Affinage

PDIA6

Protein disulfide-isomerase A6 · UniProt Q15084

Round 2 corrected
Length
440 aa
Mass
48.1 kDa
Annotated
2026-04-29
130 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDIA6 is an ER-resident protein disulfide isomerase that functions as an oxidoreductase, chaperone, and signaling modulator across multiple cellular contexts. It dimerizes via a leucine-valine adhesive motif in its N-terminal thioredoxin-like domain, and this dimer is required for structural stability, Ca²⁺-dependent chaperone activity, and inactivation of IRE1α through intermolecular disulfide bond reduction (PMID:33857433). PDIA6 forms a complex with BiP to process client proteins, preferentially associates with misfolded proinsulin, and is essential for folding and secretion of hematopoietic niche factors (Wnt3a, BAFF, IL-7) by stromal cells, such that its loss causes cell-extrinsic immune deficiency in mice (PMID:19887585, PMID:26947243, PMID:31985756). Beyond the ER, PDIA6 acts at the cell surface to promote MICA shedding through disulfide exchange-mediated immune evasion (PMID:17495932), negatively regulates the ADAM17/EGFR axis (PMID:27540907), stabilizes β-catenin by preventing its phosphorylation-dependent degradation (PMID:27462866), and possesses an unconventional RNA-binding activity required for its tumorigenic properties (PMID:35848924).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 Medium

    Cloning of PDIA6 established it as a PDI family member with two thioredoxin-like domains, placing it within the oxidoreductase superfamily but leaving its specific substrates and cellular roles unknown.

    Evidence cDNA cloning and sequence analysis of human P5

    PMID:7590364

    Open questions at the time
    • No enzymatic activity demonstrated
    • No substrates identified
    • No cellular function assigned
  2. 2007 High

    Discovery that cell-surface PDIA6 reduces the α3-domain disulfide bond of MICA to enable its proteolytic shedding revealed the first specific substrate and an extracellular function in tumor immune evasion, expanding its role beyond the ER lumen.

    Evidence Co-IP, siRNA knockdown, and pharmacological inhibition of thioreductase activity on tumor cell lines

    PMID:17495932

    Open questions at the time
    • Identity of the sheddase protease activated by MICA reduction not determined
    • Whether PDIA6 acts on other NKG2D ligands unknown
  3. 2008 High

    Detection of PDIA6 in mitochondria by multiple orthogonal methods indicated dual ER–mitochondrial localization, raising the question of organelle-specific functions.

    Evidence Affinity chromatography, Western blot, mass spectrometry, cell fractionation, proteinase protection, and immuno-electron microscopy

    PMID:18424807

    Open questions at the time
    • No mitochondrial substrate or function identified
    • Mechanism of mitochondrial targeting unknown
  4. 2009 High

    Identification of a non-covalent PDIA6–BiP complex with distinct client specificity compared to ERp57 and ERp46 established PDIA6 as a functionally specialized ER chaperone partner rather than a redundant PDI family member.

    Evidence Co-IP and substrate specificity trapping assays comparing PDI family members

    PMID:19887585

    Open questions at the time
    • Identity of endogenous BiP clients processed by PDIA6 not comprehensively defined
    • Structural basis of PDIA6–BiP interaction not resolved
  5. 2014 High

    Demonstration that PDIA6 physically interacts with IRE1α and enhances its signaling selectively during ER Ca²⁺ depletion—regulated by miR-322—revealed PDIA6 as a UPR modulator and introduced a feedback circuit connecting calcium homeostasis to UPR branch selection.

    Evidence Co-IP of PDIA6–IRE1α, miRNA manipulation, XBP1 splicing assay, in vivo mouse and C. elegans ER stress models

    PMID:24917591

    Open questions at the time
    • Whether PDIA6 acts on IRE1α via disulfide exchange or allosteric mechanism not resolved at this stage
    • Effect on ATF6 and PERK disputed between studies
  6. 2015 High

    Functional dissection in β-cells showed PDIA6 attenuates IRE1α RIDD activity toward insulin mRNA without affecting XBP1 splicing, and also interacts with PERK, demonstrating selective modulation of distinct IRE1α outputs and a broader UPR regulatory role than initially appreciated.

