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Showing KPNA2 — RCH1 is a alias.

KPNA2

Importin subunit alpha-1 · UniProt P52292

Length
529 aa
Mass
57.9 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KPNA2 is a classical importin-alpha nuclear transport adaptor that recognizes nuclear localization signals (NLS) on cargo proteins and, via importin-beta, escorts them through the nuclear pore (PMID:16188882, PMID:35301060). Cargo specificity is a defining property: KPNA2 is the only importin-alpha family member that binds the NBS1 NLS (residues 461–467) to import the MRE11-RAD50-NBS1 complex and support radiation-induced focus formation, DSB repair, and checkpoint signaling (PMID:16188882), and it shows comparable subfamily-restricted recognition of TBP-2 (PMID:15234975) and the Pax5/BSAP NLS (PMID:10748034). Its cargo repertoire spans transcription and replication regulators (E2F1, Oct4, c-Myc, SMARCC1, CBX8, YBX1), signaling effectors (NF-κB p65, IRF-1, IRF3, STAT1, STAT3, the MAP kinases JNK1/2, p38 and ERK1, NLRP3), and circadian PER proteins, with knockdown shifting each cargo's nuclear/cytoplasmic distribution (PMID:22843992, PMID:24070213, PMID:26209501, PMID:31597697, PMID:32130408, PMID:33731128, PMID:35669562, PMID:37432596, PMID:37792911, PMID:40216969). Through these import events KPNA2 drives proliferative and oncogenic programs—promoting G1/S transition via c-Myc/Akt/FOXO3a and EMT, and feeding into glycolytic metabolic reprogramming (PMID:23907459, PMID:30115078)—and shapes immune and inflammatory output by controlling nuclear delivery of NF-κB and interferon regulatory factors (PMID:32130408, PMID:37432596). KPNA2 abundance is tightly controlled: deubiquitinases USP1 and USP22 stabilize it, the E3 ligase FBXW7 targets it for proteasomal degradation, and a CMA motif requiring Gln109 routes it to chaperone-mediated autophagy (PMID:30531833, PMID:32130408, PMID:32924767, PMID:37432596), while its transcription is activated by E2F1/DP1 and CENPA/GCN-5 and antagonized by E2F7 (PMID:30254209, PMID:34508688). In viral infection KPNA2 acts as both a host import factor co-opted by pathogens (HIV-1 capsid, EBNA-1) and an antiviral restriction factor that imports and degrades viral proteins, and multiple viruses counter it by driving its degradation (PMID:9434725, PMID:32924767, PMID:35301060, PMID:38038431, PMID:38829137). At the cell surface KPNA2 binds heparan sulfate and FGF1/FGF2 to potentiate ERK1/2 signaling (PMID:26887791). Loss of Kpna2 in male mice causes infertility through failed nuclear import of testis-specific transcription factors in spermatids (PMID:37456838).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1994 Medium

    Established the first physiological binding partner of KPNA2, linking the adaptor to V(D)J recombination machinery before its general import role was defined.

    Evidence Yeast two-hybrid and dominant-negative truncation with a V(D)J recombination reporter in HeLa cells

    PMID:8016130

    Open questions at the time
    • Did not demonstrate NLS-dependent nuclear import of RAG-1
    • No reconstitution with importin-beta
  2. 1997 High

    Showed KPNA2 binds NLS-bearing cargo including a viral T antigen NLS and the EBNA-1 antigen, framing it as a classical NLS-recognition adaptor.

    Evidence GST pull-down, yeast one/two-hybrid, CoIP from nuclear extracts, and EBNA-1 NLS point-mutant analysis

    PMID:9168958 PMID:9434725

    Open questions at the time
    • Cargo set limited to a few proteins
    • Import directionality not reconstituted in vitro
  3. 2005 High

    Defined cargo specificity as a core feature by showing KPNA2 is the unique importin-alpha for NBS1, coupling import to DNA damage response function.

    Evidence Importin-alpha subfamily specificity mapping, NBS1 NLS mutagenesis, dominant-negative inhibition, and DSB repair/focus formation assays

    PMID:16188882

    Open questions at the time
    • Did not address redundancy under stress conditions
    • Structural basis of NBS1 NLS preference unresolved
  4. 2004 High

    Demonstrated cargo selectivity again with TBP-2, where KPNA2 but not related importin-alphas mediated stimulus-induced nuclear accumulation.

    Evidence Yeast two-hybrid, GST pull-down, and siRNA knockdown with nuclear fractionation

    PMID:15234975

    Open questions at the time
    • NLS within TBP-2 not finely mapped
  5. 2013 High

    Connected KPNA2 to oncogenic transcriptional programs by establishing E2F1 and Oct4 as cargo and linking their import to cell-cycle and stemness control.

    Evidence CoIP, immunofluorescence co-localization, in vitro binding, and SILAC nuclear proteomics after knockdown in cancer cells

    PMID:22843992 PMID:23907459 PMID:24070213

    Open questions at the time
    • Pathway readouts (c-Myc/Akt/FOXO3a) inferred from KD/OE, not all from direct binding
    • Causal ordering of import vs. transcriptional output not fully separated
  6. 2019 Medium

    Established a transcription-import feedback circuit in which E2F1/DP1 activates KPNA2 expression and KPNA2 imports E2F1/E2F7, with E2F7 acting as competitive antagonist.

    Evidence Promoter reporter, ChIP, E2F domain mutagenesis, and nuclear fractionation after knockdown

    PMID:30115078 PMID:30254209

    Open questions at the time
    • Feedback loop quantitation absent
    • Tissue contexts beyond cancer cells untested
  7. 2020 High

    Defined post-translational control of KPNA2 stability, showing deubiquitinases (USP1, USP22) stabilize it while chaperone-mediated autophagy (Gln109 motif) degrades it, coupling adaptor abundance to immune and antiviral outcomes.

