Alpha-kinases: Analysis of the family and comparison with conventional protein kinases

Diana Drennan, Alexey Ryazanov

Research output: Contribution to journalReview articlepeer-review

96 Scopus citations


Alpha-kinases are a recently discovered family of protein kinases that have no detectable sequence homology to conventional protein kinases (CPKs). They include elongation factor 2 kinase, Dictyostelium myosin heavy chain kinases and many other protein kinases from diverse organisms, as revealed by various genome sequencing projects. Mammals have six alpha-kinases, including two channel-kinases - novel signaling molecules that contain an alpha-kinase domain fused to an ion-channel. Analysis of all known alpha-kinase sequences reveals the presence of several highly conserved motifs. Despite the fact that alpha-kinases have no detectable sequence identity with CPKs, the recently determined three-dimensional structure of the channel-kinase TRPM7/ChaK1 kinase domain reveals that alpha-kinases have a fold very similar to CPKs. Using the structural alignment of channel-kinase TRPM7/ChaK1 with cyclic-AMP dependent kinase, the consensus motifs of alpha-kinases and CPKs were aligned and compared. Remarkably, the majority of structural elements, sequence motifs, and the position of key amino acid residues important for catalysis appear to be very similar in alpha-kinases and CPKs. Differences between alpha-kinases and CPKs, and their possible impact on substrate recognition are discussed.

Original languageEnglish (US)
Pages (from-to)1-32
Number of pages32
JournalProgress in Biophysics and Molecular Biology
Issue number1
StatePublished - May 1 2004

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Molecular Biology

Fingerprint Dive into the research topics of 'Alpha-kinases: Analysis of the family and comparison with conventional protein kinases'. Together they form a unique fingerprint.

Cite this