Genomes and Genes
Gene Symbol: KPNA5
Description: karyopherin subunit alpha 5
Alias: IPOA6, SRP6, importin subunit alpha-6, importin alpha 6, karyopherin alpha 5 (importin alpha 6)
- Pluymers W, Cherepanov P, Schols D, De Clercq E, Debyser Z. Nuclear localization of human immunodeficiency virus type 1 integrase expressed as a fusion protein with green fluorescent protein. Virology. 1999;258:327-32 pubmed..Nuclear localization of GFP-IN was also obtained after transient transfection of the cells arrested in the G1/S phase of the cell cycle. These results provide compelling evidence for the karyophilic properties of the HIV-1 integrase. ..
- Dvorin J, Bell P, Maul G, Yamashita M, Emerman M, Malim M. Reassessment of the roles of integrase and the central DNA flap in human immunodeficiency virus type 1 nuclear import. J Virol. 2002;76:12087-96 pubmed..Thus, neither the cPPT nor the valine residue at position 165 of integrase is essential for the nuclear import of HIV-1 PICs. ..
- Popov S, Rexach M, Zybarth G, Reiling N, Lee M, Ratner L, et al. Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. EMBO J. 1998;17:909-17 pubmed..These results identify the biochemical mechanism of Vpr function in transport of the viral pre-integration complex to, and across, the nuclear membrane. ..
- Gallay P, Hope T, Chin D, Trono D. HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proc Natl Acad Sci U S A. 1997;94:9825-30 pubmed..This novel function of integrase reflects the recognition of an atypical bipartite nuclear localization signal by the importin/karyopherin pathway. ..
- Depienne C, Mousnier A, Leh H, Le Rouzic E, Dormont D, Benichou S, et al. Characterization of the nuclear import pathway for HIV-1 integrase. J Biol Chem. 2001;276:18102-7 pubmed
- Ding J, Zhang Y, Zhong H, Ao C, Li J, Han J. An all-atom molecular dynamics study of the anti-interferon signaling of Ebola virus: interaction mechanisms of EBOV VP24 binding to Karyopherin alpha5. Mol Biosyst. 2017;13:1031-1045 pubmed publisher..The crystal structure of VP24-KPNA5 has been proposed in recent studies, but the precise binding mechanisms are still unclear...
- Schwarz T, Edwards M, Diederichs A, Alinger J, Leung D, Amarasinghe G, et al. VP24-Karyopherin Alpha Binding Affinities Differ between Ebolavirus Species, Influencing Interferon Inhibition and VP24 Stability. J Virol. 2017;91: pubmed publisher..evaluated eVP24, BDBV VP24 (bVP24), and RESTV VP24 (rVP24) interactions with three NPI-1 subfamily KPNAs (KPNA1, KPNA5, and KPNA6). Using purified proteins, we demonstrated that each VP24 binds to each of the three NPI-1 KPNAs...
- Song X, Lu L, Passioura T, Suga H. Macrocyclic peptide inhibitors for the protein-protein interaction of Zaire Ebola virus protein 24 and karyopherin alpha 5. Org Biomol Chem. 2017;15:5155-5160 pubmed publisher..Here we report macrocyclic peptide inhibitors of the VP24-KPNA5 protein-protein interaction (PPI) by means of the RaPID (Random non-standard Peptides Integrated Discovery) system...
- Ma L, Zhao W, Zhu F, Yuan F, Xie N, Li T, et al. Global Characteristics of CSIG-Associated Gene Expression Changes in Human HEK293 Cells and the Implications for CSIG Regulating Cell Proliferation and Senescence. Front Endocrinol (Lausanne). 2015;6:69 pubmed publisher..The differential expression of genes such as ZNF616, KPNA5, and MAP3K3 was further validated by real-time PCR and western blot analysis...
- Feagins A, Basler C. Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells. Virology. 2015;485:145-52 pubmed publisher..Additionally, LLOV VP24 blocks tyrosine phosphorylated STAT1 binding to karyopherin alpha 5 (KPNA5), STAT1 nuclear accumulation, and IFN-induced gene expression. LLOV VP40 lacks detectable IFN antagonist function...