    Evidence shRNA silencing, fluorescent RIDD reporter in intact islets, PERK inhibitor experiments

    PMID:26487694

    Open questions at the time
    • How PDIA6 differentially controls RIDD vs. XBP1 splicing mechanistically is unresolved
    • Stoichiometry and dynamics of PDIA6–IRE1α vs. PDIA6–PERK complexes not determined
  7. 2016 Medium

    Multiple studies converged to show PDIA6 stabilizes β-catenin by suppressing its phosphorylation and proteasomal degradation, promoting Wnt target gene expression, while also preferentially associating with misfolded proinsulin and negatively regulating the ADAM17/EGFR axis—broadening its known substrates and signaling roles in both cancer and ER quality control.

    Evidence Overexpression and siRNA knockdown in cancer and β-cell lines, Western blot for β-catenin phosphorylation, MG132 rescue, Co-IP of proinsulin variants, epistasis via PDIA6/ADAM17 double knockdown, in vivo xenografts

    PMID:26947243 PMID:27462866 PMID:27540907 PMID:27760590

    Open questions at the time
    • Whether β-catenin stabilization is a direct disulfide-dependent mechanism or indirect is unknown
    • ADAM17 regulation mechanism (direct disulfide exchange or indirect) not resolved
    • Cancer pathway findings each from single labs
  8. 2019 Medium

    PDIA6 was shown to interact with MAP4K1 and inhibit its phosphorylation, suppressing JNK/c-Jun signaling and cisplatin-induced apoptosis in NSCLC, establishing a new cytosolic signaling axis through which PDIA6 promotes chemoresistance.

    Evidence Phospho-kinase array, Co-IP of PDIA6–MAP4K1, gain- and loss-of-function, in vivo xenografts

    PMID:30922965

    Open questions at the time
    • Whether the PDIA6–MAP4K1 interaction is direct and disulfide-dependent not determined
    • Subcellular site of interaction (ER, cytosol, or surface) not established
    • Single lab finding
  9. 2020 High

    A forward genetic screen in mice revealed that PDIA6 is essential for hematopoiesis in a cell-extrinsic manner: it is required in stromal cells for proper folding and secretion of Wnt3a, BAFF, and IL-7, linking its ER chaperone function to immune system development.

    Evidence ENU mutagenesis screen, competitive and non-competitive bone marrow transplantation, Western blot for niche factors

    PMID:31985756

    Open questions at the time
    • Full spectrum of niche-secreted PDIA6 client proteins not defined
    • Whether other hematopoietic cytokines are also PDIA6-dependent not tested
  10. 2021 High

    Crystal structure determination resolved PDIA6 dimerization via a leucine-valine adhesive motif, and mutagenesis proved that the dimer is required for IRE1α inactivation through intermolecular disulfide reduction and for ER proteostasis, providing the first structural explanation for its signaling and chaperone functions.

    Evidence X-ray crystallography, site-directed mutagenesis of adhesive motif, in vitro IRE1α disulfide reduction assay, ER stress reporter

    PMID:33857433

    Open questions at the time
    • Structure of PDIA6 in complex with IRE1α or BiP not available
    • Whether dimerization is regulated in vivo by redox or calcium signals unknown
  11. 2022 Medium

    Identification of PDIA6 as an RNA-binding protein with a mapped RNA-binding domain that is required for metastatic progression uncovered an unexpected non-canonical activity, suggesting functional roles beyond its oxidoreductase and chaperone activities.

    Evidence RNA interactome capture in melanoma cells, domain mapping, loss-of-function in metastasis assays

    PMID:35848924

    Open questions at the time
    • RNA targets of PDIA6 not identified
    • Whether RNA binding is linked to or independent of its disulfide isomerase activity unknown
    • Single lab, single cancer type

