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PROSITE documentation PDOC51158 [for PROSITE entry PS51158]

Alpha-type protein kinase domain profile





Description

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.

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 --------------------------------------------------------------------------------.

Last update:

November 2005 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

ALPHA_KINASE, PS51158; Alpha-type protein kinase domain profile  (MATRIX)


References

1AuthorsRyazanov A.G. Shestakova E.A. Natapov P.G.
TitlePhosphorylation of elongation factor 2 by EF-2 kinase affects rate of translation.
SourceNature 334:170-173(1988).
PubMed ID3386756
DOI10.1038/334170a0

2AuthorsCote G.P. Luo X. Murphy M.B. Egelhoff T.T.
TitleMapping of the novel protein kinase catalytic domain of Dictyostelium myosin II heavy chain kinase A.
SourceJ. Biol. Chem. 272:6846-6849(1997).
PubMed ID9054368

3AuthorsRyazanov A.G. Pavur K.S. Dorovkov M.V.
TitleAlpha-kinases: a new class of protein kinases with a novel catalytic domain.
SourceCurr. Biol. 9:R43-R45(1999).
PubMed ID10021370

4AuthorsDrennan D. Ryazanov A.G.
TitleAlpha-kinases: analysis of the family and comparison with conventional protein kinases.
SourceProg. Biophys. Mol. Biol. 85:1-32(2004).
PubMed ID15050379
DOI10.1016/S0079-6107(03)00060-9

5AuthorsYamaguchi H. Matsushita M. Nairn A.C. Kuriyan J.
TitleCrystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity.
SourceMol. Cell 7:1047-1057(2001).
PubMed ID11389851

6AuthorsRunnels L.W. Yue L. Clapham D.E.
TitleTRP-PLIK, a bifunctional protein with kinase and ion channel activities.
SourceScience 291:1043-1047(2001).
PubMed ID11161216
DOI10.1126/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 prosite_license.html.

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