|PROSITE documentation PDOC51158 [for PROSITE entry PS51158]|
The α-kinases were initially identified because of the experimentally observed ability of EF-2 kinase to phosphorylate elongation factor-2 . It was shown that the EF-2 kinase and the myosin heavy chain kinase A (MHCK A) share a conserved region of about 250 amino acids, the α-kinase domain . The name α-kinase was suggested for the family according to existing evidence that eIF-2 and MHCK A phosphorylate amino acids located within α-helices whereas classical kinase proteins phosphorylate amino acids within loops . α-kinases are multi-domain proteins with a wide variety of domains present in the family. These include: ion-channels, VWFA domains (see <PDOC50234>), WD-repeats (see <PDOC00574>), TPR-repeats (see <PDOC50005>), immunoglobulin-like domains (see <PDOC50835>) and calmodulin binding domains. Members of the α-kinase family share no detectable sequence similarity with the large family of "classical" eukaryotic protein kinases (see <PDOC00100>) .
The crystal structure of the α-kinase domain of a TPR channel has been solved . The structure bears a striking resemblance to that of classical protein kinases in the catalytic core as well as to metabolic enzymes with the ATP-grasp domain. As in classical kinase the domain consists of two lobes that bind nucleotide at the interface between them. The N-terminal lobe is very similar in structure to that of classical protein kinases, whereas its C-terminal lobe resembles that of ATP-grasp proteins more closely. A conserved C-terminal glycine rich motif which locates in the region that corresponds to the activation loop of classical kinases is essential for the enzymatic activity . The C-terminal lobe contains a metal ion which is coordinated by two histidines and two cysteines.
Proteins known to contain an α-kinase domain are listed below:
The profile we developed covers the entire α-kinase domain.Last update:
November 2005 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Ryazanov A.G. Shestakova E.A. Natapov P.G.|
|Title||Phosphorylation of elongation factor 2 by EF-2 kinase affects rate of translation.|
|2||Authors||Cote G.P. Luo X. Murphy M.B. Egelhoff T.T.|
|Title||Mapping of the novel protein kinase catalytic domain of Dictyostelium myosin II heavy chain kinase A.|
|Source||J. Biol. Chem. 272:6846-6849(1997).|
|3||Authors||Ryazanov A.G. Pavur K.S. Dorovkov M.V.|
|Title||Alpha-kinases: a new class of protein kinases with a novel catalytic domain.|
|Source||Curr. Biol. 9:R43-R45(1999).|
|4||Authors||Drennan D. Ryazanov A.G.|
|Title||Alpha-kinases: analysis of the family and comparison with conventional protein kinases.|
|Source||Prog. Biophys. Mol. Biol. 85:1-32(2004).|
|5||Authors||Yamaguchi H. Matsushita M. Nairn A.C. Kuriyan J.|
|Title||Crystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity.|
|Source||Mol. Cell 7:1047-1057(2001).|
|6||Authors||Runnels L.W. Yue L. Clapham D.E.|
|Title||TRP-PLIK, a bifunctional protein with kinase and ion channel activities.|