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the identity of PDIA6's RNA targets, the structural basis of its interaction with IRE1α and PERK in the dimeric state, whether its effects on β-catenin and MAP4K1 involve direct disulfide exchange, and the functional significance of its mitochondrial localization.
  • No PDIA6–IRE1α or PDIA6–PERK co-crystal structure
  • RNA targets uncharacterized
  • Mitochondrial function undefined
  • Direct vs. indirect mechanism for β-catenin stabilization unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016853 isomerase activity 4 GO:0016491 oxidoreductase activity 3 GO:0044183 protein folding chaperone 3 GO:0098772 molecular function regulator activity 3 GO:0003723 RNA binding 1
Localization
GO:0005783 endoplasmic reticulum 7 GO:0005739 mitochondrion 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-168256 Immune System 2
Partners
COPS5EIF2AK3ERN1HSPA5INSMAP4K1MICA
Complex memberships
PDIA6 homodimer

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 The cDNA encoding human P5 (PDIA6) was cloned and sequenced. The predicted 440-amino-acid sequence contains two thioredoxin-like domains characteristic of the protein disulfide isomerase superfamily. cDNA cloning and sequence analysis Gene Medium 7590364
2007 PDIA6 (ERp5/P5) is present on the surface of tumor cells and associates with membrane-anchored MICA via transitory mixed disulfide complexes. Reduction of the alpha3 domain disulfide bond of MICA by cell-surface PDIA6 is required for proteolytic MICA shedding, promoting tumor immune evasion. Pharmacological inhibition of thioreductase activity and PDIA6 gene silencing both abolished MICA shedding. Co-immunoprecipitation, gene silencing (siRNA), pharmacological inhibition, cell-surface biochemistry Nature High 17495932
2009 P5 (PDIA6) forms a non-covalent complex with BiP (immunoglobulin heavy chain binding protein) and shows substrate specificity towards BiP client proteins, distinguishing it functionally from other PDI family members such as ERp57 and ERp46. Co-immunoprecipitation, substrate specificity trapping assays Journal of Cell Science High 19887585
2008 P5 (PDIA6) is present in mitochondria, in addition to its known ER localization. Identification was achieved via affinity chromatography using a phage antibody recognizing the CGHC motif, confirmed by Western blot, mass spectrometry, cell fractionation, proteinase protection assays, and immuno-electron microscopy. Affinity chromatography, Western blot, mass spectrometry, cell fractionation, proteinase protection, immuno-electron microscopy Journal of Biochemistry High 18424807
2010 Pig PDI-P5 (PDIA6 ortholog) exhibits anti-chaperone activity in vitro: while showing thiol-dependent disulfide reductase activity, it inhibits oxidative refolding of reduced denatured lysozyme by catalyzing formation of disulfide cross-linked, non-productively folded lysozyme, contrasting with PDIA3 which promotes refolding. PDI-P5 is down-regulated from epididymal corpus to cauda sperm. In vitro insulin turbidity reductase assay, oxidative refolding assay with lysozyme, SDS-PAGE/Western blot, 2D gel electrophoresis, peptide mass fingerprinting Biochimica et biophysica acta Medium 20152940
2014 PDIA6 physically interacts with IRE1α and enhances IRE1α activity (monitored by IRE1α phosphorylation and XBP1 mRNA splicing) selectively in response to ER Ca2+ depletion, but does not substantially affect PERK or ATF6 pathways. miR-322 suppresses PDIA6 mRNA stability; ER Ca2+ depletion reduces miR-322 abundance, increasing PDIA6 expression and consequently IRE1α activity. In vivo mouse and C. elegans experiments confirmed this feedback loop. Co-immunoprecipitation, phosphorylation assays, XBP1 mRNA splicing assay, miRNA manipulation, in vivo mouse/worm ER stress models Science Signaling High 24917591
2015 PDIA6 interacts with both PERK and IRE1α and inhibits their UPR signaling. In insulin-producing beta cells, PDIA6 knockdown selectively enhances RIDD (regulated IRE1-dependent decay) activity toward insulin transcripts up to 4-fold at physiological glucose concentrations, reducing insulin production and glucose-stimulated insulin secretion, without affecting XBP1 splicing. This demonstrates that PDIA6 attenuates IRE1 enzymatic activities to maintain physiological signaling. shRNA silencing, RT-PCR/molecular assays, fluorescent RIDD reporter in intact islets, PERK inhibitor experiments FASEB Journal High 26487694
