Affinage

PDIA6

Protein disulfide-isomerase A6 · UniProt Q15084

Length
440 aa
Mass
48.1 kDa
Annotated
2026-06-10
48 papers in source corpus 25 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDIA6 is an ER-resident thioredoxin-domain disulfide isomerase/reductase that catalyzes disulfide bond formation and rearrangement during oxidative protein folding and uses these biochemical activities to set the gain of the unfolded protein response and to chaperone secreted-protein clients (PMID:24917591, PMID:31985756, PMID:41219432). It physically engages the principal UPR sensors, binding and enhancing IRE1α activity (IRE1α phosphorylation and XBP1 splicing) in response to ER Ca2+ disruption while also interacting with PERK and IRE1 to restrain their signaling; in insulin-producing cells it selectively limits IRE1 RIDD activity toward insulin transcripts to sustain insulin production and secretion (PMID:24917591, PMID:26487694). PDIA6 chaperones proinsulin folding both as a selective reductase that recognizes misfolded (Akita) proinsulin and, upon a Ca2+ trigger, by condensing into ER quality-control granules through electrostatic interactions between its first and third thioredoxin-like domains, recruiting proinsulin to accelerate oxidative folding and suppress aggregation (PMID:26947243, PMID:41219432); consistent with a non-redundant role in β-cell biology, a missense mutation in its second thioredoxin domain causes loss of β-cell identity and overt diabetes in mice (PMID:34487921). More broadly it provides the folding capacity required for secreted factors produced by the non-hematopoietic stroma (Wnt3a, BAFF, IL-7) and for disulfide bond formation in the sperm protein ZPBP during spermatogenesis (PMID:31985756, PMID:41654813). At the platelet surface, PDIA6 (ERp5) is recruited upon activation and binds the integrin β3 subunit, inhibiting αIIbβ3–fibrinogen ligation by steric hindrance independent of its catalytic cysteines (PMID:25624318, PMID:39882729). In cancer it acts as a pro-survival and pro-metastatic factor through multiple effector interactions: it catalyzes functional disulfide bonds on TRAF4 and stabilizes it against degradation to sustain AKT/mTOR signaling, cooperates with CSN5 to deubiquitinate and stabilize β-catenin and PD-L1, stabilizes SCD1 to reprogram lipid metabolism, and additionally functions as an unconventional RNA-binding protein whose RNA-binding activity is required for its metastatic properties (PMID:41761079, PMID:34325342, PMID:42234404, PMID:35848924).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2004 Medium

    Established that PDIA6/ERp5 is not solely an intracellular folding enzyme but is surface-recruited on activated platelets and engages integrin β3, linking a thiol isomerase to hemostatic function.

    Evidence Platelet membrane fractionation, inhibitory antibody blocking, and co-IP with β3 in stimulated platelets

    PMID:15466936

    Open questions at the time
    • Whether surface engagement is catalytic or conformational was not resolved
    • Reciprocal in vivo requirement not tested
  2. 2014 High

    Defined PDIA6 as a positive regulator of IRE1α within a Ca2+/miR-322 feedback loop, providing a mechanism by which ER stress tunes UPR output through PDIA6 abundance.

    Evidence Reciprocal Co-IP, shRNA knockdown, XBP1 splicing and IRE1α phosphorylation assays, miRNA manipulation, mouse and C. elegans models

    PMID:24917591

    Open questions at the time
    • Direct enzymatic action on IRE1α cysteines not demonstrated
    • Did not reconcile with later inhibitory effect on IRE1/PERK
  3. 2015 High

    Refined PDIA6's UPR role to selective control of IRE1 RIDD activity toward insulin transcripts, distinguishing it from XBP1-splicing regulation and connecting it to β-cell insulin output.

