Gene Symbol: P5
Description: protein disulfide isomerase family A member 6
Alias: ERP5, TXNDC7, protein disulfide-isomerase A6, ER protein 5, endoplasmic reticulum protein 5, protein disulfide isomerase P5, protein disulfide isomerase-associated 6, protein disulfide isomerase-related protein, thioredoxin domain containing 7 (protein disulfide isomerase), thioredoxin domain-containing protein 7
Species: human
Products:     P5

Top Publications

  1. Barbouche R, Miquelis R, Jones I, Fenouillet E. Protein-disulfide isomerase-mediated reduction of two disulfide bonds of HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for fusion. J Biol Chem. 2003;278:3131-6 pubmed
    ..Disulfide bond restructuring within Env may constitute the molecular basis of the post-receptor binding conformational changes that induce fusion competence. ..
  2. Kaiser B, Yim D, Chow I, Gonzalez S, Dai Z, Mann H, et al. Disulphide-isomerase-enabled shedding of tumour-associated NKG2D ligands. Nature. 2007;447:482-6 pubmed
    ..Here we show that on the surface of tumour cells, MICA associates with endoplasmic reticulum protein 5 (ERp5; also called PDIA6 or P5), which, similar to protein disulphide isomerase, usually assists in ..
  3. Jordan P, Stevens J, Hubbard G, Barrett N, Sage T, Authi K, et al. A role for the thiol isomerase protein ERP5 in platelet function. Blood. 2005;105:1500-7 pubmed
    ..by a family of enzymes known as thiol isomerases, which include protein disulfide isomerase (PDI), endoplasmic reticulum protein 5 (ERP5), and ERP57...
  4. Kikuchi M, Doi E, Tsujimoto I, Horibe T, Tsujimoto Y. Functional analysis of human P5, a protein disulfide isomerase homologue. J Biochem. 2002;132:451-5 pubmed
    Human P5 (hP5) was expressed in the Escherichia coli pET system and purified by sequential Ni(2+)-chelating resin column chromatography...
  5. Gallina A, Hanley T, Mandel R, Trahey M, Broder C, Viglianti G, et al. Inhibitors of protein-disulfide isomerase prevent cleavage of disulfide bonds in receptor-bound glycoprotein 120 and prevent HIV-1 entry. J Biol Chem. 2002;277:50579-88 pubmed
    ..Conformational changes resulting from the opening of gp120-disulfide loops may drive the processes of virus-cell and cell-cell fusion. The biochemical events described identify new potential targets for anti-HIV agents. ..
  6. Reiser K, François K, Schols D, Bergman T, Jornvall H, Balzarini J, et al. Thioredoxin-1 and protein disulfide isomerase catalyze the reduction of similar disulfides in HIV gp120. Int J Biochem Cell Biol. 2012;44:556-62 pubmed publisher
    ..Our results demonstrate that both the host redox system and the viral surface glycoproteins are of interest for the development of new generations of anti-HIV therapeutics...
  7. Billington J, Hickling T, Munro G, Halai C, Chung R, Dodson G, et al. Stability of a receptor-binding active human immunodeficiency virus type 1 recombinant gp140 trimer conferred by intermonomer disulfide bonding of the V3 loop: differential effects of protein disulfide isomerase on CD4 and coreceptor binding. J Virol. 2007;81:4604-14 pubmed
    ..The relevance of these findings to the roles of the V3 domain and the timing of PDI action during the HIV infection process are discussed. ..
  8. Bi S, Hong P, Lee B, Baum L. Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry. Proc Natl Acad Sci U S A. 2011;108:10650-5 pubmed publisher
    ..In addition, galectin-9 binding to PDI on T cells potentiates infection with HIV. We identify a mechanism for regulating cell surface redox status via a galectin-glycoprotein lattice, to regulate distinct T-cell functions. ..
  9. Jessop C, Watkins R, Simmons J, Tasab M, Bulleid N. Protein disulphide isomerase family members show distinct substrate specificity: P5 is targeted to BiP client proteins. J Cell Sci. 2009;122:4287-95 pubmed publisher
    ..In addition, we analysed the specificity of substrates towards PDI, ERp72, ERp57, ERp46, ERp18 and P5. Strikingly, ERp18 shows specificity towards a component of the complement cascade, pentraxin-related protein PTX3, ..