2016 PDIA6 co-immunoprecipitates with wild-type proinsulin and preferentially associates (~10-fold more) with misfolded Akita mutant proinsulin (Cys96Tyr) compared to other PDI family members, suggesting a specific role as a reductase targeting misfolded proinsulin to the ER degradation pathway. Co-immunoprecipitation of FLAG-tagged proinsulin constructs, mass spectrometry interactome analysis Biochimica et biophysica acta Medium 26947243
2016 PDIA6 knockdown in bladder cancer cells reduces β-catenin, cyclin D1, and c-Myc protein expression, suppressing Wnt/β-catenin signaling, and decreases cell proliferation and invasion both in vitro and in vivo in xenograft models. siRNA knockdown, Western blot, proliferation/invasion assays, xenograft tumor model Oncology Research Medium 27760590
2016 PDIA6 overexpression in HeLa cells promotes proliferation by suppressing phosphorylation of β-catenin at Ser45 and Ser33/Ser37/Thr41, thereby inhibiting ubiquitin-proteasome-mediated β-catenin degradation and increasing nuclear β-catenin accumulation with upregulation of Wnt target genes cyclin D1 and c-Myc. The effect was abolished by the proteasome inhibitor MG132. Ectopic overexpression, Western blot, cell cycle analysis, ubiquitin-proteasome inhibitor rescue experiment Oncotarget Medium 27462866
2016 PDIA6 knockdown in U87MG glioblastoma cells increases ADAM17 sheddase activity and activates EGFR signaling (elevated pEGFR, pFAK, HB-EGF), enhancing MMP-2 activation and cell migration/invasion. Simultaneous double-knockdown of PDIA6 and ADAM17 reduced pEGFR and invasion, placing PDIA6 as a negative regulator of the ADAM17/EGFR signaling axis in glioblastoma. siRNA knockdown, Western blot, wound-healing assay, Matrigel invasion assay, organotypic culture, zymography Journal of Neurosurgery Medium 27540907
2019 PDIA6 interacts with MAP4K1 (HPK1) and inhibits its phosphorylation, leading to suppression of the JNK/c-Jun signaling pathway. PDIA6 knockdown increases cisplatin-induced apoptosis and autophagy in NSCLC cells, while overexpression has the opposite effect, positioning PDIA6 as an inhibitor of the MAP4K1/JNK/c-Jun apoptotic axis. Phospho-kinase array, co-immunoprecipitation, gain- and loss-of-function, in vitro and in vivo xenograft experiments EBioMedicine Medium 30922965
2020 In a forward genetic ENU screen, a hypomorphic Pdia6 mutation in mice causes lymphoid and myeloid hypoplasia. Bone marrow transplantation experiments showed the immune deficiency is cell-extrinsic: PDIA6-deficient bone marrow reconstituted wild-type hosts normally, but wild-type bone marrow failed to reconstitute PDIA6-deficient hosts. PDIA6 was shown to be required for proper folding/secretion of hematopoietic niche factors Wnt3a, BAFF, and IL-7 by extra-hematopoietic stromal cells. ENU forward genetic screen, bone marrow transplantation (competitive and non-competitive), Western blot for Wnt3a/BAFF/IL-7 Journal of Experimental Medicine High 31985756
2021 PDIA6 (P5) forms a dimer via a unique leucine-valine adhesive motif in the N-terminal thioredoxin-like domain, featuring periodic repeats of Leu/Val at the 3rd or 4th position on 15-residue anti-parallel α-helices stabilized by salt bridges and C-capping interactions. A monomeric P5 mutant with disrupted adhesive motif shows structural instability and induces ER stress. Dimerization is required for PDIA6 to inactivate IRE1α via intermolecular disulfide bond reduction and for Ca2+-dependent chaperone function regulation in vitro. X-ray crystallography/structure determination, mutagenesis, in vitro IRE1α disulfide reduction assay, ER stress reporter assay Structure High 33857433
2021 PDIA6 overexpression in pancreatic cancer cells promotes deubiquitination of β-catenin and PD-L1 through interaction with CSN5 (COP9 signalosome subunit 5), upregulating their expression and promoting cancer progression and NK cell evasion. CSN5 shRNA partially reversed these effects. Co-immunoprecipitation of PDIA6-CSN5, gain- and loss-of-function, ubiquitination assays, xenograft models, NK cell cytotoxicity assays Neoplasia Medium 34325342
2022 PDIA6 displays a novel RNA-binding activity identified by RNA interactome capture (RIC) in melanoma cells. Mapping revealed an RNA-binding domain within PDIA6, and this RNA-binding activity is required for its tumorigenic properties in metastatic progression assays. RNA interactome capture (RIC), domain mapping, loss-of-function with in vitro metastasis assays Nucleic Acids Research Medium 35848924