    Evidence shRNA silencing, IRE1 RIDD fluorescent reporter, insulin secretion assays in cells and intact islets

    PMID:26487694

    Open questions at the time
    • Structural basis for selective RIDD versus splicing modulation unknown
    • Apparent opposite sign of UPR effect versus 2014 study unexplained
  4. 2015 High

    Demonstrated in vivo that ERp5 is required for thrombus formation and binds β3 with measurable affinity independent of its catalytic cysteines, separating its binding from its enzymatic activity.

    Evidence Laser-injury mouse thrombosis model, anti-ERp5 antibody, surface plasmon resonance (KD 21 µM), active-site cysteine mutagenesis

    PMID:25624318

    Open questions at the time
    • Source of surface ERp5 (platelet vs endothelial) not fully defined
    • Mechanism of integrin inhibition not yet established here
  5. 2016 Medium

    Established PDIA6 as a selective reductase that discriminates misfolded proinsulin, beginning to define its client specificity in β-cell quality control.

    Evidence Co-IP with FLAG-proinsulin and quantitative comparison across PDI family members in two beta-cell lines

    PMID:26947243

    Open questions at the time
    • Fate of bound misfolded proinsulin (degradation vs refolding) not directly traced
    • Catalytic mechanism on proinsulin disulfides not resolved
  6. 2016 Medium

    Identified pro-tumor signaling functions in which PDIA6 stabilizes β-catenin and restrains ADAM17/EGFR-driven invasion, extending its role beyond folding into oncogenic signaling control.

    Evidence Overexpression with β-catenin phosphorylation/fractionation and MG132 rescue; siRNA with ADAM17 double-knockdown epistasis and invasion assays

    PMID:27462866 PMID:27540907

    Open questions at the time
    • Whether β-catenin stabilization requires PDIA6 catalytic activity unclear
    • Direct substrates linking PDIA6 to ADAM17 not identified
  7. 2019 Medium

    Linked PDIA6 to chemoresistance by showing it suppresses MAP4K1/JNK signaling to block cisplatin-induced apoptosis and autophagy in lung cancer.

    Evidence Co-IP, phospho-kinase array, gain/loss-of-function, in vitro and in vivo apoptosis/autophagy assays

    PMID:30922965

    Open questions at the time
    • Whether MAP4K1 is a direct disulfide substrate not tested
    • Relationship to ER stress pathways not defined
  8. 2020 High

    Defined a cell-extrinsic role: PDIA6 in the non-hematopoietic stroma is required to fold secreted factors (Wnt3a, BAFF, IL-7) needed for hematopoiesis, demonstrating client-folding function in vivo.

    Evidence ENU hypomorph mouse, bone marrow transplantation rescue, folding Western blots of secreted clients

    PMID:31985756

    Open questions at the time
    • Direct disulfide catalysis on each client not biochemically mapped
    • Which stromal cell type provides the activity not pinpointed
  9. 2021 High

    Connected PDIA6 thioredoxin-domain function to β-cell maintenance and added a CSN5-dependent deubiquitination mechanism stabilizing β-catenin and PD-L1 in cancer.

    Evidence Domain-specific Phe175Ser ENU mouse with β-cell marker analysis; Co-IP, ubiquitination, and CSN5 shRNA rescue in pancreatic cancer cells

    PMID:34325342 PMID:34487921

    Open questions at the time
    • How a catalytic-domain mutation alters identity programs mechanistically unclear
    • Whether PDIA6 directly modifies CSN5 or substrates not shown
  10. 2022 Medium

    Revealed an unconventional RNA-binding activity for PDIA6 required for its tumorigenic and metastatic properties, expanding its molecular repertoire beyond redox catalysis.

    Evidence RNA interactome capture, RNA-binding domain mapping, functional metastasis assays in melanoma

    PMID:35848924

    Open questions at the time
    • RNA targets and their downstream effects not identified
    • Relationship of RNA-binding to ER localization unresolved
  11. 2024 Medium

    Placed PDIA6 within ER homeostasis networks: it constitutively partners ERp44 with opposing roles in selective ER retention, and its loss intensifies ER stress to drive ferroptosis and impair ciliogenesis.