More Information


  1. Wang Z, Zhou Z, Guo Z, Chi C. Snapshot of the interaction between HIV envelope glycoprotein 120 and protein disulfide isomerase. Acta Biochim Biophys Sin (Shanghai). 2010;42:358-62 pubmed
    ..The present results suggested the cell surface PDI might play a role in HIV entry in vivo. ..
  2. Hayano T, Kikuchi M. Cloning and sequencing of the cDNA encoding human P5. Gene. 1995;164:377-8 pubmed
    The cDNA encoding human P5 was cloned and sequenced. The predicted 440-amino-acid (aa) sequence of human P5 contains two thioredoxin-like domains, which are also found in members of the protein disulfide isomerase superfamily...
  3. Ryser H, Fluckiger R. Progress in targeting HIV-1 entry. Drug Discov Today. 2005;10:1085-94 pubmed
    ..Inhibiting cell surface PDI prevents HIV-1 entry. The new potential targets outlined are PDI activity as well as the sites of PDI-CD4 and PDI-gp120 interaction. ..
  4. Kiouptsi K, Finger S, Garlapati V, Knorr M, Brandt M, Walter U, et al. Hypoxia evokes increased PDI and PDIA6 expression in the infarcted myocardium of ex-germ-free and conventionally raised mice. Biol Open. 2019;8: pubmed publisher
    ..However, the role of protein disulfide isomerase associated 6 (PDIA6) under hypoxic conditions in the myocardium remains enigmatic, and it is unknown whether ..
  5. Zhao Z, Wu Y, Zhou J, Chen F, Yang A, Essex D. The transmembrane protein disulfide isomerase TMX1 negatively regulates platelet responses. Blood. 2018;: pubmed publisher
    Secreted platelet protein disulfide isomerases, PDI, ERp57, ERp5 and ERp72, have important roles as positive regulators of platelet function and thrombosis...
  6. Cho S, Kim S, Son M, Rou W, Kim S, Eun H, et al. Clinical Significance of the Thioredoxin System and Thioredoxin-Domain-Containing Protein Family in Hepatocellular Carcinoma. Dig Dis Sci. 2019;64:123-136 pubmed publisher
    ..HCC patients were shown to have enhanced expression of TXN, TXNRD1, and TXNDC7/9/14 mRNA and protein compared with controls...
  7. Bai G, Cheung I, Shulha H, Coelho J, Li P, Dong X, et al. Epigenetic dysregulation of hairy and enhancer of split 4 (HES4) is associated with striatal degeneration in postmortem Huntington brains. Hum Mol Genet. 2015;24:1441-56 pubmed publisher
    ..These findings, taken together, suggest that epigenetic dysregulation of HES4 could play a critical role in modifying HD disease pathogenesis and severity. ..
  8. Montibeller L, de Belleroche J. Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are characterised by differential activation of ER stress pathways: focus on UPR target genes. Cell Stress Chaperones. 2018;23:897-912 pubmed publisher
    ..Our results identify IRE1? and ATF6 specific targets that can have major implications in the development of new therapeutic strategies and potential biomarkers. ..
  9. Silva Z, Veríssimo T, Videira P, Novo C. Protein disulfide isomerases: Impact of thapsigargin treatment on their expression in melanoma cell lines. Int J Biol Macromol. 2015;79:44-8 pubmed publisher
    ..The differences in PDIs' gene expression in MNT-1 suggest a different response to ER stress compared to the other cell lines and highlight the importance of understanding the diversity among cancer cells. ..
  10. Negroni L, Taouji S, Arma D, Pallares Lupon N, Leong K, Beausang L, et al. Integrative quantitative proteomics unveils proteostasis imbalance in human hepatocellular carcinoma developed on nonfibrotic livers. Mol Cell Proteomics. 2014;13:3473-83 pubmed publisher
    ..As such, this model could provide an additional therapeutic opportunity for those tumors arising on normal liver by targeting the tumor proteostasis network. Data are available via ProteomeXchange with identifier PXD001253. ..
  11. Tapia Limonchi R, Díaz I, Cahuana G, Bautista M, Martín F, Soria B, et al. Impact of exposure to low concentrations of nitric oxide on protein profile in murine and human pancreatic islet cells. Islets. 2014;6:e995997 pubmed publisher
    ..The results indicate that exposure to exogenous NO counteracts the impact of serum deprivation on pancreatic β cell proteome. Species differences in the proteins involved are apparent. ..