    Evidence Ubiquitination assays, USP22 conditional KO with KPNA2 reconstitution, CMA motif and LAMP2A mutagenesis, and viral challenge

    PMID:30531833 PMID:32130408 PMID:32924767

    Open questions at the time
    • Relative contribution of each degradation route in normal physiology unclear
    • Signals selecting KPNA2 for CMA vs. proteasome not defined
  8. 2022 Medium

    Expanded the regulatory network to mRNA-level (m6A/RBM15) and additional E3 ligase (FBXW7) control of KPNA2, and broadened cargo to inflammatory and angiogenic signaling effectors.

    Evidence MeRIP, dual-luciferase, FBXW7 ubiquitination assay, IP-MS/CoIP, and in vivo inflammation/ischemia models

    PMID:29777028 PMID:36578083 PMID:37432596 PMID:39488447

    Open questions at the time
    • Some signaling effects shown by fractionation without direct NLS mapping
    • Cross-talk between mRNA stabilization and protein turnover not integrated
  9. 2023 Medium

    Provided in vivo physiological proof of function: Kpna2 is required for nuclear import of spermatid transcription factors and for male fertility.

    Evidence Kpna2 knockout mice with spermatid transcription-factor localization analysis, RNA-seq, and sperm function assays

    PMID:37456838

    Open questions at the time
    • Specific cargo transcription factors not individually identified
    • Whether infertility reflects loss of a single key cargo or many is unresolved
  10. 2024 Medium

    Extended KPNA2 function into RNA regulation, showing it imports YBX1 to drive nonsense-mediated decay and alternative splicing of DDX3X.

    Evidence CoIP, nuclear fractionation after knockdown, and RNA-seq/splicing analysis in osteosarcoma

    PMID:40216969

    Open questions at the time
    • YBX1 NLS recognition by KPNA2 not mapped
    • Generality of the splicing effect beyond osteosarcoma untested
  11. 2024 Medium

    Clarified the dual host/restriction role of KPNA2 in infection, showing it can import viral proteins yet also degrade them, and that viruses degrade KPNA2 to escape import-dependent antiviral signaling.

    Evidence CoIP with viral capsid/E/N proteins, domain mapping, lysosomal-pathway rescue, and viral yield assays for HIV-1, PEDV, PDCoV, and ZIKV

    PMID:32924767 PMID:35301060 PMID:38038431 PMID:38829137

    Open questions at the time
    • Determinants of whether KPNA2 imports vs. degrades a viral cargo are unknown
    • In vivo relevance of restriction activity not established for all viruses

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what structural and sequence features dictate KPNA2's strong cargo selectivity over other importin-alpha paralogs, and how its many regulatory inputs (transcription, m6A, deubiquitination, FBXW7, CMA) are integrated to set adaptor abundance in a given cell state.
  • No structural model explaining NLS preference in the corpus
  • No quantitative integration of competing stability pathways
  • Cargo prioritization when adaptor is limiting is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140104 molecular carrier activity 3 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 4 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 2 R-HSA-73894 DNA Repair 1
Partners
CBX8E2F1IRF3KPNB1NBS1RELASTAT3YBX1

