NME4

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

Full Name

non-metastatic cells 4, protein expressed in

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).

Biological Process

CTP biosynthetic processIEA:InterPro
GTP biosynthetic processIEA:InterPro
Lipid transportManual Assertion Based On ExperimentIDA:BHF-UCL
Nucleoside metabolic processManual Assertion Based On ExperimentTAS:ProtInc
UTP biosynthetic processIEA:InterPro

Cellular Location

Mitochondrion intermembrane space
Mitochondrion matrix
Predominantly localized in the mitochondrion intermembrane space (PubMed:18635542).
Colocalizes with OPA1 in mitochondria (PubMed:24970086).