Kinase Family Alpha
Kinase Classification: Group PKL: Family Alpha
This divergent family includes eEF2K (eukaryotic elongation factor 2 kinase) in most eukaryotes, and a variety of other kinases in individual phyla. Reviewed in [1].
Domain Structure
Subfamilies have quite different domain structures (below).
Major Subfamilies
The Alpha family has the following subfamilies:
eEF2K
Universal regulator of protein translation.
ChaK
Vertebrate-specific fusion of a mechanosensory ion channel with an alpha kinase.
AlphaK1
Metazoan kinase implicated in epithelial cell vesicle trafficking and NFkB induction in response to bacterial metabolite.
AlphaK2
Vertebrate specific alpha kinases expressed in skeletal and cardiac muscle
Other Subfamilies
The only other apparently deeply conserved alpha kinase is the Alpha-VWL subfamily, that encodes an N-terminal VWL domain and a C-terminal alpha kinase. This was first found in Dictyostelium [2], and later in the ciliate Tetrahymena [3]. These are also found in many animals, though lost from vertebrates, insects, and nematodes.
MHCKs are myosin heavy chain kinases from Dictyostelium, and among the best studied of alpha kinases. Dictyostelium also was the first to contain a VWL-kinase, an alpha kinase including a VWL domain that is also characterized from ciliates, and found in a number of animals, though not in vertebrates, insects, or nematodes.
Other expansions of uncharacterized alpha kinases have been found in kinome analyses of Leishmania (4 genes), mushroom (10), and sponge (8).
References
- Middelbeek J, Clark K, Venselaar H, Huynen MA, and van Leeuwen FN. The alpha-kinase family: an exceptional branch on the protein kinase tree. Cell Mol Life Sci. 2010 Mar;67(6):875-90. DOI:10.1007/s00018-009-0215-z |
- Goldberg JM, Manning G, Liu A, Fey P, Pilcher KE, Xu Y, and Smith JL. The dictyostelium kinome--analysis of the protein kinases from a simple model organism. PLoS Genet. 2006 Mar;2(3):e38. DOI:10.1371/journal.pgen.0020038 |
- Eisen JA, Coyne RS, Wu M, Wu D, Thiagarajan M, Wortman JR, Badger JH, Ren Q, Amedeo P, Jones KM, Tallon LJ, Delcher AL, Salzberg SL, Silva JC, Haas BJ, Majoros WH, Farzad M, Carlton JM, Smith RK Jr, Garg J, Pearlman RE, Karrer KM, Sun L, Manning G, Elde NC, Turkewitz AP, Asai DJ, Wilkes DE, Wang Y, Cai H, Collins K, Stewart BA, Lee SR, Wilamowska K, Weinberg Z, Ruzzo WL, Wloga D, Gaertig J, Frankel J, Tsao CC, Gorovsky MA, Keeling PJ, Waller RF, Patron NJ, Cherry JM, Stover NA, Krieger CJ, del Toro C, Ryder HF, Williamson SC, Barbeau RA, Hamilton EP, and Orias E. Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote. PLoS Biol. 2006 Sep;4(9):e286. DOI:10.1371/journal.pbio.0040286 |
- Yamaguchi H, Matsushita M, Nairn AC, and Kuriyan J. Crystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity. Mol Cell. 2001 May;7(5):1047-57. DOI:10.1016/s1097-2765(01)00256-8 |
