Kinase Family NKF5

Kinase Classification: Group Other: Family NKF5

This is probably the oddest of ePK families. It is almost entirely restricted to chordates, with SgK307 (TEX14) found mostly in chordates*, and SgK424 found only in placental mammals. The kinase domain of SgK307 is very divergent, with only about 25% sequence identity in the kinase domain relative to any other kinase. SgK424 is even more divergent, and while clearly a paralog of SgK307, the kinase domain shows only weak similarity (~28% ID) to SgK307 and just marginal similarity in the C lobe to other kinases.

Even odder is that it is dubious whether SgK424 is a real gene. There are very few ESTs in any species, and genomic comparisons show that the ORFs encoded by these ESTs are often interrupted by stops and frameshifts, or lack correct splice sites in other species. A plausible ORF can be constructed in most non-primate mammals, and shows reasonable Ka/Ks scores, indicating that it is under constraint. Prediction of the most similar ORF in several primates comes up with stops and frameshifts and a missing start, and those regions of the ORF that do align have low Ka/Ks scores, suggesting that it is no longer under evolutionary constraint. Pig and rat genes are supported by single ESTs, and the mouse also has a full length cDNA, but that has two errors in splicing, leading to a truncated protein.

• There is an SgK307 homolog in honey bee (Genbank: XP_625262.2) which is supported by 4 ESTs and includes both the ankyrin repeats and kinase domain of SgK307 as well as a long C-terminal extension. By contrast, SgK307 is found in Danio rerio but is absent from the four sequenced percomorph fish genomes.