Kinase Subfamily AlphaK1
Kinase Classification: Group PKL: Family Alpha: Subfamily AlphaK1
Domain Structure
Members have a helical N-terminal region followed by a poorly conserved linker and an alpha kinase domain.
Evolution
AlphaK1 (ALPK1) is a single-copy gene in vertebrates. Clear orthologs have also been detected in the chordate Branchiostoma floridae (lancelet) and the sea anemone, Nematostella, as well as several lophotrochozoa, suggesting that the gene was born in early metazoan evolution, but then lost from many lineages. Multiple invertebrate orthologs conserve the kinase domain and N-terminal helical domain, and have poor conservation of the intervening region.
Functions
ALPK1 has been implicated in vesicle transport from the Golgi to the plasma membrane [1], perhaps by myosin phosphorylation. Mouse ALPK1 mutants were associated with motor co-ordination defects [2], and the gene has been associated with both gout and kidney disease. Human ALPK1 has also been shown to be a receptor for the bacterial ADP-heptose[3]. ADP-heptose binding causes ALPK1 to phosphorylate TIFA and activate NFkB signaling.
References
- Heine M, Cramm-Behrens CI, Ansari A, Chu HP, Ryazanov AG, Naim HY, and Jacob R. Alpha-kinase 1, a new component in apical protein transport. J Biol Chem. 2005 Jul 8;280(27):25637-43. DOI:10.1074/jbc.M502265200 |
- Chen M and Xu R. Motor coordination deficits in Alpk1 mutant mice with the inserted piggyBac transposon. BMC Neurosci. 2011 Jan 5;12:1. DOI:10.1186/1471-2202-12-1 |
- Zhou P, She Y, Dong N, Li P, He H, Borio A, Wu Q, Lu S, Ding X, Cao Y, Xu Y, Gao W, Dong M, Ding J, Wang DC, Zamyatina A, and Shao F. Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose. Nature. 2018 Sep;561(7721):122-126. DOI:10.1038/s41586-018-0433-3 |
