Gene Symbol: P4hb
Description: prolyl 4-hydroxylase, beta polypeptide
Alias: ERp59, PDI, Pdia1, Thbp, protein disulfide-isomerase, ER protein 59, cellular thyroid hormone-binding protein, endoplasmic reticulum resident protein 59, p55, prolyl 4-hydroxylase subunit beta
Species: mouse
Products:     P4hb

Top Publications

  1. Higuchi T, Watanabe Y, Waga I. Protein disulfide isomerase suppresses the transcriptional activity of NF-kappaB. Biochem Biophys Res Commun. 2004;318:46-52 pubmed
    We report here that the transcriptional activity of NF-kappaB is negatively regulated by protein disulfide isomerase (PDI). Over-expression of PDI in RAW 264...
  2. Nakamura K, Itoh K, Yaoi T, Fujiwara Y, Sugimoto T, Fushiki S. Murine neocortical histogenesis is perturbed by prenatal exposure to low doses of Bisphenol A. J Neurosci Res. 2006;84:1197-205 pubmed
    ..5 in the BPA-treated group. These results suggested that BPA might disrupt normal neocortical development by accelerating neuronal differentiation/migration. ..
  3. Grigaravicius P, Kaminska E, Hübner C, McKinnon P, von Deimling A, Frappart P. Rint1 inactivation triggers genomic instability, ER stress and autophagy inhibition in the brain. Cell Death Differ. 2016;23:454-68 pubmed publisher
    ..Altogether, our findings highlight the crucial roles of Rint1 in vivo in genomic stability maintenance, as well as in prevention of ER stress and autophagy. ..
  4. Cho J, Kennedy D, Lin L, Huang M, Merrill Skoloff G, Furie B, et al. Protein disulfide isomerase capture during thrombus formation in vivo depends on the presence of ?3 integrins. Blood. 2012;120:647-55 pubmed publisher
    Extracellular protein disulfide isomerase (PDI) is required for platelet thrombus formation and fibrin generation after arteriolar wall injury in live mice...
  5. Nakamura T, Yabe D, Kanazawa N, Tashiro K, Sasayama S, Honjo T. Molecular cloning, characterization, and chromosomal localization of FKBP23, a novel FK506-binding protein with Ca2+-binding ability. Genomics. 1998;54:89-98 pubmed
    ..FKBP23 mRNA is expressed most strongly in heart, lung, and testis, beginning at day 8.5 of embryonic development. The FKBP23 gene was mapped to mouse chromosome 2. ..
  6. Morris D, Robinson T. Thymidine kinase (Tk-1) maps below the T42H breakpoint on mouse chromosome 11. Mamm Genome. 1991;1:263-4 pubmed
  7. Gong Q, Fukuda T, Parkison C, Cheng S. Nucleotide sequence of a full-length cDNA clone encoding a mouse cellular thyroid hormone binding protein (p55) that is homologous to protein disulfide isomerase and the beta-subunit of prolyl-4-hydroxylase. Nucleic Acids Res. 1988;16:1203 pubmed
  8. Dandoy Dron F, Griffond B, Mishal Z, Tovey M, Dron M. Scrg1, a novel protein of the CNS is targeted to the large dense-core vesicles in neuronal cells. Eur J Neurosci. 2003;18:2449-59 pubmed
    ..Our findings strongly suggest that Scrg1 is associated with the secretory pathway of neuronal cells. ..
  9. Hahm E, Li J, Kim K, Huh S, Rogelj S, Cho J. Extracellular protein disulfide isomerase regulates ligand-binding activity of ?M?2 integrin and neutrophil recruitment during vascular inflammation. Blood. 2013;121:3789-800, S1-15 pubmed publisher
    ..Using fluorescence intravital microscopy in mice generated by crossing protein disulfide isomerase (PDI) floxed mice with lysozyme-Cre transgenic mice, we demonstrate that neutrophil PDI is required for ..

More Information


  1. Zhang Y, Zhang M, Wu J, Lei G, Li H. Transcriptional regulation of the Ufm1 conjugation system in response to disturbance of the endoplasmic reticulum homeostasis and inhibition of vesicle trafficking. PLoS ONE. 2012;7:e48587 pubmed publisher
    ..Taken together, our study provided critical insight into the regulatory mechanism of the Ufm1 system and established a direct link between this novel Ubl system and the ER network. ..
  2. Jaronen M, Vehviläinen P, Malm T, Keksa Goldsteine V, Pollari E, Valonen P, et al. Protein disulfide isomerase in ALS mouse glia links protein misfolding with NADPH oxidase-catalyzed superoxide production. Hum Mol Genet. 2013;22:646-55 pubmed publisher
    b>Protein disulfide isomerase (PDI) is an oxidoreductase assisting oxidative protein folding in the endoplasmic reticulum of all types of cells, including neurons and glia...