    Evidence Pulse-chase with PDIA6/ERp44 deletion cells and disulfide-interaction Co-IP; PDIA6 knockdown with ER-stress markers and ferroptosis-inhibitor rescue in HK2 cells

    PMID:39044457 PMID:39621446

    Open questions at the time
    • Molecular determinants of sERr client partitioning not fully defined
    • Direct link between ER stress and cilia machinery unresolved
  12. 2025 High

    Provided a structural-mechanistic basis for proinsulin folding: Ca2+ drives PDIA6 condensation via first/third thioredoxin-domain electrostatics, concentrating proinsulin to accelerate folding and suppress aggregation, and confirmed steric (non-catalytic) integrin inhibition in platelets.

    Evidence In vitro phase-separation reconstitution, NMR/structural domain mapping, proinsulin folding kinetics; platelet-specific KO mice with wild-type and active-site-mutant recombinant ERp5

    PMID:39882729 PMID:41219432

    Open questions at the time
    • In vivo physiological trigger and dynamics of condensation not fully characterized
    • Stoichiometry of condensate clients beyond proinsulin/PDIA3 not defined
  13. 2026 High

    Demonstrated catalytic and stabilizing control of oncogenic effectors: PDIA6 forms functional disulfides on TRAF4 and protects it from SMURF1-mediated degradation to sustain AKT/mTOR, stabilizes SCD1 to reprogram lipid metabolism, and is required for ZPBP disulfide formation in spermatogenesis.

    Evidence Pull-down MS, Cys-mutant rescue, ubiquitination and CHX-chase assays for TRAF4; Co-IP/interface analysis and ubiquitination for SCD1; conditional KO mouse with proteomics for ZPBP

