Affinage

KPNA5

Importin subunit alpha-6 · UniProt O15131

Round 2 corrected Audit flag: rerun needed
Length
539 aa
Mass
60.7 kDa
Annotated
2026-04-28
50 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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Mechanism profile

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Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 Crystal structure of the human KPNA5 C-terminus in complex with Ebola virus VP24 (eVP24) revealed that eVP24 recognizes a unique nonclassical NLS binding site on KPNA5 that is necessary for efficient PY-STAT1 nuclear transport. eVP24 binds KPNA5 with very high affinity at this site to competitively inhibit PY-STAT1 nuclear import without affecting classical NLS cargo transport. X-ray crystallography of KPNA5 C-terminus/eVP24 complex; binding affinity measurements; cell-based nuclear transport assays Cell host & microbe High 25121748
2015 Lloviu virus VP24 (LLOV VP24) blocks tyrosine-phosphorylated STAT1 (PY-STAT1) binding to KPNA5, preventing STAT1 nuclear accumulation and IFN-induced gene expression, demonstrating that KPNA5's role in PY-STAT1 nuclear import is targeted by multiple filovirus VP24 proteins. Co-immunoprecipitation; nuclear accumulation assays; IFN-induced gene expression assays in human and bat cells Virology Medium 26255028
2015 PHB2 interacts with KPNA1, KPNA5, and KPNA6, and these interactions mediate estrogen-dependent translocation of PHB2 into the nuclei of breast cancer cells. BIG3 blocks the KPNA-binding region(s) of PHB2, thereby inhibiting KPNA-mediated PHB2 nuclear translocation. Co-immunoprecipitation; siRNA knockdown of individual KPNAs; nuclear translocation assays in breast cancer cells PloS one Medium 26052702
2017 VP24 proteins from different Ebolavirus species (EBOV, BDBV, RESTV) all bind KPNA1, KPNA5, and KPNA6, but with differing affinities; BDBV VP24 shows ~10-fold lower KPNA5 binding affinity than EBOV or RESTV VP24. Reduced VP24-KPNA binding affinity decreases IFN inhibition and shortens VP24 half-life, revealing that KPNA interaction stabilizes VP24. Binding affinity measurements with purified proteins; cell-based VP24 half-life assays; IFN-induced gene expression assays; alanine-scanning mutagenesis Journal of virology High 27974555
2017 Molecular dynamics simulations of the VP24-KPNA5 complex identified key hydrogen bonds (D480-T138, E483-R137, D205-R396) critical for the interaction interface. VP24 residues R137 and T138, and KPNA5 residues R396, R398, R480, Y477, and F484, were identified as hotspot residues essential for complex stability. All-atom molecular dynamics simulation; MM-GB/SA energy calculation; computational alanine scanning Molecular bioSystems Low 28418440
2017 Macrocyclic peptide inhibitors of the VP24-KPNA5 protein-protein interaction were identified with dissociation constants in the single-digit nanomolar range for eVP24, and these peptides successfully disrupted the eVP24-KPNA interaction, providing the first chemical probes capable of modulating this PPI. RaPID (Random non-standard Peptides Integrated Discovery) system; binding affinity measurements; PPI disruption assays with purified proteins Organic & biomolecular chemistry Medium 28574091
2025 miR-153 directly targets two binding sites in the 3'UTR of KPNA5 mRNA to suppress KPNA5 expression. KPNA5 facilitates nuclear translocation of NRF2 by binding to three nuclear localization sequences (NLS) of NRF2, and miR-153-mediated suppression of KPNA5 impairs NRF2-mediated antioxidant responses, promoting oxidative stress and cognitive deficits in chronic cerebral hypoperfusion models. Luciferase reporter assays for miR-153 binding sites; Co-IP for KPNA5-NRF2 interaction; knockdown and overexpression in vivo (rat basal forebrain) and in vitro; nuclear fractionation assays The Journal of neuroscience Medium 40816766
2025 KPNA5 recognizes nuclear localization signals (NLS) in the protein tyrosine phosphatase PTPN4 and mediates its nuclear transport. Nuclear PTPN4 inhibits STAT3 phosphorylation and its downstream signaling pathway. KPNA5 overexpression suppressed ovarian cancer cell proliferation, tumor growth, and invasion in vitro and in vivo. Co-IP for KPNA5-PTPN4 interaction; Western blot for STAT3 phosphorylation; xenograft tumor model; CCK-8, colony formation, Transwell assays Cancer medicine Medium 40145330
2025 miR-153-3p derived from bone marrow mesenchymal stem cell exosomes targets KPNA5, and this targeting promotes M2 macrophage polarization to facilitate wound healing. Target prediction and validation; co-culture assays; exosome transfer experiments; macrophage polarization assays Applied biochemistry and biotechnology Low 40053206
2025 Nuclear trafficking of eVP24 by KPNA5 requires simultaneous binding of cellular NLS-containing cargo; eVP24 binding to KPNA5 does not impair cargo NLS binding at the major NLS binding site, indicating that eVP24 and classical cargo can simultaneously associate with KPNA5 for co-transport into the nucleus. Hydrogen-deuterium exchange mass spectrometry (HDX-MS); native MS; biophysical binding assays with purified proteins; nuclear localization assays Viruses Medium 40872766

