KAP95

Summary

Gene Symbol: KAP95
Description: karyopherin beta
Alias: RSL1, karyopherin beta
Species: Saccharomyces cerevisiae S288c
Products:     KAP95

Top Publications

  1. Liu S, Stewart M. Structural basis for the high-affinity binding of nucleoporin Nup1p to the Saccharomyces cerevisiae importin-beta homologue, Kap95p. J Mol Biol. 2005;349:515-25 pubmed
    ..The length and composition of this linker is crucial and suggests how differences in affinity for Kap95p both between and within FG-nucleoporins arise. ..
  2. Hood J, Casolari J, Silver P. Nup2p is located on the nuclear side of the nuclear pore complex and coordinates Srp1p/importin-alpha export. J Cell Sci. 2000;113 ( Pt 8):1471-80 pubmed
    ..Taken together, these data suggest that Nup2p is an important NPC docking site in the Srp1p export pathway. ..
  3. Marelli M, Aitchison J, Wozniak R. Specific binding of the karyopherin Kap121p to a subunit of the nuclear pore complex containing Nup53p, Nup59p, and Nup170p. J Cell Biol. 1998;143:1813-30 pubmed
    ..Interestingly, Nup53p is specifically phosphorylated during mitosis. This phenomenon is correlated with a transient decrease in perinuclear-associated Kap121p. ..
  4. Rosenblum J, Pemberton L, Blobel G. A nuclear import pathway for a protein involved in tRNA maturation. J Cell Biol. 1997;139:1655-61 pubmed
    ..In addition, through its association with ribosomal proteins, Sxm1p may have a role in coordinating ribosome biogenesis with tRNA processing. ..
  5. Solsbacher J, Maurer P, Vogel F, Schlenstedt G. Nup2p, a yeast nucleoporin, functions in bidirectional transport of importin alpha. Mol Cell Biol. 2000;20:8468-79 pubmed
    ..The changed distribution of Cse1p at the NPC in nup2 mutants also supports a role for Nup2p in Srp1p export from the nucleus. ..
  6. Fries T, Betz C, Sohn K, Caesar S, Schlenstedt G, Bailer S. A novel conserved nuclear localization signal is recognized by a group of yeast importins. J Biol Chem. 2007;282:19292-301 pubmed
  7. Gilchrist D, Mykytka B, Rexach M. Accelerating the rate of disassembly of karyopherin.cargo complexes. J Biol Chem. 2002;277:18161-72 pubmed
    ..In that way, Nup1p, Nup2p, Cse1p, and Gsp1p may function as karyopherin release factors (or KaRFs) in the nuclear basket structure of the S. cerevisiae NPC. ..
  8. Denning D, Mykytka B, Allen N, Huang L, Al Burlingame -, Rexach M. The nucleoporin Nup60p functions as a Gsp1p-GTP-sensitive tether for Nup2p at the nuclear pore complex. J Cell Biol. 2001;154:937-50 pubmed
    ..The results suggest a dynamic interaction, controlled by the nucleoplasmic concentration of Gsp1p-GTP, between Nup60p and Nup2p at the NPC. ..
  9. Dilworth D, Suprapto A, Padovan J, Chait B, Wozniak R, Rout M, et al. Nup2p dynamically associates with the distal regions of the yeast nuclear pore complex. J Cell Biol. 2001;153:1465-78 pubmed
    ..Together, our data support a model in which Nup2p movement facilitates the transition between the import and export phases of nucleocytoplasmic transport...

More Information

Publications65

  1. Seedorf M, Damelin M, Kahana J, Taura T, Silver P. Interactions between a nuclear transporter and a subset of nuclear pore complex proteins depend on Ran GTPase. Mol Cell Biol. 1999;19:1547-57 pubmed
    ..These data indicate that transport receptors such as Pse1p interact in a Ran-dependent manner with certain nucleoporins. These nucleoporins may represent major docking sites for Pse1p as it moves in or out of the nucleus via the NPC. ..
  2. Floer M, Blobel G. The nuclear transport factor karyopherin beta binds stoichiometrically to Ran-GTP and inhibits the Ran GTPase activating protein. J Biol Chem. 1996;271:5313-6 pubmed
    ..It was shown recently that Ran-GTP dissociated the karyopherin heterodimer and, in doing so, associated with karyopherin beta (Rexach, M., and Blobel, G. (1995) Cell 83, 683-692)...
