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| Functional site class: | APCC-binding Destruction motifs |
| Functional site description: | The anaphase-promoting ubiquitin ligase complex APC/C selectively targets numerous cell cycle-regulatory proteins for ubiquitin-mediated proteasome-dependent degradation. The targets of the APC/C are degraded in an ordered, sequential manner which ensures the correct progression of the cell cycle. Cdh1 and Cdc20 are WD-repeat containing proteins which act as co-activators of the APC/C at distinct steps of the cycle. Cdc20 joins the APC/C in early mitosis and is then replaced by Cdh1 during anaphase. Both Cdh1 and Cdc20 recognize the target proteins via short, very specific "destruction motifs". The motifs allow recruitment of the targets, to the APC/C complex which subsequently poly-ubiquitinates them. |
|---|---|
| ELMs: | LIG_APCC_Dbox_1 LIG_APCC_KENbox_2 |
| Description: | The Destruction Box is a short sequence motif, usually depicted as an RxxL motif. However, in preparing this entry we noted that the conservation is better described as RxxLxx[LIVM]. This larger motif has been conserved for many 100s of Myr in Cyclins A and B, ID, Geminin, Securin and PLK1. In these cell cycle proteins the DBox acts as a signal for cycle-dependent proteolysis in anaphase. The motif as described for the ELM Dbox entry does not match to the reported Dboxes of Cdc6 or Nek2A. The reported Dboxes of Aurora kinases are deeply buried in the kinase domain itself. |
| Pattern: | .R..L..[LIVM]. (Probability: 0.0007677) |
| Present in taxons: | Eukaryota |
| Interaction Domain: |
WD40 (PF00400) |
See 9 Instances for LIG_APCC_Dbox_1
|
| Progress of cell division is governed by the sequential degradation, mediated by the ubiquitination pathway, of proteins playing a key role in the cell cycle. There are two E3 ubiquitin protein ligase complexes which play a role in the cell cycle: the SCF (Skp1/Cullin/F-box) complex and the anaphase-promoting complex (APC/C) (Peters 2006, Castro et al. 2005). The APC/C complex contains at least a dozen different subunits, but it can ubiquitylate substrates only in the presence of the co-activator proteins Cdc20 (also known as fizzy) or Cdh1(also called fzr or Hct1). Cdh1 and Cdc20 are WD40-repeat proteins (well known linear motif-binding domains, folded as 7-blade beta-propellers), which recognise their target proteins via short "degradation motifs". Cdc20 and Cdh1 act at distinct phases of the cell cycle. Early in mitosis, during the metaphase-anaphase transition, APC/Cdc20 is mostly active, whereas Cdh1 is present, but as a phosphorylated inactive form which cannot bind to the APC/C. Later, in mitotic exit and further during the G1 phases, Cdh1 is activated by dephosphorylation, and binds to the APC/C by replacing Cdc20 and promoting its rapid degradation. |
(click table headers for sorting)
| Sequence | Start | End | Subsequence | Instance Logic | PDB | Organism |
|---|---|---|---|---|---|---|
| AURKB_HUMAN | 314 | 322 | RHNPSERLPLAQVSAHPWVR | false positive | --- | Homo sapiens (Human) |
| STK6_HUMAN | 370 | 378 | KHNPSQRPMLREVLEHPWIT | false positive | --- | Homo sapiens (Human) |
| CCNA1_XENLA | 40 | 48 | QPNLPQRTVLGVIGDNEQRR | true positive | --- | Xenopus laevis (African clawed frog) |
| O93355_XENLA | 32 | 40 | NEALAPRRTLKVIQQSASGC | true positive | --- | Xenopus laevis (African clawed frog) |
| STK6A_XENLA | 377 | 385 | KHNPNHRLPLKGVLEHPWII | false positive | --- | Xenopus laevis (African clawed frog) |
| CCNB_ARBPU | 41 | 49 | VQKPAQRAALGNISNVVRTA | true positive | --- | Arbacia punctulata (Punctuate urchin) |
| ID2_HUMAN | 99 | 107 | GQNQASRTPLTTLNTDISIL | true positive | --- | Homo sapiens (Human) |
| PLK1_HUMAN | 336 | 344 | SLDPSNRKPLTVLNKGLENP | true positive | --- | Homo sapiens (Human) |
| Q9IA80_XENLA | 54 | 62 | MVSKPSRKALGNVNKQILPK | true positive | --- | Xenopus laevis (African clawed frog) |
