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CCNT1

Domain

The histidine-rich domain (HRD) region is intrinsically disordered and promotes the formation of phase-separated liquid droplets that enhance binding of the P-TEFb complex to the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II).

Function

Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II) (PubMed:16109376, PubMed:16109377, PubMed:30134174, PubMed:35393539). Required to activate the protein kinase activity of CDK9: acts by mediating formation of liquid-liquid phase separation (LLPS) that enhances binding of P-TEFb to the CTD of RNA Pol II (PubMed:29849146, PubMed:35393539).

(Microbial infection) In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.

Post-translational modifications

ADP-ribosylation on serine residues by PARP1 in response to DNA damage disrupts the phase separation activity of CCNT1, thereby preventing activation of CDK9.

Sequence Similarities

Belongs to the cyclin family. Cyclin C subfamily.

Tissue Specificity

Ubiquitously expressed.

Cellular localization

Alternative names

Cyclin-T1, CycT1, Cyclin-T, CCNT1

swissprot:O60563 omim:143055 entrezGene:904