CCNT2: Human Cyclin T2 isoform A
PDB Code: 2IVX
Cyclins are regulatory subunits of cyclin-dependent kinases (CDKs). The cyclin T subfamily consists of three isoforms: cyclin T1, cyclin T2a, and T2b which are all structurally similar. Our structure corresponds to the N-terminal cyclin domain of T2 over which cyclin T2a and T2b are identical in sequence (the two proteins just differ in their extreme C-termini). Cyclin T1 has 80% sequence identity with our structure.
The CDK9/cyclin T complex, also known as positive transcription elongation factor b (P-TEFb), is essential for transcriptional elongation in human cells and activates gene expression in a kinase-dependent manner, phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II. The activity of the P-TEFb complex is regulated by the binding of 7SK RNA and HEXIM1 which sequester the P-TEFb in a large kinase-inactive complex.
CDK9/cyclin T2 complexes are involved in the regulation of terminal differentiation in muscle cells and in different forms of autosomal dominant myopathies. MyoD is reported to recruit CDK9/cyclin T2 to the promoters of muscle-specific genes and PKNalpha, a newly identified binding partner of cyclin T2A cooperates with T2A to enhance MyoD-dependent transcription. Expression of cyclin T2 is regulated during muscle cell differentiation and is undetectable in skeletal muscle cells from patients with centronuclear myopathy but high in normal skeletal muscle. Cyclin T2 is widely expressed in all cell types with high expression levels detected in differentiated tissues like blood, muscle, lymphoid tissue and connective tissue cells.
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