- Hultquist J, Schumann K, Woo J, Manganaro L, McGregor M, DOUDNA J, et al. A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells. Cell Rep. 2016;17:1438-1452 pubmed publisher..This technology should accelerate target validation for pharmaceutical and cell-based therapies to cure HIV infection. ..
- Park Y, Kang J, Lee D, Kim M, Bak Y, Yang Y, et al. Interleukin-32Î± modulates promyelocytic leukemia zinc finger gene activity by inhibiting protein kinase CÉ›-dependent sumoylation. Int J Biochem Cell Biol. 2014;55:136-43 pubmed publisher..Together, our data suggest that IL-32Î± associates with PLZF and PKCÉ›, and then inhibits PLZF sumoylation, resulting in suppression of the transcriptional activity of PLZF. ..
- von Schwedler U, Kornbluth R, Trono D. The nuclear localization signal of the matrix protein of human immunodeficiency virus type 1 allows the establishment of infection in macrophages and quiescent T lymphocytes. Proc Natl Acad Sci U S A. 1994;91:6992-6 pubmed
- Zhong J, Ogura K, Wang Z, Inuzuka H. Degradation of the transcription factor Twist, an oncoprotein that promotes cancer metastasis. Discov Med. 2013;15:7-15 pubmed
- Patenaude A, Orthwein A, Hu Y, Campo V, Kavli B, Buschiazzo A, et al. Active nuclear import and cytoplasmic retention of activation-induced deaminase. Nat Struct Mol Biol. 2009;16:517-27 pubmed publisher..Blocking nuclear import alters the balance between these processes in favor of cytoplasmic retention, resulting in reduced isotype class switching. ..
- Nie Z, Bergeron D, Subbramanian R, Yao X, Checroune F, Rougeau N, et al. The putative alpha helix 2 of human immunodeficiency virus type 1 Vpr contains a determinant which is responsible for the nuclear translocation of proviral DNA in growth-arrested cells. J Virol. 1998;72:4104-15 pubmed..The results of this study provide evidence that a putative amphipathic alpha-helical structure in the central region of Vpr contains a determinant involved in the nuclear translocation of the preintegration complex in nondividing cells. ..
- Lischka P, Sorg G, Kann M, Winkler M, Stamminger T. A nonconventional nuclear localization signal within the UL84 protein of human cytomegalovirus mediates nuclear import via the importin alpha/beta pathway. J Virol. 2003;77:3734-48 pubmed..Although containing a cluster of basic amino acids similar to classical NLSs, this cluster did not contain the NLS activity. Thus, a complex structure appears to be essential for importin alpha binding and import activity. ..
- Rey F, Bouhamdan M, Navarro J, Agostini I, Willetts K, Bouyac M, et al. A role for human immunodeficiency virus type 1 Vpr during infection of peripheral blood mononuclear cells. J Gen Virol. 1998;79 ( Pt 5):1083-7 pubmed..Our data indicate that Vpr is involved in the virus life-cycle during infection of dividing PBMC, presumably as it is during infection of MDMs. ..
- Sato A, Yoshimoto J, Isaka Y, Miki S, Suyama A, Adachi A, et al. Evidence for direct association of Vpr and matrix protein p17 within the HIV-1 virion. Virology. 1996;220:208-12 pubmed..Association of Vpr and the matrix protein p17 within the mature virion is consistent with their collaborative role in the nuclear transportation of the viral preintegration complex in nondividing cells such as macrophages. ..
- Dubrovsky L, Ulrich P, Nuovo G, Manogue K, Cerami A, Bukrinsky M. Nuclear localization signal of HIV-1 as a novel target for therapeutic intervention. Mol Med. 1995;1:217-30 pubmed..In combination with other drugs, potential therapeutics exploiting this target may also help to control the progression of HIV-1 infection and disease. ..
- Levin A, Armon Omer A, Rosenbluh J, Melamed Book N, Graessmann A, Waigmann E, et al. Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal. Retrovirology. 2009;6:112 pubmed publisher..This import could be blocked by NLS-IN peptide, resulting in inhibition of viral infection, confirming the view that nuclear import of the viral pre-integration complex is mediated by viral IN. ..
