Gene Symbol: PDIA4
Description: protein disulfide isomerase family A member 4
Alias: ERP70, ERP72, ERp-72, protein disulfide-isomerase A4, ER protein 70, ER protein 72, endoplasmic reticulum resident protein 70, endoplasmic reticulum resident protein 72, protein disulfide isomerase related protein (calcium-binding protein, intestinal-related), protein disulfide isomerase-associated 4, testicular tissue protein Li 137
Species: human
Products:     PDIA4

Top Publications

  1. Weisbart R. An antibody that binds a neutrophil membrane protein, ERp72, primes human neutrophils for enhanced oxidative metabolism in response to formyl-methionyl-leucyl-phenylalanine. Implications for ERp72 in the signal transduction pathway for neutrophil pri. J Immunol. 1992;148:3958-63 pubmed
    ..the protein associated with neutrophil priming was sequenced and identified as the endoplasmic reticulum protein, ERp72, which contains three copies of the active site sequences of protein disulfide isomerase...
  2. Mazzarella R, Srinivasan M, Haugejorden S, Green M. ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase. J Biol Chem. 1990;265:1094-101 pubmed
    ..full length cDNA clones encoding two abundant, luminal endoplasmic reticulum proteins (ERp), ERp59/PDI and ERp72. ERp59/PDI has been identified as the microsomal enzyme protein disulfide isomerase (PDI)...
  3. 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...
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. 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. ..
  8. 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. ..
  9. Chan J, Lee K, Maxwell E, Liang C, Laybutt D. Macrophage alterations in islets of obese mice linked to beta cell disruption in diabetes. Diabetologia. 2019;: pubmed publisher
    ..channel (Kcnj11), incretin receptor (Gipr) and adaptive unfolded protein response (UPR) genes (Xbp1, Hspa5, Pdia4 and Fkbp11) were increased in db/db islets after macrophage depletion, whereas the mRNA levels of the deleterious ..

More Information


  1. 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...
  2. Liu C, Ran X, Niu X, Li S, Wang J, Zhang Q. Insertion of 275-bp SINE into first intron of PDIA4 gene is associated with litter size in Xiang pigs. Anim Reprod Sci. 2018;: pubmed publisher
    ..based detection method was conducted to identify the short interspersed nuclear element (SINE) polymorphism in the PDIA4 gene. There were greater frequencies of the SINE-/- genotypes in Xiang pigs (55...
  3. Kim Y, Chang K. Protein disulfide isomerases as potential therapeutic targets for influenza A and B viruses. Virus Res. 2018;247:26-33 pubmed publisher
    ..Furthermore, siRNAs specific to three PDI family members (PDI1, PDIA3 or PDIA4) also significantly reduced the replication of influenza A and B viruses in cells...
  4. Zhou J, Wu Y, Chen F, Wang L, Rauova L, Hayes V, et al. The disulfide isomerase ERp72 supports arterial thrombosis in mice. Blood. 2017;130:817-828 pubmed publisher
    ..We here report that endoplasmic reticulum protein 72 (ERp72), with 3 CGHC redox-active sites (ao, a, and a'), supports thrombosis...
  5. Kupsco A, Schlenk D. Molecular mechanisms of selenium-Induced spinal deformities in fish. Aquat Toxicol. 2016;179:143-50 pubmed publisher
    ..induced apoptosis deformed embryos after 5?M SeMet, accompanied by a significant decrease in PDIA4 (protein disulfide isomerase A4) and no change in Dnajb9 (ER DNA J Domain-Containing Protein 4)...
  6. Torres M, Medinas D, Matamala J, Woehlbier U, Cornejo V, Soldà T, et al. The Protein-disulfide Isomerase ERp57 Regulates the Steady-state Levels of the Prion Protein. J Biol Chem. 2015;290:23631-45 pubmed publisher
    ..we found that PrP physically interacts with ERp57, and also with the closest family member PDIA1, but not ERp72. Furthermore, we generated a conditional knock-out mouse for ERp57 in the nervous system and detected a reduction ..
  7. Sowers C, Wang R, Bourne R, McGrath B, Hu J, Bevilacqua S, et al. The protein kinase PERK/EIF2AK3 regulates proinsulin processing not via protein synthesis but by controlling endoplasmic reticulum chaperones. J Biol Chem. 2018;293:5134-5149 pubmed publisher
    ..Furthermore, we show that PERK regulates proinsulin proteostasis by modulating ER chaperones, including BiP and ERp72. Transgenic overexpression of BiP and BiP knockdown (KD) both promoted proinsulin aggregation, whereas ERp72 ..
  8. Xie J, Zhu Y, Chen H, Shi M, Gu J, Zhang J, et al. The Immunohistochemical Evaluation of Solid Pseudopapillary Tumors of the Pancreas and Pancreatic Neuroendocrine Tumors Reveals ERO1Lβ as a New Biomarker. Medicine (Baltimore). 2016;95:e2509 pubmed publisher
    ..We performed immunohistochemistry (IHC) for 6 representative proteins (ERO1Lβ, TRAM1, GRP94, BIP, P4HB, and PDIA4) involved in the ER pathway in both SPTP and PNET specimens...
