The NM23 family in development

Mol Cell Biochem. 2009 Sep;329(1-2):17-33. doi: 10.1007/s11010-009-0121-6. Epub 2009 May 7.


The NM23 (non-metastatic 23) family is almost universally conserved across all three domains of life: eubacteria, archaea and eucaryotes. Unicellular organisms possess one NM23 ortholog, whilst vertebrates possess several. Gene multiplication through evolution has been accompanied by structural and functional diversification. Many NM23 orthologs are nucleoside diphosphate kinases (NDP kinases), but some more recently evolved members lack NDP kinase activity and/or display other functions, for instance, acting as protein kinases or transcription factors. These members display overlapping but distinct expression patterns during vertebrate development. In this review, we describe the functional differences and similarities among various NM23 family members. Moreover, we establish orthologous relationships through a phylogenetic analysis of NM23 members across vertebrate species, including Xenopus laevis and zebrafish, primitive chordates and several phyla of invertebrates. Finally, we summarize the involvement of NM23 proteins in development, in particular neural development. Carcinogenesis is a process of misregulated development, and NM23 was initially implicated as a metastasis suppressor. A more detailed understanding of the evolution of the family and its role in vertebrate development will facilitate elucidation of the mechanism of NM23 involvement in human cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Embryo, Nonmammalian / metabolism
  • Gene Expression
  • Growth and Development*
  • Humans
  • Male
  • Molecular Sequence Data
  • NM23 Nucleoside Diphosphate Kinases / genetics*
  • NM23 Nucleoside Diphosphate Kinases / metabolism
  • Neoplasms / genetics
  • Neurogenesis / genetics*
  • Nucleoside-Diphosphate Kinase / genetics*
  • Nucleoside-Diphosphate Kinase / metabolism
  • Nucleoside-Diphosphate Kinase / physiology
  • Phylogeny
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Xenopus laevis / embryology
  • Xenopus laevis / growth & development
  • Xenopus laevis / metabolism


  • NM23 Nucleoside Diphosphate Kinases
  • Transcription Factors
  • Nucleoside-Diphosphate Kinase