SMART: CYCLIN domain annotation

The domain within your query sequence starts at position 531 and ends at position 647; the E-value for the CYCLIN domain shown below is 2188.56032.

CLVREYGSLERSPEKISATVVEIAGYSMSEDVRQRHRYLSHLPLTCEFSICELALQPPVV
SKETLEMFSDDIEKRKRQRQKKAREERRRERRIEIEENKKQGKYPEVHIPLENLQQF

CYCLIN domain 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 (IPR006670):	Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles (PUBMED:12910258), and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple forms of G1 and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three G1 cyclins, C, D, and E. Cyclin homologues have been found in various viruses, including herpesvirus saimiri and Kaposi's sarcoma-associated herpesvirus. These viral homologues differ from their cellular counterparts in that the viral proteins have gained new functions and eliminated others to harness the cell and benefit the virus (PUBMED:11056549). This domain is also found in transcription factor IIB (TFIIB) and retinoblastoma.
Family alignment:	View or

There are 4029 CYCLIN domains in 2802 proteins in SMART's nrdb database.

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 (SRS)(SMART) OMIM:180200: Retinoblastoma ; Osteosarcoma
OMIM:259500: Bladder cancer
OMIM:109800: Pinealoma with bilateral retinoblastoma
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

Protein	Disease
Retinoblastoma-associated protein (SRS)(SMART)	OMIM:180200: Retinoblastoma ; Osteosarcoma OMIM:259500: Bladder cancer OMIM:109800: Pinealoma with bilateral retinoblastoma

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
2w96
2w99
2w9f
2w9z
2wev
2wfy
2wha
2whb
2wih
2wip
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
3eid
3ej1
3eoc
3f5x
3g33
3k7a

Links (links to other resources describing this domain)
PFAM cyclin
INTERPRO IPR006670
PROSITE CYCLINS

PFAM	cyclin
INTERPRO	IPR006670
PROSITE	CYCLINS