Kinase Subfamily CDK11

Kinase Classification: Group CMGC: Family CDK

CDK11 (PITSLRE, CDC2L)

This subfamily is found in almost all eukaryotes. Originally named PITSLRE, from the sequence of the Cyclin-binding motif, it is now named CDK11. The CDK19 gene (CDK8 subfamily) was named CDK11 in the original human kinome nomenclature, leading to some literature and database confusion.

CDK11 human duplication

The CDK11 gene is tandemly duplicated in the human genome, but is a single copy in chimp and other vertebrates (other than rat, which has a retrotransposed copy on the X chromosome). Whether the second copy is functional, or even real, is still somewhat uncertain. The two copies of the gene, and most of the tandemly duplicated region is very similar by sequence, and in the reference human genome (GRCh37) a region spanning exons 3-4 of the CDK11B copy are missing.

The two genes differ at 25 positions, including a 6 nt coding indel and 9 other non-synonymous changes. The CDK11 sequence is highly conserved across vertebrates: in 9 of these 11 AA polymorphisms, CDK11A agrees with all or almost all vertebrate homologs, suggesting that the B form is either under strong positive selection or is degenerating into a pseudogene.

Most polymorphisms map to the exon 3-4 region, but there are? positions in ESTs and expressed sequences that suggest that both isoforms are expressed. However, it's not entirely possible to tell that these are not population variants. In the independently-assembled Craig Venter genome, the two loci are collapsed into one, while in several other individual human genomes, which are assembled by mapping to the NCBI reference, both loci are found, but contain many gaps. Both forms are seen in trace reads from the Venter (and...?) genome, suggesting that both loci are present, or CV is heterozygote for both forms. The fact that so many of the B polymorphisms are radical suggests that this is a duplication and not a radical haplotype variant.