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2008 Identification of host proteins required for HIV infection through a functional genomic screen. Science (New York, N.Y.) 1165 18187620
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2013 The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. The Journal of biological chemistry 413 23463506
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2004 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking. The Biochemical journal 372 14744259
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2007 Disulphide-isomerase-enabled shedding of tumour-associated NKG2D ligands. Nature 303 17495932
2020 Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis. Med (New York, N.Y.) 291 32838362
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
1978 Structural analysis and in vitro processing to p5 rRNA of a 9S RNA molecule isolated from an rne mutant of E. coli. Cell 224 365352
2005 Lipid modification of GRN163, an N3'-->P5' thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition. Oncogene 196 15940257
1996 Cocrystal structure of YY1 bound to the adeno-associated virus P5 initiator. Proceedings of the National Academy of Sciences of the United States of America 171 8942976
2009 Protein disulphide isomerase family members show distinct substrate specificity: P5 is targeted to BiP client proteins. Journal of cell science 170 19887585
1979 Increased nuclease activity in cells treated with pppA2'p5'A2'p5' A. Proceedings of the National Academy of Sciences of the United States of America 169 114998
1989 Adeno-associated virus P5 promoter contains an adenovirus E1A-inducible element and a binding site for the major late transcription factor. Journal of virology 155 2545917
1985 Purification and partial characterization of outer membrane proteins P5 and P6 from Haemophilus influenzae type b. Infection and immunity 139 2411657
1995 Oligonucleotide N3'-->P5' phosphoramidates. Proceedings of the National Academy of Sciences of the United States of America 136 7541136
2004 A role for the thiol isomerase protein ERP5 in platelet function. Blood 132 15466936
2001 The variable P5 proteins of typeable and non-typeable Haemophilus influenzae target human CEACAM1. Molecular microbiology 96 11251807
1996 Oligonucleotide N3'-->P5' phosphoramidates as antisense agents. Nucleic acids research 93 8628685
2014 Interplay between the oxidoreductase PDIA6 and microRNA-322 controls the response to disrupted endoplasmic reticulum calcium homeostasis. Science signaling 92 24917591
2004 Characterization of the P5 subfamily of P-type transport ATPases in mice. Biochemical and biophysical research communications 90 15381061
2019 PDIA6 modulates apoptosis and autophagy of non-small cell lung cancer cells via the MAP4K1/JNK signaling pathway. EBioMedicine 84 30922965
2002 Oligonucleotide N3'-->P5' phosphoramidates as efficient telomerase inhibitors. Oncogene 81 11850790
1997 Antileukemia effect of c-myc N3'-->P5' phosphoramidate antisense oligonucleotides in vivo. Proceedings of the National Academy of Sciences of the United States of America 75 9108088
2011 High ERp5/ADAM10 expression in lymph node microenvironment and impaired NKG2D ligands recognition in Hodgkin lymphomas. Blood 74 22167753
1994 Analysis of adeno-associated virus (AAV) wild-type and mutant Rep proteins for their abilities to negatively regulate AAV p5 and p19 mRNA levels. Journal of virology 73 8151765
2015 Both platelet- and endothelial cell-derived ERp5 support thrombus formation in a laser-induced mouse model of thrombosis. Blood 72 25624318
2011 Distinct roles of protein disulfide isomerase and P5 sulfhydryl oxidoreductases in multiple pathways for oxidation of structurally diverse storage proteins in rice. The Plant cell 67 21278127
2002 Promoters P3, Pa/Pb, P4, and P5 upstream from bla(TEM) genes and their relationship to beta-lactam resistance. Antimicrobial agents and chemotherapy 67 12435720