    PMID:41654813 PMID:41761079 PMID:42234404

    Open questions at the time
    • Whether SCD1 stabilization requires catalytic cysteines not established
    • How a single isomerase coordinates such diverse client outcomes unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PDIA6's distinct activities—disulfide catalysis, Ca2+-driven condensation, UPR-sensor modulation, integrin steric inhibition, and RNA binding—are integrated and selectively deployed across cell types and stimuli.
  • No unified model linking catalytic versus non-catalytic functions
  • RNA-binding targets and their interplay with folding activity unknown
  • Reconciliation of IRE1α-enhancing versus IRE1/PERK-inhibitory reports incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0098772 molecular function regulator activity 4 GO:0016491 oxidoreductase activity 3 GO:0044183 protein folding chaperone 2 GO:0003723 RNA binding 1
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-109582 Hemostasis 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
CSN5ERP44IRE1ΑITGB3MAP4K1PERKSCD1TRAF4
Complex memberships
ER quality control granule (Ca2+-induced PDIA6 condensate)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 ERp5/PDIA6 is present on platelet intracellular membranes and is rapidly recruited to the cell surface upon platelet agonist stimulation; blocking surface ERp5 with inhibitory antibodies decreases platelet aggregation, fibrinogen binding, and P-selectin exposure, and ERp5 physically associates with integrin β3 subunit during platelet stimulation. Platelet membrane fractionation, inhibitory antibody blocking, co-immunoprecipitation Blood Medium 15466936
2014 PDIA6 interacts with IRE1α and enhances IRE1α activity (monitored by IRE1α phosphorylation and XBP1 mRNA splicing) in response to ER Ca2+ disruption; miR-322 suppresses PDIA6 mRNA stability, and ER Ca2+ depletion reduces miR-322 abundance, thereby increasing PDIA6 levels and IRE1α activity in a feedback loop modulating the UPR. Co-immunoprecipitation, shRNA knockdown, XBP1 mRNA splicing assay, IRE1α phosphorylation assay, miRNA manipulation, in vivo mouse and C. elegans experiments Science signaling High 24917591
2014 PDIA6 knockdown in cisplatin-resistant lung adenocarcinoma cells stimulates cell death via a non-canonical pathway sharing necroptosis features, distinct from the mitochondrial apoptosis pathway restored by PDIA4 inactivation, indicating PDIA6 mediates a specific pro-survival signaling branch in chemoresistant cells. shRNA knockdown, pharmacological inhibition, cell death assays, ER proteomics Cell death and differentiation Medium 24464223
2015 ERp5/PDIA6 is released at thrombus sites in vivo and its inhibition with anti-ERp5 antibody decreases platelet deposition (70%) and fibrin accumulation (62%) in a laser-injury mouse model; ERp5 binds β3 integrin with a KD of 21 µM (measured by surface plasmon resonance), and active-site cysteine residues are not required for this binding. Laser-injury mouse thrombosis model, anti-ERp5 antibody inhibition, surface plasmon resonance, in vitro disulfide reductase assay Blood High 25624318
2015 PDIA6 interacts with PERK and IRE1 and inhibits their UPR signaling; in insulin-producing cells, PDIA6 silencing reduces insulin production ~5-fold and glucose-stimulated insulin secretion 3–4-fold by enhancing IRE1 RIDD activity toward insulin transcripts (up to 4-fold), while not substantially affecting XBP1 splicing or PERK activity under physiological glucose conditions. shRNA silencing, insulin secretion assay, IRE1 RIDD fluorescent reporter assay, XBP1 mRNA splicing assay, intact islet assays FASEB journal High 26487694
2016 PDIA6 overexpression in HeLa cells promotes cell proliferation by suppressing phosphorylation of β-catenin at Ser45 and Ser33/Ser37/Thr41, thereby inhibiting its ubiquitin-proteasome-mediated degradation, increasing nuclear β-catenin accumulation, and upregulating Wnt/β-catenin target genes cyclin D1 and c-Myc. Ectopic overexpression, Western blot for β-catenin phosphorylation and nuclear fractionation, proteasome inhibitor (MG132) rescue, proliferation assays Oncotarget Medium 27462866
2016 PDIA6 co-immunoprecipitates with wild-type proinsulin and approximately 10-fold more PDIA6 (but not other PDI family members) is associated with misfolded Akita proinsulin (Cys96Tyr mutation) in pancreatic beta cells, identifying PDIA6 as a selective reductase that may target misfolded proinsulin to ER degradation. Co-immunoprecipitation with FLAG-tagged proinsulin, quantitative comparison across PDI family members, two independent beta cell lines (MIN6 and βTC-6) Biochimica et biophysica acta Medium 26947243
