CDK5RAP2
Description
The CDK5RAP2 (CDK5 regulatory subunit associated protein 2) is a protein-coding gene located on chromosome 9.
CDK5 regulatory subunit-associated protein 2 is a protein that in humans is encoded by the CDK5RAP2 gene. It has necessary roles in the formation and stability of microtubules from the centrosome and has been found to be linked to human brain size variation in males. Multiple transcript variants exist for this gene, but the full-length nature of only two has been determined. CDK5RAP2 is homologous to the Drosophila protein centrosomin (cnn) and paralogous to myomegalin, which in mammals contains an Olduvai domain, a domain implicated in human brain size evolution.
== Function == CDK5RAP2 is necessary for the proper formation, anchoring and orientation of microtubules from the centrosome. It binds with the γ-tubulin ring complex (γTuRC), and this is required for the γTuRC to attach to the centrosome. CDK5RAP2 also binds to p25, a form of CDK5R1 that serves as the activating subunit of CDK5, which is involved in the regulation of neuronal differentiation. CDK5RAP2 therefore has a role in neuronal differentiation. CDK5RAP2 is also necessary as a scaffolding protein in the centrosomal corona of Dictyostelium.
== Clinical significance ==
=== Human brain size variation === An MRI study has demonstrated a link between common human variation in the CDK5RAP2 gene and brain structure.
CDK5RAP2 regulates the activity of CDK5 by interacting with its regulatory subunit CDK5R1. It acts as a negative regulator of centriole disengagement, maintaining their attachment and cohesion. CDK5RAP2 is involved in mitotic spindle orientation and activates the spindle checkpoint by regulating the expression of BUBR1 and MAD2. It collaborates with EB1/MAPRE1 to promote microtubule polymerization, bundling, growth, and dynamics at microtubule plus ends. CDK5RAP2 promotes centrosomal maturation by recruiting the gamma-tubulin ring complex (gamma-TuRC) to centrosomes. Together with PDE4DIP isoform 13/MMG8/SMYLE, MAPRE1, and AKAP9, it contributes to microtubule nucleation and extension from the centrosome to the cell periphery. It is essential for recruiting AKAP9 to centrosomes and plays a role in neurogenesis.
CDK5RAP2 is also known as C48, Cep215, MCPH3.