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1994 The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proceedings of the National Academy of Sciences of the United States of America 736 8041786
1993 A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 708 8105392
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
1995 Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. Nature 660 7566098
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
1992 Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proceedings of the National Academy of Sciences of the United States of America 513 1631159
2011 The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3. Molecular and cellular biology 437 21555454
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1997 HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway. Proceedings of the National Academy of Sciences of the United States of America 415 9275210
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2007 Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Molecular cell 367 17643375
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
1997 HIV-1 infection of non-dividing cells: evidence that the amino-terminal basic region of the viral matrix protein is important for Gag processing but not for post-entry nuclear import. The EMBO journal 313 9303297
1995 HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase. Cell 312 7585960
1995 HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator. Cell 288 7859280
1998 Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. The EMBO journal 275 9463369
1995 Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection. Journal of virology 271 7745752
2017 Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT-mTORC1 activation. Nature medicine 251 28805822
1995 Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr. Journal of virology 245 7494303
2014 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 187 25121748
2007 An intracellular serpin regulates necrosis by inhibiting the induction and sequelae of lysosomal injury. Cell 133 17889653
2012 Somatic mutations in the Notch, NF-KB, PIK3CA, and Hedgehog pathways in human breast cancers. Genes, chromosomes & cancer 63 22302350
2015 Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells. Virology 40 26255028
2017 Macrocyclic peptide inhibitors for the protein-protein interaction of Zaire Ebola virus protein 24 and karyopherin alpha 5. Organic & biomolecular chemistry 39 28574091
2017 VP24-Karyopherin Alpha Binding Affinities Differ between Ebolavirus Species, Influencing Interferon Inhibition and VP24 Stability. Journal of virology 33 27974555
2016 Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses. Scientific reports 28 27009368
2022 Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins. Communications biology 23 35022507
2015 BIG3 Inhibits the Estrogen-Dependent Nuclear Translocation of PHB2 via Multiple Karyopherin-Alpha Proteins in Breast Cancer Cells. PloS one 23 26052702
2021 Molecular profiling of nucleocytoplasmic transport factor genes in breast cancer. Heliyon 12 33553736
2023 LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944. Pharmaceuticals (Basel, Switzerland) 11 37259332
2021 Effect of Ivermectin and Atorvastatin on Nuclear Localization of Importin Alpha and Drug Target Expression Profiling in Host Cells from Nasopharyngeal Swabs of SARS-CoV-2- Positive Patients. Viruses 9 34696514
2017 An all-atom molecular dynamics study of the anti-interferon signaling of Ebola virus: interaction mechanisms of EBOV VP24 binding to Karyopherin alpha5. Molecular bioSystems 9 28418440
2017 Investigating Ebola virus pathogenicity using molecular dynamics. BMC genomics 8 28812539
2018 Ebolavirus interferon antagonists-protein interaction perspectives to combat pathogenesis. Briefings in functional genomics 7 29140409
2002 Physical map of the chromosome 6q22 region containing the oculodentodigital dysplasia locus: analysis of thirteen candidate genes and identification of novel ESTs and DNA polymorphisms. Cytogenetic and genome research 5 12584438
2025 MiR-153 Prevents NRF2 Nuclear Translocation to Drive Hypoperfusion-Related Cognitive Deficits by Targeting KPNA5. The Journal of neuroscience : the official journal of the Society for Neuroscience 4 40816766
2025 Mesenchymal Stem Cell-Derived Exosome miR-153-3 Induced M2-Type Polarization of Macrophages to Improve the Healing Effect of Burn Wounds. Applied biochemistry and biotechnology 2 40053206
2025 KPNA5 Suppresses Malignant Progression of Ovarian Cancer Through Importing the PTPN4 Into the Nucleus. Cancer medicine 2 40145330
2025 The Biophysical Basis for Karyopherin-Dependent Ebola Virus VP24 Nuclear Transport. Viruses 1 40872766