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| Domain hiding | Altered binding specificity | Motif hiding | Composite binding site formation |
| Uncategorised | Rheostatic | Allostery | Avidity-sensing |
| Physicochemical compatibility | Pre-translational | Competition |
| Motif | Start | End | Switch Type | Switch Subtype | Switch Description | Information |
Breast cancer type 1 susceptibility protein - BRCA1 - Homo sapiens | |||||||
| TRG_NLS_MonoExtN_4 | 501 | 508 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of Breast cancer type 1 susceptibility protein (BRCA1), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. The study compared the full-length Brca1 splice variant (Isoform 1 of Breast cancer type 1 susceptibility protein (BRCA1)) to the Delta11b isoform (Isoform Delta11b of Breast cancer type 1 susceptibility protein (BRCA1)). The shorter isoform is missing exon 11b and differs in a number of ways. Firstly, it lacks an NLS and therefore has a cytoplasmic localisation. Also, when over-expressed, the Delta11b isoform was not toxic, suggesting nuclear localisation is important for Brca1's toxic behaviour. | ||
Calcium/calmodulin-dependent protein kinase type II subunit delta - Camk2d - Rattus norvegicus | |||||||
| TRG_NLS_MonoCore_2 | 327 | 332 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of Isoform Delta 3 of Calcium/calmodulin-dependent protein kinase type II subunit delta (Camk2d), abrogating binding to Importin subunit alpha-1 (KPNA1) and nuclear import. This is due to an 11 amino acid insert encoded by exon 14. | ||
Cyclin-dependent kinase inhibitor 1B - CDKN1B - Homo sapiens | |||||||
| TRG_NLS | 152 | 166 | Specificity | Motif hiding | Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details). | ||
DNA polymerase processivity factor - UL44 - Human cytomegalovirus (strain AD169) | |||||||
| TRG_NLS_MonoExtN_4 | 425 | 432 | Specificity | Motif hiding | Inhibition of nuclear import of DNA polymerase processivity factor (UL44) by phosphorylation-dependent (T427) binding of BRCA1-associated protein (BRAP). | ||
E3 ubiquitin-protein ligase Mdm2 - MDM2 - Homo sapiens | |||||||
| TRG_NLS_MonoExtC_3 | 181 | 187 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of E3 ubiquitin-protein ligase Mdm2 (MDM2), abrogating binding to Importin subunit alpha-1 (KPNA1). The exclusion from the nucleus is not complete however, as another NLS (466-473) is speculated to target splice variants to the nucleus, however, to the annotator it seems more likely that splice variants can dimerise with full-length MDM2 and be simultaneously transported into nucleus. | ||
F-box/WD repeat-containing protein 7 - FBXW7 - Homo sapiens | |||||||
| TRG_NLS_MonoCore_2 | 10 | 15 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of F-box/WD repeat-containing protein 7 (FBXW7), abrogating binding to Importin subunit alpha-1 (KPNA1). There are two other NLS motifs in the protein, meaning the isoform can still enter the nucleus. | ||
Large T antigen - - Simian virus 40 | |||||||
| TRG_NLS_MonoExtN_4 | 126 | 132 | Specificity | Motif hiding | Inhibition of nuclear import of Large T antigen by phosphorylation-dependent (T124) binding of BRCA1-associated protein (BRAP). | ||
N-glycosylase/DNA lyase - OGG1 - Homo sapiens | |||||||
| TRG_NLS_MonoExtN_4 | 332 | 339 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) motif of N-glycosylase/DNA lyase (OGG1), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. OGG1-1a (also known as Isoform Alpha of N-glycosylase/DNA lyase (OGG1)) has a C-terminal NLS motif that is absent in OGG1-2a (also known as Isoform Beta of N-glycosylase/DNA lyase (OGG1)) . Both have a weak mitochondrial localisation signal (MLS) in the N-terminal. | ||
Protein PML - PML - Homo sapiens | |||||||
| TRG_NLS | 476 | 490 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of Protein PML (PML), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. | ||
Uracil-DNA glycosylase - UNG - Homo sapiens | |||||||
| TRG_NLS_MonoExtN_4 | 15 | 21 | Binary | Pre‑translational | Alternative splicing removes the nuclear localisation signal (NLS) of Uracil-DNA glycosylase (UNG), abrogating binding to Importin subunit alpha-1 (KPNA1) and import into the nucleus. In Isoform UNG1 of Uracil-DNA glycosylase (UNG) the NLS present in Isoform UNG2 of Uracil-DNA glycosylase (UNG) is replaced with a mitochondrial localisation signal (MLS), promoting different localisations of the different protein isoforms. | ||