Affinage

TNPO1

Transportin-1 · UniProt Q92973

Length
898 aa
Mass
102.4 kDa
Annotated
2026-06-10
10 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNPO1 (transportin-1) is a soluble nuclear/ciliary import receptor that recognizes diverse cargoes through dedicated targeting determinants to direct their subcellular localization (PMID:32553752, PMID:36907439). In its classic nuclear-import role it mediates translocation of multiple cargoes, including the LINE-1 ribonucleoprotein (where TNPO1 levels set the rate of L1 retrotransposition) (PMID:28974576), FUBP1 (whose TNPO1-dependent nuclear accumulation drives transcription of the immune checkpoint gene NRP1) (PMID:33987449), and the chromatin remodeler ARID1B (loss of which reduces chromatin accessibility, depletes H3K4me1/H3K27ac, and impairs AP-1 and PI3K/AKT signaling) (PMID:34044070). Cargo engagement can be redox-gated: TNPO1 forms an H2O2-induced disulfide complex with PPARγ2 via Cys512 of TNPO1 and Cys176/Cys180 of PPARγ2, enhancing PPARγ2 nuclear entry and promoting hepatic triglyceride accumulation (PMID:32553752). Beyond the nucleus, TNPO1 acts as a ciliary transport adapter: together with Rab8-GDP it binds RVEP-motif ciliary targeting sequences to deliver Arl13b and multiple GPCRs, including the β2 adrenergic receptor, to the cilium, with Rab8-GDP strongly enhancing recognition of the targeting sequence (PMID:36907439, PMID:42036045).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2017 Medium

    Established TNPO1 as the import factor controlling nuclear entry of the LINE-1 RNP, linking it to retrotransposon mobility rather than only canonical protein cargoes.

    Evidence TNPO1 overexpression/knockdown with L1 retrotransposition reporter and ORF1p nuclear import assays

    PMID:28974576

    Open questions at the time
    • Does not define the targeting motif on the L1-RNP recognized by TNPO1
    • Whether TNPO1 binds ORF1p directly or via another adaptor is not resolved
  2. 2020 High

    Showed that TNPO1 cargo recognition can be redox-regulated, identifying a specific disulfide interface (TNPO1 Cys512 with PPARγ2 Cys176/Cys180) that couples oxidative state to nuclear import.

    Evidence Co-IP, cysteine mutagenesis, hepatocyte overexpression/knockdown, and mouse models

    PMID:32553752

    Open questions at the time
    • Whether redox gating applies to other TNPO1 cargoes is untested
    • Structural basis of the disulfide-stabilized complex is not determined
  3. 2021 Medium

    Extended TNPO1 cargo repertoire to transcription/chromatin regulators (FUBP1 and ARID1B), connecting its import function to downstream transcriptional and chromatin outputs in cancer.

    Evidence Co-IP, knockdown, subcellular fractionation, chromatin accessibility and ChIP assays in cancer cells

    PMID:33987449 PMID:34044070

    Open questions at the time
    • Targeting sequences on FUBP1 and ARID1B recognized by TNPO1 are not mapped
    • Cargo selectivity versus other karyopherins is not established
  4. 2023 High

    Revealed a non-nuclear function: TNPO1 acts with Rab8-GDP as a ciliary transport adapter that recognizes an RVEP-containing ciliary targeting sequence on Arl13b.

    Evidence Pull-downs with purified proteins, TurboID proximity ligation, RVEP point mutagenesis, and siRNA with ciliary imaging

    PMID:36907439

    Open questions at the time
    • Mechanism by which a nuclear import receptor is repurposed for ciliary delivery is unclear
    • How Rab8 nucleotide state is coordinated with cargo handoff at the cilium is unknown
  5. 2026 Medium

    Generalized the ciliary adapter role, showing TNPO1/Rab8 recognize C-terminal CTSs of multiple ciliary GPCRs and are required for their ciliary localization.

    Evidence Interaction screening of nine ciliary GPCRs, CTS truncation/mutation mapping, and Rab8/TNPO1 siRNA with ciliary localization readout

    PMID:42036045

    Open questions at the time
    • Consensus features defining a TNPO1-recognized ciliary CTS are not fully defined
    • In vitro reconstitution with purified GPCR CTSs is not reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how TNPO1 partitions between nuclear-import and ciliary-adapter functions and what structural determinants distinguish nuclear targeting signals from RVEP ciliary targeting sequences.
  • No unified structural model of TNPO1 cargo recognition across nuclear and ciliary cargoes
  • Regulation of TNPO1 localization and function across compartments is uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140104 molecular carrier activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2 GO:0005929 cilium 2
Pathway
R-HSA-9609507 Protein localization 4
Partners
ARID1BARL13BFUBP1PPARGRAB8A