1999 Oligonucleotide N3'-->P5' phosphoramidates as potential therapeutic agents. Biochimica et biophysica acta 67 10807003
2003 Effects of oligonucleotide N3'-->P5' thio-phosphoramidate (GRN163) targeting telomerase RNA in human multiple myeloma cells. Cancer research 64 14559802
2017 Comprehensive genomic analysis of a plant growth-promoting rhizobacterium Pantoea agglomerans strain P5. Scientific reports 63 29142289
2012 Effects of dietary supplementation with antimicrobial peptide-P5 on growth performance, apparent total tract digestibility, faecal and intestinal microflora and intestinal morphology of weanling pigs. Journal of the science of food and agriculture 63 22903784
1999 Structure and thermodynamics of metal binding in the P5 helix of a group I intron ribozyme. Journal of molecular biology 63 10388561
1988 Structure of the complex of adenylate kinase from Escherichia coli with the inhibitor P1,P5-di(adenosine-5'-)pentaphosphate. Journal of molecular biology 63 2845103
2019 Synergistic and antibiofilm activity of the antimicrobial peptide P5 against carbapenem-resistant Pseudomonas aeruginosa. Biochimica et biophysica acta. Biomembranes 60 31095945
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
2019 MPL nano-liposomal vaccine containing P5 HER2/neu-derived peptide pulsed PADRE as an effective vaccine in a mice TUBO model of breast cancer. Journal of controlled release : official journal of the Controlled Release Society 59 30999007
2007 Antiadhesive effects of GRN163L--an oligonucleotide N3'->P5' thio-phosphoramidate targeting telomerase. Cancer research 58 17283146
2019 Rice black-streaked dwarf virus-encoded P5-1 regulates the ubiquitination activity of SCF E3 ligases and inhibits jasmonate signaling to benefit its infection in rice. The New phytologist 55 31318448
1997 RNase H-independent antisense activity of oligonucleotide N3 '--> P5 ' phosphoramidates. Nucleic acids research 55 9016628
2002 Efficient integration of recombinant adeno-associated virus DNA vectors requires a p5-rep sequence in cis. Journal of virology 50 11991970
1997 Molecular variation in the major outer membrane protein P5 gene of nonencapsulated Haemophilus influenzae during chronic infections. Infection and immunity 49 9119473
1996 Oligo-2'-fluoro-2'-deoxynucleotide N3'-->P5' phosphoramidates: synthesis and properties. Nucleic acids research 49 8760881
2007 A carcinoembryonic antigen-related cell adhesion molecule 1 homologue plays a pivotal role in nontypeable Haemophilus influenzae colonization of the chinchilla nasopharynx via the outer membrane protein P5-homologous adhesin. Infection and immunity 46 17938212
1999 The P5 multicopy gene family in the MHC is related in sequence to human endogenous retroviruses HERV-L and HERV-16. Immunogenetics 46 10199916
2020 Myricetin, the Main Flavonoid in Syzygium cumini Leaf, Is a Novel Inhibitor of Platelet Thiol Isomerases PDI and ERp5. Frontiers in pharmacology 45 32116678
2010 Oligonucleotide n3'-->p5' phosphoramidates and thio-phoshoramidates as potential therapeutic agents. Chemistry & biodiversity 43 20232321
2013 Outer membrane protein P5 is required for resistance of nontypeable Haemophilus influenzae to both the classical and alternative complement pathways. Infection and immunity 42 24478079
2000 Epitope mapping of the outer membrane protein P5-homologous fimbrin adhesin of nontypeable Haemophilus influenzae. Infection and immunity 42 10722609
2010 Structural divergence between the two subgroups of P5 ATPases. Biochimica et biophysica acta 41 20416272
1998 Secondary structure and molecular analysis of interstrain variability in the P5 outer-membrane protein of non-typable Haemophilus influenzae isolated from diverse anatomical sites. Journal of medical microbiology 40 9856641
2000 Assembly of bacteriophage PRD1 spike complex: role of the multidomain protein P5. Biochemistry 39 10956048
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
2013 Synthesis of N3'-P5'-linked phosphoramidate DNA by nonenzymatic template-directed primer extension. Journal of the American Chemical Society 37 23252395
