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PROSITE documentation PDOC51158Alpha-type protein kinase domain profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC51158
The α-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 α-kinase domain [2]. 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 [3]. 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>) [4].
The crystal structure of the α-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 α-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 α-kinase.
- Neurospora α-kinase with a VWFA domain.
The profile we developed covers the entire α-kinase domain.
Last update:November 2005 / First entry.
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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. | |
| Source | Nature 334:170-173(1988). | |
| PubMed ID | 3386756 | |
| DOI | 10.1038/334170a0 |
| 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). | |
| PubMed ID | 9054368 |
| 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). | |
| PubMed ID | 10021370 |
| 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). | |
| PubMed ID | 15050379 | |
| DOI | 10.1016/S0079-6107(03)00060-9 |
| 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). | |
| PubMed ID | 11389851 |
| 6 | Authors | Runnels L.W. Yue L. Clapham D.E. |
| Title | TRP-PLIK, a bifunctional protein with kinase and ion channel activities. | |
| Source | Science 291:1043-1047(2001). | |
| PubMed ID | 11161216 | |
| DOI | 10.1126/science.1058519 |
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