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 TNPO1 (transportin-1) mediates nuclear import of the LINE-1 ribonucleoprotein complex (using ORF1p as a proxy); induction or depletion of TNPO1 directly affects L1 retrotransposition and nuclear import of the L1-RNP, and TNPO1 overexpression partially reverses the repressive effect of miR-128 on L1 retrotransposition. Overexpression and knockdown of TNPO1 combined with L1 retrotransposition reporter assay and nuclear import assay for ORF1p The Journal of biological chemistry Medium 28974576
2021 TNPO1 mediates nuclear import of FUBP1 (far upstream element binding protein 1) in cervical cancer cells; FUBP1 physically interacts with TNPO1, and nuclear localization of FUBP1 — dependent on this interaction — drives transcriptional regulation of the immune checkpoint gene NRP1. Co-immunoprecipitation (FUBP1–TNPO1 interaction), knockdown experiments, subcellular fractionation, and gene expression analysis of NRP1 Journal of immunology research Medium 33987449
2021 TNPO1 selectively mediates nuclear import of ARID1B in gynecologic cancer cells; loss of TNPO1 or ARID1B reduces chromatin accessibility, depletes H3K4me1 and H3K27ac histone marks, diminishes AP-1 transcription factor activity, and inactivates PI3K/AKT signaling by reducing PIK3CA and FGFR2 expression. Genetic knockdown (in vitro and in vivo xenograft), chromatin accessibility assay (ATAC-seq implied), ChIP for histone marks, gene expression profiling Cancer letters Medium 34044070
2020 PPARγ2 forms a redox-dependent complex with Tnpo1 via disulfide bonds between Cys176/Cys180 of PPARγ2 and Cys512 of Tnpo1; H2O2-driven complex formation enhances nuclear translocation of PPARγ2, increases DNA-bound PPARγ, and promotes downstream signaling leading to hepatic triglyceride accumulation. Co-immunoprecipitation, cysteine mutagenesis, hepatocyte culture overexpression/knockdown, mouse models, subcellular fractionation Free radical biology & medicine High 32553752
2023 TNPO1 directly binds the ciliary targeting sequence (CTS) of Arl13b — a C-terminal 17-amino-acid stretch containing the RVEP motif — together with Rab8-GDP (but not Rab8-GTP); Rab8-GDP substantially enhances TNPO1–CTS interaction, and knockdown of endogenous TNPO1 decreases ciliary localization of Arl13b. Pull-down assays with cell lysates and purified recombinant proteins, TurboID-based proximity ligation, RVEP point-mutation analysis, siRNA knockdown with ciliary imaging The Journal of biological chemistry High 36907439
2026 TNPO1, together with Rab8, functions as a ciliary transport adapter for multiple cilium-localized GPCRs; for β2 adrenergic receptor, TNPO1 and Rab8 interact specifically with the C-terminal CTS (not the third intracellular loop CTS), and both adapters are required for ciliary localization of this GPCR. Pull-down interaction screening of nine ciliary GPCRs, CTS truncation/mutation mapping, siRNA knockdown of Rab8 and TNPO1 with ciliary localization readout The Journal of biological chemistry Medium 42036045

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 MicroRNA miR-128 represses LINE-1 (L1) retrotransposition by down-regulating the nuclear import factor TNPO1. The Journal of biological chemistry 27 28974576
2018 Potentially critical roles of TNPO1, RAP1B, ZDHHC17, and PPM1B in the progression of coronary atherosclerosis through microarray data analysis. Journal of cellular biochemistry 20 30269354
2021 TNPO1-Mediated Nuclear Import of FUBP1 Contributes to Tumor Immune Evasion by Increasing NRP1 Expression in Cervical Cancer. Journal of immunology research 14 33987449
2021 TNPO1-mediated nuclear import of ARID1B promotes tumor growth in ARID1A-deficient gynecologic cancer. Cancer letters 11 34044070
2020 Redox-dependent PPARγ/Tnpo1 complex formation enhances PPARγ nuclear localization and signaling. Free radical biology & medicine 10 32553752
2023 Rab8 and TNPO1 are ciliary transport adaptors for GTPase Arl13b by interacting with its RVEP motif containing ciliary targeting sequence. The Journal of biological chemistry 9 36907439
2023 Heavy Ion-Responsive lncRNA EBLN3P Functions in the Radiosensitization of Non-Small Cell Lung Cancer Cells Mediated by TNPO1. Cancers 7 36672460
2022 Role of miR-181b/Notch1 Axis in circ_TNPO1 Promotion of Proliferation and Migration of Atherosclerotic Vascular Smooth Muscle Cells. Journal of healthcare engineering 5 35388333
2025 CircBRWD1 promotes hepatitis B virus replication and hepatocellular carcinoma progression by regulating the miR-513a-5p/TNPO1 axis. Experimental cell research 1 40216011
2026 Rab8 and TNPO1 function as the ciliary transport adapters for GPCRs. The Journal of biological chemistry 0 42036045

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