  3. Iovine M, Wente S. A nuclear export signal in Kap95p is required for both recycling the import factor and interaction with the nucleoporin GLFG repeat regions of Nup116p and Nup100p. J Cell Biol. 1997;137:797-811 pubmed
    ..Srp1p, the yeast nuclear localization signal-receptor, also accumulated in the nuclei of the arrested kap95 mutant cells...
  4. Iovine M, Watkins J, Wente S. The GLFG repetitive region of the nucleoporin Nup116p interacts with Kap95p, an essential yeast nuclear import factor. J Cell Biol. 1995;131:1699-713 pubmed
    ..These data show that Nup116p's GLFG region has an essential role in mediating nuclear transport. ..
  5. Panse V, Kuster B, Gerstberger T, Hurt E. Unconventional tethering of Ulp1 to the transport channel of the nuclear pore complex by karyopherins. Nat Cell Biol. 2003;5:21-7 pubmed
    ..bulk of cellular Ulp1 is not associated with nucleoporins but instead associates with three karyopherins (Pse1, Kap95 and Kap60), in a complex that is not dissociated by RanGTP in vitro...
  6. Koepp D, Wong D, Corbett A, Silver P. Dynamic localization of the nuclear import receptor and its interactions with transport factors. J Cell Biol. 1996;133:1163-76 pubmed
  7. Aitchison J, Blobel G, Rout M. Kap104p: a karyopherin involved in the nuclear transport of messenger RNA binding proteins. Science. 1996;274:624-7 pubmed
    ..This finding suggests that the major function of Kap104p lies in returning mRNA binding proteins to the nucleus after mRNA export. ..
  8. Belanger K, Griffith A, Baker H, Hansen J, Kovacs L, Seconi J, et al. The karyopherin Kap95 and the C-termini of Rfa1, Rfa2, and Rfa3 are necessary for efficient nuclear import of functional RPA complex proteins in Saccharomyces cerevisiae. DNA Cell Biol. 2011;30:641-51 pubmed publisher
    ..RPA associates with two different karyopherins in yeast, Kap95, and Msn5/Kap142. However, it is unclear which of these karyopherins is responsible for RPA nuclear import...
  9. Floer M, Blobel G, Rexach M. Disassembly of RanGTP-karyopherin beta complex, an intermediate in nuclear protein import. J Biol Chem. 1997;272:19538-46 pubmed
    We previously showed that RanGTP forms a 1:1 complex with karyopherin beta that renders RanGTP inaccessible to RanGAP (Floer, M., and Blobel, G. (1996) J. Biol. Chem. 271, 5313-5316) and karyopherin beta functionally inactive (Rexach, M...
  10. Enenkel C, Blobel G, Rexach M. Identification of a yeast karyopherin heterodimer that targets import substrate to mammalian nuclear pore complexes. J Biol Chem. 1995;270:16499-502 pubmed
    ..15 gene product is the closest structural homologue of vertebrate karyopherin beta. The yeast alpha and beta karyopherin subunits were expressed in Escherichia coli and were purified...
  11. Maurer P, Redd M, Solsbacher J, Bischoff F, Greiner M, Podtelejnikov A, et al. The nuclear export receptor Xpo1p forms distinct complexes with NES transport substrates and the yeast Ran binding protein 1 (Yrb1p). Mol Biol Cell. 2001;12:539-49 pubmed
    ..This Yrb1p/Xpo1p/Gsp1p complex is then completely dissociated after GTP hydrolysis catalyzed by the cytoplasmic GTPase activating protein Rna1p. ..
  12. Pemberton L, Rosenblum J, Blobel G. A distinct and parallel pathway for the nuclear import of an mRNA-binding protein. J Cell Biol. 1997;139:1645-53 pubmed
    ..Thus, at least two parallel pathways function in the import of mRNA-binding proteins, suggesting the need for the coordination of these pathways. ..
