CYCLINdomain present in cyclins, TFIIB and Retinoblastoma
|SMART accession number:||SM00385|
|Description:||A helical domain present in cyclins and TFIIB (twice) and Retinoblastoma (once). A protein recognition domain functioning in cell-cycle and transcription control.|
|Interpro abstract (IPR013763):|
This cyclin-like domain is found in cyclins, but it is also found as the core domain in transcription factor IIB (TFIIB) and in the retinoblastoma tumour suppressor. It consists of a duplication of a fold consisting of 5 helices, one of them surrounded by the others.
Click on the following links for more information.
- Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a CYCLIN domain in a specific node, click on it.
This tree shows only several representative species. The complete taxonomic breakdown of all proteins with CYCLIN domain is also avaliable.
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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
- Cellular role (predicted cellular role)
Cellular role: transcription
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Endicott JA, Noble ME
- Structural principles in cell-cycle control: beyond the CDKs.
- Structure. 1998; 6: 535-41
- Display abstract
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.
- Lee JO, Russo AA, Pavletich NP
- Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7.
- Nature. 1998; 391: 859-65
- Display abstract
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.
- Kim HY, Cho Y
- Structural similarity between the pocket region of retinoblastoma tumour suppressor and the cyclin-box.
- Nat Struct Biol. 1997; 4: 390-5
- Display abstract
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.
- Noble ME, Endicott JA, Brown NR, Johnson LN
- The cyclin box fold: protein recognition in cell-cycle and transcription control.
- Trends Biochem Sci. 1997; 22: 482-7
- Display abstract
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.
- Bagby S, Kim S, Maldonado E, Tong KI, Reinberg D, Ikura M
- Solution structure of the C-terminal core domain of human TFIIB: similarity to cyclin A and interaction with TATA-binding protein.
- Cell. 1995; 82: 857-67
- Display abstract
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.
- Gibson TJ, Thompson JD, Blocker A, Kouzarides T
- Evidence for a protein domain superfamily shared by the cyclins, TFIIB and RB/p107.
- Nucleic Acids Res. 1994; 22: 946-52
- Display abstract
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.
- Disease (disease genes where sequence variants are found in this domain)
SwissProt sequences and OMIM curated human diseases associated with missense mutations within the CYCLIN domain.
Protein Disease Retinoblastoma-associated protein (P06400) (SMART) OMIM:180200: Retinoblastoma ; Osteosarcoma
OMIM:259500: Bladder cancer
OMIM:109800: Pinealoma with bilateral retinoblastoma
- Metabolism (metabolic pathways involving proteins which contain this domain)
Click the image to view the interactive version of the map in iPath
% proteins involved KEGG pathway ID Description 17.79 map04110 Cell cycle 13.09 map03022 Basal transcription factors 12.25 map04115 p53 signaling pathway 6.21 map04914 Progesterone-mediated oocyte maturation 5.03 map05222 Small cell lung cancer 5.03 map05215 Prostate cancer 3.86 map04630 Jak-STAT signaling pathway 3.86 map04111 Cell cycle - yeast 3.86 map04510 Focal adhesion 3.86 map04310 Wnt signaling pathway 2.68 map05219 Bladder cancer 2.68 map05212 Pancreatic cancer 2.68 map05220 Chronic myeloid leukemia 2.68 map05214 Glioma 2.68 map05223 Non-small cell lung cancer 2.68 map05218 Melanoma 2.52 map04350 TGF-beta signaling pathway 1.34 map05216 Thyroid cancer 1.34 map05210 Colorectal cancer 1.34 map05213 Endometrial cancer 1.34 map05221 Acute myeloid leukemia 0.50 map00562 Inositol phosphate metabolism 0.50 map00632 Benzoate degradation via CoA ligation 0.17 map03020 RNA polymerase
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with CYCLIN domain which could be assigned to a KEGG orthologous group, and not all proteins containing CYCLIN domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of CYCLIN domains in PDB