2016 PDIA6 knockdown in U87MG glioblastoma cells increases ADAM17 sheddase activity, MMP-2 activation, and EGFR pathway signaling (pEGFR, pFAK, integrin α5β3, MT1-MMP), leading to increased cell migration and invasion; simultaneous double-knockdown of PDIA6 and ADAM17 reduces pEGFR and pFAK, suggesting PDIA6 normally suppresses EGFR-mediated invasion by restraining ADAM17 activity. siRNA knockdown, wound-healing assay, Matrigel invasion assay, Western blot, zymography, EGFR inhibitor rescue Journal of neurosurgery Medium 27540907
2019 PDIA6 interacts with MAP4K1 and inhibits its phosphorylation, thereby suppressing the downstream JNK/c-Jun signaling pathway to inhibit cisplatin-induced apoptosis and autophagy in NSCLC cells. Co-immunoprecipitation, human phospho-kinase array, gain-of-function and loss-of-function strategies, in vitro and in vivo apoptosis/autophagy assays EBioMedicine Medium 30922965
2020 PDIA6 deficiency in mice caused by a hypomorphic ENU allele results in lymphoid and myeloid hypoplasia that is rescued by transplanting PDIA6-deficient bone marrow into wild-type irradiated recipients, demonstrating the requirement for PDIA6 is extrinsic to hematopoietic cells; PDIA6 is required for proper folding of Wnt3a, BAFF, IL-7, and other factors produced by the extra-hematopoietic compartment. ENU forward genetic screen, bone marrow transplantation rescue, Western blot for Wnt3a/BAFF/IL-7 folding The Journal of experimental medicine High 31985756
2021 PDIA6 interacts with CSN5 (COP9 signalosome subunit 5) in pancreatic cancer cells; PDIA6 overexpression promotes CSN5-mediated deubiquitination of β-catenin and PD-L1, stabilizing their expression, and these effects are partially reversed by CSN5 shRNA knockdown. Co-immunoprecipitation, ubiquitination assay, shRNA rescue experiments, gain-of-function and loss-of-function studies Neoplasia Medium 34325342
2021 A point mutation (Phe175Ser) in the second thioredoxin domain of Pdia6 in mice causes progressive loss of pancreatic β-cell identity (reduced Ins2, Mafa, Slc2a2; increased α-cell markers Mafb and glucagon) without increased apoptosis, leading to hypoinsulinemia and overt diabetes. ENU mouse model with missense mutation, immunofluorescence, molecular marker analysis, glucose/insulin measurements, histology Molecular metabolism High 34487921
2022 PDIA6 displays a novel RNA-binding activity in melanoma cells; its RNA-binding domain was mapped, and RNA binding is required for PDIA6's tumorigenic/metastatic properties, as demonstrated by RNA interactome capture and functional validation assays. RNA interactome capture (RIC), RNA-binding domain mapping, functional in vitro assays for metastatic properties Nucleic acids research Medium 35848924
2024 PDIA6 and ERp44 constitutively interact via disulfide bonds in the ER; they have opposing effects on selective ER retention (sERr) of glycoproteins during ER stress recovery—ERp44 deletion accelerates recovery while PDIA6 deletion slows it; when ERp44 is absent, PDIA6 partitions more into sERr complexes with tyrosine kinase receptor clients. Pulse-chase analysis, PDIA6 and ERp44 deletion cell lines, co-immunoprecipitation, disulfide interaction analysis The Biochemical journal Medium 39621446
2024 PDIA6 depletion in kidney proximal tubule cells (HK2) intensifies ER stress and impairs primary ciliogenesis; ferroptosis inhibition corrects the disrupted ciliogenesis caused by PDIA6 depletion, placing PDIA6-mediated ER stress upstream of ferroptotic death and cilia regulation. PDIA6 knockdown, cilia imaging, ER stress markers, ferroptosis inhibitor rescue BMB reports Medium 39044457
2025 Ca2+ triggers PDIA6 condensation into quality control granules in the ER via transient electrostatic interactions between its first and third thioredoxin-like domains (not low-complexity domains); PDIA6 condensates recruit proinsulin, accelerating oxidative proinsulin folding and suppressing proinsulin aggregation, essential for insulin secretion. Phase separation assays, NMR/structural analysis of domain interactions, proinsulin folding kinetics assay, aggregation suppression assay, live-cell imaging of ER condensates Nature cell biology High 41219432
2025 ERp5/PDIA6 deficiency in platelets (platelet-specific knockout mice) increases platelet aggregation, granule secretion, and integrin αIIbβ3 activation; recombinant ERp5 (both wild-type and active-site mutant) inhibits fibrinogen binding to platelets via steric hindrance interfering with integrin αIIbβ3 ligation, demonstrating enzymatic activity is not required for this inhibitory function. Platelet-specific conditional knockout mice, platelet aggregation assays, integrin activation assays, recombinant protein (wild-type and active-site mutant) treatment, FeCl3 thrombosis model Platelets High 39882729