  3. Turano C, Coppari S, Altieri F, Ferraro A. Proteins of the PDI family: unpredicted non-ER locations and functions. J Cell Physiol. 2002;193:154-63 pubmed
  4. Cheng H, Lei H, Lin C, Luo Y, Wan S, Liu H, et al. Anti-dengue virus nonstructural protein 1 antibodies recognize protein disulfide isomerase on platelets and inhibit platelet aggregation. Mol Immunol. 2009;47:398-406 pubmed publisher
    ..In the present study, we demonstrate that protein disulfide isomerase (PDI) on the platelet surface is recognized by anti-DV NS1 antibodies...
  5. Wang W, Li Q, Xu J, Cvekl A. Lens fiber cell differentiation and denucleation are disrupted through expression of the N-terminal nuclear receptor box of NCOA6 and result in p53-dependent and p53-independent apoptosis. Mol Biol Cell. 2010;21:2453-68 pubmed publisher
    ..Our data demonstrate a cell-autonomous role of Ncoa6 in lens fiber cell differentiation and suggest novel insights into the process of lens fiber cell denucleation and apoptosis. ..
  6. Kelkar N, Standen C, Davis R. Role of the JIP4 scaffold protein in the regulation of mitogen-activated protein kinase signaling pathways. Mol Cell Biol. 2005;25:2733-43 pubmed
    ..The JIP4 scaffold protein therefore appears to be a new component of the p38 MAP kinase signaling pathway. ..
  7. Rao R, Poksay K, Castro Obregon S, Schilling B, Row R, Del Rio G, et al. Molecular components of a cell death pathway activated by endoplasmic reticulum stress. J Biol Chem. 2004;279:177-87 pubmed
    ..Our data identify two molecules, valosin-containing protein and apoptosis-linked gene-2 (ALG-2), that appear to play a role in mediating ER stress-induced cell death. ..
  8. Mouri T, Kittaka N, Horio Y, Copeland N, Gilbert D, Jenkins N, et al. Assignment of mouse inwardly rectifying potassium channel Kcnj16 to the distal region of mouse chromosome 11. Genomics. 1998;54:181-2 pubmed
  9. Alkema M, Jacobs J, Voncken J, Jenkins N, Copeland N, Satijn D, et al. MPc2, a new murine homolog of the Drosophila polycomb protein is a member of the mouse polycomb transcriptional repressor complex. J Mol Biol. 1997;273:993-1003 pubmed
    ..Ts and Rbt hemizygous mice display anemia and transformations of the axial skeleton reminiscent of phenotypes observed in mice with mutated polycomb or trithorax-group genes, suggesting that MPc2 is a candidate gene for Ts and Rbt. ..
  10. Smith C, Baek S, Sung C, Tallquist M. Epicardial-derived cell epithelial-to-mesenchymal transition and fate specification require PDGF receptor signaling. Circ Res. 2011;108:e15-26 pubmed publisher
    ..Signaling through both PDGF receptors is necessary for epicardial EMT and formation of epicardial-mesenchymal derivatives. PDGF receptors also have independent functions in the development of specific epicardial-derived cell fates. ..
  11. Ai Y, Jenkins N, Copeland N, Gilbert D, Bergsma D, Stambolian D. Mouse galactokinase: isolation, characterization, and location on chromosome 11. Genome Res. 1995;5:53-9 pubmed
    ..The availability of the mouse gene provides an opportunity to make a knockout model for galactokinase deficiency. ..
  12. Schmitt K, Foster J, Feakes R, Knights C, Davis M, Spillett D, et al. Construction of a mouse whole-genome radiation hybrid panel and application to MMU11. Genomics. 1996;34:193-7 pubmed
    ..Our results suggest that whole-genome radiation hybrid technology will be a useful adjunct to mapping the genomes of nonhuman mammalian species. ..
  13. Kim K, Hahm E, Li J, Holbrook L, Sasikumar P, Stanley R, et al. Platelet protein disulfide isomerase is required for thrombus formation but not for hemostasis in mice. Blood. 2013;122:1052-61 pubmed publisher
    b>Protein disulfide isomerase (PDI) derived from intravascular cells is required for thrombus formation. However, it remains unclear whether platelet PDI contributes to the process...
  14. Morris Rosendahl D, Schriever Schwemmer G, Robinson T. Derivation and characterization of a somatic cell hybrid containing the portion of mouse chromosome 11 (MMU11) homologous to human chromosome 17q. J Hered. 1996;87:252-8 pubmed
    ..Loci for D11Mit5, Rpo2-1, Trp53, Glut4, Acrb, and Atplb2 could all be localized proximal to the T16Ad breakpoint in band B5, between bands B1 and B5 on MMU11. ..
