Kinase Subfamily CDK11

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Kinase Classification: Group CMGC: Family CDK: Subfamily CDK11

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 (no gap is annotated, but is is a clear deletion, relative to the A locus and to EST sequences).

Two EST sequences (dbj|DC409145.1, dbj|DC387671.1) cover exons 1 – 4 of CDK11A and CDK11B respectively and DC387671.1 fills in the genomic gap covering exons 3 - 4 of CDK11B. The two loci are collapsed into one in the independently assembled personal genome of Craig Venter, but individual sequence reads (ABSL01045045.1, ABSL01045046.1) show both genes to be present in this genome. Other personal genomes have been assembled on the GRCh37 and so, unsurprisingly, have both loci, though several gaps in both, including exons 3-4 of CDK11B, making it difficult to conclude whether there are two loci or one.

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, CDK11B agrees with all or almost all vertebrate homologs, suggesting that the A gene is either under strong positive selection or is degenerating into a pseudogene. It also suggests that the CDK11A is a separate gene, and not a radical haplotype variant.

Evolution

Domain Structure

Functions

References