Switches.ELM

Switch #:

SWTI000607

Switch type:
Binary

Description:
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.

Participants:
(1) E3 ubiquitin-protein ligase Mdm2 (MDM2)
(2) Importin subunit alpha-1 (KPNA1)

Interactions

Interaction #1 MDM2 - KPNA1

Interfaces
(1) TRG_NLS_MonoExtC_3 motif (₁₈₁RKRHKSD₁₈₇) in E3 ubiquitin-protein ligase Mdm2 (MDM2)
(2) Armadillo/beta-catenin-like repeat_(115-451) in Importin subunit alpha-1 (KPNA1)

Interaction Regulation
Alternative splicing Abrogation of the E3 ubiquitin-protein ligase Mdm2 (MDM2) TRG_NLS_MonoExtC_3 motif - Importin subunit alpha-1 (KPNA1) Armadillo/beta-catenin-like repeat interaction

Context

Switch localisation
Curated: cytosol
ELM curated: Nuclear pore, nucleus, NLS-dependent protein nuclear import complex

Inferred: cytosol, nucleoplasm

References

(1) MDM2 splice variants predominantly localize to the nucleoplasm mediated by a COOH-terminal nuclear localization signal.
Schuster et al. Mol. Cancer Res. (2007)