Affinage

IPO11

Importin-11 · UniProt Q9UI26

Round 2 corrected
Length
975 aa
Mass
112.5 kDa
Annotated
2026-04-28
38 papers in source corpus 3 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IPO11 (Importin-11) is a nuclear import receptor that mediates the translocation of specific cargo proteins from the cytoplasm to the nucleus. In APC-mutant colorectal cancer cells, IPO11 is required for β-catenin nuclear import and consequent β-catenin-dependent transcriptional activation; its deletion reduces nuclear β-catenin levels and impairs Wnt-driven proliferation in patient-derived organoids (PMID:31881079). IPO11 also imports CDK4/6-phosphorylated RPRM (Reprimo) into the nucleus following ionizing radiation, where RPRM promotes ATM nuclear export and proteasomal degradation, thereby attenuating the DNA damage response (PMID:36185355).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2020 High

    A genome-wide CRISPR screen resolved how β-catenin reaches the nucleus in APC-mutant colorectal cancer, identifying IPO11 as the import receptor required for β-catenin nuclear accumulation and Wnt target gene transcription.

    Evidence DEADPOOL CRISPR screen in APC-mutant CRC lines, IPO11 knockout, nuclear fractionation, transcriptional reporters, patient-derived organoid proliferation assays

    PMID:31881079

    Open questions at the time
    • Whether IPO11 binds β-catenin directly or through an adaptor has not been established
    • The nuclear localization signal or recognition motif on β-catenin used by IPO11 is undefined
    • Relevance of IPO11-mediated β-catenin import in non-APC-mutant Wnt-active contexts is untested
  2. 2022 High

    Discovery that IPO11 imports phosphorylated RPRM into the nucleus after irradiation established a second cargo and linked IPO11 to the DNA damage response via ATM degradation.

    Evidence Reciprocal co-immunoprecipitation, CRISPR IPO11 knockout, RPRM S98 phosphosite mutagenesis, CDK4/6 inhibitor treatment, subcellular fractionation, in vivo irradiation

    PMID:36185355

    Open questions at the time
    • Structural basis for IPO11 recognition of CDK4/6-phosphorylated RPRM is unknown
    • Whether IPO11 has additional DNA-damage-responsive cargoes has not been explored
    • RanGTP-dependent release of RPRM in the nucleus has not been directly demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • A comprehensive cargo repertoire for IPO11 remains undefined; beyond β-catenin and RPRM, no systematic identification of physiological import substrates has been performed.
  • No unbiased proteomics-based cargo identification has been reported
  • Structural determinants of cargo specificity (NLS-like motifs recognized by IPO11) are uncharacterized
  • Physiological roles of IPO11 in normal tissues (e.g., spermatogenesis) lack mechanistic validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-9609507 Protein localization 2 R-HSA-162582 Signal Transduction 1
Partners
CTNNB1RPRM

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 IPO11 (Importin-11) was identified as a required factor for β-catenin nuclear import in APC-mutant colorectal cancer cells. A genome-wide CRISPR screen (DEADPOOL) identified IPO11, and IPO11 knockout cells exhibited reduced nuclear β-catenin protein levels and decreased β-catenin target gene activation, demonstrating that IPO11 facilitates β-catenin nucleocytoplasmic shuttling and is required for β-catenin-mediated transcription in cells with high Wnt activity. Genome-wide CRISPR screen (DEADPOOL positive selection), IPO11 knockout cell lines, nuclear fractionation, β-catenin target gene expression analysis, colony formation assay, patient-derived CRC organoid proliferation assay The Journal of cell biology High 31881079
2022 IPO11 (Importin-11) mediates the nuclear import of RPRM (Reprimo) upon X-irradiation. RPRM is primarily cytoplasmic but translocates to the nucleus after irradiation, a process requiring phosphorylation of RPRM at serine 98 by CDK4/6 and requiring IPO11. Once nuclear, RPRM interacts with ATM and promotes its nuclear export and proteasomal degradation, thereby downregulating ATM protein levels and impairing DNA repair. IPO11 deletion abrogated RPRM nuclear import and prevented ATM downregulation. Co-immunoprecipitation, subcellular fractionation, CRISPR-based IPO11 knockout, site-directed mutagenesis (S98 phospho-site), CDK4/6 inhibitor treatment, in vivo irradiation experiments, proteasome inhibition assay iScience High 36185355
2009 Ipo11 expression is associated with spermiogenesis in mouse testis; treatment with Tripterygium wilfordii (GTW) caused abnormal expression of Ipo11 (along with Herc4 and Mrto4) in testicular tissue, correlating with disrupted spermatogenic cell populations and infertility, indicating a role for Ipo11 in male germ cell development. Gene chip (microarray) expression profiling of testis tissue from GTW-treated versus control mice, histological analysis of seminiferous tubules Yi chuan = Hereditas Low 19819847

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
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
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
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
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2006 Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 517 17110338
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Science signaling 383 24255178
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
2020 Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis. Med (New York, N.Y.) 291 32838362
2003 The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome research 285 12975309
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2014 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Molecular cell 173 25544563
2012 Genome-wide significant association signals in IPO11-HTR1A region specific for alcohol and nicotine codependence. Alcoholism, clinical and experimental research 36 23216389
2017 Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes. Clinical pharmacology and therapeutics 32 28736931
2020 IPO11 mediates βcatenin nuclear import in a subset of colorectal cancers. The Journal of cell biology 31 31881079
2019 Nicotiana benthamiana RanBP1-1 Is Involved in the Induction of Disease Resistance via Regulation of Nuclear-Cytoplasmic Transport of Small GTPase Ran. Frontiers in plant science 9 30906303
2009 [Influence of Tripterygium wilfordii on the expression of spermiogenesis related genes Herc4, Ipo11 and Mrto4 in mice]. Yi chuan = Hereditas 8 19819847
2015 Significant association between rare IPO11-HTR1A variants and attention deficit hyperactivity disorder in Caucasians. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 6 26079129
2022 RPRM negatively regulates ATM levels through its nuclear translocation on irradiation mediated by CDK4/6 and IPO11. iScience 4 36185355
2023 Protocol for IPO11 deletion and re-expression in H460 lung cancer cells using CRISPR-Cas9 and plasmid transfection. STAR protocols 0 37195868