title: Alpha-kinases: analysis of the family and comparison with conventional protein kinases.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Drennan
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Ryazanov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics; D020134:Catalytic Domain; D002678:Chimera / Q000235:genetics; D016384:Consensus Sequence; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D015800:Protozoan Proteins; D016415:Sequence Alignment; D050053:TRPM Cation Channels; D019892:eIF-2 Kinase / Q000737:chemistry / Q000235:genetics
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; D015800:Protozoan Proteins; D050053:TRPM Cation Channels; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D019892:eIF-2 Kinase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C033142:myosin-heavy-chain kinase