b ^ 8 ^ 9 ^ 10a · 10b
SP1: - - -
SP2: -
SP3: -
SP4: - - -
SP5: - - - - - -
SP6: -
SP7:

Relevant External Links for NME4 Gene

GeneLoc Exon Structure for
NME4
ECgene alternative splicing isoforms for
NME4

Expression for NME4 Gene

mRNA expression in normal human tissues for NME4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for NME4 Gene

SOURCE GeneReport for Unigene cluster for NME4 Gene Hs.9235

mRNA Expression by UniProt/SwissProt for NME4 Gene

O00746-NDKM_HUMAN
Tissue specificity: 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
genes like me logo Genes that share expressions with NME4: view

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for NME4 Gene

Orthologs for NME4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NME4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NME4 35
  • 96.5 (n)
  • 98.15 (a)
NME4 36
  • 98 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NME4 36
  • 50 (a)
OneToOne
dog
(Canis familiaris)
Mammalia -- 36
  • 80 (a)
OneToMany
-- 36
  • 77 (a)
OneToMany
NME4 35
  • 86.63 (n)
  • 83.87 (a)
mouse
(Mus musculus)
Mammalia Nme4 35
  • 82.16 (n)
  • 83.78 (a)
Nme4 16
Nme4 36
  • 83 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NME4 36
  • 66 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nme4 35
  • 82.7 (n)
  • 83.24 (a)
chicken
(Gallus gallus)
Aves NME4 36
  • 56 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NME4 36
  • 61 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.9894 35
tropical clawed frog
(Silurana tropicalis)
Amphibia nme4 35
  • 67.06 (n)
  • 71.18 (a)
zebrafish
(Danio rerio)
Actinopterygii nme4 35
  • 67.33 (n)
  • 72.19 (a)
nme4 36
  • 59 (a)
OneToOne
zgc56482 35
fruit fly
(Drosophila melanogaster)
Insecta awd 36
  • 47 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea ndk-1 36
  • 52 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes YNK1 36
  • 49 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 51 (a)
OneToMany
Species with no ortholog for NME4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NME4 Gene

ENSEMBL:
Gene Tree for NME4 (if available)
TreeFam:
Gene Tree for NME4 (if available)

Paralogs for NME4 Gene

Paralogs for NME4 Gene

Selected SIMAP similar genes for NME4 Gene using alignment to 7 proteins:

Pseudogenes.org Pseudogenes for NME4 Gene

genes like me logo Genes that share paralogs with NME4: view

Variants for NME4 Gene

Sequence variations from dbSNP and Humsavar for NME4 Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type MAF
rs14293 -- 399,659(+) GCCTC(A/G)AGGGC synonymous-codon, reference
rs387290 -- 398,479(+) CGGGG(C/T)TTCAG intron-variant
rs431324 -- 398,172(+) GGACT(A/G)TAGGA intron-variant, utr-variant-5-prime
rs763151 -- 399,345(+) TTACT(C/G)TCTGC intron-variant
rs2071914 -- 399,554(+) CAAAG(C/G)GAGGG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NME4 Gene

Variant ID Type Subtype PubMed ID
esv2422427 CNV Duplication 17116639
nsv904652 CNV Loss 21882294
dgv32n68 CNV Loss 17160897
dgv2469n71 CNV Loss 21882294
dgv2473n71 CNV Loss 21882294
nsv904707 CNV Loss 21882294
dgv2474n71 CNV Loss 21882294
nsv904709 CNV Gain+Loss 21882294
nsv904711 CNV Loss 21882294
nsv457303 CNV Loss 19166990
nsv904713 CNV Loss 21882294
nsv904714 CNV Loss 21882294
nsv904715 CNV Gain 21882294

Relevant External Links for NME4 Gene

HapMap Linkage Disequilibrium report
NME4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NME4 Gene

Disorders for NME4 Gene

MalaCards: The human disease database

MalaCards: The human disease database. (2) Diseases for NME4 Gene including...

Search for NME4 Gene in MalaCards »

(4) Novoseek inferred disease relationships for NME4 Gene

Disease -log(P) Hits PubMed IDs
cystic fibrosis 43.4 1
metastasis 14.7 4
tumors 0 4
tuberculosis 0 2

Relevant External Links for NME4

Genetic Association Database (GAD)
NME4
Human Genome Epidemiology (HuGE) Navigator
NME4
genes like me logo Genes that share disorders with NME4: view

No data available for UniProtKB/Swiss-Prot for NME4 Gene

Publications for NME4 Gene

  1. nm23-H4, a new member of the family of human nm23/nucleoside diphosphate kinase genes localised on chromosome 16p13. (PMID: 9099850) Milon L. … Lacombe M.-L. (Hum. Genet. 1997) 2 3 4 23
  2. The human nm23-H4 gene product is a mitochondrial nucleoside diphosphate kinase. (PMID: 10799505) Milon L. … Lacombe M.-L. (J. Biol. Chem. 2000) 3 4 23
  3. The nucleoside diphosphate kinase D (NM23-H4) binds the inner mitochondrial membrane with high affinity to cardiolipin and couples nucleotide transfer with respiration. (PMID: 18635542) Tokarska-Schlattner M. … Lacombe M.L. (J. Biol. Chem. 2008) 4 23
  4. Localization and characterization of the mitochondrial isoform of the nucleoside diphosphate kinase in the pancreatic beta cell: evidence for its complexation with mitochondrial succinyl-CoA synthetase. (PMID: 11831846) Kowluru A. … Chen H.Q. (Arch. Biochem. Biophys. 2002) 3 23
  5. Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16. (PMID: 11157797) Daniels R.J. … Higgs D.R. (Hum. Mol. Genet. 2001) 3 4

Products for NME4 Gene

  • Addgene plasmids for NME4

Sources for NME4 Gene

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