2026 PDIA6 directly interacts with TRAF4 at its N-terminal (1-277) domain and catalyzes disulfide bond formation at Cys39/Cys42 and Cys83/Cys106 of TRAF4; these disulfide bonds are required for TRAF4's E3 ubiquitin ligase activity facilitating AKT ubiquitination; PDIA6 also stabilizes TRAF4 by competing with SMURF1 to prevent TRAF4 ubiquitination and proteasomal degradation, sustaining AKT/mTOR signaling in ESCC. Pull-down mass spectrometry, co-immunoprecipitation, protein-protein docking, ubiquitination assay, cycloheximide chase, TRAF4 Cys mutant rescue experiments (C42A, C83A) Cellular & molecular biology letters High 41761079
2026 PDIA6 deficiency in spermatocytes (Stra8-Cre/Pdia6fl/fl mice) causes acrosome fragmentation and detachment, disrupted acroplaxome, disorganized flagellar axonemes, and impaired acrosome reaction and calcium mobilization; PDIA6 is required for disulfide bond formation in zona pellucida binding protein (ZPBP) synthesis, and its loss induces ER stress and apoptosis in testes. Conditional knockout mouse model, electron microscopy, immunofluorescence, calcium measurement, MPB labeling, quantitative proteomics mass spectrometry Cell communication and signaling High 41654813
2026 PDIA6 directly associates with SCD1 (stearoyl-CoA desaturase 1) through an interface centered on Asp44 of SCD1, restricting SCD1 ubiquitin-proteasome-mediated degradation and maintaining SCD1-dependent fatty acid desaturation; PDIA6 drives lipid metabolic reprogramming sustaining monounsaturated fatty acid-enriched neutral lipid pools in gastric cancer. Co-immunoprecipitation, structural interface analysis, ubiquitination assay, multi-omics profiling, in vivo xenograft Advanced science Medium 42234404
2026 PCA (protocatechuic acid) binds PDIA6 (identified by activity-based protein profiling), and Co-IP mass spectrometry shows PCA enhances the interaction between PDIA6 and IRE1, suppressing the IRE1-XBP1s signaling pathway; PDIA6 knockdown alone inhibits lipid accumulation in hepatocytes and eliminates PCA's therapeutic effect. Activity-based protein profiling (ABPP), Co-IP mass spectrometry, PDIA6 knockdown, lipid accumulation assays Free radical biology & medicine Medium 41831804
2023 GRh2 (ginsenoside Rh2) directly binds ERp5/PDIA6 protein (confirmed by molecular docking, microscale thermophoresis, and cellular thermal shift assay), reduces ERp5 expression, prevents soluble MICA shedding, and upregulates membrane MICA expression, thereby enhancing NK cell cytotoxicity against breast cancer cells via the NKG2D-MICA axis. Molecular docking, microscale thermophoresis, cellular thermal shift assay, flow cytometry, ELISA, immunofluorescence Phytomedicine Medium 38043385
2024 RBM47 binds the 3'-UTR of PDIA6 mRNA (confirmed by RIP-PCR and dual-luciferase reporter assay) and stabilizes PDIA6 mRNA, increasing PDIA6 protein expression in pancreatic cancer cells; PDIA6 overexpression rescues the proliferation and immune evasion defects caused by RBM47 knockdown, placing PDIA6 downstream of RBM47. RNA immunoprecipitation (RIP)-PCR, dual-luciferase reporter assay, rescue experiments, metabolomics Journal of translational medicine Medium 39741300
2024 Ca2+-driven PDIA6 phase separation into liquid-like condensates (mediated by electrostatic interactions between its first and third thioredoxin-like domains) recruits PDIA3 and proinsulin, increasing local concentrations and achieving ~30-fold enhancement of proinsulin folding while inhibiting proinsulin aggregation. Phase separation/condensate assays, domain interaction mapping, proinsulin folding kinetics, aggregation assays bioRxivpreprint Medium
2019 Myricetin inhibits ERp5/PDIA6 reductase activity in vitro; fluorescence quenching showed myricetin binds ERp5 with similar affinity to PDI, and molecular docking identified non-covalent binding sites; myricetin inhibited only PDI and ERp5 reductase activities and not other thiol isomerases tested. In vitro reductase activity assay, fluorescence quenching, molecular docking Frontiers in pharmacology Medium 32116678
2026 Pachymic acid binds specifically to residues D221 and T166 of PDIA6 (identified by chemical proteomics and co-immunoprecipitation), leading to upregulation of G6PD and STAT3; through this PDIA6/G6PD/STAT3 axis, PA delays mesenchymal stem cell senescence and ameliorates senile osteoporosis in vivo. Chemical proteomics, co-immunoprecipitation, G6PD and STAT3 activity assays, in vivo senile osteoporosis mouse model Journal of advanced research Medium 41707960