  15. Zhou J, Wu Y, Wang L, Rauova L, Hayes V, Poncz M, et al. The C-terminal CGHC motif of protein disulfide isomerase supports thrombosis. J Clin Invest. 2015;125:4391-406 pubmed publisher
    b>Protein disulfide isomerase (PDI) has two distinct CGHC redox-active sites; however, the contribution of these sites during different physiologic reactions, including thrombosis, is unknown...
  16. Helaakoski T, Pajunen L, Kivirikko K, Pihlajaniemi T. Increases in mRNA concentrations of the alpha and beta subunits of prolyl 4-hydroxylase accompany increased gene expression of type IV collagen during differentiation of mouse F9 cells. J Biol Chem. 1990;265:11413-6 pubmed
    ..The F9 cell differentiation system appears to provide a useful model for studies on the regulation of prolyl 4-hydroxylase synthesis. ..
  17. Tamang D, Alves B, Elliott V, Redelman D, Wadhwa R, Fraser S, et al. Regulation of perforin lysis: implications for protein disulfide isomerase proteins. Cell Immunol. 2009;255:82-92 pubmed publisher
    ..Through mass spectrometric analysis of active 50-100 kDa proteins, we identified CxRP2 candidates. Protein disulfide isomerase A3 was the strongest candidate but was unavailable for testing; however, protein disulfide isomerase A1 ..
  18. 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
    ..ERp59/PDI has been identified as the microsomal enzyme protein disulfide isomerase (PDI)...
  19. Haque N, Buchberg A, Khalili K. Isolation and characterization of MRF-1, a brain-derived DNA-binding protein with a capacity to regulate expression of myelin basic protein gene. J Biol Chem. 1994;269:31149-56 pubmed
    ..8, 2.5, and 3.0 kilobases which are expressed in all tissues analyzed. The gene encoding MRF-1 is located on the distal half of mouse chromosome 11 in a region where the human homolog would be predicted to reside on human chromosome 17. ..
  20. Goodchild R, Dauer W. The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein. J Cell Biol. 2005;168:855-62 pubmed
  21. Yang Y, Womack J. Human chromosome 17 comparative anchor loci are conserved on bovine chromosome 19. Genomics. 1995;27:293-7 pubmed
    Eight comparative anchor loci on human chromosome 17, TP53, CHRNB1, THRA1, CRYB1, NF1, MPO, MYL4, and P4HB, were mapped to bovine chromosome 19 using bovine x hamster and bovine x mouse hybrid somatic cell lines...
  22. Valenti G, Quinn H, Heynen G, Lan L, Holland J, Vogel R, et al. Cancer Stem Cells Regulate Cancer-Associated Fibroblasts via Activation of Hedgehog Signaling in Mammary Gland Tumors. Cancer Res. 2017;77:2134-2147 pubmed publisher
    ..Targeting CAFs with Hedgehog inhibitors may offer a novel therapeutic strategy against breast cancer. Cancer Res; 77(8); 2134-47. ©2017 AACR. ..
  23. Rutkowski D, Arnold S, Miller C, Wu J, Li J, Gunnison K, et al. Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLoS Biol. 2006;4:e374 pubmed
    ..It underscores the contribution of posttranscriptional and posttranslational mechanisms in influencing this outcome. ..
  24. de la Chesnaye E, Kerr B, Paredes A, Merchant Larios H, Mendez J, Ojeda S. Fbxw15/Fbxo12J is an F-box protein-encoding gene selectively expressed in oocytes of the mouse ovary. Biol Reprod. 2008;78:714-25 pubmed
    ..The specific expression of Fbxw15/Fbxp12J in oocytes and its developmental pattern of expression suggest a role for this gene in the regulation of oocyte physiology. ..
  25. 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
    ..ER)-localized multiprotein complex that is comprised of the molecular chaperones BiP; GRP94; CaBP1; protein disulfide isomerase (PDI); ERdj3, a recently identified ER Hsp40 cochaperone; cyclophilin B; ERp72; GRP170; UDP-..
  26. Miyaishi O, Kozaki K, Iida K, Isobe K, Hashizume Y, Saga S. Elevated expression of PDI family proteins during differentiation of mouse F9 teratocarcinoma cells. J Cell Biochem. 1998;68:436-45 pubmed
    We investigated the expression of protein disulfide isomerase family proteins (PDI, ERp61, and ERp72) in mouse F9 teratocarcinoma cells during differentiation induced by treatment with retinoic acid and dibutyryl cAMP...
  27. De Maria A, Bassnett S. Birc7: A Late Fiber Gene of the Crystalline Lens. Invest Ophthalmol Vis Sci. 2015;56:4823-34 pubmed publisher
    ..Its expression in cells bordering the OFZ is consistent with a role in organelle degradation, a process in which the ubiquitin proteasome pathway has been implicated previously. ..
