NME1 Active Protein

This gene (NME1) was identified because of its reduced mRNA transcript levels in highly metastatic cells. Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by this gene) and 'B' (encoded by NME2) isoforms. Mutations in this gene have been identified in aggressive neuroblastomas. Two transcript variants encoding different isoforms have been found for this gene. Co-transcription of this gene and the neighboring downstream gene (NME2) generates naturally-occurring transcripts (NME1-NME2), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Jul 2008]

NME1: an enzyme with multiple activities including histidine protein kinase, nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase and 3'-5' exonuclease activities. Plays a 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. Involved in cell proliferation, differentiation and development, G protein-coupled receptor endocytosis, cytotoxic T cell and NK cell-mediated cell death, and gene expression. Required for neural development including neural patterning and cell fate determination. During granzyme A (GZMA)-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair. Three alternatively spliced human proteins have been reported.

Protein type: Kinase, other; Tumor suppressor; Nucleotide Metabolism - purine; Kinase, nucleoside diphosphate; Protein kinase, histidine; Nucleotide Metabolism - pyrimidine; EC 2.7.4.6; Other group; NDK family

Chromosomal Location of Human Ortholog: 17q21.3

Cellular Component: mitochondrion; membrane; cytoplasm; cytosol; nucleus

Molecular Function: identical protein binding; protein binding; GTP binding; nucleoside diphosphate kinase activity; deoxyribonuclease activity; magnesium ion binding; ATP binding; ribosomal small subunit binding

Biological Process: GTP biosynthetic process; nervous system development; nucleobase, nucleoside and nucleotide metabolic process; nucleobase, nucleoside and nucleotide interconversion; UTP biosynthetic process; nucleoside diphosphate phosphorylation; endocytosis; DNA catabolic process; regulation of apoptosis; negative regulation of cell proliferation; CTP biosynthetic process; pyrimidine nucleotide metabolic process; nucleoside triphosphate biosynthetic process; cell differentiation; positive regulation of epithelial cell proliferation; purine nucleotide metabolic process; positive regulation of DNA binding

Disease: Neuroblastoma, Susceptibility To