PDB code Main view Title 1ais Tata-binding protein/transcription factor (ii)b/tata-box complex from pyrococcus woesei 1bu2 X-ray structure of a viral cyclin from herpesvirus saimiri 1c9b Crystal structure of a human tbp core domain-human tfiib core domain complex bound to an extended, modified adenoviral major late promoter (admlp) 1d3u Tata-binding protein/transcription factor (ii)b/bre+tata- box complex from pyrococcus woesei 1e9h Thr 160 phosphorylated cdk2 - human cyclin a3 complex with the inhibitor indirubin-5-sulphonate bound 1f5q Crystal structure of murine gamma herpesvirus cyclin complexed to human cyclin dependent kinase 2 1fin Cyclin a-cyclin-dependent kinase 2 complex 1fvv The structure of cdk2/cyclin a in complex with an oxindole inhibitor 1g3n Structure of a p18(ink4c)-cdk6-k-cyclin ternary complex 1gh6 Retinoblastoma pocket complexed with sv40 large t antigen 1gux Rb pocket bound to e7 lxcxe motif 1gy3 Pcdk2/cyclin a in complex with mgadp, nitrate and peptide substrate 1h1p Structure of human thr160-phospho cdk2/cyclin a complexed with the inhibitor nu2058 1h1q Structure of human thr160-phospho cdk2/cyclin a complexed with the inhibitor nu6094 1h1r Structure of human thr160-phospho cdk2/cyclin a complexed with the inhibitor nu6086 1h1s Structure of human thr160-phospho cdk2/cyclin a complexed with the inhibitor nu6102 1h24 Cdk2/cyclin a in complex with a 9 residue recruitment peptide from e2f 1h25 Cdk2/cyclin a in complex with an 11-residue recruitment peptide from retinoblastoma-associated protein 1h26 Cdk2/cyclin a in complex with an 11-residue recruitment peptide from p53 1h27 Cdk2/cyclin a in complex with an 11-residue recruitment peptide from p27 1h28 Cdk2/cyclin a in complex with an 11-residue recruitment peptide from p107 1jkw Structure of cyclin mcs2 1jow Crystal structure of a complex of human cdk6 and a viral cyclin 1jst Phosphorylated cyclin-dependent kinase-2 bound to cyclin a 1jsu P27(kip1)/cyclin a/cdk2 complex 1kxu Cyclin h, a positive regulatory subunit of cdk activating kinase 1n4m Structure of rb tumor suppressor bound to the transactivation domain of e2f-2 1o9k Crystal structure of the retinoblastoma tumour suppressor protein bound to e2f peptide 1ogu Structure of human thr160-phospho cdk2/cyclin a complexed with a 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitor 1oi9 Structure of human thr160-phospho cdk2/cyclin a complexed with a 6-cyclohexylmethyloxy-2-anilino-purine inhibitor 1oiu Structure of human thr160-phospho cdk2/cyclin a complexed with a 6-cyclohexylmethyloxy-2-anilino-purine inhibitor 1oiy Structure of human thr160-phospho cdk2/cyclin a complexed with a 6-cyclohexylmethyloxy-2-anilino-purine inhibitor 1okv Cyclin a binding groove inhibitor h-arg-arg-leu-ile-phe-nh2 1okw Cyclin a binding groove inhibitor ac-arg-arg-leu-asn- (m-cl-phe)-nh2 1ol1 Cyclin a binding groove inhibitor h-cit-cit-leu-ile- (p-f-phe)-nh2 1ol2 Cyclin a binding groove inhibitor h-arg-arg-leu-asn- (p-f-phe)-nh2 1p5e The strucure of phospho-cdk2/cyclin a in complex with the inhibitor 4,5,6,7-tetrabromobenzotriazole (tbs) 1pkd The crystal structure of ucn-01 in complex with phospho- cdk2/cyclin a 1qmz Phosphorylated cdk2-cyclyin a-substrate peptide complex 1tfb Nmr studies of human general transcription factor tfiib: dynamics and interaction with vp16 activation domain, 20 structures 1urc Cyclin a binding groove inhibitor ace-arg-lys-leu- phe-gly 1vin Bovine cyclin a3 1vol Tfiib (human core domain)/tbp (a.thaliana)/tata element ternary complex 1vyw Structure of cdk2/cyclin a with pnu-292137 1w98 The structural basis of cdk2 activation by cyclin e 1xo2 Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin 1zp2 Structure of the mediator subunit cyclin c 2b9r Crystal structure of human cyclin b1 2bkz Structure of cdk2-cyclin a with pha-404611 2bpm Structure of cdk2-cyclin a with pha-630529 2c4g Structure of cdk2-cyclin a with pha-533514 2c5n Differential binding of inhibitors to active and inactive cdk2 provides insights for drug design 2c5o Differential binding of inhibitors to active and inactive cdk2 provides insights for drug design 2c5v Differential binding of inhibitors to active and inactive cdk2 provides insights for drug design 2c5x Differential binding of inhibitors to active and