  28. Jasuja R, Furie B, Furie B. Endothelium-derived but not platelet-derived protein disulfide isomerase is required for thrombus formation in vivo. Blood. 2010;116:4665-74 pubmed publisher
    b>Protein disulfide isomerase (PDI) catalyzes the oxidation reduction and isomerization of disulfide bonds. We have previously identified an important role for extracellular PDI during thrombus formation in vivo...
  29. Werner P, Raducha M, Prociuk U, Henthorn P, Patterson D. Physical and linkage mapping of human chromosome 17 loci to dog chromosomes 9 and 5. Genomics. 1997;42:74-82 pubmed
    ..were mapped to the centromeric two-thirds of dog chromosome 9 (CFA9), an acrocentric chromosome of medium size: P4HB, GALK1, TK1, GH1, MYL4, BRCA1, RARA, THRA1, MPO, NF1, and CRYBA1...
  30. Helaakoski T, Annunen P, Vuori K, MacNeil I, Pihlajaniemi T, Kivirikko K. Cloning, baculovirus expression, and characterization of a second mouse prolyl 4-hydroxylase alpha-subunit isoform: formation of an alpha 2 beta 2 tetramer with the protein disulfide-isomerase/beta subunit. Proc Natl Acad Sci U S A. 1995;92:4427-31 pubmed
    ..This property may explain why the type II enzyme was not recognized earlier, as an early step in the standard purification procedure for prolyl 4-hydroxylase is affinity chromatography on a poly(L-proline) column. ..
  31. 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
    ..On Th2 cells, galectin-9 binds cell surface protein disulfide isomerase (PDI), increasing retention of PDI on the cell surface and altering the redox status at the plasma ..
  32. Heckler E, Crassous P, Baskaran P, Beuve A. Protein disulfide-isomerase interacts with soluble guanylyl cyclase via a redox-based mechanism and modulates its activity. Biochem J. 2013;452:161-9 pubmed publisher
    ..In our previous work, which identified Hsp (heat-shock protein) 70 as a modulator of sGC, we determined that PDI (protein disulfide-isomerase) bound to an sGC-affinity matrix...
  33. Nomura M, Takihara Y, Shimada K. Isolation and characterization of retinoic acid-inducible cDNA clones in F9 cells: one of the early inducible clones encodes a novel protein sharing several highly homologous regions with a Drosophila polyhomeotic protein. Differentiation. 1994;57:39-50 pubmed
    ..As the Drosophila polyhomeotic gene is involved in regulating morphogenesis, the rae-28 gene may participate in regulating early mammalian development...
  34. Morishige K, Takahashi N, Findlay I, Koyama H, Zanelli J, Peterson C, et al. Molecular cloning, functional expression and localization of an inward rectifier potassium channel in the mouse brain. FEBS Lett. 1993;336:375-80 pubmed
    ..These results provide the first demonstration of the cloning and distribution of an inward rectifier potassium channel from the nervous system. ..
  35. Shirozu M, Tada H, Tashiro K, Nakamura T, Lopez N, Nazarea M, et al. Characterization of novel secreted and membrane proteins isolated by the signal sequence trap method. Genomics. 1996;37:273-80 pubmed
    ..These results indicate that the SST method is effective and useful for the isolation of secreted and membrane proteins without knowledge of their functions. ..
  36. Briquet Laugier V, Xia Y, Rooke K, Mehrabian M, Lusis A, Doolittle M. Mapping of three members of the mouse protein disulfide isomerase family. Mamm Genome. 1998;9:176-7 pubmed
  37. Merte J, Jensen D, Wright K, Sarsfield S, Wang Y, Schekman R, et al. Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure. Nat Cell Biol. 2010;12:41-6; sup pp 1-8 pubmed publisher
    ..Thus, during COPII vesicle formation, Sec24b shows cargo specificity for a core PCP component, Vangl2, of which proper ER-to-Golgi transport is essential for the establishment of PCP, convergent extension and closure of the neural tube. ..
  38. Lan H, Rabaglia M, Schueler K, Mata C, Yandell B, Attie A. Distinguishing covariation from causation in diabetes: a lesson from the protein disulfide isomerase mRNA abundance trait. Diabetes. 2004;53:240-4 pubmed
    b>Protein disulfide isomerase (Pdi) is reported to be an insulin-regulated gene whose expression level is increased in the livers of rats with streptozotocin-induced diabetes...
  39. Ramsdell C, Thames E, Weston J, Dewey M. Development of a deer mouse whole-genome radiation hybrid panel and comparative mapping of Mus chromosome 11 loci. Mamm Genome. 2006;17:37-48 pubmed
    ..Furthermore, this separate linkage group is likely to reside in a chromosomal region of inversion polymorphism between P. maniculatus and P. polionotus. ..