Kinase Subfamily PLK2
Kinase Classification: Group Other: Family PLK: Subfamily PLK2
PLK2 is a deuterostome-specific subfamily of the PLK mitotic kinase family. Unlike the other subfamilies, PLK1 and SAK, PLK2 kinases are expressed in many post-mitotic tissues, and have known functions focused on neurobiology [1].
Evolution
PLK2 is likely deuterostome-specific, though a possible remote ortholog has been found in Nematostella (a basal animal). A single PLK2 is found in the sea urchin, while vertebrates have duplicated the gene to form PLK2 and PLK3. An additional duplication gave rise to PLK5 in mammals and in Xenopus, but it appears to have been lost from birds and lizards, and is frequently pseudogenized (see below).
Domain Structure
PLK2 proteins have an N-terminal kinase domain and a pair of polo boxes implicated in substrate binding. Various orthologs of PLK5 have mutations that lead to the expression of truncated proteins, lacking the kinase domain and/or one of the polo boxes.
Functions
PLK5
PLK5 is a vertebrate-specific member of the PLK2 subfamily, with a volatile evolutionary history. PLK5 is an apparent pseudogene in human and chimp, as well as cow. though it is still expressed in human and cow [1]. PLK5 is absent from bird and reptile genomes and highly divergent in frog. Compared with the mouse sequence, the human is well aligned, but has an inframe stop codon in exon 6, within the kinase domain (between the APE and DxW motifs). The stop is found in ESTs, cDNAs, and 9 personal human genomes (available as of May 2010). It also has a frameshift in exon 11, but this is compensated in EST/cDNA sequences by an extension of exon 11, skipping of exon 12, and a return to the normal reading frame in exon 13. The loss of exon 12 substantially disrupts the first PBD (polo box).
The premature stop codon, and frameshift/extension of exon 11 is human-specific, and not found in chimp or other primates. Conversely, chimp has an independent internal frameshift mutation, verified by 4/4 genomic reads, that suggest the ORF was disabled independently in the human and chimp lineages. Other primate genomes (Gorilla, Rhesus, Marmoset) also lack the chimp frameshift but are poorly assembled in this region, so it's not clear if they have a functional PLK5 or not. A rough Ka/Ks analysis indicates that PLK5 is not under constraint within primates, but is under purifying selection in rodents.
A putative PLK5 in Xenopus tropicalis shares synteny with the mammalian gene, as both have ADAMTSL5 as one of their immediate neighbors (synteny is not conserved on the other side of the gene; a set of Xenopus genes (Neurolysin, SGTA, SLC39A3 map to another locus in human, where no PLK is found). No PLK5 could be found by sequence homology or synteny in chicken, zebra finch, or lizard genomes, or any of five sequenced fish genomes.
PLK5 appears to be more divergent and faster evolving that PLK2 or PLK3. It lacks the activatory phosphorlyation sites T210(Plk1) found in other PLKs, and the PBD2 polo box is also particularly fast evolving, lacking some residues involved in substrate binding in PLK1-3.
However, the human gene expresses a truncated protein, starting soon after the stop within the kinase domain, and this protein has been shown to have biological activity [2, 3].
References
- de Cárcer G, Manning G, and Malumbres M. From Plk1 to Plk5: functional evolution of polo-like kinases. Cell Cycle. 2011 Jul 15;10(14):2255-62. DOI:10.4161/cc.10.14.16494 |
- de Cárcer G, Escobar B, Higuero AM, García L, Ansón A, Pérez G, Mollejo M, Manning G, Meléndez B, Abad-Rodríguez J, and Malumbres M. Plk5, a polo box domain-only protein with specific roles in neuron differentiation and glioblastoma suppression. Mol Cell Biol. 2011 Mar;31(6):1225-39. DOI:10.1128/MCB.00607-10 |
- Andrysik Z, Bernstein WZ, Deng L, Myer DL, Li YQ, Tischfield JA, Stambrook PJ, and Bahassi el M. The novel mouse Polo-like kinase 5 responds to DNA damage and localizes in the nucleolus. Nucleic Acids Res. 2010 May;38(9):2931-43. DOI:10.1093/nar/gkq011 |