2007 Intracellular localization of human Ins(1,3,4,5,6)P5 2-kinase. The Biochemical journal 36 17705785
2000 Aphid Acquisition and Cellular Transport of Potato leafroll virus-like Particles Lacking P5 Readthrough Protein. Phytopathology 36 18944480
1998 RNA mimetics: oligoribonucleotide N3'-->P5' phosphoramidates. Nucleic acids research 36 9722635
2016 A prominent role of PDIA6 in processing of misfolded proinsulin. Biochimica et biophysica acta 34 26947243
2003 The fourth surface-exposed region of the outer membrane protein P5-homologous adhesin of nontypable Haemophilus influenzae is an immunodominant but nonprotective decoying epitope. Journal of immunology (Baltimore, Md. : 1950) 34 12902501
2016 The Inhibitory Effect of PDIA6 Downregulation on Bladder Cancer Cell Proliferation and Invasion. Oncology research 32 27760590
2021 PDIA6 promotes pancreatic cancer progression and immune escape through CSN5-mediated deubiquitination of β-catenin and PD-L1. Neoplasia (New York, N.Y.) 30 34325342
2000 Characterization of P5, a novel NFAT/AP-1 site in the human IL-4 promoter. Biochemical and biophysical research communications 30 10772943
1990 Mammalian drug resistant mutants with multiple gene amplifications: genes encoding the M1 component of ribonucleotide reductase, the M2 component of ribonucleotide reductase, ornithine decarboxylase, p5-8, the H-subunit of ferritin and the L-subunit of ferritin. Biochimica et biophysica acta 29 2223878
2016 Comparative evaluation of p5+14 with SAP and peptide p5 by dual-energy SPECT imaging of mice with AA amyloidosis. Scientific reports 28 26936002
1977 Insect immunity. III. Purification and partial characterization of immune protein P5 from hemolymph of Hyalophora cecropia pupae. Infection and immunity 28 330409
2008 Structural basis for executioner caspase recognition of P5 position in substrates. Apoptosis : an international journal on programmed cell death 27 18780184
2000 Synthetic oligonucleotides as RNA mimetics: 2'-modified Rnas and N3'-->P5' phosphoramidates. Cellular and molecular life sciences : CMLS 27 11078022
1995 Cloning and sequencing of the cDNA encoding human P5. Gene 27 7590364
2019 The P5-type ATPase Spf1 is required for development and virulence of the rice blast fungus Pyricularia oryzae. Current genetics 26 31471638
2014 Protein disulfide isomerase P5-immunopositive inclusions in patients with Alzheimer's disease. Journal of Alzheimer's disease : JAD 26 24037032
2006 Haemophilus influenzae outer membrane protein P5 is associated with inorganic polyphosphate and polyhydroxybutyrate. Biophysical journal 26 17056737
1994 TRiC-P5, a novel TCP1-related protein, is localized in the cytoplasm and in the nuclear matrix. Journal of cell science 26 7876352
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 25 38043385
2013 Interactions between the P6 and P5-1 proteins of southern rice black-streaked dwarf fijivirus in yeast and plant cells. Archives of virology 25 23474918
2003 PTEN M-CBR3, a versatile and selective regulator of inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5). Evidence for Ins(1,3,4,5,6)P5 as a proliferative signal. The Journal of biological chemistry 25 14561749
2002 Allosteric inhibitors of telomerase: oligonucleotide N3'-->P5' phosphoramidates. Nucleic acids research 25 11788719
2016 PDIA6 promotes the proliferation of HeLa cells through activating the Wnt/β-catenin signaling pathway. Oncotarget 24 27462866
2008 Evidence for mitochondrial localization of P5, a member of the protein disulphide isomerase family. Journal of biochemistry 24 18424807
1999 Synthesis and properties of RNA analogs-oligoribonucleotide N3'-->P5' phosphoramidates. Nucleic acids research 23 10497261
2022 Preventing packaging of translatable P5-associated DNA contaminants in recombinant AAV vector preps. Molecular therapy. Methods & clinical development 22 35211640
2015 Relative Contribution of P5 and Hap Surface Proteins to Nontypable Haemophilus influenzae Interplay with the Host Upper and Lower Airways. PloS one 22 25894755