- Tsujii A, Miyamoto Y, Moriyama T, Tsuchiya Y, Obuse C, Mizuguchi K, et al. Retinoblastoma-binding Protein 4-regulated Classical Nuclear Transport Is Involved in Cellular Senescence. J Biol Chem. 2015;290:29375-88 pubmed publisher..This is the first report to identify a factor that competes with importin Î²1 to bind to importin Î±, and it demonstrates that the loss of this factor can trigger cellular senescence. ..
- Banerjee A, Pal A, Pal D, Mitra P. Ebolavirus interferon antagonists-protein interaction perspectives to combat pathogenesis. Brief Funct Genomics. 2017;: pubmed publisher..critical interacting residues of the VP (VP24) responsible for the formation of a stable complex with the human KPNA5 (karyopherin alpha proteins 5)...
- Petit C, Schwartz O, Mammano F. The karyophilic properties of human immunodeficiency virus type 1 integrase are not required for nuclear import of proviral DNA. J Virol. 2000;74:7119-26 pubmed..Besides reinforcing the association between dimerization of IN and nuclear accumulation of the enzyme, our data demonstrate that subcellular localization of IN alone cannot predict the fate of the PICs. ..
- Sharova N, Bukrinskaya A. p17 and p17-containing gag precursors of input human immunodeficiency virus are transported into the nuclei of infected cells. AIDS Res Hum Retroviruses. 1991;7:303-6 pubmed..The data presented confirm the presence of karyotypic signal at the N terminus of p55 gag precursor. The potential role of nuclear localization of gag precursor is discussed. ..
- Gallay P, Stitt V, Mundy C, Oettinger M, Trono D. Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import. J Virol. 1996;70:1027-32 pubmed..In addition, our data suggest that Vpr governs HIV-1 nuclear import through a distinct pathway. ..
- Besancon F, Just J, Bourgeade M, Van Weyenbergh J, Solomon D, Guillozo H, et al. HIV-1 p17 and IFN-gamma both induce fructose 1,6-bisphosphatase. J Interferon Cytokine Res. 1997;17:461-7 pubmed
- Bukrinsky M, Haffar O. HIV-1 nuclear import: matrix protein is back on center stage, this time together with Vpr. Mol Med. 1998;4:138-43 pubmed
- Gu J, Chen M, Shete S, Amos C, Kamat A, Ye Y, et al. A genome-wide association study identifies a locus on chromosome 14q21 as a predictor of leukocyte telomere length and as a marker of susceptibility for bladder cancer. Cancer Prev Res (Phila). 2011;4:514-21 pubmed publisher..In conclusion, we found that the SNP rs398652 on 14q21 was associated with longer telomere length and a reduced risk of bladder cancer and that a portion of the effect of this SNP on bladder cancer risk was mediated by telomere length. ..
- Bukrinsky M, Sharova N, Dempsey M, Stanwick T, Bukrinskaya A, Haggerty S, et al. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc Natl Acad Sci U S A. 1992;89:6580-4 pubmed
- Pappalardo M, Collu F, Macpherson J, Michaelis M, Fraternali F, Wass M. Investigating Ebola virus pathogenicity using molecular dynamics. BMC Genomics. 2017;18:566 pubmed publisher..we used protein structural analysis and molecular dynamics to further elucidate the interaction between VP24 and KPNA5. As a control experiment, we compared the interaction of wild-type and R137A-mutant (known to affect KPNA5 binding)..
- Bukrinsky M, Haffar O. HIV-1 nuclear import: in search of a leader. Front Biosci. 1997;2:d578-87 pubmed..We also describe a class of novel anti-HIV compounds which target the NLSs of HIV-1 and effectively block viral replication in T cells and macrophages. ..
- Echeverria P, Bernthaler A, Dupuis P, Mayer B, Picard D. An interaction network predicted from public data as a discovery tool: application to the Hsp90 molecular chaperone machine. PLoS ONE. 2011;6:e26044 pubmed publisher..Thus, we both describe how to build a custom database and introduce a powerful new resource for the scientific community...
- Hearps A, Jans D. Regulating the functions of the HIV-1 matrix protein. AIDS Res Hum Retroviruses. 2007;23:341-6 pubmed..J Virol 2005;79:13028-13036) confirms the importance of this protein for HIV infection and highlights a potentially new avenue in multivalent drug therapy. ..
