CDK5 regulatory subunit-associated protein 2 is a protein that in humans is encoded by the CDK5RAP2gene. Multiple transcript variants exist for this gene, but the full-length nature of only two has been determined.[1][2] CDK5RAP2 is homologous to the Drosophila protein centrosomin (cnn).[3]
Neuronal CDC2-like kinase, which is involved in the regulation of neuronal differentiation, is composed of a catalytic subunit, CDK5, and an activating subunit, p25NCK5A. The protein encoded by this gene binds to p25NCK5A and therefore may be involved in neuronal differentiation. The encoded protein may also be a substrate of neuronal CDC2-like kinase.[2]
Clinical significance
A magnetic resonance imaging study has demonstrated a link between common variation in the CDK5RAP2 gene and brain structure.[4] More specifically, associations were found between several single nucleotide polymorphisms (SNPs) and brain cortical surface area and total brain volume. These associations were found exclusively in male subjects and all SNPs were located upstream in non-exonic regions. The functional significance of these loci is not yet known. However, given their location close to regulatory elements, it is possible that they are involved in gene regulation, which suggests that common variance in brain structure could be associated with differences in gene regulation rather than protein structure, consistent with findings in other complex human traits.
↑Wang X, Ching YP, Lam WH, Qi Z, Zhang M, Wang JH (October 2000). "Identification of a common protein association region in the neuronal Cdk5 activator". J. Biol. Chem. 275 (41): 31763–9. doi:10.1074/jbc.M004358200. PMID10915792.
Wang X, Ching YP, Lam WH, et al. (2000). "Identification of a common protein association region in the neuronal Cdk5 activator". J. Biol. Chem. 275 (41): 31763–9. doi:10.1074/jbc.M004358200. PMID10915792.
Nagase T, Kikuno R, Nakayama M, et al. (2001). "Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (4): 273–81. doi:10.1093/dnares/7.4.271. PMID10997877.
Ching YP, Pang AS, Lam WH, et al. (2002). "Identification of a neuronal Cdk5 activator-binding protein as Cdk5 inhibitor". J. Biol. Chem. 277 (18): 15237–40. doi:10.1074/jbc.C200032200. PMID11882646.
Andersen JS, Wilkinson CJ, Mayor T, et al. (2003). "Proteomic characterization of the human centrosome by protein correlation profiling". Nature. 426 (6966): 570–4. doi:10.1038/nature02166. PMID14654843.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Bond J, Roberts E, Springell K, et al. (2005). "A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size". Nat. Genet. 37 (4): 353–5. doi:10.1038/ng1539. PMID15793586.