Kinase Subfamily HYKK
Kinase Classification: Group PKL: Family CAK: Subfamily HYKK
HYKK is a eukaryotic kinase recently shown to phosphorylate a lysine derivative during collagen catabolism
Evolution
HYKK is found in in most animals and some bacteria. It is lost from most nematodes.
Function
Human HYKK was recently shown to phosphorylate 5-hydroxy-lysine, as part of the breakdown process for collagen (collagen has a unique post-translational modification of some lysines to form 5-hydroxy-lysine, and so requires a specific degradation mechanism) [1]. Its role was elegantly revealed using a phylogenetic tip: HYKK is also found in some bacteria, where it frequently is fused with homologs of AGXT2L1/2. Biochemical analysis showed HYKK to be a GTP-dependent kinase of 5-hydroxy-lysine, and AGXT2L2 to carryout an aminotransferase reaction on the phosphorylated 5-hydoxy-lysine. This function is reminiscent of Fructosamine Kinase, which phosphorlyates glycated residues on aged proteins, providing the phosphate energy for a later deglycation step.
Domain Structure
Most animal HYKK have a sole domain, the kinase domain. This domain conserves the key catalytic motifs of the PKL fold, and is similar to both the CAK and HSK2 families of small molecule kinases.
Evolution
Found in most or all animals, in some other eukaryotes (algae and some heterokonts) and in some bacteria. Bacterial forms are frequently fused to an OAT aminotransferase domain and a single fungal homolog (XP_384884.1 from Gibberella zeae) has the same domain arrangement, probably a case of horizontal transfer.