  12. Zhong Y, Sun X, Zhang P, Qin X, Chen W, Guo Y, et al. Identification and localization of xylose-binding proteins as potential biomarkers for liver fibrosis/cirrhosis. Mol Biosyst. 2016;12:598-605 pubmed publisher
  13. Eletto D, Eletto D, Boyle S, Argon Y. PDIA6 regulates insulin secretion by selectively inhibiting the RIDD activity of IRE1. FASEB J. 2016;30:653-65 pubmed publisher
    b>Protein disulfide isomerase A6 (PDIA6) interacts with protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme (IRE)-1 and inhibits their unfolded protein response signaling...
  14. Kung P, Hsieh P, Lin Y, Lee J, Chen I, Wu C. HPW-RX40 prevents human platelet activation by attenuating cell surface protein disulfide isomerases. Redox Biol. 2017;13:266-277 pubmed publisher
    ..HPW-RX40 inhibited the activity of recombinant PDI family proteins (PDI, ERp57, and ERp5) as well as suppressed cell surface PDI activity of platelets in a reversible manner...
  15. Sun B, Bai Y, Zhang L, Gong L, Qi X, Li H, et al. Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in Lung Squamous Carcinoma Cells. PLoS ONE. 2016;11:e0163622 pubmed publisher
    ..This study might provide a new insight into the mechanism of ANXA5 in lung cancer. ..
  16. Chapman D, Stocki P, Williams D. Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules. PLoS ONE. 2015;10:e0145458 pubmed publisher
    ..This was specific to US2 rather than general ER-associated degradation since depletion of these proteins did not impede the degradation of a misfolded substrate, the null Hong Kong variant of α1-antitrypsin. ..
  17. Vinaik R, Kozlov G, Gehring K. Structure of the non-catalytic domain of the protein disulfide isomerase-related protein (PDIR) reveals function in protein binding. PLoS ONE. 2013;8:e62021 pubmed publisher
    ..The results suggest that the non-catalytic domain of PDIR plays a key role in the recognition of protein partners and substrates. ..
  18. Samanta S, Tamura S, Dubeau L, Mhawech Fauceglia P, Miyagi Y, Kato H, et al. Expression of protein disulfide isomerase family members correlates with tumor progression and patient survival in ovarian cancer. Oncotarget. 2017;8:103543-103556 pubmed publisher
    ..046 for ERp72, p = 0.040 for AGR3) with the exception of PDIA6 (p = 0.381). Our findings demonstrate that select PDI family members (PDI, PDIR, ERp72, ERp57 and AGR3) are potential prognostic markers for ovarian cancer. ..
  19. Krossa S, Scheidig A, Grötzinger J, Lorenzen I. Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17. Sci Rep. 2018;8:1103 pubmed publisher
    ..However, different PDIs might be required in vivo for disulfide switches in different tissues and under different cellular and physiological situations. ..
  20. Da Costa G, Gomig T, Kaviski R, Santos Sousa K, Kukolj C, de Lima R, et al. Comparative Proteomics of Tumor and Paired Normal Breast Tissue Highlights Potential Biomarkers in Breast Cancer. Cancer Genomics Proteomics. 2015;12:251-61 pubmed
    ..Taking the fold change as a parameter, we point to future targets to be studied by functional methods in a search for biomarkers for initiation and progress of breast cancer. ..
  21. Gorasia D, Dudek N, Safavi Hemami H, Perez R, Schittenhelm R, Saunders P, et al. A prominent role of PDIA6 in processing of misfolded proinsulin. Biochim Biophys Acta. 2016;1864:715-723 pubmed publisher
    ..Thus, this study has identified several chaperones/foldases that associated with wild type proinsulin and has also provided a comprehensive interactome for Akita misfolded proinsulin. ..
  22. Ben Salem I, Prola A, Boussabbeh M, Guilbert A, Bacha H, Abid Essefi S, et al. Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress. Cell Stress Chaperones. 2015;20:927-38 pubmed publisher
    ..Our results suggest that antioxidant molecule might be helpful to prevent ZEN-induced ER stress and toxicity. ..
  23. Tavender T, Springate J, Bulleid N. Recycling of peroxiredoxin IV provides a novel pathway for disulphide formation in the endoplasmic reticulum. EMBO J. 2010;29:4185-97 pubmed publisher
    ..Oxidation of PDI by PrxIV may therefore increase efficiency of disulphide formation by Ero1 and also allows disulphide formation via alternative sources of H(2)O(2). ..
