switches.ELM

Group by :Switch type Motif class Protein Enzyme Pathway Group Index Colouring Info Filtered: ELM:TRG_NLS (21 hits) x

x Coloured by switch type.

Domain hiding	Altered binding specificity	Motif hiding	Composite binding site formation
Uncategorised	Rheostatic	Allostery	Avidity-sensing
Physicochemical compatibility	Pre-translational	Competition

x Index

Breast cancer type 1 susceptibility protein	Calcium/calmodulin-dependent protein kinase type II subunit delta (Rattus)	Cyclin-dependent kinase inhibitor 1B
DNA polymerase processivity factor (Human)	E3 ubiquitin-protein ligase Mdm2	F-box/WD repeat-containing protein 7
Importin subunit alpha (Saccharomyces)	Large T antigen (Simian)	MKL/myocardin-like protein 1 (Mus)
N-glycosylase/DNA lyase	Nuclear factor of activated T-cells, cytoplasmic 1	Parathyroid hormone-related protein
Phosphate system positive regulatory protein PHO4 (Saccharomyces)	Protein PML	Regulatory protein SWI6 (Saccharomyces)
S-phase kinase-associated protein 2	Uracil-DNA glycosylase

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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.	details
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.	details
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).	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).	details
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).	details
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.	details
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.	details
Importin subunit alpha - SRP1 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
TRG_NLS_Bipartite_1	44	58	Specificity	Domain hiding	An intramolecular interaction between the importin beta-binding (IBB) domain and the NLS-binding pocket of Importin subunit alpha (SRP1) prevents binding of NLS cargo (e.g. Large T antigen) in the absence of Importin subunit beta-1 (KAP95) by hiding of the NLS-binding pocket. Binding of the IBB of Importin subunit alpha (SRP1) to Importin subunit beta-1 (KAP95) relieves this auto-inhibitory interaction and increases the affinity of Importin subunit alpha (SRP1) for NLS cargo.	details
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).	details
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).	details
TRG_NLS_MonoExtN_4	126	132	Specificity	Domain hiding	An intramolecular interaction between the importin beta-binding (IBB) domain and the NLS-binding pocket of Importin subunit alpha (SRP1) prevents binding of NLS cargo (e.g. Large T antigen) in the absence of Importin subunit beta-1 (KAP95) by hiding of the NLS-binding pocket. Binding of the IBB of Importin subunit alpha (SRP1) to Importin subunit beta-1 (KAP95) relieves this auto-inhibitory interaction and increases the affinity of Importin subunit alpha (SRP1) for NLS cargo.	details
MKL/myocardin-like protein 1 - Mkl1 - Mus musculus
TRG_NLS_MonoExtN_4	62 95	67 101	Specificity	Motif hiding	Hiding of the NLS of MKL/myocardin-like protein 1 (Mkl1) by binding of G-actin to the RPEL motifs of MKL/myocardin-like protein 1 (Mkl1) prevents translocation of this transcription factor to the nucleus.	details
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.	details
Nuclear factor of activated T-cells, cytoplasmic 1 - NFATC1 - Homo sapiens
TRG_NLS_MonoExtN_4	262	269	Binary	Physicochemical compatibility	Phosphorylation of S241 and S290 adjacent to the NLS of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by Glycogen synthase kinase-3 beta (GSK3B) and Glycogen synthase kinase-3 beta (GSK3B) inhibits nuclear import of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) by disrupting its interaction with Importin subunit alpha-2 (KPNA2). Calcium-dependent dephosphorylation by calcineurin promotes nuclear import.	details
Parathyroid hormone-related protein - PTHLH - Homo sapiens
TRG_NLS_Bipartite_1	124	144	Binary	Physicochemical compatibility	Phosphorylation of T121 adjacent to the NLS of Parathyroid hormone-related protein (PTHLH) by Cyclin-dependent kinase 2 (CDK2) disrupts the interaction with Importin subunit beta-1 (KPNB1) and down-regulates nuclear import.	details
Phosphate system positive regulatory protein PHO4 - PHO4 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
TRG_NLS_MonoExtC_3	156	161	Binary	Physicochemical compatibility	Phosphorylation of S152 adjacent to the NLS of Phosphate system positive regulatory protein PHO4 (PHO4) by the Pho80-Pho85 CDK-Cyclin complex inhibits nuclear import this protein by blocking its interaction with Importin subunit beta-3 (PSE1). Upon phosphate starvation, Pho81 inhibits the Pho80-Pho85 complex, leading to translocation of Phosphate system positive regulatory protein PHO4 (PHO4) to the nucleus, where it regulates expression of phosphate-responsive genes.	details
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.	details
Regulatory protein SWI6 - SWI6 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
TRG_NLS_MonoExtN_4	161	167	Binary	Physicochemical compatibility	Phosphorylation of S160 adjacent to the NLS of Regulatory protein SWI6 (SWI6) decreases nuclear import of this protein by decreasing the affinity for Importin subunit alpha (SRP1).	details
S-phase kinase-associated protein 2 - SKP2 - Homo sapiens
TRG_NLS_MonoExtN_4	65	72	Binary	Physicochemical compatibility	Acetylation of S-phase kinase-associated protein 2 (SKP2) in its NLS inhibits binding to the Importin subunit alpha-6 (KPNA5). p300 acetylates SKP2 at K68 and K71 within SKP2's nuclear localisation signal, this stabilises SKP2 from Fizzy-related protein homolog (FZR1)-mediated degradation and facilitates its translocation into the cytoplasm. This process can be reversed by NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) that specifically deacetylates SKP2 facilitating its translocation back into the nucleus. In the cytosol, SKP2 acts to promote Cadherin-1 (CDH1) degradation in a Casein Kinase I dependent manner to promote cell migration. Casein kinase I recognises the MOD_CK1_1 motif in CDH1 phosphorylating at residues Ser840 and Ser842.	details
TRG_NLS_MonoExtN_4	65	72	Binary	Physicochemical compatibility	Acetylation of S-phase kinase-associated protein 2 (SKP2) in its NLS inhibits binding to the Importin subunit alpha-7 (KPNA6). p300 acetylates SKP2 at K68 and K71 within SKP2's nuclear localisation signal, this stabilises SKP2 from Fizzy-related protein homolog (FZR1)-mediated degradation and facilitates its translocation into the cytoplasm. This process can be reversed by NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) that specifically deacetylates SKP2 facilitating its translocation back into the nucleus. In the cytosol, SKP2 acts to promote Cadherin-1 (CDH1) degradation in a Casein Kinase I dependent manner to promote cell migration. Casein kinase I recognises the MOD_CK1_1 motif in CDH1 phosphorylating at residues Ser840 and Ser842.	details
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.	details