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 RCH1 (KPNA2) was identified as a protein that specifically interacts with RAG-1 recombination-activating protein; a truncated form of Rch1 retaining the RAG-1 interaction domain reduces V(D)J recombination activity in HeLa cells. Yeast two-hybrid assay; dominant-negative truncation overexpression with V(D)J recombination reporter assay Proceedings of the National Academy of Sciences of the United States of America Medium 8016130
1997 KPNA2 (Rch1) and the related importin-alpha Qip1 both physically interact with DNA helicase Q1/RecQL (but not hSrp1), as demonstrated by GST pull-down from cell lysates and confirmed by yeast two-hybrid. KPNA2 also binds the SV40 T antigen NLS in two-hybrid assays. GST pull-down from human cell lysates; yeast two-hybrid Biochemical and biophysical research communications Medium 9168958
1997 KPNA2 (Rch1/hSRP1α) physically interacts with EBV nuclear antigen-1 (EBNA1) when bound to oriP in vivo; interaction confirmed by coimmunoprecipitation from nuclear extracts and direct in vitro binding of recombinant proteins. Mutations in the EBNA1 NLS reduced Rch1 binding. Yeast one-hybrid assay; coimmunoprecipitation from nuclear extracts; in vitro direct binding assay with recombinant proteins; NLS point-mutant analysis Virology High 9434725
2000 KPNA2 (karyopherin alpha2/hRch1) interacts with EBNA-1 proteins endogenous in B cells, confirmed by coimmunoprecipitation and GST-fusion pull-down. An additional karyopherin alpha1 was also shown to bind EBNA-1, establishing two distinct karyopherin alpha proteins for EBNA-1 nuclear transport. Yeast two-hybrid; GST pull-down; coimmunoprecipitation from B cell extracts Virology Medium 10612665
2000 KPNA2 (importin alpha1/Rch1) physically interacts with BSAP (Pax5) through a defined NLS sequence (NKRKRDE, amino acids 195–201 in the central domain); the interaction was confirmed by GST pull-down in vitro and yeast two-hybrid, and the NLS is sufficient to confer nuclear localization to a GFP fusion protein. Yeast two-hybrid; GST pull-down; GFP-fusion nuclear localization assay; NLS deletion/mutation analysis The Journal of biological chemistry High 10748034
2003 KPNA2 (Rch1) is localized not only to the nuclear envelope/cytoplasm but also to the plasma membrane in lymphocytes and melanoma cells; upon lymphocyte activation with phytohemagglutinin, KPNA2 protein levels increase dramatically and it redistributes from cytoplasm to both plasma membrane and nuclear interior. Immunoelectron microscopy; Western blotting after lymphocyte activation Chromosoma Medium 12883947
2004 KPNA2 (importin alpha1/Rch1) physically interacts with TBP-2 (thioredoxin-binding protein-2) and mediates its nuclear translocation; the interaction is specific to KPNA2 among importin-alpha subfamilies tested (Qip1, NPI-1 did not interact), and siRNA knockdown of KPNA2 suppresses HDAC-inhibitor-induced nuclear accumulation of TBP-2. Yeast two-hybrid screening; GST pull-down; siRNA knockdown with nuclear fractionation/immunofluorescence The Journal of biological chemistry High 15234975
2005 KPNA2 is the only importin-alpha family member that physically interacts with NBS1; it mediates normal nuclear localization of the MRE11-RAD50-NBS1 (MRN) complex by binding NLS residues 461–467 of NBS1. Inhibition of KPNA2 or blockage of KPNA2-NBS1 interaction reduces radiation-induced nuclear focus formation, DSB repair, and cell-cycle checkpoint signaling. Physical interaction mapping by importin-alpha subfamily specificity assay; NLS deletion/mutation analysis; KPNA2 inhibition with dominant-negative constructs; radiation-induced focus formation and DSB repair assays The Journal of biological chemistry High 16188882
2007 KPNA2 physically binds IRF-1 (interferon regulatory factor-1) and mediates its nuclear translocation in normal human epidermal keratinocytes. IFN-γ downregulates KPNA2 expression at the promoter level, while TGF-β1 downregulates it post-transcriptionally. KPNA2 overexpression/knockdown alters epidermal gene expression programs including involucrin. Co-immunoprecipitation; immunofluorescence nuclear translocation assay; promoter reporter analysis; microarray with KPNA2 knockdown/overexpression The Journal of investigative dermatology Medium 17255955
2012 KPNA2 knockdown causes subcellular redistribution of E2F1 in lung cancer cells; E2F1 is a cargo of KPNA2, demonstrated by co-immunoprecipitation, co-localization by immunofluorescence, and direct in vitro protein binding assay. Quantitative proteomics revealed multiple KPNA2-regulated proteins in the nuclear proteome. Co-immunoprecipitation; immunofluorescence co-localization; in vitro protein binding assay; SILAC quantitative proteomics with subcellular fractionation after KPNA2 knockdown Molecular & cellular proteomics : MCP High 22843992
2013 KPNA2 overexpression promotes G1/S cell cycle transition in epithelial ovarian carcinoma cells by upregulating c-Myc transcriptional activity, activating Akt, suppressing FOXO3a, downregulating p21Cip1 and p27Kip1, and upregulating cyclin D1; knockdown reverses these effects. KPNA2 overexpression and shRNA knockdown in cancer cells; cell cycle analysis; Western blot for pathway components; in vivo xenograft Cell death & disease Medium 23907459
2013 KPNA2 physically interacts with Oct4 in lung cancer cell lines, as demonstrated by co-immunoprecipitation; knockdown of KPNA2 significantly reduces nuclear Oct4 protein levels and mRNA, establishing KPNA2 as a mediator of Oct4 nuclear import. Co-immunoprecipitation; nuclear/cytoplasmic fractionation; double immunofluorescence; siRNA knockdown with Western blot Journal of translational medicine Medium 24070213
2014 KPNA2 facilitates cytoplasmic localization of PER1/2 (period circadian proteins) during mouse ESC differentiation. Constitutive expression of Kpna2 during differentiation impairs circadian clock development and leads to sustained cytoplasmic accumulation of PER proteins. Constitutive expression of Kpna2 in differentiating ESCs; subcellular localization of PER1/2 by immunofluorescence; global gene expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 25389311