  24. Gao H, Sun B, Fu H, Chi X, Wang F, Qi X, et al. PDIA6 promotes the proliferation of HeLa cells through activating the Wnt/?-catenin signaling pathway. Oncotarget. 2016;7:53289-53298 pubmed publisher
    ..These results demonstrated that PDIA6 overexpression promoted the proliferation of HeLa cells by suppressing the phosphorylation of ?-catenin, thereby inhibiting the degradation of ?-catenin through the ubiquitin-proteasome pathway. ..
  25. Tufo G, Jones A, Wang Z, Hamelin J, Tajeddine N, Esposti D, et al. The protein disulfide isomerases PDIA4 and PDIA6 mediate resistance to cisplatin-induced cell death in lung adenocarcinoma. Cell Death Differ. 2014;21:685-95 pubmed publisher
    ..Overexpression of both proteins has also been found in lung adenocarcinoma patients, suggesting a clinical importance of these proteins in chemoresistance. ..
  26. Hulleman J, Genereux J, Nguyen A. Mapping wild-type and R345W fibulin-3 intracellular interactomes. Exp Eye Res. 2016;153:165-169 pubmed publisher
    ..These F3 interactome results can serve as the basis for pursuing targeted genetic or pharmacologic approaches in an effort to alter the fate of either WT or mutant F3. ..
  27. Cheng H, Liu Q, Li Y, Li X, Zhu C. The Inhibitory Effect of PDIA6 Downregulation on Bladder Cancer Cell Proliferation and Invasion. Oncol Res. 2017;25:587-593 pubmed publisher
    ..Furthermore, PDIA6 downregulation reduced the protein expression of ?-catenin, cyclin D1, and c-Myc and thus suppressed the Wnt/?-catenin signaling pathway. In conclusion, we suggest that PDIA6 could be targeted for the treatment of BC. ..
  28. Fellenberg J, Sähr H, Kunz P, Zhao Z, Liu L, Tichy D, et al. 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 Lett. 2016;371:134-41 pubmed publisher
  29. Barbouche R, Lortat Jacob H, Jones I, Fenouillet E. Glycosaminoglycans and protein disulfide isomerase-mediated reduction of HIV Env. Mol Pharmacol. 2005;67:1111-8 pubmed
  30. Holbrook L, Sandhar G, Sasikumar P, Schenk M, Stainer A, Sahli K, et al. A humanized monoclonal antibody that inhibits platelet-surface ERp72 reveals a role for ERp72 in thrombosis. J Thromb Haemost. 2017;: pubmed publisher
    ..Several thiol isomerases are known to be present on the resting platelet surface including PDI, ERp5 and ERp57 and levels are increased following platelet activation...
  31. Bromfield E, McLaughlin E, Aitken R, Nixon B. Heat Shock Protein member A2 forms a stable complex with angiotensin converting enzyme and protein disulfide isomerase A6 in human spermatozoa. Mol Hum Reprod. 2016;22:93-109 pubmed publisher
    ..In view of the findings in this study we propose that angiotensin converting enzyme (ACE) and protein disulfide isomerase A6 (PDIA6) are novel interacting proteins of HSPA2 and that this multimeric complex may participate in ..
  32. Schäfer M, Granato D, Krossa S, Bartels A, Yokoo S, Düsterhöft S, et al. GRP78 protects a disintegrin and metalloprotease 17 against protein-disulfide isomerase A6 catalyzed inactivation. FEBS Lett. 2017;591:3567-3587 pubmed publisher
    ..Here, we show that the chaperone 78-kDa glucose-regulated protein (GRP78) protects the MPD against PDI-dependent disulfide-bond isomerization by binding to this domain and, thereby, preventing ADAM17 inhibition. ..
  33. Huergo Zapico L, Gonzalez Rodriguez A, Contesti J, Gonzalez E, Lopez Soto A, Fernández Guizán A, et al. Expression of ERp5 and GRP78 on the membrane of chronic lymphocytic leukemia cells: association with soluble MICA shedding. Cancer Immunol Immunother. 2012;61:1201-10 pubmed publisher
    ..b>ERp5 and GRP78 are endoplasmic reticulum-resident proteins that are translocated to the surface of epithelial tumor ..
  34. Ramos F, Serino L, Carvalho C, Lima R, Urban C, Cavalli I, et al. PDIA3 and PDIA6 gene expression as an aggressiveness marker in primary ductal breast cancer. Genet Mol Res. 2015;14:6960-7 pubmed publisher
    ..0351). Our results suggest that alterations in PDIA3/6 expression levels may be involved in the breast carcinogenic process and should be further investigated as a marker of aggressiveness. ..