2005 The cellular TATA binding protein is required for rep-dependent replication of a minimal adeno-associated virus type 2 p5 element. Journal of virology 22 16103159
1986 Inhibition of thymidine kinase by P1-(adenosine-5')-P5-(thymidine-5')-pentaphosphate. The Journal of biological chemistry 22 3457791
2021 PDIA6 contributes to aerobic glycolysis and cancer progression in oral squamous cell carcinoma. World journal of surgical oncology 21 33761940
2022 Heterostructured V-Doped Ni2 P/Ni12 P5 Electrocatalysts for Hydrogen Evolution in Anion Exchange Membrane Water Electrolyzers. Small (Weinheim an der Bergstrasse, Germany) 20 36058652
2011 Developmental expression of P5 ATPase mRNA in the mouse. Cellular & molecular biology letters 20 22207337
1985 n-Decyl-NHpppA2'p5'A2'p5'A A phosphatase-resistant, active pppA2'p5'A2'p5'A analog. Biochemical and biophysical research communications 20 2581566
2020 Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development. The Journal of experimental medicine 19 31985756
2001 Thermodynamic and kinetic effects of N3'-->P5' phosphoramidate modification on pyrimidine motif triplex DNA formation. Biochemistry 19 11170429
2010 Protein disulfide isomerase-P5, down-regulated in the final stage of boar epididymal sperm maturation, catalyzes disulfide formation to inhibit protein function in oxidative refolding of reduced denatured lysozyme. Biochimica et biophysica acta 18 20152940
1996 Novel NTP binding property of rice dwarf phytoreovirus minor core protein P5. Virology 18 8638413
1987 Biochemistry of terminal deoxynucleotidyltransferase (TdT): characterization and mechanism of inhibition of TdT by P1, P5-bis(5'-adenosyl) pentaphosphate. Biochemistry 18 2439117
2022 Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis. Nucleic acids research 17 35848924
2021 Dynamic membranes: the multiple roles of P4 and P5 ATPases. Plant physiology 17 33822217
2020 Rabies virus phosphoprotein P5 binding to BECN1 regulates self-replication by BECN1-mediated autophagy signaling pathway. Cell communication and signaling : CCS 17 32948206
2018 Preparation of nanoliposomes linked to HER2/neu-derived (P5) peptide containing MPL adjuvant as vaccine against breast cancer. Journal of cellular biochemistry 17 30378147
2020 Immunoliposomes bearing lymphocyte activation gene 3 fusion protein and P5 peptide: A novel vaccine for breast cancer. Biotechnology progress 16 33118322
2020 Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer Cells. Cancer management and research 16 33173338
2019 Hypoxia evokes increased PDI and PDIA6 expression in the infarcted myocardium of ex-germ-free and conventionally raised mice. Biology open 16 30498015
2016 PDIA6 regulation of ADAM17 shedding activity and EGFR-mediated migration and invasion of glioblastoma cells. Journal of neurosurgery 15 27540907
2003 Synthesis of novel mRNA 5' cap-analogues: dinucleoside P1, P3-tri-, P1, P4-tetra-, and P1, P5-pentaphosphates. Nucleosides, nucleotides & nucleic acids 15 14565255
1999 A method for the purification and refolding of a recombinant form of the nontypeable Haemophilus influenzae P5 outer membrane protein fused to polyhistidine. Protein expression and purification 15 10024463
2021 A unique leucine-valine adhesive motif supports structure and function of protein disulfide isomerase P5 via dimerization. Structure (London, England : 1993) 14 33857433
2017 Enhanced immune response induced by P5 HER2/neu-derived peptide-pulsed dendritic cells as a preventive cancer vaccine. Journal of cellular and molecular medicine 14 28944998
2001 Thermodynamic analysis of the interaction between YY1 and the AAV P5 promoter initiator element. Chemistry & biology 14 11251291
1998 Physical and comparative mapping of distal mouse chromosome 16. 5 p5. Genome research 14 9750193
1994 Bovine rotavirus V1005 a P5, not a P12, type like all viruses in a German survey. Journal of clinical microbiology 14 7852595