  13. Rout M, Blobel G, Aitchison J. A distinct nuclear import pathway used by ribosomal proteins. Cell. 1997;89:715-25 pubmed
    ..We show that the related protein Pse1p is also a karyopherin and can functionally substitute for Kap123p; both are capable of specifically directing a ribosomal nuclear localization signal reporter to the nucleus in vivo. ..
  14. Pelaez R, Fernández García P, Herrero P, Moreno F. Nuclear import of the yeast hexokinase 2 protein requires ?/?-importin-dependent pathway. J Biol Chem. 2012;287:3518-29 pubmed publisher
    ..we report that the Hxk2 protein is an import substrate of the carriers ?-importin (Kap60 in yeast) and ?-importin (Kap95 in yeast)...
  15. Pyhtila B, Rexach M. A gradient of affinity for the karyopherin Kap95p along the yeast nuclear pore complex. J Biol Chem. 2003;278:42699-709 pubmed
    ..We conclude that a high affinity binding site for Kap95p at the nuclear basket increases the translocation efficiency of Kap95p import complexes across the NPC. ..
  16. Neville M, Stutz F, Lee L, Davis L, Rosbash M. The importin-beta family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export. Curr Biol. 1997;7:767-75 pubmed
    ..Our findings also agree well with current experiments on Crm1p orthologs in Schizosaccharomyces pombe and in vertebrate systems. ..
  17. MacKinnon M, Curwin A, Gaspard G, Suraci A, Fernández Murray J, McMaster C. The Kap60-Kap95 karyopherin complex directly regulates phosphatidylcholine synthesis. J Biol Chem. 2009;284:7376-84 pubmed publisher
    ..Pct1 also interacted with the beta-importin Kap95 in cell extracts, implying a model whereby Pct1 interacts with Kap60 and Kap95 with this tripartite complex ..
  18. Makhnevych T, Ptak C, Lusk C, Aitchison J, Wozniak R. The role of karyopherins in the regulated sumoylation of septins. J Cell Biol. 2007;177:39-49 pubmed
    ..We present a model in which Ulp1p is maintained at the NPC during interphase and transiently interacts with the septin ring during mitosis. ..
  19. Quilis I, Igual J. Molecular basis of the functional distinction between Cln1 and Cln2 cyclins. Cell Cycle. 2012;11:3117-31 pubmed publisher
    ..In short, a region from Cln2 controlling an Msn5-dependent nuclear export mechanism confers a specific functionality to Cln2 compared with Cln1. ..
  20. Strawn L, Shen T, Wente S. The GLFG regions of Nup116p and Nup100p serve as binding sites for both Kap95p and Mex67p at the nuclear pore complex. J Biol Chem. 2001;276:6445-52 pubmed
    ..Taken together, our in vivo and in vitro results define an essential role for a direct Mex67p-GLFG interaction during mRNA export. ..
  21. Greiner M, Caesar S, Schlenstedt G. The histones H2A/H2B and H3/H4 are imported into the yeast nucleus by different mechanisms. Eur J Cell Biol. 2004;83:511-20 pubmed
    ..We conclude from our in vivo and in vitro experiments that import of the essential histones is mediated mainly by the essential importin Pse1p, while the non-essential Kap114p functions in a parallel import pathway for H2A and H2B. ..
  22. Forwood J, Lange A, Zachariae U, Marfori M, Preast C, Grubmuller H, et al. Quantitative structural analysis of importin-? flexibility: paradigm for solenoid protein structures. Structure. 2010;18:1171-83 pubmed publisher
    ..We determined the crystal structure of unliganded Saccharomyces cerevisiae importin-? (Kap95) to allow a quantitative comparison with importin-? bound to different partners...
  23. King M, Lusk C, Blobel G. Karyopherin-mediated import of integral inner nuclear membrane proteins. Nature. 2006;442:1003-7 pubmed
    ..We also provide evidence that specific nuclear pore complex proteins contribute to this process, suggesting a role for signal-mediated alterations in the nuclear pore complex to allow for passage of INM proteins along the pore membrane. ..