2015 KPNA2 physically interacts with p65 (NF-κB subunit) and promotes its nuclear translocation in IL-1β-stimulated chondrocytes; knockdown of KPNA2 reduces nuclear translocation of p65/p50 NF-κB complex and decreases expression of MMP13 and ADAMTS-5. Co-immunoprecipitation; subcellular fractionation with immunoblot; immunofluorescence; siRNA knockdown Experimental and molecular pathology Medium 26209501
2015 MIR517C degrades KPNA2 in glioblastoma cells and subsequently disrupts nuclear translocation of wild-type TP53, inhibiting autophagy and EMT. This effect was TP53-dependent (not seen in TP53-mutant cells), defining a MIR517C-KPNA2-cytoplasmic TP53 signaling pathway. MiRNA overexpression/knockdown; Western blot; immunofluorescence for TP53 nuclear translocation; TP53 wild-type vs mutant cell comparison; in vivo xenograft Autophagy Medium 26553592
2016 KPNA2 is localized to the cell surface in cancer cell lines and is secreted into conditioned medium; cell-surface KPNA2 associates with heparan sulfate and directly binds FGF1 and FGF2 (cNLS-containing growth factors), enhancing ERK1/2 activation in FGF1-stimulated cells; anti-KPNA2 antibody suppresses this FGF1-KPNA2 complex formation, ERK1/2 activation, and cell growth. Cell surface biotinylation; conditioned medium analysis; direct binding assay; co-immunoprecipitation; ERK1/2 phosphorylation assay; antibody blocking experiment Scientific reports Medium 26887791
2016 mTOR activity positively regulates KPNA2 protein and mRNA levels in NSCLC cells; mTOR inhibition induces proteasomal degradation of KPNA2 and decreases Dp1/E2F1-driven KPNA2 transcription; KPNA2 physically associates with phospho-mTOR/mTOR by co-immunoprecipitation and this association is abolished by rapamycin. mTOR inhibitors and siRNA knockdown; proteasome inhibitor rescue; KPNA2 mRNA and protein quantification; co-immunoprecipitation of KPNA2 with mTOR Oncotarget Medium 27009856
2018 USP1 deubiquitinates and stabilizes KPNA2 protein; pharmacological or genetic inhibition of USP1 destabilizes KPNA2 and suppresses breast cancer metastasis. KPNA2 stabilization is the downstream effector of USP1's pro-metastatic function. USP1 overexpression/inhibition; ubiquitination assay; Western blot; in vivo lung metastasis model; USP1 inhibitor (pimozide, ML323) treatment Oncogene Medium 30531833
2018 KPNA2 aberrant expression changes subcellular distribution and expression levels of c-Myc; E2F1 is a cargo protein of KPNA2 and mediates KPNA2-dependent c-Myc transcriptional upregulation, linking KPNA2 to metabolic reprogramming (glycolysis) in glioblastoma. Co-IP and subcellular fractionation confirmed KPNA2-c-Myc and KPNA2-E2F1 interactions. Co-immunoprecipitation; subcellular fractionation; Western blot; immunofluorescence; luciferase assay; glycolysis assays; KPNA2 knockdown Journal of experimental & clinical cancer research : CR Medium 30115078
2018 E2F1 (bound to DP1) activates KPNA2 transcription by binding the KPNA2 promoter; atypical E2F7 competes with DP1 and blocks E2F1-induced KPNA2 gene activation. KPNA2 in turn mediates nuclear localization of E2F1 and E2F7, creating a feedback loop. Mutation of E2F7 dimerization residues or E2F1 DNA-binding domain abolishes this regulation. Promoter reporter assay; ChIP; mutagenesis of E2F domains; nuclear fractionation after KPNA2 knockdown; co-immunoprecipitation Oncogene Medium 30254209
2019 NLRP3 physically interacts with KPNA2 and translocates to the nucleus via KPNA2 under Treg-polarizing conditions; NLRP3-mediated suppression of Foxp3 expression and Treg differentiation is dependent on its interaction with KPNA2 and is independent of inflammasome activation. Co-immunoprecipitation; nuclear fractionation; NLRP3-deficient mice; NLRP3 overexpression in T cells The Journal of biological chemistry Medium 31597697
2019 KPNA2 overexpression promotes EOC cell migration and invasion via activation of the Akt/GSK-3β/Snail signaling pathway and induction of EMT; knockdown of KPNA2 suppresses these effects. Stable overexpression and shRNA knockdown; migration/invasion assays; Western blot for Akt/GSK-3β/Snail pathway components; immunofluorescence Journal of Cancer Low 29290781
2020 USP22 deubiquitinates and stabilizes KPNA2 after viral infection, facilitating efficient nuclear translocation of IRF3; USP22 knockout impairs IRF3 nuclear translocation and type I IFN expression after viral infection; reconstitution of KPNA2 into USP22-knockout cells restores virus-triggered IRF3 nuclear translocation. USP22 knockout (Cre-ER and Lyz2-Cre conditional mouse models); KPNA2 reconstitution in KO cells; ubiquitination assay; nuclear fractionation for IRF3; viral challenge in vivo The Journal of experimental medicine High 32130408
2020 KPNA2 physically associates with JNK1/JNK2 and p38 MAP kinases and promotes their nuclear translocation in EV71-infected cells; the miR-302 cluster targets KPNA2 to downregulate this nuclear translocation and dampen EV71-induced cytokine expression. Intracellular co-immunoprecipitation; miR-302 knockdown/overexpression; nuclear fractionation; cytokine measurement Journal of immunology Medium 29777028
2020 KPNA2 is degraded via chaperone-mediated autophagy (CMA); a CMA motif containing indispensable residue Gln109 is required for this degradation. Zika virus NS2A protein (via its Thr100 residue) enhances KPNA2 CMA-mediated degradation; LAMP2A knockdown elevates KPNA2 levels; KPNA2 knockdown increases ZIKV yield, indicating an antiviral role. CMA motif mutagenesis (Q109 mutation); LAMP2A siRNA knockdown; ZIKV NS2A mutant (T100A) virus construction; viral yield quantification; Western blot Autophagy High 32924767
2021 KPNA2 promotes nuclear import of CBX8; CBX8, once nuclear, recruits BCOR to the PRDM1 promoter to downregulate PRDM1, which in turn reduces c-FOS expression and promotes bladder cancer progression. KPNA2-CBX8 interaction confirmed by co-immunoprecipitation; CBX8 promoter binding confirmed by chromatin immunoprecipitation. Co-immunoprecipitation; ChIP; nuclear fractionation after KPNA2 knockdown; rescue experiments; xenograft Journal of translational medicine Medium 33731128
2021 KPNA2 modulates PD-L1 expression in pancreatic ductal adenocarcinoma by mediating nuclear translocation of STAT3; KPNA2 knockdown reduces nuclear STAT3 levels and suppresses PD-L1 expression in vivo. KPNA2 siRNA knockdown; nuclear/cytoplasmic fractionation for STAT3; Western blot for PD-L1; in vivo xenograft Journal of immunology research Low 33728352