  35. Salah A, Bouaziz C, Prola A, Pires Da Silva J, Bacha H, Abid Essefi S, et al. Citrinin induces apoptosis in human HCT116 colon cancer cells through endoplasmic reticulum stress. J Toxicol Environ Health A. 2017;80:1230-1241 pubmed publisher
    ..glucose-regulated protein-94), GADD34 (growth arrest and DNA damage-inducible protein-34), the protein disulfide isomerase associated 6 (PDIA6), CHOP (C/EBP-homologous protein) and the splicing of XBP1 (X-Box Binding Protein 1)...
  36. Zheng G, Yang Y. ZNF76, a novel transcriptional repressor targeting TATA-binding protein, is modulated by sumoylation. J Biol Chem. 2004;279:42410-21 pubmed
    ..These results suggest that ZNF76 functions as a transcriptional repressor through its interaction with TBP and that sumoylation modulates its transcriptional repression activity. ..
  37. Kapoor I, Kanaujiya J, Kumar Y, Thota J, Bhatt M, Chattopadhyay N, et al. Proteomic discovery of MNT as a novel interacting partner of E3 ubiquitin ligase E6AP and a key mediator of myeloid differentiation. Oncotarget. 2016;7:7640-56 pubmed publisher
  38. Stantchev T, Paciga M, Lankford C, Schwartzkopff F, Broder C, Clouse K. Cell-type specific requirements for thiol/disulfide exchange during HIV-1 entry and infection. Retrovirology. 2012;9:97 pubmed publisher
  39. Hashimoto N, Hamamura K, Kotani N, Furukawa K, Kaneko K, Honke K, et al. Proteomic analysis of ganglioside-associated membrane molecules: substantial basis for molecular clustering. Proteomics. 2012;12:3154-63 pubmed publisher
    ..Representative examples of GD3-associated molecules such as neogenin and MCAM were shown...
  40. Zocchi M, Catellani S, Canevali P, Tavella S, Garuti A, Villaggio B, et al. High ERp5/ADAM10 expression in lymph node microenvironment and impaired NKG2D ligands recognition in Hodgkin lymphomas. Blood. 2012;119:1479-89 pubmed publisher
    ..the lymph node (LN) stroma displayed in situ high levels of transcription and expression of the disulfide-isomerase ERp5 and of the disintegrin-metalloproteinase ADAM10, able to shed the ligands for NKG2D (NKG2D-L) from the cell ..
  41. Herr I, Sähr H, Zhao Z, Yin L, Omlor G, Lehner B, et al. MiR-127 and miR-376a act as tumor suppressors by in vivo targeting of COA1 and PDIA6 in giant cell tumor of bone. Cancer Lett. 2017;409:49-55 pubmed publisher
    ..7% and 42.7%, while the tumor take rates remained stable. Our results indicate that re-expression of miR-127-3p and miR-376a-3p induces a strong tumor suppressor effect in GCTSC, which is partially mediated via COA1 and PDIA6. ..
  42. Lee S, Min Kim S, Dotimas J, Li L, Feener E, Baldus S, et al. Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress. EMBO Mol Med. 2014;6:732-43 pubmed publisher
    ..Our results reveal Txnip as a novel direct regulator of PDI activity and a feedback mechanism of UPR signaling to decrease ER stress. ..
  43. Galligan J, Petersen D. The human protein disulfide isomerase gene family. Hum Genomics. 2012;6:6 pubmed publisher
    ..Understanding the mechanisms of protein-folding, specifically thiol-disulfide exchange, may lead to development of a novel class of therapeutics that would help alleviate a wide range of diseases by targeting the UPR. ..
  44. Alanen H, Salo K, Pirneskoski A, Ruddock L. pH dependence of the peptide thiol-disulfide oxidase activity of six members of the human protein disulfide isomerase family. Antioxid Redox Signal. 2006;8:283-91 pubmed
    ..chemistry, we have recombinantly expressed and purified six members of the family, PDI, PDIp, ERp57, ERp72, P5, and PDIr from a single organism, human...
  45. Holbrook L, Watkins N, Simmonds A, Jones C, Ouwehand W, Gibbins J. Platelets release novel thiol isomerase enzymes which are recruited to the cell surface following activation. Br J Haematol. 2010;148:627-37 pubmed publisher
    The thiol isomerase enzymes protein disulphide isomerase (PDI) and endoplasmic reticulum protein 5 (ERp5) are released by resting and activated platelets...