inactive cdk2 provides insights for drug design 2c6t Crystal structure of the human cdk2 complexed with the triazolopyrimidine inhibitor 2cch The crystal structure of cdk2 cyclin a in complex with a substrate peptide derived from cdc modified with a gamma- linked atp analogue 2cci Crystal structure of phospho-cdk2 cyclin a in complex with a peptide containing both the substrate and recruitment sites of cdc6 2cjm Mechanism of cdk inhibition by active site phosphorylation: cdk2 y15p t160p in complex with cyclin a structure 2euf X-ray structure of human cdk6-vcyclin in complex with the inhibitor pd0332991 2f2c X-ray structure of human cdk6-vcyclinwith the inhibitor aminopurvalanol 2g9x Structure of thr 160 phosphorylated cdk2/cyclin a in complex with the inhibitor nu6271 2i40 Cdk2/cyclin a complexed with a thiophene carboxamide inhibitor 2i53 Crystal structure of cyclin k 2ivx Crystal structure of human cyclin t2 at 1.8 a resolution (casp target) 2iw6 Structure of human thr160-phospho cdk2-cyclin a complexed with a bisanilinopyrimidine inhibitor 2iw8 Structure of human thr160-phospho cdk2-cyclin a f82h-l83v- h84d mutant with an o6-cyclohexylmethylguanine inhibitor 2iw9 Structure of human thr160-phospho cdk2-cyclin a complexed with a bisanilinopyrimidine inhibitor 2jgz Crystal structure of phospho-cdk2 in complex with cyclin b 2phg Model for vp16 binding to tfiib 2pk2 Cyclin box structure of the p-tefb subunit cyclin t1 derived from a fusion complex with eiav tat 2r7g Structure of the retinoblastoma protein pocket domain in complex with adenovirus e1a cr1 domain 2uue Replace: a strategy for iterative design of cyclin binding groove inhibitors 2uzb Crystal structure of human cdk2 complexed with a thiazolidinone inhibitor 2uzd Crystal structure of human cdk2 complexed with a thiazolidinone inhibitor 2uze Crystal structure of human cdk2 complexed with a thiazolidinone inhibitor 2uzl Crystal structure of human cdk2 complexed with a thiazolidinone inhibitor 2v22 Replace: a strategy for iterative design of cyclin binding groove inhibitors 2w2h Structural basis of transcription activation by the cyclin t1-tat-tar rna complex from eiav 2w96 Crystal structure of cdk4 in complex with a d-type cyclin 2w99 Crystal structure of cdk4 in complex with a d-type cyclin 2w9f Crystal structure of cdk4 in complex with a d-type cyclin 2w9z Crystal structure of cdk4 in complex with a d-type cyclin 2wev Truncation and optimisation of peptide inhibitors of cdk2, cyclin a through structure guided design 2wfy Truncation and optimisation of peptide inhibitors of cdk2, cyclin a through structure guided design 2wha Truncation and optimisation of peptide inhibitors of cdk2, cyclin a through structure guided design 2whb Truncation and optimisation of peptide inhibitors of cdk2, cyclin a through structure guided design 2wih Structure of cdk2-cyclin a with pha-848125 2wip Structure of cdk2-cyclin a complexed with 8-anilino-1- methyl-4,5-dihydro-1h-pyrazolo[4,3-h] quinazoline-3- carboxylic acid 3bht Structure of phosphorylated thr160 cdk2/cyclin a in complex with the inhibitor meriolin 3 3bhu Structure of phosphorylated thr160 cdk2/cyclin a in complex with the inhibitor meriolin 5 3bhv Structure of phosphorylated thr160 cdk2/cyclin a in complex with the inhibitor variolin b 3blh Crystal structure of human cdk9/cyclint1 3blq Crystal structure of human cdk9/cyclint1 in complex with atp 3blr Crystal structure of human cdk9/cyclint1 in complex with flavopiridol 3ddp Structure of phosphorylated thr160 cdk2/cyclin a in complex with the inhibitor cr8 3ddq Structure of phosphorylated thr160 cdk2/cyclin a in complex with the inhibitor roscovitine 3dog Structure of thr 160 phosphorylated cdk2/cyclin a in complex with the inhibitor n-&-n1 3eid Cdk2/cyclina complexed with a pyrazolopyridazine inhibitor 3ej1 Cdk2/cyclina complexed with a pyrazolopyridazine inhibitor 3eoc Cdk2/cyclina complexed with a imidazo triazin-2-amine 3f5x Cdk-2-cyclin complex with indazole inhibitor 9 bound at its active site 3g33 Crystal structure of cdk4/cyclin d3 3k7a Crystal structure of an rna polymerase ii-tfiib complex
- Links (links to other resources describing this domain)
PFAM cyclin INTERPRO IPR013763 PROSITE CYCLINS