{"gene":"KPNA5","run_date":"2026-06-13T19:06:35","timeline":{"discoveries":[],"current_model":"Parse failed"},"narrative":{"mechanistic_narrative":"No mechanistic discoveries found in literature.","teleology":[],"mechanism_profile":null},"prefetch_data":{"uniprot":{"accession":"O15131","full_name":"Importin subunit alpha-6","aliases":["Karyopherin subunit alpha-5"],"length_aa":539,"mass_kda":60.7,"function":"Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Mediates nuclear import of STAT1 homodimers and STAT1/STAT2 heterodimers by recognizing non-classical NLSs of STAT1 and STAT2 through ARM repeats 8-9. Recognizes influenza A virus nucleoprotein through ARM repeat 7-9 In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/O15131/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KPNA5","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"KPNB1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/KPNA5","total_profiled":1310},"omim":[{"mim_id":"610563","title":"KARYOPHERIN ALPHA-6; KPNA6","url":"https://www.omim.org/entry/610563"},{"mim_id":"604545","title":"KARYOPHERIN ALPHA-5; KPNA5","url":"https://www.omim.org/entry/604545"},{"mim_id":"603948","title":"NUCLEOPORIN, 153-KD; NUP153","url":"https://www.omim.org/entry/603948"},{"mim_id":"600555","title":"SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 1; STAT1","url":"https://www.omim.org/entry/600555"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"testis","ntpm":39.2}],"url":"https://www.proteinatlas.org/search/KPNA5"},"hgnc":{"alias_symbol":["SRP6","IPOA6"],"prev_symbol":[]},"alphafold":{"accession":"O15131","domains":[{"cath_id":"1.25.10.10","chopping":"81-241","consensus_level":"medium","plddt":96.2127,"start":81,"end":241},{"cath_id":"1.25.10.10","chopping":"379-505","consensus_level":"medium","plddt":95.3811,"start":379,"end":505}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O15131","model_url":"https://alphafold.ebi.ac.uk/files/AF-O15131-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O15131-F1-predicted_aligned_error_v6.png","plddt_mean":85.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KPNA5","jax_strain_url":"https://www.jax.org/strain/search?query=KPNA5"},"sequence":{"accession":"O15131","fasta_url":"https://rest.uniprot.org/uniprotkb/O15131.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O15131/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O15131"}},"corpus_meta":[{"pmid":"25121748","id":"PMC_25121748","title":"Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1.","date":"2014","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/25121748","citation_count":187,"is_preprint":false},{"pmid":"17889653","id":"PMC_17889653","title":"An intracellular serpin regulates necrosis by inhibiting the induction and sequelae of lysosomal injury.","date":"2007","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/17889653","citation_count":133,"is_preprint":false},{"pmid":"22302350","id":"PMC_22302350","title":"Somatic mutations in the Notch, NF-KB, PIK3CA, and Hedgehog pathways in human breast cancers.","date":"2012","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/22302350","citation_count":63,"is_preprint":false},{"pmid":"26255028","id":"PMC_26255028","title":"Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells.","date":"2015","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/26255028","citation_count":40,"is_preprint":false},{"pmid":"28574091","id":"PMC_28574091","title":"Macrocyclic peptide inhibitors for the protein-protein interaction of Zaire Ebola virus protein 24 and karyopherin alpha 5.","date":"2017","source":"Organic & biomolecular chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28574091","citation_count":39,"is_preprint":false},{"pmid":"27974555","id":"PMC_27974555","title":"VP24-Karyopherin Alpha Binding Affinities Differ between Ebolavirus Species, Influencing Interferon Inhibition and VP24 Stability.","date":"2017","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/27974555","citation_count":33,"is_preprint":false},{"pmid":"27009368","id":"PMC_27009368","title":"Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27009368","citation_count":28,"is_preprint":false},{"pmid":"35022507","id":"PMC_35022507","title":"Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins.","date":"2022","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/35022507","citation_count":24,"is_preprint":false},{"pmid":"26052702","id":"PMC_26052702","title":"BIG3 Inhibits the Estrogen-Dependent Nuclear Translocation of PHB2 via Multiple Karyopherin-Alpha Proteins in Breast Cancer Cells.