2021 CENPA recruits histone acetyltransferase GCN-5 to the KPNA2 promoter via H3K27ac modification to activate KPNA2 transcription in colon cancer cells; overexpression of CENPA or GCN-5 rescues KPNA2 shRNA-mediated growth and glycolysis inhibition. ChIP assay for H3K27ac and GCN-5 at KPNA2 promoter; co-immunoprecipitation of CENPA with GCN-5; rescue experiments by CENPA/GCN-5 overexpression The American journal of pathology Medium 34508688
2021 KPNA2 physically interacts with NPM (nucleophosmin) in renal cell carcinoma; NPM overexpression attenuates the growth-suppressive effects of KPNA2 knockdown, establishing NPM as a functional downstream effector of KPNA2. Co-IP/MS to identify interaction; bioinformatics; rescue by NPM overexpression after KPNA2 knockdown Journal of cellular and molecular medicine Low 34469024
2021 SMARCC1 is transported into the nucleus via KPNA2 (and nucleoporins Nup50/Nup153); knockdown of KPNA2 increases cytoplasmic SMARCC1 and decreases nuclear SMARCC1, shown by Co-IP and immunofluorescence. Co-immunoprecipitation; immunofluorescence; nuclear fractionation after KPNA2, Nup50, and Nup153 knockdown Frontiers in molecular biosciences Medium 35669562
2022 KPNA2 promotes STAT3 phosphorylation by promoting STAT3-JAK1 binding under hypoxia, enhancing angiogenesis and upregulating VEGF/ANGPT2; hypoxia promotes STAT3-KPNA2 binding as detected by IP-MS and Co-IP. Immunoprecipitation-mass spectrometry (IP-MS); co-immunoprecipitation; Western blot for STAT3 phosphorylation; KPNA2 OE/KO in HUVEC and in murine hindlimb ischemia model Journal of translational medicine Medium 36578083
2022 KPNA2 physically interacts with p65 and IRF3; KPNA2 knockdown blocks nuclear translocation of p65 and IRF3, reducing LPS-induced pro-inflammatory cytokine secretion in endothelial cells; FBXW7 E3 ubiquitin ligase ubiquitinates and promotes proteasomal degradation of KPNA2. Co-immunoprecipitation; nuclear fractionation; siRNA knockdown; FBXW7 overexpression with ubiquitination assay; ApoE-/- mouse atherosclerosis model Inflammation Medium 37432596
2022 RBM15 stabilizes KPNA2 mRNA via m6A methylation, promoting breast cancer cell proliferation and immune escape; interaction between RBM15 and KPNA2 mRNA confirmed by MeRIP and dual-luciferase assay. Methylated RNA immunoprecipitation (MeRIP); dual-luciferase reporter assay; RBM15 siRNA knockdown; Western blot; in vivo xenograft Clinical breast cancer Medium 39488447
2022 KPNA2 mediates nuclear import of HIV-1 pre-integration complex (PIC) by interacting with the N-terminal of the capsid protein p24; KPNA2 knockdown reduces HIV-1 replication; disruption of capsid-KPNA2 binding impairs PIC nuclear import; KPNB1 participates in KPNA2-mediated PIC nuclear import. siRNA knockdown; quantitative PCR for cDNA integration; co-immunoprecipitation of KPNA2 with p24; overexpression of full-length or N-terminal p24 as dominant negative Antiviral research Medium 35301060
2023 Kpna2 knockout male mice are infertile; loss of Kpna2 impairs translocation of testis-specific transcription factors to the nucleus of spermatid cells, dysregulates expression of genes related to cell adhesion and ECM organization in spermatocytes/spermatids, and causes sperm motility defects and abnormalities. Kpna2 knockout mice; nuclear localization analysis of transcription factors in spermatids; RNA-seq; sperm functional assays iScience Medium 37456838
2023 ERK1 preferentially interacts with KPNA2 over ERK2; a cell-penetrating peptide (RB5) disrupts KPNA2-ERK1 interaction, facilitates ERK1/2 nuclear translocation, and enhances global ERK nuclear activity, conferring neuroprotection in mouse models of Huntington's, Alzheimer's, and Parkinson's disease. Co-immunoprecipitation of ERK1/2 with KPNA2; cell-penetrating peptide disruption assay; nuclear ERK activity measurement; multiple in vivo neurodegeneration mouse models EMBO molecular medicine Medium 37792911
2023 HBV-elevated HAT1 promotes KPNA2 expression via acetylation of H4K5 and H4K12, resulting in nuclear translocation of cGAS and suppression of cGAS-STING/IFN-I signaling as a mechanism of innate immune evasion. HAT1 knockout mouse model; ChIP for H4K5ac and H4K12ac at KPNA2 promoter; nuclear fractionation for cGAS; ELISA for IFN-I; cell line experiments Journal of medical virology Medium 37466313
2024 KPNA2 transports splicing factor YBX1 into the nucleus; nuclear YBX1 then promotes nonsense-mediated decay of DDX3X mRNA to reduce DDX3X protein, regulating alternative splicing (intron retention of DDX3X) and cell cycle progression in osteosarcoma. Nuclear fractionation after KPNA2 KD; co-immunoprecipitation of KPNA2 with YBX1; RNA-seq/AS analysis; DDX3X NMD pathway analysis; KPNA2 loss-of-function osteosarcoma model Oncogene Medium 40216969
2024 KPNA2 promotes nuclear import of PEDV envelope (E) protein; KPNA2 also degrades PEDV E protein via selective autophagy to suppress PEDV replication. KPNA2 overexpression inhibits PEDV replication; knockdown enhances it. Co-immunoprecipitation of KPNA2 with PEDV E protein; KPNA2 KD/OE in Vero and IEC cells; viral yield quantification; autophagy pathway analysis Journal of virology Medium 38038431
2024 PDCoV nucleocapsid (N) protein inhibits STAT1 nuclear translocation by targeting KPNA2 for degradation through the lysosomal pathway via the N protein's C-terminal domain; N protein interacts directly with STAT1 and KPNA2 is required for STAT1 nuclear import. Co-immunoprecipitation of N protein with STAT1 and KPNA2; lysosomal inhibitor rescue; nuclear fractionation for STAT1; domain deletion analysis of N protein Journal of virology Medium 38829137
2025 H2B lysine lactylation (H2BK16la), modulated by the LDHA-lactate axis, activates NF-κB p65 nuclear translocation via KPNA2, inducing type III IFN expression and inhibiting CSFV replication; H2B interacts with CSFV NS4A protein; KPNA2 mediates p65 nuclear transport in this context. Immunoprecipitation for H2B-Kla; H2B K16R mutant plasmid; LDHA siRNA/lactate modulation; nuclear fractionation for p65; KPNA2 involvement assessed by co-immunoprecipitation; CSFV replication assay International journal of biological macromolecules Low 39826749

