Assignment of CDK5R2 coding for the cyclin-dependent kinase 5, regulatory subunit 2 (NCK5AI protein) to human chromosome band 2q35 by fluorescent in situ hybridization.

Abstract

Neuronal CDC2-like kinase (OMIM: 116940) is a heterodimer of CDK5 (OMIM: 123831) and p25 (nck5a), a neuronspecific 25-kDa regulatory subunit derived proteolytically from NCK5A, encoded by CDK5R1 (neuronal CDK5 activator or cyclin-dependent kinase 5 regulatory subunit 1 gene) (Lew et al., 1994; Tsai et al., 1994). By screening a human hippocampus library with a bovine Nck5a cDNA, Tang et al. (1995) isolated cDNAs encoding NCK5AI, a distinct NCK5A isoform. They also referred to the protein as p39 (nck5ai) based on its calculated molecular mass of 39 kDa. This isoform showed a high degree of sequence similarity to p35 (NCK5A) with 57% amino acid identity. A 30-kDa truncated form of p39 (nck5ai) activated both recombinant and native CDK5 in vitro, as does p25 (nck5a). Northern blot analysis of rat tissues indicated that both NCK5A and p39 (nck5ai) are expressed exclusively in brain. In situ hybridization to rat brain sections revealed that p39 (nck5ai) mRNA was highly expressed in the CA1 to CA3 zone of the hippocampal formation, an area highly enriched in neurons. There was no expression in the fimbria hippocampi, where glial cells predominate. Tang et al. (1995) concluded that p39 (nck5ai) shares many common characteristics with NCK5A, including CDK5-activating activity and brainand neuron-specific expression. Both proteins show limited sequence homology to cyclins, suggesting that they define a new family of cyclin-dependent kinase-activating proteins. The gene encoding p39 (nck5ai) was called CDK5R2. Partial sequencing of the NotI linking clone NR3-007 (Zabarovsky et al., 1994) revealed that it is 100% identical to CDK5R2 over 378 bp (aa 110–235). We concluded that NR3-007 contains part of CDK5R2 and mapped this gene using the NR3-007 clone.