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 A role for the thiol isomerase protein ERP5 in platelet function. Blood 133 15466936
2014 The protein disulfide isomerases PDIA4 and PDIA6 mediate resistance to cisplatin-induced cell death in lung adenocarcinoma. Cell death and differentiation 101 24464223
2014 Interplay between the oxidoreductase PDIA6 and microRNA-322 controls the response to disrupted endoplasmic reticulum calcium homeostasis. Science signaling 93 24917591
2019 PDIA6 modulates apoptosis and autophagy of non-small cell lung cancer cells via the MAP4K1/JNK signaling pathway. EBioMedicine 85 30922965
2011 High ERp5/ADAM10 expression in lymph node microenvironment and impaired NKG2D ligands recognition in Hodgkin lymphomas. Blood 75 22167753
2015 Both platelet- and endothelial cell-derived ERp5 support thrombus formation in a laser-induced mouse model of thrombosis. Blood 74 25624318
2015 PDIA6 regulates insulin secretion by selectively inhibiting the RIDD activity of IRE1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 60 26487694
2020 Myricetin, the Main Flavonoid in Syzygium cumini Leaf, Is a Novel Inhibitor of Platelet Thiol Isomerases PDI and ERp5. Frontiers in pharmacology 46 32116678
2012 Expression of ERp5 and GRP78 on the membrane of chronic lymphocytic leukemia cells: association with soluble MICA shedding. Cancer immunology, immunotherapy : CII 38 22215138
2016 A prominent role of PDIA6 in processing of misfolded proinsulin. Biochimica et biophysica acta 34 26947243
2016 The Inhibitory Effect of PDIA6 Downregulation on Bladder Cancer Cell Proliferation and Invasion. Oncology research 33 27760590
2017 MiR-127 and miR-376a act as tumor suppressors by in vivo targeting of COA1 and PDIA6 in giant cell tumor of bone. Cancer letters 32 28866093
2021 PDIA6 promotes pancreatic cancer progression and immune escape through CSN5-mediated deubiquitination of β-catenin and PD-L1. Neoplasia (New York, N.Y.) 31 34325342
2023 Ginsenoside Rh2 enhances immune surveillance of natural killer (NK) cells via inhibition of ERp5 in breast cancer. Phytomedicine : international journal of phytotherapy and phytopharmacology 27 38043385
2015 Restoration of miR-127-3p and miR-376a-3p counteracts the neoplastic phenotype of giant cell tumor of bone derived stromal cells by targeting COA1, GLE1 and PDIA6. Cancer letters 26 26655997
2016 PDIA6 promotes the proliferation of HeLa cells through activating the Wnt/β-catenin signaling pathway. Oncotarget 24 27462866
2021 PDIA6 contributes to aerobic glycolysis and cancer progression in oral squamous cell carcinoma. World journal of surgical oncology 21 33761940
2020 Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development. The Journal of experimental medicine 19 31985756
2022 Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis. Nucleic acids research 18 35848924
2021 Biallelic loss of function variant in the unfolded protein response gene PDIA6 is associated with asphyxiating thoracic dystrophy and neonatal-onset diabetes. Clinical genetics 17 33495992
2019 Hypoxia evokes increased PDI and PDIA6 expression in the infarcted myocardium of ex-germ-free and conventionally raised mice. Biology open 17 30498015
2020 Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer Cells. Cancer management and research 16 33173338
2016 PDIA6 regulation of ADAM17 shedding activity and EGFR-mediated migration and invasion of glioblastoma cells. Journal of neurosurgery 15 27540907
2021 Long non-coding RNA PCAT6 regulates bladder cancer progression via the microRNA-143-3p/PDIA6 axis. Experimental and therapeutic medicine 13 34335889
