Nucleocytoplasmic trafficking of large macromolecules requires an active transport machinery. In many cases, this is initiated by binding of the @entity2631 ( @entity2631 ) peptide of cargo proteins to importin-a molecules. Fine orchestration of nucleocytoplasmic trafficking is of particularly high importance for proteins involved in maintenance of genome integrity, such as dUTPases, which are responsible for prevention of @entity5537 incorporation into the genome. In most eukaryotes, @entity1977 ases have two homotrimeric isoforms: one of these contains three NLSs and is present in the cell nucleus, while the other is located in the cytoplasm or the mitochondria. Here we focus on the unusual occurrence of a pseudo-heterotrimeric @entity35113 in @entity18308 that contains one @entity2631 , and investigate its localization pattern compared to the homotrimeric @entity35113 isoforms of @entity238 . Although the interaction of individual NLSs with importin-a has been well characterized, the question of how multiple NLSs of oligomeric cargo proteins affect their trafficking has been less frequently addressed in adequate detail. Using the @entity18308 @entity35113 as a fully relevant physiologically occurring model protein, we show that @entity2631 copy number influences the efficiency of nuclear import in both insect and @entity1 cell lines, as well as in @entity238 and @entity18308 tissues. Biophysical data indicate that @entity2631 copy number determines the stoichiometry of complexation between importin-a and dUTPases. The main conclusion of our study is that, in @entity18308 , a single @entity35113 isoform efficiently reproduces the cellular @entity35113 distribution pattern that requires two isoforms in @entity238 . STRUCTURED DIGITAL ABSTRACT:       ABC @entity35113  and  importin-a  bind  by  molecular sieving  (View interaction)       AAA @entity35113  and  importin-a bind  by  molecular sieving  (View interaction)       ABC @entity35113  and  importin-a  bind  by  comigration in non denaturing gel electrophoresis  (View interaction)       AAA @entity35113  and  importin-a  bind  by  comigration in non denaturing gel electrophoresis  (View interaction)       ABC @entity35113  and  importin-a  bind  by  isothermal titration calorimetry  (View interaction) _#x2022; AAA @entity35113  and  importin-a   bind  by  isothermal titration calorimetry  (View interaction).

XXXX copy-number variation governs efficiency of nuclear import - case study on dUTPases.

@entity1 :: ('9606', 'Species') :: ['mammalian'] @entity1977 :: ('CHEBI:17625', 'Chemical') :: ['dUTP'] @entity2631 :: ('MESH:D012594', 'Disease') :: ['nuclear localization signal', 'NLS'] @entity238 :: ('7227', 'Species') :: ['Drosophila  melanogaster', 'D.  melanogaster'] @entity35113 :: ('34529(Tax:7227)', 'Gene') :: ['dUTPase'] @entity5537 :: ('MESH:D014498', 'Chemical') :: ['uracil'] @entity18308 :: ('7244', 'Species') :: ['Drosophila  virilis', 'D.  virilis']
@entity2631 :: (MESH:D012594,Disease) :: ['NLS']