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein. Proceedings of the National Academy of Sciences of the United States of America 166 8016130
2004 Importin alpha1 (Rch1) mediates nuclear translocation of thioredoxin-binding protein-2/vitamin D(3)-up-regulated protein 1. The Journal of biological chemistry 104 15234975
2018 USP1 inhibition destabilizes KPNA2 and suppresses breast cancer metastasis. Oncogene 103 30531833
2014 Identification of miR-26 as a key mediator of estrogen stimulated cell proliferation by targeting CHD1, GREB1 and KPNA2. Breast cancer research : BCR 96 24735615
2013 KPNA2 promotes cell proliferation and tumorigenicity in epithelial ovarian carcinoma through upregulation of c-Myc and downregulation of FOXO3a. Cell death & disease 94 23907459
2005 Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1. The Journal of biological chemistry 90 16188882
2011 KPNA2 expression is an independent adverse predictor of biochemical recurrence after radical prostatectomy. Clinical cancer research : an official journal of the American Association for Cancer Research 88 21220479
2019 The emerging roles of KPNA2 in cancer. Life sciences 86 31812670
2015 MIR517C inhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation. Autophagy 84 26553592
1997 Cloning of a cDNA encoding a novel importin-alpha homologue, Qip1: discrimination of Qip1 and Rch1 from hSrp1 by their ability to interact with DNA helicase Q1/RecQL. Biochemical and biophysical research communications 82 9168958
2012 Quantitative proteomics reveals regulation of karyopherin subunit alpha-2 (KPNA2) and its potential novel cargo proteins in nonsmall cell lung cancer. Molecular & cellular proteomics : MCP 80 22843992
2010 Significance of karyopherin-{alpha} 2 (KPNA2) expression in esophageal squamous cell carcinoma. Anticancer research 71 20393006
2020 USP22 promotes IRF3 nuclear translocation and antiviral responses by deubiquitinating the importin protein KPNA2. The Journal of experimental medicine 69 32130408
2014 Transcriptional program of Kpna2/Importin-α2 regulates cellular differentiation-coupled circadian clock development in mammalian cells. Proceedings of the National Academy of Sciences of the United States of America 60 25389311
2019 NLRP3 negatively regulates Treg differentiation through Kpna2-mediated nuclear translocation. The Journal of biological chemistry 58 31597697
2018 KPNA2 promotes metabolic reprogramming in glioblastomas by regulation of c-myc. Journal of experimental & clinical cancer research : CR 56 30115078
2016 MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer. Oncotarget 56 27078844
2015 MiR-26b/KPNA2 axis inhibits epithelial ovarian carcinoma proliferation and metastasis through downregulating OCT4. Oncotarget 53 26204489
2018 E2F1 and E2F7 differentially regulate KPNA2 to promote the development of gallbladder cancer. Oncogene 52 30254209
2021 HIF-1α-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p/KPNA2/AKT pathway. Cell death & disease 50 34903711
2013 Downregulation of KPNA2 in non-small-cell lung cancer is associated with Oct4 expression. Journal of translational medicine 49 24070213
2006 Importin KPNA2, NBS1, DNA repair and tumorigenesis. Journal of molecular histology 49 16752129
2021 Increased Nuclear Transporter KPNA2 Contributes to Tumor Immune Evasion by Enhancing PD-L1 Expression in PDAC. Journal of immunology research 43 33728352
2022 KPNA2 promotes angiogenesis by regulating STAT3 phosphorylation. Journal of translational medicine 42 36578083
1997 An imperfect correlation between DNA replication activity of Epstein-Barr virus nuclear antigen 1 (EBNA1) and binding to the nuclear import receptor, Rch1/importin alpha. Virology 41 9434725
2007 Differential regulation of karyopherin alpha 2 expression by TGF-beta1 and IFN-gamma in normal human epidermal keratinocytes: evident contribution of KPNA2 for nuclear translocation of IRF-1. The Journal of investigative dermatology 40 17255955
2016 Cell surface localization of importin α1/KPNA2 affects cancer cell proliferation by regulating FGF1 signalling. Scientific reports 36 26887791
2018 KPNA2 promotes migration and invasion in epithelial ovarian cancer cells by inducing epithelial-mesenchymal transition via Akt/GSK-3β/Snail activation. Journal of Cancer 35 29290781
2016 The plasma membrane protein Rch1 is a negative regulator of cytosolic calcium homeostasis and positively regulated by the calcium/calcineurin signaling pathway in budding yeast. European journal of cell biology 35 26832117
2024 Hsa_Circ_0000021 Sponges miR-3940-3p/KPNA2 Expression to Promote Cervical Cancer Progression. Current molecular pharmacology 28 36799424
2014 KPNA2 is overexpressed in human and mouse endometrial cancers and promotes cellular proliferation. The Journal of pathology 28 24930886
2014 KPNA2 is a promising biomarker candidate for esophageal squamous cell carcinoma and correlates with cell proliferation. Oncology reports 28 25109899
2000 Epstein-barr virus nuclear antigen-1 binds to nuclear transporter karyopherin alpha1/NPI-1 in addition to karyopherin alpha2/Rch1. Virology 28 10612665
2000 BSAP (Pax5)-importin alpha 1 (Rch1) interaction identifies a nuclear localization sequence. The Journal of biological chemistry 27 10748034
