NME1
Description
The NME1 (NME/NM23 nucleoside diphosphate kinase 1) is a protein-coding gene located on chromosome 17.
The NME1 gene encodes Nucleoside diphosphate kinase A (NDK A), an enzyme that is believed to be a metastasis suppressor. This gene was identified due to its reduced mRNA transcript levels in highly metastatic cells. NDK exists as a hexamer composed of 'A' (encoded by NME1) and 'B' (encoded by NME2) isoforms. Mutations in NME1 have been linked to aggressive neuroblastomas. Two transcript variants encoding different isoforms have been found for NME1. Co-transcription of NME1 and its neighboring downstream gene (NME2) generates naturally occurring transcripts (NME1-NME2), which encode a fusion protein containing sequences from each individual gene product. A bioinformatics study in 2023 suggested a potential prognostic role for NME1 in neuroblastoma.
NME1 plays a crucial role in synthesizing nucleoside triphosphates, excluding ATP. This process involves transferring the gamma phosphate from ATP to the beta phosphate of NDPs through a ping-pong mechanism utilizing a phosphorylated active site intermediate. NME1 exhibits a variety of enzymatic activities including nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase, and 3'-5' exonuclease. It is involved in various cellular processes, including cell proliferation, differentiation, development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. NME1 is essential for neural development, including neural patterning and cell fate determination. During GZMA-mediated cell death, NME1 cooperates with TREX1. NME1 introduces a nick in one DNA strand, while TREX1 removes bases from the free 3' end, amplifying DNA damage, preventing DNA end reannealing, and hindering rapid repair.
NME1 is also known as AWD, GAAD, NB, NBS, NDKA, NDPK-A, NDPKA, NM23, NM23-H1.