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26052702","citation_count":23,"is_preprint":false},{"pmid":"33553736","id":"PMC_33553736","title":"Molecular profiling of nucleocytoplasmic transport factor genes in breast cancer.","date":"2021","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/33553736","citation_count":12,"is_preprint":false},{"pmid":"37259332","id":"PMC_37259332","title":"LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944.","date":"2023","source":"Pharmaceuticals (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/37259332","citation_count":11,"is_preprint":false},{"pmid":"28418440","id":"PMC_28418440","title":"An all-atom molecular dynamics study of the anti-interferon signaling of Ebola virus: interaction mechanisms of EBOV VP24 binding to Karyopherin alpha5.","date":"2017","source":"Molecular bioSystems","url":"https://pubmed.ncbi.nlm.nih.gov/28418440","citation_count":9,"is_preprint":false},{"pmid":"34696514","id":"PMC_34696514","title":"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.","date":"2021","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/34696514","citation_count":9,"is_preprint":false},{"pmid":"28812539","id":"PMC_28812539","title":"Investigating Ebola virus pathogenicity using molecular dynamics.","date":"2017","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/28812539","citation_count":8,"is_preprint":false},{"pmid":"29140409","id":"PMC_29140409","title":"Ebolavirus interferon antagonists-protein interaction perspectives to combat pathogenesis.","date":"2018","source":"Briefings in functional genomics","url":"https://pubmed.ncbi.nlm.nih.gov/29140409","citation_count":7,"is_preprint":false},{"pmid":"12584438","id":"PMC_12584438","title":"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.","date":"2002","source":"Cytogenetic and genome research","url":"https://pubmed.ncbi.nlm.nih.gov/12584438","citation_count":5,"is_preprint":false},{"pmid":"40053206","id":"PMC_40053206","title":"Mesenchymal Stem Cell-Derived Exosome miR-153-3 Induced M2-Type Polarization of Macrophages to Improve the Healing Effect of Burn Wounds.","date":"2025","source":"Applied biochemistry and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/40053206","citation_count":5,"is_preprint":false},{"pmid":"40816766","id":"PMC_40816766","title":"MiR-153 Prevents NRF2 Nuclear Translocation to Drive Hypoperfusion-Related Cognitive Deficits by Targeting KPNA5.","date":"2025","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/40816766","citation_count":4,"is_preprint":false},{"pmid":"40145330","id":"PMC_40145330","title":"KPNA5 Suppresses Malignant Progression of Ovarian Cancer Through Importing the PTPN4 Into the Nucleus.","date":"2025","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40145330","citation_count":2,"is_preprint":false},{"pmid":"40872766","id":"PMC_40872766","title":"The Biophysical Basis for Karyopherin-Dependent Ebola Virus VP24 Nuclear Transport.","date":"2025","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/40872766","citation_count":1,"is_preprint":false},{"pmid":"42235722","id":"PMC_42235722","title":"Genome-wide association analysis for resistance against iridovirus disease in large yellow croaker (Larimichthys crocea) from a natural outbreak population.","date":"2026","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/42235722","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12039,"output_tokens":759,"usd":0.023751,"stage1_stop_reason":"refusal"},"stage2":{"model":"","input_tokens":0,"output_tokens":0,"usd":0.0},"total_usd":0.023751,"stage1_batch_id":"msgbatch_0147LFpL5iCPFZF66xp23BqC","stage2_batch_id":"msgbatch_01Crtwc6eCsZh1CrnfJhY7J7","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"Crystal structure of 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 (tyrosine-phosphorylated STAT1) nuclear transport; eVP24 binds this site with very high affinity to compete with and inhibit PY-STAT1 nuclear import without affecting classical NLS cargo transport.\",\n      \"method\": \"X-ray crystallography, binding affinity measurements, nuclear transport assays, mutagenesis\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with functional validation (mutagenesis + transport assays), single rigorous study with multiple orthogonal methods\",\n      \"pmids\": [\"25121748\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"KPNA5 mediates estrogen-dependent nuclear translocation of PHB2 (Prohibitin 2) in breast cancer cells; siRNA knockdown of KPNA5 inhibited E2-dependent PHB2 nuclear import and enhanced ERα activation, and PHB2 interaction with KPNA5 was demonstrated by co-immunoprecipitation.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, nuclear translocation assays, confocal microscopy\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and siRNA KD with defined cellular phenotype, single lab with two orthogonal methods\",\n      \"pmids\": [\"26052702\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Quantitative comparison of VP24 proteins from EBOV, BDBV, and RESTV showed differential binding affinities to KPNA5 (and KPNA1, KPNA6); lower KPNA binding affinity of BDBV VP24 correlated with decreased IFN signaling suppression and shorter VP24 half-life, revealing that KPNA5 interaction modulates VP24 protein stability.\",\n      \"method\": \"Purified protein binding assays (quantitative), cell-based IFN suppression assays, VP24 half-life measurements, amino acid sequence alignments with mutagenesis\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — pur","stage2_raw":"","audit_flag":null,"evaluation":null}