  9. Yi M, Melkonian A, Ousey J, Khosla C. Endoplasmic reticulum-resident protein 57 (ERp57) oxidatively inactivates human transglutaminase 2. J Biol Chem. 2018;293:2640-2649 pubmed publisher
    ..was also markedly higher than those of other secreted redox proteins, including protein disulfide isomerase (PDI), ERp72, TRX, and quiescin sulfhydryl oxidase 1 (QSOX1)...
  10. 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
    ..bridge with a positively charged binding surface for interactions with the ER chaperones, calreticulin and ERp72. Crystal contacts between molecules potentially mimic the interactions of PDIR with misfolded substrate proteins...
  11. 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
    ..We sought to evaluate the expression of PDI, PDIA6, PDIR, ERp57, ERp72 and AGR3 in ovarian cancer patient samples and examine their prognostic significance...
  12. Xu W, Liu L, Hornby D. c-IAP1 binds and processes PCSK9 protein: linking the c-IAP1 in a TNF-α pathway to PCSK9-mediated LDLR degradation pathway. Molecules. 2012;17:12086-101 pubmed publisher
    ..The novel pathway described here will open new avenues for exploring novel disease treatments. ..
  13. Schaiff W, Hruska K, McCourt D, Green M, Schwartz B. HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells. J Exp Med. 1992;176:657-66 pubmed
    ..revealed the identity of two of the proteins as the endoplasmic reticulum (ER) resident stress proteins GRP94 and ERp72. Neither of these proteins was found to have an increased level of synthesis in the Ii- versus the Ii+ ..
  14. Chien C, Hung Y, Shieh Y, Hsieh C, Lu C, Lin F, et al. A novel potential biomarker for metabolic syndrome in Chinese adults: Circulating protein disulfide isomerase family A, member 4. PLoS ONE. 2017;12:e0179963 pubmed publisher
    ..However, the metabolic effects of PDIA4 remain unclear in humans...
  15. Di Jeso B, Morishita Y, Treglia A, Lofrumento D, Nicolardi G, Beguinot F, et al. Transient covalent interactions of newly synthesized thyroglobulin with oxidoreductases of the endoplasmic reticulum. J Biol Chem. 2014;289:11488-96 pubmed publisher
    ..adduct C primarily engages the CaBP1/P5 oxidoreductase, whereas the slower migrating Tg adduct A primarily engages ERp72. Upon siRNA-mediated knockdown of CaBP1/P5 or ERp72, adducts C or A, respectively, are decreased...
  16. 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
    ..proteins identified by proteomics) and exhibit a dramatic overexpression of two protein disulfide isomerases, PDIA4 and PDIA6, without any alteration in ER-cytosol Ca(2+) fluxes...
  17. Wei P, Hsieh Y, Su M, Jiang X, Hsu P, Lo W, et al. Loss of the oxidative stress sensor NPGPx compromises GRP78 chaperone activity and induces systemic disease. Mol Cell. 2012;48:747-59 pubmed publisher
    ..These results suggest that NPGPx is essential for releasing excessive ER stress by enhancing GRP78 chaperone activity to maintain physiological homeostasis...
  18. Huang S, Tomich J, Wu H, Jong A, Holcenberg J. Human deoxycytidine kinase. Sequence of cDNA clones and analysis of expression in cell lines with and without enzyme activity. J Biol Chem. 1989;264:14762-8 pubmed
    ..Genomic restriction fragments were similar between the active and inactive CCRF/CEM cell lines. These data suggest that the cells deficient in dC kinase activity have a small defect in the structural gene. ..
  19. Linnik K, Herscovitz H. Multiple molecular chaperones interact with apolipoprotein B during its maturation. The network of endoplasmic reticulum-resident chaperones (ERp72, GRP94, calreticulin, and BiP) interacts with apolipoprotein b regardless of its lipidation state. J Biol Chem. 1998;273:21368-73 pubmed
    ..The endoplasmic reticulum (ER)-resident molecular chaperones GRP94, calreticulin, and ERp72 were co-immunoprecipitated with apoB-100 from HepG2 cell lysates following cross-linking of proteins in living ..
  20. Chen W, Shang W, Adachi Y, Hirose K, Ferrari D, Kamata T. A possible biochemical link between NADPH oxidase (Nox) 1 redox-signalling and ERp72. Biochem J. 2008;416:55-63 pubmed publisher
    ..In the present study we show that one of the proteins selectively oxidized in response to Nox1-generated ROS was ERp72 (endoplasmic reticulum protein 72 kDa) with TRX (thioredoxin) homology domains...
