Tbio NME4 Nucleoside diphosphate kinase, mitochondrial

Protein Summary

Description

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). 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]

Uniprot Accession IDs

• O00746
• A2IDD0
• Q5U0M9
• NDK

Gene Name

• NME4

Ensembl ID

• ENST00000219479
• ENSP00000219479
• ENSG00000103202
• ENST00000397722
• ENSP00000380834
• ENST00000450036
• ENSP00000389048
• ENST00000620944
• ENSP00000479996

Symbol

• NM23D
• NDPK-D
• NM23H4
• nm23-H4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.96
transcription factor perturbation	0.8
cellular component	0.76
gene perturbation	0.74
biological process	0.72

Protein Classes

DTO Classes

Protein / Kinase / Unclassified Protein / Nucleoside Diphosphate Kinase, Mitochondrial

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 37.98   (req: < 5)

Gene RIFs: 13   (req: <= 3)

Antibodies: 342   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 37.98   (req: >= 5)

Gene RIFs: 13   (req: > 3)

Antibodies: 342   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 10

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0