{PDOC51158} {PS51158; ALPHA_KINASE} {BEGIN} ******************************************** * Alpha-type protein kinase domain profile * ******************************************** The alpha-kinases were initially identified because of the experimentally observed ability of EF-2 kinase to phosphorylate elongation factor-2 [1]. 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 alpha-kinase domain [2]. The name alpha-kinase was suggested for the family according to existing evidence that eIF-2 and MHCK A phosphorylate amino acids located within alpha- helices whereas classical kinase proteins phosphorylate amino acids within loops [3]. Alpha-kinases are multi-domain proteins with a wide variety of domains present in the family. These include: ion-channels, VWFA domains (see ), WD-repeats (see ), TPR-repeats (see ), immunoglobulin-like domains (see ) and calmodulin binding domains. Members of the alpha-kinase family share no detectable sequence similarity with the large family of "classical" eukaryotic protein kinases (see ) [4]. The crystal structure of the alpha-kinase domain of a TPR channel has been solved [5]. 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 [6]. The C-terminal lobe contains a metal ion which is coordinated by two histidines and two cysteines. Proteins known to contain an alpha-kinase domain are listed below: - Eukaryotic elongation factor 2 kinase (EC 2.7.11.20) (eEF-2 kinase). It phosphorylates eukaryotic elongation factor 2. - Dictyostelium myosin heavy chain kinase A (EC 2.7.11.7) (MHCK A). It phosphorylates a threonine in the C-terminal tail region of myosin II heavy chain. This phosphorylation is critical in regulating the assembly and disassembly of myosin II filament. - A mammalian subclass of long transient receptor potential channels (TRPM7/ChaK1). An essential ion channel and serine/threonine-protein kinase. - Mammalian muscle alpha-kinase. - Neurospora alpha-kinase with a VWFA domain. The profile we developed covers the entire alpha-kinase domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: November 2005 / First entry. [ 1] Ryazanov A.G., Shestakova E.A., Natapov P.G. "Phosphorylation of elongation factor 2 by EF-2 kinase affects rate of translation." Nature 334:170-173(1988). PubMed=3386756; DOI=10.1038/334170a0 [ 2] Cote G.P., Luo X., Murphy M.B., Egelhoff T.T. "Mapping of the novel protein kinase catalytic domain of Dictyostelium myosin II heavy chain kinase A." J. Biol. Chem. 272:6846-6849(1997). PubMed=9054368 [ 3] Ryazanov A.G., Pavur K.S., Dorovkov M.V. "Alpha-kinases: a new class of protein kinases with a novel catalytic domain." Curr. Biol. 9:R43-R45(1999). PubMed=10021370 [ 4] Drennan D., Ryazanov A.G. "Alpha-kinases: analysis of the family and comparison with conventional protein kinases." Prog. Biophys. Mol. Biol. 85:1-32(2004). PubMed=15050379; DOI=10.1016/S0079-6107(03)00060-9 [ 5] Yamaguchi H., Matsushita M., Nairn A.C., Kuriyan J. "Crystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity." Mol. Cell 7:1047-1057(2001). PubMed=11389851 [ 6] Runnels L.W., Yue L., Clapham D.E. "TRP-PLIK, a bifunctional protein with kinase and ion channel activities." Science 291:1043-1047(2001). PubMed=11161216; DOI=10.1126/science.1058519 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}