  24. Hirano H, Kobayashi J, Matsuura Y. Structures of the Karyopherins Kap121p and Kap60p Bound to the Nuclear Pore-Targeting Domain of the SUMO Protease Ulp1p. J Mol Biol. 2017;429:249-260 pubmed publisher
  25. Martínez Bono B, Quilis I, Zalve E, Igual J. Yeast karyopherins Kap123 and Kap95 are related to the function of the cell integrity pathway. FEMS Yeast Res. 2010;10:28-37 pubmed publisher
    ..Finally, we identified karyopherin Kap95 as the transport factor responsible for the nuclear import of Slt2 and Rlm1.
  26. Huang H, Hopper A. In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic. Genes Dev. 2015;29:772-83 pubmed publisher
    ..Assembly and/or stability of this quaternary complex requires Tef1/2, thereby facilitating efficient re-export of aminoacylated tRNAs to the cytoplasm. ..
  27. Fernández Cid A, Vega M, Herrero P, Moreno F. Yeast importin-? is required for nuclear import of the Mig2 repressor. BMC Cell Biol. 2012;13:31 pubmed publisher
    ..Here, we report that the Mig2 protein is an import substrate of the carrier Kap95 (importin-?)...
  28. Mirallas O, Ballega E, Samper Martín B, García Márquez S, Carballar R, Ricco N, et al. Intertwined control of the cell cycle and nucleocytoplasmic transport by the cyclin-dependent kinase Pho85 and RanGTPase Gsp1 in Saccharomyces cerevisiae. Microbiol Res. 2018;206:168-176 pubmed publisher
    ..Furthermore, our results suggest that the physical interaction of Gsp1 and the Kap95 karyopherin, essential to the release of nuclear cargoes, is altered...
  29. Fahrenkrog B, Hubner W, Mandinova A, Pante N, Keller W, Aebi U. The yeast nucleoporin Nup53p specifically interacts with Nic96p and is directly involved in nuclear protein import. Mol Biol Cell. 2000;11:3885-96 pubmed
    ..Whereas Nup53p is directly involved in NLS-mediated protein import by its interaction with the yeast nuclear import receptor Kap95p, it appears not to participate in NES-dependent nuclear export. ..
  30. Harreman M, Hodel M, Fanara P, Hodel A, Corbett A. The auto-inhibitory function of importin alpha is essential in vivo. J Biol Chem. 2003;278:5854-63 pubmed
    ..We propose a model where the auto-inhibitory activity of importin alpha is required for NLS-cargo release and the subsequent Cse1p-dependent recycling of importin alpha to the cytoplasm. ..
  31. Yan C, Lee L, Davis L. Crm1p mediates regulated nuclear export of a yeast AP-1-like transcription factor. EMBO J. 1998;17:7416-29 pubmed
    ..Thus, disassembly of export complexes in response to RanGTP hydrolysis may be required for release of substrate from a terminal binding site at the nuclear pore complex (NPC). ..
  32. Lee S, Matsuura Y, Liu S, Stewart M. Structural basis for nuclear import complex dissociation by RanGTP. Nature. 2005;435:693-6 pubmed
    ..This interaction produces a change in helicoidal pitch that locks Kap95p in a conformation that cannot bind importin-alpha or cargo. We suggest an allosteric mechanism for nuclear import complex disassembly by RanGTP. ..
  33. Mészáros N, Cibulka J, Mendiburo M, Romanauska A, Schneider M, Köhler A. Nuclear pore basket proteins are tethered to the nuclear envelope and can regulate membrane curvature. Dev Cell. 2015;33:285-98 pubmed publisher
    ..Basket amphipathic helices are functionally linked to distinct transmembrane nucleoporins of the NPC core, suggesting a key contribution to the membrane remodeling events that underlie NPC assembly. ..
  34. Zeitler B, Weis K. The FG-repeat asymmetry of the nuclear pore complex is dispensable for bulk nucleocytoplasmic transport in vivo. J Cell Biol. 2004;167:583-90 pubmed
    ..Surprisingly, we were unable to detect any defects in the Kap95, Kap121, Xpo1, or mRNA transport pathways in cells expressing the mutant FG Nups...
  35. Kosova B, Pante N, Rollenhagen C, Podtelejnikov A, Mann M, Aebi U, et al. Mlp2p, a component of nuclear pore attached intranuclear filaments, associates with nic96p. J Biol Chem. 2000;275:343-50 pubmed
    ..Double disruption mutants of MLP1 and MLP2 are viable and apparently not impaired in nucleocytoplasmic transport. However, overproduction of MLP1 causes nuclear accumulation of poly(A)(+) RNA in a chromatin-free area of the nucleus...
