Affinage

IPO13

Importin-13 · UniProt O94829

Length
963 aa
Mass
108.2 kDa
Annotated
2026-06-10
12 papers in source corpus 5 papers cited in narrative 5 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IPO13 is a nuclear transport receptor that mediates the nuclear import of developmentally important transcription factors and steroid receptors, coupling cargo recognition in the cytoplasm to RanGTP-dependent release in the nucleus (PMID:20148114). It recognizes nuclear localization sequences flanking the ARX homeodomain, and missense mutations in these NLS regions trap IPO13 with mutant ARX even in the RanGTP-rich nuclear environment, preventing normal ARX nuclear distribution (PMID:20148114). Beyond ARX, IPO13 mediates nuclear translocation of the glucocorticoid receptor, and competition for this interaction by RSV nonstructural protein NS1 reduces GR nuclear entry and blunts glucocorticoid-induced anti-inflammatory gene expression (PMID:28968829). Consistent with a role in cargo delivery during development, IPO13 is required for neuronal differentiation of embryonic stem cells in part through nuclear transport of Pax6 (PMID:35741036), and is essential for eye morphogenesis, with loss of function producing microphthalmia and coloboma (PMID:29700284). Its own subcellular distribution is developmentally regulated, shifting from cytoplasmic in early embryonic neurons to nuclear at later stages (PMID:23605716).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2010 Medium

    Established that IPO13 is the receptor that drives ARX nuclear import by binding NLS sequences flanking the homeodomain, and that disease-associated NLS mutations act by trapping cargo with the receptor rather than abolishing binding.

    Evidence Reciprocal Co-immunoprecipitation and immunofluorescence in vitro using wild-type and NLS-mutant ARX

    PMID:20148114

    Open questions at the time
    • RanGTP-dependent release step inferred but not directly reconstituted
    • Binding affinity and structural basis of NLS recognition not defined
  2. 2013 Medium

    Showed that IPO13's own localization is dynamically regulated during brain development, implying its cargo transport activity is stage-dependent rather than constitutive.

    Evidence Immunohistochemistry of mouse embryonic brain across staged timepoints (E13.5 to adult)

    PMID:23605716

    Open questions at the time
    • Single method (IHC) without functional readout
    • Mechanism controlling the cytoplasmic-to-nuclear shift unknown
    • Cargo specificity at each stage not determined
  3. 2017 Medium

    Extended IPO13's cargo repertoire to the glucocorticoid receptor and demonstrated a viral mechanism of glucocorticoid resistance through competitive inhibition of IPO13-GR binding.

    Evidence IPO13 knockdown in A549 cells and infected mouse lungs, GR nuclear translocation assays, and NS1/IPO13 competition binding

    PMID:28968829

    Open questions at the time
    • GR NLS determinants recognized by IPO13 not mapped
    • Whether NS1 directly displaces IPO13 versus indirect effects not fully resolved
  4. 2018 Medium

    Demonstrated an essential organismal requirement for IPO13 in eye morphogenesis via a rescuable loss-of-function phenotype.

    Evidence Morpholino knockdown of ipo13 in zebrafish with full-length mRNA rescue plus visual motor and optokinetic functional assays

    PMID:29700284

    Open questions at the time
    • Specific cargo(s) driving the ocular phenotype not identified
    • Morpholino-based knockdown not corroborated by a genetic mutant
  5. 2022 Medium

    Linked IPO13 to a defined cellular program—neuronal differentiation—mechanistically through nuclear import of Pax6.

    Evidence IPO13 knockout mouse ESC differentiation model with Pax6 nuclear localization, marker expression, and glutamate response assays

    PMID:35741036

    Open questions at the time
    • Relative contribution of Pax6 versus other cargoes to the differentiation defect unquantified
    • Direct IPO13-Pax6 binding not biochemically characterized here

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of IPO13 NLS recognition, its full cargo spectrum, and the mechanism regulating its developmental cytoplasmic-to-nuclear redistribution remain unresolved.
  • No structural model of IPO13-cargo complexes
  • RanGTP-dependent cargo release not directly reconstituted for any cargo
  • Mechanism driving stage-regulated IPO13 localization unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140104 molecular carrier activity 3
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-9609507 Protein localization 2
Partners
ARXNR3C1PAX6