2020 The miR-26b-5p/KPNA2 Axis Is an Important Regulator of Burkitt Lymphoma Cell Growth. Cancers 26 32512858
2020 Zika virus NS2A protein induces the degradation of KPNA2 (karyopherin subunit alpha 2) via chaperone-mediated autophagy. Autophagy 26 32924767
2018 MicroRNA-302 Cluster Downregulates Enterovirus 71-Induced Innate Immune Response by Targeting KPNA2. Journal of immunology (Baltimore, Md. : 1950) 26 29777028
2021 KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway. Journal of translational medicine 25 33731128
2023 HBV confers innate immune evasion through triggering HAT1/acetylation of H4K5/H4K12/miR-181a-5p or KPNA2/cGAS-STING/IFN-I signaling. Journal of medical virology 24 37466313
2021 Centromere Protein A (CENPA) Regulates Metabolic Reprogramming in the Colon Cancer Cells by Transcriptionally Activating Karyopherin Subunit Alpha 2 (KPNA2). The American journal of pathology 24 34508688
2018 Knockdown of KPNA2 inhibits autophagy in oral squamous cell carcinoma cell lines by blocking p53 nuclear translocation. Oncology reports 24 29781035
2022 Long non-coding RNA HAGLROS facilitates tumorigenesis and progression in hepatocellular carcinoma by sponging miR-26b-5p to up-regulate karyopherin α2 (KPNA2) and inactivate p53 signaling. Bioengineered 23 35291921
1997 Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene that is highly homologous to genes encoding Xenopus importin, yeast SRP1 and human RCH1. Cytogenetics and cell genetics 23 9154134
2019 SNHG8 is upregulated in esophageal squamous cell carcinoma and directly sponges microRNA-411 to increase oncogenicity by upregulating KPNA2. OncoTargets and therapy 22 31695414
2023 Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2. EMBO molecular medicine 20 37792911
2019 Wip1 cooperates with KPNA2 to modulate the cell proliferation and migration of colorectal cancer via a p53-dependent manner. Journal of cellular biochemistry 20 31127650
2020 A long non-coding RNA LINC00461-dependent mechanism underlying breast cancer invasion and migration via the miR-144-3p/KPNA2 axis. Cancer cell international 19 32355466
2015 KPNA2 interacts with P65 to modulate catabolic events in osteoarthritis. Experimental and molecular pathology 19 26209501
2015 Genetic interactions between Rch1 and the high-affinity calcium influx system Cch1/Mid1/Ecm7 in the regulation of calcium homeostasis, drug tolerance, hyphal development and virulence in Candida albicans. FEMS yeast research 19 26323599
2021 Oncogenic role of karyopherin α2 (KPNA2) in human tumors: A pan-cancer analysis. Computers in biology and medicine 18 34735944
2016 mTOR regulates proteasomal degradation and Dp1/E2F1- mediated transcription of KPNA2 in lung cancer cells. Oncotarget 17 27009856
2020 Silencing KPNA2 inhibits IL-6-induced breast cancer exacerbation by blocking NF-κB signaling and c-Myc nuclear translocation in vitro. Life sciences 16 32360571
2019 IRF1 Negatively Regulates Oncogenic KPNA2 Expression Under Growth Stimulation and Hypoxia in Lung Cancer Cells. OncoTargets and therapy 16 31920336
2023 KPNA2 suppresses porcine epidemic diarrhea virus replication by targeting and degrading virus envelope protein through selective autophagy. Journal of virology 15 38038431
2003 Localization of importin alpha (Rch1) at the plasma membrane and subcellular redistribution during lymphocyte activation. Chromosoma 14 12883947
2021 Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1-STAT1 loop in lung adenocarcinoma. Cancer science 13 34773335
2020 MiR-1297 negatively regulates metabolic reprogramming in glioblastoma via repressing KPNA2. Human cell 13 32124270
2001 Genomic structure of karyopherin alpha2 ( KPNA2) within a low-copy repeat on chromosome 17q23-q24 and mutation analysis in patients with Russell-Silver syndrome. Human genetics 13 11735022
2016 mTORC1 alters the expression of glycolytic genes by regulating KPNA2 abundances. Journal of proteomics 12 26844761
2025 Histone H2B lysine lactylation modulates the NF-κB response via KPNA2 during CSFV infection. International journal of biological macromolecules 11 39826749
2024 RBM15 Drives Breast Cancer Cell Progression and Immune Escape via m6A-Dependent Stabilization of KPNA2 mRNA. Clinical breast cancer 11 39488447
2022 SMARCC1 Enters the Nucleus via KPNA2 and Plays an Oncogenic Role in Bladder Cancer. Frontiers in molecular biosciences 11 35669562
2021 BBOX1-AS1 Accelerates Nasopharyngeal Carcinoma Progression by Sponging miR-3940-3p and Enhancing KPNA2 Upregulation. Cancer management and research 11 34938119
2020 KPNA2 expression is a potential marker for differential diagnosis between osteosarcomas and other malignant bone tumor mimics. Diagnostic pathology 11 33176814
2011 Karyopherin alpha 2 (KPNA2) is associated with the natural resistance to Schistosoma japanicum infection in Microtus fortis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11 21658898
2025 Tumor-derived exosomal KPNA2 activates fibroblasts and interacts with KIFC1 to promote bladder cancer progression, a process inhibited by miR-26b-5p. Cellular & molecular biology letters 10 39956902
2024 Silencing KPNA2 Promotes Ferroptosis in Laryngeal Cancer by Activating the FoxO Signaling Pathway. Biochemical genetics 10 38379037
