Taxonomic distribution of proteins containing CYCLIN domains

The CYCLIN domain within your query sequence starts at position 199 and ends at position 284, and its E-value is 1.3e-9.

Structural principles in cell-cycle control: beyond the CDKs.

Endicott JA, Noble ME
Structure. 1998; 6: 535-41

Retinoblastoma protein (Rb) interacts with cyclin-dependent kinases and regulates the transcription of genes necessary for progression through the S phase of the cell cycle. Clues to the atomic mechanisms involved are offered by the structure of the two pocket regions of Rb in complex with a short peptide from a viral oncoprotein. Structures of cyclins, Rb and TFIIB reveal that a common motif occurs in proteins regulating three consecutive events of cell-cycle control.

Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7.

Lee JO, Russo AA, Pavletich NP
Nature. 1998; 391: 859-65

The pocket domain of the retinoblastoma (Rb) tumour suppressor is central to Rb function, and is frequently inactivated by the binding of the human papilloma virus E7 oncoprotein in cervical cancer. 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 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.

Structural similarity between the pocket region of retinoblastoma tumour suppressor and the cyclin-box.

Kim HY, Cho Y
Nat Struct Biol. 1997; 4: 390-5

The pocket region of retinoblastoma tumour suppressor (Rb) is essential for tumour suppressing activity. The Rb pocket is primarily composed of two domains, A and B. We have determined the X-ray crystal structure of domain A (residues 378-562) at 2.3 A resolution. Domain A consists of nine alpha-helices. The overall arrangement of helices in domain A is remarkably similar to the cyclin-box folds found in the crystal structures of cyclin A and TFIIB. This structure, along with domain B which is predicted to be homologous to the cyclin-box, suggests that the Rb pocket is composed of two cyclin-box fold domains. We present the structural/functional features of the Rb pocket, and the potential binding region for cellular or viral proteins within domain A.

The cyclin box fold: protein recognition in cell-cycle and transcription control.

Noble ME, Endicott JA, Brown NR, Johnson LN
Trends Biochem Sci. 1997; 22: 482-7

Regulation of both the cell cycle and gene transcription is essential for orderly progression of cell growth and division. Recent results on the structures of two cyclins, cyclin A and cyclin H, and two transcription factor mediator proteins, TFIIB and the A pocket region of the retinoblastoma tumour suppressor protein (Rb), show that they share domains with a strikingly similar alpha-helical topology, despite remote sequence identity.

Solution structure of the C-terminal core domain of human TFIIB: similarity to cyclin A and interaction with TATA-binding protein.

Bagby S, Kim S, Maldonado E, Tong KI, Reinberg D, Ikura M
Cell. 1995; 82: 857-67

TFIIB is an essential component of the machinery that transcribes protein-coding genes. The three-dimensional structure of the human TFIIB core domain (TFIIBc) has been determined using multidimensional heteronuclear magnetic resonance spectroscopy. The molecule consists of two direct repeats that adopt similar alpha-helical folds, conferring pseudo-twofold symmetry. An extensive, central basic surface including an amphipathic alpha helix is critical to the function of TFIIB as a bridge between the TBP-promoter complex and RNA polymerase II and associated general and regulatory transcription factors. Similarities between the TFIIBc and cyclin A folds indicate that elements of the eukaryotic cell cycle control apparatus evolved from more fundamental transcriptional control components, demonstrating a link between the transcription and cell cycle molecular machineries.

Evidence for a protein domain superfamily shared by the cyclins, TFIIB and RB/p107.

Gibson TJ, Thompson JD, Blocker A, Kouzarides T
Nucleic Acids Res. 1994; 22: 946-52

Cyclins, TFIIB and RB play major roles in cell cycle and/or gene regulation. Earlier work has suggested common ancestry for the TFIIB repeats and RB pocket B which share 20% sequence identity. We now report that database searches with profiles based on a multiple alignment of cyclin core regions (the 'cyclin box') detect the TFIIB repeats with equivalent scores to divergent cyclins. Several features of the sequences support the notion of common ancestry: e.g. cyclins A/B, C and D share approximately 20-30% identity but each have approximately 15-20% identity with vertebrate TFIIB, showing that conserved cyclin features underlie the match. These results suggest the presence of a domain superfamily, which we term the TR domain, in nuclear regulatory proteins belonging to the TFIIB, cyclin and RB families, that has been duplicated many times during eukaryotic evolution. The TR domain appears to function in protein-protein interactions.