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 IPO13 (Importin 13) binds the nuclear localization sequences (NLS) flanking the ARX homeodomain to facilitate nuclear import of ARX. Missense mutations in either the N- or C-terminal NLS regions of the ARX homeodomain disrupt nuclear localization but do not abolish ARX-IPO13 binding; instead, IPO13 remains sequestered with mutant ARX even in the RanGTP-rich nuclear environment, preventing normal ARX nuclear distribution. Co-immunoprecipitation and immunofluorescence studies in vitro PathoGenetics Medium 20148114
2017 IPO13 mediates nuclear translocation of the glucocorticoid receptor (GR). RSV nonstructural protein 1 (NS1) competes with IPO13 for GR binding, reducing GR nuclear translocation and thereby suppressing GR-induced anti-inflammatory gene expression, accounting for glucocorticoid insensitivity during RSV infection. IPO13 expression knockdown in A549 cells and infected mouse lungs, GR nuclear translocation assay, competition binding assay between NS1 and IPO13 for GR The Journal of infectious diseases Medium 28968829
2013 IPO13 (Imp13) subcellular distribution is developmentally regulated in mouse brain: it is predominantly cytoplasmic in early embryonic neuronal cells and relocates to the nucleus at later developmental stages, suggesting dynamic regulation of its cargo transport activity during brain development. Immunohistochemical analysis of mouse embryonic brain sections at multiple developmental stages (E13.5, E15.5, E17.5, P0, adult) using a custom anti-imp13 polyclonal antibody In vitro cellular & developmental biology. Animal Medium 23605716
2018 Loss of IPO13 function causes ocular coloboma, microphthalmia, and cataract. Morpholino-induced knockdown of ipo13 in zebrafish produced dose-dependent microphthalmia and coloboma phenotypes that were rescued by full-length ipo13 mRNA, establishing IPO13 as required for eye morphogenesis. Morpholino-oligonucleotide knockdown in zebrafish with mRNA rescue experiment; visual motor response and optokinetic response functional assays Experimental & molecular medicine Medium 29700284
2022 IPO13 is required for efficient neuronal differentiation of mouse embryonic stem cells (ESCs). IPO13-/- ESCs show reduced nuclear localization and transcriptional activity of import cargo Pax6, reduced expression of progenitor markers (Pax6, Nestin), impaired neuronal morphology, reduced neuronal marker expression, and altered glutamate response, establishing IPO13's role in neuronal differentiation in part through nuclear transport of Pax6. IPO13 knockout mouse ESC model with monolayer-based differentiation protocol; immunofluorescence for nuclear localization of Pax6; marker expression analysis; glutamate response assay Cells Medium 35741036

Source papers

Stage 0 corpus · 12 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Nosocomial outbreak caused by multidrug-resistant Pseudomonas aeruginosa producing IMP-13 metallo-beta-lactamase. Journal of clinical microbiology 71 16081918
2012 Occurrence of IMP-8, IMP-10, and IMP-13 metallo-β-lactamases located on class 1 integrons and other extended-spectrum β-lactamases in bacterial isolates from Tunisian rivers. Scandinavian journal of infectious diseases 34 22992193
2010 Mutations in the nuclear localization sequence of the Aristaless related homeobox; sequestration of mutant ARX with IPO13 disrupts normal subcellular distribution of the transcription factor and retards cell division. PathoGenetics 33 20148114
2018 Mutation of IPO13 causes recessive ocular coloboma, microphthalmia, and cataract. Experimental & molecular medicine 22 29700284
2017 Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1-3 family. Genes & development 19 28446596
2017 Respiratory Syncytial Virus Nonstructural Protein 1 Blocks Glucocorticoid Receptor Nuclear Translocation by Targeting IPO13 and May Account for Glucocorticoid Insensitivity. The Journal of infectious diseases 15 28968829
2020 Structure and Molecular Recognition Mechanism of IMP-13 Metallo-β-Lactamase. Antimicrobial agents and chemotherapy 14 32205343
2013 Expression and subcellular distribution of imp13 are regulated in brain development. In vitro cellular & developmental biology. Animal 13 23605716
2024 Regional dissemination of NDM-1 producing Enterobacter hormaechei ST1740, with a subset of strains co-producing VIM-4 or IMP-13, France, 2019 to 2022. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 6 38487887
2022 Transcriptomic profile dataset of embryonic stem cells (Wild-type and IPO13-Knock Out) with and without oxidative stress. Data in brief 3 35434231
2022 Nuclear Transporter IPO13 Is Central to Efficient Neuronal Differentiation. Cells 3 35741036
2024 Mobilization of an ICEclc-Like Element as a Potential Mechanism for the Spread of IMP-13 Carbapenemase in Pseudomonas aeruginosa. Journal of global antimicrobial resistance 2 39706477

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