2023 ZNF143 facilitates the growth and migration of glioma cells by regulating KPNA2-mediated Hippo signalling. Scientific reports 10 37423952
2022 Ivermectin Inhibits HBV Entry into the Nucleus by Suppressing KPNA2. Viruses 10 36366568
2021 KPNA2 promotes renal cell carcinoma proliferation and metastasis via NPM. Journal of cellular and molecular medicine 10 34469024
2021 MiR-101-3p Suppresses Progression of Cervical Squamous Cell Carcinoma by Targeting and Down-Regulating KPNA2. Technology in cancer research & treatment 10 34816790
2020 Circular RNA circ_0079593 promotes glioma development through regulating KPNA2 expression by sponging miR-499a-5p. European review for medical and pharmacological sciences 10 32096160
2018 The plasma membrane protein Rch1 and the Golgi/ER calcium pump Pmr1 have an additive effect on filamentation in Candida albicans. Fungal genetics and biology : FG & B 10 29621626
2023 KPNA2 Silencing, Regulated by E3 Ubiquitin Ligase FBXW7, Alleviates Endothelial Dysfunction and Inflammation Through Inhibiting the Nuclear Translocation of p65 and IRF3: A Possible Therapeutic Approach for Atherosclerosis. Inflammation 9 37432596
2022 CircMYH9 increases KPNA2 mRNA stability to promote hepatocellular carcinoma progression in an EIF4A3-dependent manner. American journal of cancer research 9 36225644
2022 CREB1 regulates KPNA2 by inhibiting mir-495-3p transcription to control melanoma progression : The role of the CREB1/miR-495-3p/KPNA2 axis in melanoma progression. BMC molecular and cell biology 9 36522613
2016 Aptamers that bind specifically to human KPNA2 (importin-α1) and efficiently interfere with nuclear transport. Journal of biochemistry 9 27154959
2014 KPNA2 predicts long term survival in patients with anaplastic oligoastrocytomas. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 9 24929863
2015 KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells. Inflammation 8 26135850
2024 Porcine deltacoronavirus nucleocapsid protein antagonizes JAK-STAT signaling pathway by targeting STAT1 through KPNA2 degradation. Journal of virology 7 38829137
2024 Weifuchun suppresses the malignancy of gastric cancer cells by targeting KPNA2 through miR-26a-5p-mediated destabilization and the deactivation of the MAPK signaling pathway. Journal of ethnopharmacology 7 38992399
2022 MicroRNA-517c Functions as a Tumor Suppressor in Hepatocellular Carcinoma via Downregulation of KPNA2 and Inhibition of PI3K/AKT Pathway. Journal of healthcare engineering 7 35075389
2022 Importin KPNA2 confers HIV-1 pre-integration complex nuclear import by interacting with the capsid protein. Antiviral research 7 35301060
2022 Long noncoding RNA TUG1 decreases bladder cancer chemo-sensitivity toward doxorubicin through elevating KPNA2 expression and activating the PI3K/AKT pathway via adsorbing miR-582-5p. Anti-cancer drugs 7 36539367
2022 MiR-101-3p targets KPNA2 to inhibit the progression of lung squamous cell carcinoma cell lines. Histology and histopathology 7 36583484
2019 Silencing of KPNA2 inhibits high glucose-induced podocyte injury via inactivation of mTORC1/p70S6K signaling pathway. Biochemical and biophysical research communications 7 31727365
2023 Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors. iScience 6 37456838
2025 miR-17-5p-Mediated RNA Activation Upregulates KPNA2 Expression and Inhibits High-Glucose-Induced Apoptosis of Sheep Granulosa Cells. International journal of molecular sciences 5 39940713
2024 Inhibition of KPNA2 by ivermectin reduces E2F1 nuclear translocation to attenuate keratinocyte proliferation and ameliorate psoriasis-like lesions. International immunopharmacology 5 39388894
2022 IRF2 Destabilizes Oncogenic KPNA2 to Modulate the Development of Osteosarcoma. Journal of oncology 5 36199790
2021 Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma. PeerJ 5 34616632
2015 Low cytoplasmic and nuclear KPNA2 expression in radiotherapy-treated head and neck squamous cell cancer is associated with an adverse outcome. International journal of clinical and experimental pathology 5 26884852
2004 Specific monoclonal antibody against nuclear import factor, importin alpha1/Rch1. Hybridoma and hybridomics 5 15672608
2025 Molecular Mechanism of Ginsenoside Rg3 Alleviation in Osteoporosis via Modulation of KPNA2 and the NF-κB Signalling Pathway. Clinical and experimental pharmacology & physiology 4 39821958
2025 KPNA2 promotes osteosarcoma progression by regulating the alternative splicing of DDX3X mediated by YBX1. Oncogene 4 40216969
2024 KPNA2 promotes the progression of gastric cancer by regulating the alternative splicing of related genes. Scientific reports 4 39060340
2023 Hsa_circ_0022383 promote non-small cell lung cancer tumorigenesis through regulating the miR-495-3p/KPNA2 axis. Cancer cell international 4 37981709
2020 KPNA2/ERG Coexpression is Associated With Early Recurrence in Advanced Prostate Cancers. Applied immunohistochemistry & molecular morphology : AIMM 4 31809312
2025 MiR-20a-5p Inhibits Bladder Cancer Proliferation and Migration by Targeting KPNA2. Journal of cellular and molecular medicine 3 40830912
2025 Coordinating oncogenesis and immune evasion: KPNA2, GOLM1, and TK1 as novel CAR T-cell targets in lung adenocarcinoma. European journal of medical research 3 40830974

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