  36. Patel S, Rexach M. Discovering novel interactions at the nuclear pore complex using bead halo: a rapid method for detecting molecular interactions of high and low affinity at equilibrium. Mol Cell Proteomics. 2008;7:121-31 pubmed
    ..Bead Halo uncovered novel interactions between the importin Kap95 and the nucleoporins (nups) Nic96, Pom34, Gle1, Ndc1, Nup84, and Seh1, which likely occur during nuclear pore ..
  37. Synowsky S, van Wijk M, Raijmakers R, Heck A. Comparative multiplexed mass spectrometric analyses of endogenously expressed yeast nuclear and cytoplasmic exosomes. J Mol Biol. 2009;385:1300-13 pubmed publisher
    ..We show that the nuclear exosome selectively copurifies with the alpha/beta importin heterodimer, which is known to be involved in the transport of proteins across the nuclear membrane. ..
  38. Hahn S, Schlenstedt G. Importin ?-type nuclear transport receptors have distinct binding affinities for Ran-GTP. Biochem Biophys Res Commun. 2011;406:383-8 pubmed publisher
    ..We found that the number of ?-receptors altogether about equals the amounts of yeast Ran, but Ran-GTP is not limiting in the nucleus. The implications of our results for nucleocytoplasmic transport mechanisms are discussed. ..
  39. Shevchenko A, Schaft D, Roguev A, Pijnappel W, Stewart A, Shevchenko A. Deciphering protein complexes and protein interaction networks by tandem affinity purification and mass spectrometry: analytical perspective. Mol Cell Proteomics. 2002;1:204-12 pubmed
    ..Concordance with the results of genome-wide two-hybrid screening was poor (14% of identified interactors overlapped) suggesting that the two approaches may provide complementary views on physical interactions within the proteome. ..
  40. Hodel A, Harreman M, Pulliam K, Harben M, Holmes J, Hodel M, et al. Nuclear localization signal receptor affinity correlates with in vivo localization in Saccharomyces cerevisiae. J Biol Chem. 2006;281:23545-56 pubmed
    ..This correlation, however, is not maintained for cargoes that bind to the NLS receptor with very weak or very strong affinity. ..
  41. Mosammaparast N, Jackson K, Guo Y, Brame C, Shabanowitz J, Hunt D, et al. Nuclear import of histone H2A and H2B is mediated by a network of karyopherins. J Cell Biol. 2001;153:251-62 pubmed
    ..In addition, we detected a specific mislocalization in a kap95 temperature-sensitive strain, suggesting that this Kap is also involved in the import of H2A and H2B in vivo...
  42. Baker R, Harreman M, Eccleston J, Corbett A, Stewart M. Interaction between Ran and Mog1 is required for efficient nuclear protein import. J Biol Chem. 2001;276:41255-62 pubmed
    ..Our results indicate that a primary function of Mog1 requires binding to Ran and that the Mog1-Ran interaction is necessary for efficient nuclear protein import in vivo. ..
  43. Sydorskyy Y, Srikumar T, Jeram S, Wheaton S, Vizeacoumar F, Makhnevych T, et al. A novel mechanism for SUMO system control: regulated Ulp1 nucleolar sequestration. Mol Cell Biol. 2010;30:4452-62 pubmed publisher
    ..We further show that the Ulp1 region previously demonstrated to interact with the karyopherins Kap95 and Kap60 (amino acids 150 to 340) is necessary and sufficient for nucleolar targeting and that enforced ..
  44. Lonhienne T, Forwood J, Marfori M, Robin G, Kobe B, Carroll B. Importin-beta is a GDP-to-GTP exchange factor of Ran: implications for the mechanism of nuclear import. J Biol Chem. 2009;284:22549-58 pubmed publisher
    ..The exchange is also inhibited by nuclear-transport factor-2 (NTF2). We suggest a mechanism for nuclear import, additional to the established RCC1 (Ran-guanine exchange factor)-dependent pathway that incorporates these results. ..
