View source for Kinase Subfamily PI4K2

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[[kinase classification|Kinase Classification]]: [[Kinase_Group_PKL|Group PKL]]: [[Kinase_Family_PIK|Family PIK]]: [[Kinase_Subfamily_PI4K2|Subfamily PI4K2]]

PI4K2 are phosphatidyl inositol 4' kinases. They are members of the [[PKL]] fold of protein kinases and appear to be highly distant members of the [[Kinase_Family_PIK|PIK]] family of phosphatidyl inositol 3' and 4' kinases.

====Evolution====
PI4K2 are found in almost all eukaryotes, and in several clades of bacteria. There are two human members, PI4K2A and PI4K2B.

====Catalytic Activity====
Despite the name, plant members of this family from wheat and Arabidopsis have shown protein autophosphorylation activity, but not lipid kinase activity  <cite>Liu, Galvao</cite>. Yeast and mammalian forms are known to have lipid kinase activity.

====Sequence Notes====
The catalytic loop is uncertain, as PI4K2 have two adjacent DxxxxN motifs close to where the catalytic loop can be, and neither ones gives a uniquely good alignment to other PKL kinases. The first of these motifs has a consensus of NT'''D'''Rgnd'''N'''. The fourth position R is also absolutely conserved in PI3K and PI4K1, and the DN residues are also mostly conserved in PI3K, suggesting that this may be the correct activation loop. Mutation of the putative D166 and N171 residues of this first motif in rat PI4K2 resulted in complete or almost complete loss of activity <cite>Barylko</cite>, but both motifs are conserved even in bacteria, suggesting that both D and both N residues are critical for function.

Apart from this similarity, PI4K2 have no obvious remote sequence similarity to the other PIK subfamilies beyond its similarity to the PKL fold (and their common substrates). Some remote searches suggest that [[Kinase_Family_GASK|GASK]] kinases are weakly related to PI4K2, and that the remote actin-fragmin kinase (AFK) structure from ''Physarum polycephalum'' may also be related. A published alignment of actin-fragmin kinase with PI4K2 and other kinases does support that the second DxxxxN motif is the catalytic loop, and shows the first DxxxxN to be present in AFK <cite>Steinbacher</cite>. There is as yet no published structure for a PI4K2.

====References====
<biblio>
#Barylko pmid=12215430
#Galvao pmid=17880284
#Liu pmid=23682116
#Steinbacher pmid=10357805
</biblio>