2021 A point mutation in the Pdia6 gene results in loss of pancreatic β-cell identity causing overt diabetes. Molecular metabolism 13 34487921
2012 Channel catfish (Ictalurus punctatus) protein disulphide isomerase, PDIA6: molecular characterization and expression regulated by bacteria and virus inoculation. Fish & shellfish immunology 10 22561356
2023 Venezuelan equine encephalitis virus E1 protein interacts with PDIA6 and PDI inhibition reduces alphavirus production. Antiviral research 9 36822370
2023 PDIA6, which is regulated by TRPM2-AS/miR-424-5p axis, promotes endometrial cancer progression via TGF-beta pathway. Cell death & disease 8 38097564
2024 The SOX2/PDIA6 axis mediates aerobic glycolysis to promote stemness in non-small cell lung cancer cells. Journal of bioenergetics and biomembranes 7 38441855
2022 Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts. Anais brasileiros de dermatologia 6 36244946
2013 How to exploit stress-related immunity against Hodgkin's lymphoma: Targeting ERp5 and ADAM sheddases. Oncoimmunology 6 24498565
2025 Ca2+-driven PDIA6 biomolecular condensation ensures proinsulin folding. Nature cell biology 5 41219432
2024 Increased ER stress by depletion of PDIA6 impairs primary ciliogenesis and enhances sensitivity to ferroptosis in kidney cells. BMB reports 5 39044457
2024 RBM47 promotes cell proliferation and immune evasion by upregulating PDIA6: a novel mechanism of pancreatic cancer progression. Journal of translational medicine 5 39741300
2025 Extracellular thiol isomerase ERp5 regulates integrin αIIbβ3 activation by inhibition of fibrinogen binding. Platelets 4 39882729
2024 Opposing regulation of endoplasmic reticulum retention under stress by ERp44 and PDIA6. The Biochemical journal 4 39621446
2022 PDIA6 involves the thermal stress response of razor clam, Sinonovacula constricta. Fish & shellfish immunology 4 36349651
2019 Functional Assays of Thiol Isomerase ERp5. Methods in molecular biology (Clifton, N.J.) 3 31069769
2026 Pachymic acid targets PDIA6 to delay mesenchymal stem cell senescence through the G6PD/STAT3 signaling axis and prevent senile osteoporosis. Journal of advanced research 1 41707960
2026 Protein disulfide isomerase A6 (PDIA6) is essential for acrosome biogenesis and male fertility in mice. Cell communication and signaling : CCS 0 41654813
2026 PDIA6 promotes the cell proliferation of ESCC by enhancing the disulfide bond formation in TRAF4. Cellular & molecular biology letters 0 41761079
2026 KRAS-elicited PDIA6 blocks PERK-dependent immunogenic cell death in pancreatic carcinoma. Oncoimmunology 0 41797299
2026 PDIA6 as a novel pharmacological target for metabolic dysfunction-associated steatohepatitis via alleviating endoplasmic reticulum stress. Free radical biology & medicine 0 41831804
2026 Endoplasmic reticulum stress-induced histone lactylation mediating immune escape of gastric cancer via PDIA6 overexpression in dendritic cells. Cell death & disease 0 41896533
2026 PDIA6-SCD1 Axis Rewires Lipid Metabolism to Drive Gastric Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 42234404
2025 Identification of PDIA6 Mutation in a Case of Autosomal Recessive Polycystic Kidney Disease: A Case Report and Review of Literature. Clinical genetics 0 40974269
2025 circSETD3 confers radiotherapy resistance in nasopharyngeal carcinoma by attenuating ER stress-induced autophagy and apoptosis via PDIA6 upregulation. Oncogene 0 41361078
2023 PDIA6 and Maspin in Prostate Cancer. Anticancer research 0 38030170

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