The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Accession:
Functional site class:
Cyclin docking motif
Functional site description:
Substrate recognition site that interacts with cyclin and thereby increases phosphorylation by cyclin/Cdk complexes. Predicted proteins should have a Cdk phosphorylation site. Also used by cyclin/Cdk inhibitors.
ELM Description:
The classical cyclin docking motif pattern is mainly derived from peptides bound to Cyclin A, for which there are several structures in complex with the peptide. Although the motif is often called RxL, there are actually four core binding residues, with only the Leucine being fully conserved. The motif binds in a hydrophobic groove with charged residues lining the edge. Peptide backbone hydrogen bonds guide the four core binding residues into the groove. Preceding the core motif, there is a clear but non-essential preference for basic residues. After the core, there is a clear but flexible preference for acidic residues. The first core binding position is quite shallow, accepting either hydrophobic or basic residues. It is followed by a residue facing outwards which cannot accept the short acidic residue Asp. The next residue lies in a pocket and must be either Arg or Lys. It is followed by a residue facing outwards which cannot accept the short acidic residue Asp. Then comes the Leu residue fitting into the hydrophobic groove. Flexible spacing then allows one optional externally facing residue. The final core hydrophobic residue is one of Phe, Pro, Leu or Met. The derived regular expression pattern captures the core motif and approximates the weaker charge preference to either side.


Pattern: (.|([KRH].{0,3}))[^EDWNSG][^D][RK][^D]L.{0,1}[FLMP].{0,3}[EDST]
Pattern Probability: 0.0042105
Present in taxon: Eukaryota
PDB Structure: 1JSU
o See 28 Instances for DOC_CYCLIN_RxL_1
o Abstract
The cyclin recognition site (alias Cy or RxL motif) is found in a wide range of cyclin/CDK interacting proteins (Wohlschlegel,2001). The presence of this docking motif in Cdk substrates substantially increases the level of phosphorylation at ([ST])Px(0,2)[KR] motifs (MOD_CDK_SPxK_1). Example proteins are the retinoblastoma protein, E2F1-3, and p53. Much of Cdk phosphorylation activity occurs during the cell cycle (Loog,2005). Much Cdk phosphorylation occurs in the nucleus but some Cdks are also active in the cytoplasm: For example, the cytoplasmic SRC and TAU proteins are known CDK targets. The motif is recognised by a conserved region in the cyclin protein and binds in a similar manner as the p21Kip cyclin inhibitor (1JSU) which hides the site from substrates. In mammals, the cyclin-binding RxL motif is best described for Cyclin A (Schulman,1998). It is likely that some of the other cyclins may have different specificities that are not yet described. In yeast, for example, cyclin Cln2 binds a hydrophobic LLPP motif (Ear,2013; Bhaduri,2011).
o 11 selected references:

o 13 GO-Terms:

o 28 Instances for DOC_CYCLIN_RxL_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q03898 FIN1
FIN1_YEAST
191 199 LPRAKLKGKNLLVELKKEEE TP 1 Saccharomyces cerevisiae S288c
Q13352-2 ITGB3BP
CENPR_HUMAN
2 10 MPVKRSLKLDGLLEENSFDP TP 3 Homo sapiens (Human)
Q14207 NPAT
NPAT_HUMAN
1059 1070 AAKPCHRRVLCFDSTTAPVA TP 2 Homo sapiens (Human)
Q7Z2Z1 TICRR
TICRR_HUMAN
911 920 VQEVTKVRRNLFNQELLSPS TP 1 Homo sapiens (Human)
O43303 CCP110
CP110_HUMAN
583 593 NSFEKVKRRLDLDIDGLQKE TP 3 Homo sapiens (Human)
Q14493 SLBP
SLBP_HUMAN
94 103 NKEMARYKRKLLINDFGRER TP 1 Homo sapiens (Human)
P30291 WEE1
WEE1_HUMAN
177 187 TPPHKTFRKLRLFDTPHTPK TP 2 Homo sapiens (Human)
Q9BY12 SCAPER
SCAPE_HUMAN
196 207 NVTSNARRSLNFGGSTGTVP TP 3 Homo sapiens (Human)
O75179 ANKRD17
ANR17_HUMAN
1927 1938 TWGPFPVRPLSPARATNSPK TP 3 Homo sapiens (Human)
A8T798 UL32
A8T798_HCMV
415 427 PPARKPSASRRLFGSSADED TP 2 Human herpesvirus 5 (Human cytomegalovirus)
P50445 rux
RUX_DROME
245 254 PTARRCVRRTLFTEENTQKE TP 1 Drosophila melanogaster (Fruit fly)
P30304 CDC25A
MPIP1_HUMAN
9 18 GPEPPHRRRLLFACSPPPAS TP 1 Homo sapiens (Human)
P06789 E1
VE1_HPV18
124 134 SGQKKAKRRLFTISDSGYGC TP 4 Human papillomavirus type 18
1 
P38936 CDKN1A
CDN1A_HUMAN
16 26 PCGSKACRRLFGPVDSEQLS TP 4 Homo sapiens (Human)
1 
P28749 RBL1
RBL1_HUMAN
655 664 SPTAGSAKRRLFGEDPPKEM TP 3 Homo sapiens (Human)
Q13352 ITGB3BP
CENPR_HUMAN
2 10 MPVKRSLKLDGLLEENSFDP TP 1 Homo sapiens (Human)
P38826 ORC6
ORC6_YEAST
175 186 ESPSITRRKLAFEEDEDEDE TP 1 Saccharomyces cerevisiae (Baker"s yeast)
P39880 CUX1
CUX1_HUMAN
1298 1307 HNYRSRIRRELFIEEIQAGS TP 1 Homo sapiens (Human)
P04637 TP53
P53_HUMAN
378 388 GQSTSRHKKLMFKTEGPDSD TP 4 Homo sapiens (Human)
P46527 CDKN1B
CDN1B_HUMAN
27 37 HPKPSACRNLFGPVDHEELT TP 5 Homo sapiens (Human)
1 
Q08999 RBL2
RBL2_HUMAN
677 687 PPASTTRRRLFVENDSPSDG TP 1 Homo sapiens (Human)
Q14209 E2F2
E2F2_HUMAN
84 92 PAGRLPAKRKLDLEGIGRPV TP 1 Homo sapiens (Human)
P49918 CDKN1C
CDN1C_HUMAN
28 38 LVRTSACRSLFGPVDHEELS TP 1 Homo sapiens (Human)
O00716 E2F3
E2F3_HUMAN
131 141 GGGPPAKRRLELGESGHQYL TP 1 Homo sapiens (Human)
Q9WTQ5 Akap12
AKA12_MOUSE
498 507 IKVQGSPLKKLFSSSGLKKL TP 1 Mus musculus (House mouse)
Q99741 CDC6
CDC6_HUMAN
91 99 PHSHTLKGRRLVFDNQLTIK TP 2 Homo sapiens (Human)
Q01094 E2F1
E2F1_HUMAN
87 97 LGRPPVKRRLDLETDHQYLA TP 3 Homo sapiens (Human)
P06400 RB1
RB_HUMAN
870 880 SNPPKPLKKLRFDIEGSDEA TP 3 Homo sapiens (Human)
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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