Nucleoside diphosphate kinase 3
Developmental stage
Preferentially expressed at early stages of myeloid differentiation of highly purified CD34+ cells.
Domain
The N-terminal hydrophobic region (1-17) is critical for mitochondrial outer membrane targeting and phosphatidic acid binding.
Function
Catalyzes the phosphorylation of ribonucleosides and deoxyribonucleoside diphosphates, other than ATP, into the corresponding triphosphates with ATP as the major phosphate donor (PubMed:11277919, PubMed:30587587). The ATP gamma phosphate is transferred to the nucleoside diphosphate 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:11277919, PubMed:30587587). Inhibits granulocyte differentiation (PubMed:7638209). May be required for ciliary function during renal development (By similarity).
Independently of its kinase activity, facilitates mitochondrial tethering prior to membrane fusion through its direct membrane-binding and hexamerization (PubMed:30587587, PubMed:37584589). Implicated in repair of both single- and double-stranded breaks in DNA through its association with the ribonucleotide reductase complex (RNR complex) via its interaction with the histone acetyltransferase KAT5, this interaction enables recruitment of NME3 at DNA damage sites where it plays a role in the repair of DNA, independently of its kinase activity (PubMed:37584589).
Involvement in disease
A substitution in the initiation codon of the NME3 gene substitution (p.Met1Val), resulting in lack of full protein expression has been found in a female infant with an early-onset fatal neurodegenerative disorder.
Sequence Similarities
Belongs to the NDK family.
Cellular localization
- Mitochondrion outer membrane
- Peripheral membrane protein
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Cilium basal body
Alternative names
Nucleoside diphosphate kinase 3, NDK 3, NDP kinase 3, DR-nm23, Nucleoside diphosphate kinase C, nm23-H3, NDPKC, NME3