Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose activity depends on a regulatory subunit - a cyclin. Cyclins are a large family of approximately 30 proteins varying in mass from 35 to 90 kDa. These proteins are structurally defined by the presence of the so-called cyclin box, a domain of approximately 100 amino acid residues that forms a stack of five α-helices. Many cyclins have two cyclin boxes, one amino-terminal box for binding to CDKs, and a carboxy-terminal box that is usually required for the proper folding of the cyclin molecule.The cyclin box is also present in other molecules such as the retinoblastoma protein (Rb), the transcription factor TFIIB and Cables (CDK5 and ABL1 enzyme substrate 1), which are unlikely to function as CDK activators. In general, cyclins show less sequence similarity than the CDKs. The cyclin family contains approximately 29 protein in humans, clustered in 16 subfamilies and three major groups: group I (cyclin B group: A-, B-, D-, E-, F-, G, J, I and O); group II (cyclin Y group - a partner of the Cdk5 subfamily); and group III (cyclin C group: C-, H-, K-, L- and T- - major partners of transcriptional CDKs). 
Cyclin D and cyclin E clades (partners of Cdk1 and Cdk4 subfamilies) have undergone lineage-specific expansion and specialization in metazoa and plants. Based on the sequence of the kinase domain, CDKs belong to the CMGC group of kinases (named for the initials of some members), along with mitogen-activated protein kinases (MAPKs), glycogen synthase kinase-3 beta (Gsk3β), members of the dual-specificity tyrosine-regulated kinase (DYRK) family and CDK-like kinases. In related kinases such as MAPKs, substrate specificity is conferred by docking sites separated from the catalytic site, whereas CDKs are characterized by dependency on separate protein subunits that provide additional sequences required for enzymatic activity. To aid nomenclature and analysis of CDKs, proteins belonging to this family have been recently renamed as Cdk1 through to Cdk20.  Despite their function in eukaryotic cell division and transcription, CDKs have undergone an extraordinary degree of evolutionary divergence and specialization. Transcriptional CDKs are more conserved, both in sequence and function.


1.Malumbres M. Genome Biol. 2014;15(6):122.