- Bukrinsky M, Haffar O. HIV-1 nuclear import: in search of a leader. Front Biosci. 1999;4:D772-81 pubmed..We also describe a class of novel anti-HIV compounds that target the NLSs of HIV-1 and effectively block viral replication in T cells and macrophages. ..
- Agostini I, Popov S, Li J, Dubrovsky L, Hao T, Bukrinsky M. Heat-shock protein 70 can replace viral protein R of HIV-1 during nuclear import of the viral preintegration complex. Exp Cell Res. 2000;259:398-403 pubmed..These results suggest the presence of a novel regulatory site on karyopherin alpha which is used by Hsp70 and Vpr to stimulate interaction between the HIV-1 PIC and karyopherin alpha and thus promote viral nuclear import. ..
- Kohler M, Ansieau S, Prehn S, Leutz A, Haller H, Hartmann E. Cloning of two novel human importin-alpha subunits and analysis of the expression pattern of the importin-alpha protein family. FEBS Lett. 1997;417:104-8 pubmed..We show by immunoblotting that the different importin-alpha subfamilies are expressed in a variety of human tissues and mammalian cell lines. ..
- Gallay P, Swingler S, Aiken C, Trono D. HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator. Cell. 1995;80:379-88 pubmed..MA tyrosine phosphorylation thus reveals the karyophilic properties of this protein within the HIV-1 preintegration complex, thereby playing a critical role for infection of nondividing cells. ..
- Melen K, Fagerlund R, Franke J, Kohler M, Kinnunen L, Julkunen I. Importin alpha nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein. J Biol Chem. 2003;278:28193-200 pubmed
- Singh A, Buscaglia C, Wang Q, Levay A, Nussenzweig D, Walker J, et al. Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite. Cell. 2007;131:492-504 pubmed..The presence of CS in the hepatocyte enhances parasite growth of the liver stages in vitro and in vivo. These findings have far reaching implications for drug and vaccine development against the liver stages of the malaria parasite. ..
- Xu W, Edwards M, Borek D, Feagins A, Mittal A, Alinger J, et al. Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1. Cell Host Microbe. 2014;16:187-200 pubmed publisher..We describe the structure of human KPNA5 C terminus in complex with eVP24...
- Sekimoto T, Fukumoto M, Yoneda Y. 14-3-3 suppresses the nuclear localization of threonine 157-phosphorylated p27(Kip1). EMBO J. 2004;23:1934-42 pubmed..These findings indicate that 14-3-3 suppresses importin alpha/beta-dependent nuclear localization of Thr157-phosphorylated p27, suggesting implications for cell cycle disorder in Akt-activated cancer cells. ..
- Friedler A, Zakai N, Karni O, Broder Y, Baraz L, Kotler M, et al. Backbone cyclic peptide, which mimics the nuclear localization signal of human immunodeficiency virus type 1 matrix protein, inhibits nuclear import and virus production in nondividing cells. Biochemistry. 1998;37:5616-22 pubmed..These properties make BCvir a potential candidate for the development of a novel class of antiviral drugs which will be based on blocking nuclear import of viral genomes. ..
- Depienne C, Roques P, Creminon C, Fritsch L, Casseron R, Dormont D, et al. Cellular distribution and karyophilic properties of matrix, integrase, and Vpr proteins from the human and simian immunodeficiency viruses. Exp Cell Res. 2000;260:387-95 pubmed..These results indicate that the viral proteins IN and Vpr, which are strongly associated with the viral DNA within PIC, may participate in the nuclear import of the HIV PIC. ..
- Matreyek K, Engelman A. Viral and cellular requirements for the nuclear entry of retroviral preintegration nucleoprotein complexes. Viruses. 2013;5:2483-511 pubmed publisher..In this review, we describe our current understanding of retroviral nuclear import, with emphasis on recent developments on the role of the HIV-1 capsid protein. ..
- Haffar O, Smithgall M, Popov S, Ulrich P, Bruce A, Nadler S, et al. CNI-H0294, a nuclear importation inhibitor of the human immunodeficiency virus type 1 genome, abrogates virus replication in infected activated peripheral blood mononuclear cells. Antimicrob Agents Chemother. 1998;42:1133-8 pubmed..These results support nuclear importation as a novel target and CNI-H0294 and its derivatives as novel compounds for therapeutic intervention in HIV infection and AIDS. ..