  21. 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
  22. Allen S, Abuzenadah A, Hinks J, Blagg J, Gursel T, Ingerslev J, et al. A novel von Willebrand disease-causing mutation (Arg273Trp) in the von Willebrand factor propeptide that results in defective multimerization and secretion. Blood. 2000;96:560-8 pubmed
    ..The R273W mutation did not affect the ability of VWF to bind to BiP, Grp94, ERp72, calnexin, and calreticulin in COS-7 cells. (Blood. 2000;96:560-568)
  23. Meunier L, Usherwood Y, Chung K, Hendershot L. A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins. Mol Biol Cell. 2002;13:4456-69 pubmed
    ..GRP94; CaBP1; protein disulfide isomerase (PDI); ERdj3, a recently identified ER Hsp40 cochaperone; cyclophilin B; ERp72; GRP170; UDP-glucosyltransferase; and SDF2-L1...
  24. 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
  25. Kuo T, Chen T, Jiang S, Chen K, Chiang Y, Hsu Y, et al. Protein disulfide isomerase a4 acts as a novel regulator of cancer growth through the procaspase pathway. Oncogene. 2017;36:5484-5496 pubmed publisher
    b>Protein disulfide isomerase a4 (PDIA4) is implicated in the growth and death of tumor cells; however, its molecular mechanism and therapeutic potential in cancer are unclear...
  26. Winship A, Sorby K, Correia J, Rainczuk A, Yap J, Dimitriadis E. Interleukin-11 up-regulates endoplasmic reticulum stress induced target, PDIA4 in human first trimester placenta and in vivo in mice. Placenta. 2017;53:92-100 pubmed publisher
    ..Using mass spectrometry, we identified protein disulfide isomerase 4 (PDIA4) in IL11-treated first trimester human placental explants (100 ng/ml, 24 h, n = 3), but not PBS control ..
  27. Sørensen S, Ranheim T, Bakken K, Leren T, Kulseth M. Retention of mutant low density lipoprotein receptor in endoplasmic reticulum (ER) leads to ER stress. J Biol Chem. 2006;281:468-76 pubmed
    ..In the present study we show that the G544V mutant LDLR associates with the chaperones Grp78, Grp94, ERp72, and calnexin in the ER of transfected Chinese hamster ovary cells...
  28. 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...
  29. Pawar H, Kashyap M, Sahasrabuddhe N, Renuse S, Harsha H, Kumar P, et al. Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery. Cancer Biol Ther. 2011;12:510-22 pubmed publisher
    ..novel biomarker candidates included prosaposin (PSAP), plectin 1 (PLEC1) and protein disulfide isomerase A 4 (PDIA4) that were further validated to be overexpressed by immunohistochemical labeling using tissue microarrays...
  30. 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 presence of five additional thiol isomerases in human and mouse platelets and megakaryocytes, namely; ERp57, ERp72, ERp44, ERp29 and TMX3...
  31. Appenzeller Herzog C, Riemer J, Zito E, Chin K, Ron D, Spiess M, et al. Disulphide production by Ero1?-PDI relay is rapid and effectively regulated. EMBO J. 2010;29:3318-29 pubmed publisher
    ..complexes of Ero1 primarily form with PDI, to a lesser extent with the PDI-family members ERp57 and ERp72, but are not detectable with another homologue TMX3...
  32. 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
    ..Inhibition of the catalytic activity of these enzymes results in diminished platelet function and thrombosis...
  33. Zhang J, Herscovitz H. Nascent lipidated apolipoprotein B is transported to the Golgi as an incompletely folded intermediate as probed by its association with network of endoplasmic reticulum molecular chaperones, GRP94, ERp72, BiP, calreticulin, and cyclophilin B. J Biol Chem. 2003;278:7459-68 pubmed
    ..12 g/ml and, like the membrane-bound pool, was associated with GRP94, ERp72, BiP, calreticulin, and cyclophilin B...
  34. 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. ..
  35. Kuznetsov G, Chen L, Nigam S. Multiple molecular chaperones complex with misfolded large oligomeric glycoproteins in the endoplasmic reticulum. J Biol Chem. 1997;272:3057-63 pubmed
    ..269, 22990-22995). By coimmunoprecipitation in rat thyroid cells, we were able to demonstrate that BiP, grp94, ERp72, and grp170, four proteins believed to function as specific molecular chaperones, complex with Tg during its ..
  36. Jansen G, Maattanen P, Denisov A, Scarffe L, Schade B, Balghi H, et al. An interaction map of endoplasmic reticulum chaperones and foldases. Mol Cell Proteomics. 2012;11:710-23 pubmed publisher
    ..We have examined in detail a novel ERp72-cyclophilin B complex that enhances the rate of folding of immunoglobulin G...
  37. Huang S, Tomich J, Wu H, Jong A, Holcenberg J. Human deoxycytidine kinase. Sequence of cDNA clones and analysis of expression in cell lines with and without enzyme activity. J Biol Chem. 1991;266:5353 pubmed
  38. Hulleman J, Genereux J, Nguyen A. Mapping wild-type and R345W fibulin-3 intracellular interactomes. Exp Eye Res. 2016;153:165-169 pubmed publisher
    ..Eight of these interactions (ANXA5, ERdj5, PDIA4, P4HB, PDIA6, RCN1, SDF2L1, and TXNDC5) were verified at the western blotting level...