  45. Braunwarth A, Fromont Racine M, Legrain P, Bischoff F, Gerstberger T, Hurt E, et al. Identification and characterization of a novel RanGTP-binding protein in the yeast Saccharomyces cerevisiae. J Biol Chem. 2003;278:15397-405 pubmed
    ..Based on these results and the exclusive conservation of the protein in the fungal kingdom, we hypothesize that Yrb30p represents a novel modulator of the Ran GTPase switch related to fungal lifestyle. ..
  46. Tetenbaum Novatt J, Hough L, Mironska R, McKenney A, Rout M. Nucleocytoplasmic transport: a role for nonspecific competition in karyopherin-nucleoporin interactions. Mol Cell Proteomics. 2012;11:31-46 pubmed publisher
  47. Forwood J, Lonhienne T, Marfori M, Robin G, Meng W, Guncar G, et al. Kap95p binding induces the switch loops of RanGDP to adopt the GTP-bound conformation: implications for nuclear import complex assembly dynamics. J Mol Biol. 2008;383:772-82 pubmed publisher
    ..The structure of the complex provides insights into the structural basis for the gradation of affinities regulating nuclear protein transport. ..
  48. Jani D, Valkov E, Stewart M. Structural basis for binding the TREX2 complex to nuclear pores, GAL1 localisation and mRNA export. Nucleic Acids Res. 2014;42:6686-97 pubmed publisher
  49. Mnaimneh S, Davierwala A, Haynes J, Moffat J, Peng W, Zhang W, et al. Exploration of essential gene functions via titratable promoter alleles. Cell. 2004;118:31-44 pubmed
    ..We furthermore show that these strains are compatible with automated genetic analysis. This study underscores the importance of analyzing mutant phenotypes and provides a resource to complement the yeast knockout collection. ..
  50. Peña C, Schütz S, Fischer U, Chang Y, Panse V. Prefabrication of a ribosomal protein subcomplex essential for eukaryotic ribosome formation. elife. 2016;5: pubmed publisher
    ..Thus, prefabrication of a native-like r-protein subcomplex drives efficient and accurate construction of the eukaryotic ribosome. ..
  51. Gonzales Zubiate F, Okuda E, da Cunha J, Oliveira C. Identification of karyopherins involved in the nuclear import of RNA exosome subunit Rrp6 in Saccharomyces cerevisiae. J Biol Chem. 2017;292:12267-12284 pubmed publisher
    ..By investigating the biological importance of these protein interactions, we identified Srp1, Kap95, and Sxm1 as the most important karyopherins for Rrp6 nuclear import and the nuclear localization signals ..
  52. Lau D, Kunzler M, Braunwarth A, Hellmuth K, Podtelejnikov A, Mann M, et al. Purification of protein A-tagged yeast ran reveals association with a novel karyopherin beta family member, Pdr6p. J Biol Chem. 2000;275:467-71 pubmed
    ..After affinity purification of protein A-tagged Gsp1p or Gsp2p by IgG-Sepharose chromatography, known karyopherin beta transport receptors (e.g...
  53. Ryan K, Zhou Y, Wente S. The karyopherin Kap95 regulates nuclear pore complex assembly into intact nuclear envelopes in vivo. Mol Biol Cell. 2007;18:886-98 pubmed
    ..Here we characterize loss-of-function Saccharomyces cerevisiae mutants in KAP95 with blocks in NPC assembly...
  54. Vega M, Riera A, Fernández Cid A, Herrero P, Moreno F. Hexokinase 2 Is an Intracellular Glucose Sensor of Yeast Cells That Maintains the Structure and Activity of Mig1 Protein Repressor Complex. J Biol Chem. 2016;291:7267-85 pubmed publisher
    ..Thus, our data indicate that Hxk2 is more intimately involved in gene regulation than previously thought. ..
  55. Caesar S, Greiner M, Schlenstedt G. Kap120 functions as a nuclear import receptor for ribosome assembly factor Rpf1 in yeast. Mol Cell Biol. 2006;26:3170-80 pubmed
  56. Kunzler M, Hurt E. Cse1p functions as the nuclear export receptor for importin alpha in yeast. FEBS Lett. 1998;433:185-90 pubmed
    ..These findings suggest that Cse1p is the exportin of importin alpha in yeast. ..