- Freed E, Englund G, Maldarelli F, Martin M. Phosphorylation of residue 131 of HIV-1 matrix is not required for macrophage infection. Cell. 1997;88:171-3; discussion 173-4 pubmed
- Kim N, Yoshimaru T, Chen Y, Matsuo T, Komatsu M, Miyoshi Y, et al. BIG3 Inhibits the Estrogen-Dependent Nuclear Translocation of PHB2 via Multiple Karyopherin-Alpha Proteins in Breast Cancer Cells. PLoS ONE. 2015;10:e0127707 pubmed publisher..We found that overexpressed PHB2 interacted with KPNA1, KPNA5, and KPNA6, thereby leading to the E2-dependent translocation of PHB2 into the nuclei of breast cancer cells...
- Popov S, Dubrovsky L, Lee M, Pennathur S, Haffar O, Al Abed Y, et al. Critical role of reverse transcriptase in the inhibitory mechanism of CNI-H0294 on HIV-1 nuclear translocation. Proc Natl Acad Sci U S A. 1996;93:11859-64 pubmed..Our results provide a basis for the development of a novel class of compounds that inhibit nuclear translocation and that can, in principle, be modified to target specific infectious agents. ..
- Jayappa K, Ao Z, Yao X. The HIV-1 passage from cytoplasm to nucleus: the process involving a complex exchange between the components of HIV-1 and cellular machinery to access nucleus and successful integration. Int J Biochem Mol Biol. 2012;3:70-85 pubmed..Hereby we aim to further our understanding on molecular mechanism of HIV-1 nuclear import and its potential usefulness for anti-HIV-1 strategies. ..
- Zhan P, Liu X, De Clercq E. Blocking nuclear import of pre-integration complex: an emerging anti-HIV-1 drug discovery paradigm. Curr Med Chem. 2010;17:495-503 pubmed
- Kootstra N, Schuitemaker H. Phenotype of HIV-1 lacking a functional nuclear localization signal in matrix protein of gag and Vpr is comparable to wild-type HIV-1 in primary macrophages. Virology. 1999;253:170-80 pubmed..In conclusion, our results confirm the dependency of the process of HIV-1 reverse transcriptase on cell proliferation in primary macrophages and exclude an important role of MA-NLS and Vpr in macrophage infection. ..
- Bukrinskaya A, Ghorpade A, Heinzinger N, Smithgall T, Lewis R, Stevenson M. Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA. Proc Natl Acad Sci U S A. 1996;93:367-71 pubmed..These results reveal a novel level of regulation of primate lentivirus infectivity. ..
- Di Marzio P, Choe S, Ebright M, Knoblauch R, Landau N. Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr. J Virol. 1995;69:7909-16 pubmed..We speculate that Vpr has two sites for interaction with cellular factors: one in the alpha-helical region that specifies nuclear localization and one in the carboxy-terminal domain that is required for Cdc2 inhibition. ..
- Inuzuka H, Gao D, Finley L, Yang W, Wan L, Fukushima H, et al. Acetylation-dependent regulation of Skp2 function. Cell. 2012;150:179-93 pubmed publisher..Thus, our study identifies an acetylation-dependent regulatory mechanism governing Skp2 oncogenic function and provides insight into how cytoplasmic Skp2 controls cellular migration. ..
- Hariton Gazal E, Friedler D, Friedler A, Zakai N, Gilon C, Loyter A. Inhibition of nuclear import by backbone cyclic peptidomimetics derived from the HIV-1 MA NLS sequence. Biochim Biophys Acta. 2002;1594:234-42 pubmed..Being only inhibitory, these BC peptides resemble classic receptor antagonists. ..
- Hurst D, Mehta A, Moore B, Phadke P, Meehan W, Accavitti M, et al. Breast cancer metastasis suppressor 1 (BRMS1) is stabilized by the Hsp90 chaperone. Biochem Biophys Res Commun. 2006;348:1429-35 pubmed..We further found that BRMS1 is stabilized by Hsp90, and its turnover is proteasome dependent. The stability of BRMS1 protein may be important in maintaining the functional role of BRMS1 in metastasis suppression. ..