Retinoblastoma-associated protein <p>The retinoblastoma protein functions in cell cycle regulation to hold cells in G1 phase by binding to and inactivating members of the E2F family of transcription factors. The target genes of E2F transcription factor complexes encode proteins that are required for passage into S-phase, such as Cyclin E. Phosphorylation of the retinoblastoma protein by Cyclin D/Cdk4/6 complexes results in its inactivation and the release of the E2F proteins.</p> <p>Retinoblastoma-like and retinoblastoma-associated proteins may have a function in cell cycle regulation. They form a complex with adenovirus E1A and SV40 large T antigen, and may bind and modulate the function of certain cellular proteins with which T and E1A compete for pocket binding. The proteins may act as tumour suppressors, and are potent inhibitors of E2F-mediated trans-activation. This domain has the cyclin fold [<cite idref="PUB00004458"/>].</p> <p>The crystal structure of the Rb pocket bound to a nine-residue E7 peptide containing the LxCxE motif, shared by other Rb-binding viral and cellular proteins, shows that the LxCxE peptide binds a highly conserved groove on the B-box portion of the pocket; the A-box portion (see <db_xref db="INTERPRO" dbkey="IPR002720"/>) appears to be required for the stable folding of the B box. Also highly conserved is the extensive A-B interface, suggesting that it may be an additional protein-binding site. The A and B boxes each contain the cyclin-fold structural motif, with the LxCxE-binding site on the B-box cyclin fold being similar to a Cdk2-binding site of cyclin A and to a TBP-binding site of TFIIB [<cite idref="PUB00005809"/>].</p> <p>This entry is comprised of Rb associated proteins from a wide variety of vertebrates.</p>