The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Pdia3  -  protein disulfide isomerase family A,...

Rattus norvegicus

Synonyms: 58 kDa glucose-regulated protein, 58 kDa microsomal protein, Disulfide isomerase ER-60, ER protein 57, ER protein 60, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Pdia3

  • The human ER-60 protease cDNA was expressed in Escherichia coli BL21 (DE3) cells using the pET-20b(+) T7 promoter [1].
  • COPI is recruited onto pre-Golgi intermediates where it initiates segregation of the anterograde transported protein vesicular stomatitis virus glycoprotein (VSV-G) from the retrograde transported protein p58, a protein which actively recycles between the ER and pre-Golgi intermediates [2].
  • Antibody against p58 surface antigen of RA-2 rat rhabdomyosarcoma cells inhibits their metastatic activity [3].
  • The data indicate that masking of p58 surface antigen by antibodies could make RA-2 cells unable to form experimental metastases in lung [3].
  • 4. The elevated efficacy of clonazepam (CNZ) in NRT neurons relative to thalamic and cortical neurons, particularly in neurons isolated from adult (> p58) rats, is consistent with the anticonvulsant profile of this drug in controlling Generalized Absence epilepsy [4].

High impact information on Pdia3

  • HIP-70: a protein induced by estrogen in the brain and LH-RH in the pituitary [5].
  • Our results suggest that ERp57 modulates the redox state of ER facing thiols in SERCA 2b in a Ca2+-dependent manner, providing dynamic control of ER Ca2+ homeostasis [6].
  • Here we present evidence that this antibody arrests the anterograde transport of vesicular stomatitis virus glycoprotein and leads to the accumulation of p58 in pre-Golgi intermediates [7].
  • In nuclear pores p62 forms a tight complex with at least two other proteins, p58 and p54, which can be extracted from isolated rat liver nuclei (Finlay, D. R., E. Meier, P. Bradley, J. Horecka, and D. J. Forbes. 1991. J. Cell Biol. 114:169-183) [8].
  • Both proteins are retained in the Golgi complex at 20 degrees C and in the IC at 15 degrees C. Incubation of cells with BFA results in relocation of gp74 to p58 positive IC elements [9].

Biological context of Pdia3


Anatomical context of Pdia3


Associations of Pdia3 with chemical compounds

  • Previously, ER60 was identified as a cysteine protease and named ER-60 protease (Urade, R., Nasu, M., Moriyama, T., Wada, K., and Kito, M. (1992) J. Biol. Chem. 267, 15152-15159; Urade, R., and Kito, M. (1992) FEBS Lett. 312, 83-86) [18].
  • As with soluble proteins, the binding of ERp57 to an integral membrane protein is dependent upon the protein bearing an N-glycan that has undergone glucose trimming [19].
  • A subset of these luminal components are specific for glycoproteins, and, like calnexin and calreticulin, the thiol-dependent reductase ERp57 has been shown to interact specifically with soluble secretory proteins bearing N-linked carbohydrate [19].
  • We propose that ERp57 acts in concert with calnexin and calreticulin to modulate glycoprotein folding and enforce the glycoprotein specific quality control mechanism operating in the endoplasmic reticulum [19].
  • A protein (ER60) with sequence similarity to phosphoinositide-specific phospholipase C-alpha purified from rat liver endoplasmic reticulum (ER) degraded ER resident proteins and is really a protease [(1992) J. Biol. Chem. 265, 15152-15159] [16].

Other interactions of Pdia3

  • We further demonstrated that the residues 225-251 at the tip of the CRT P-domain are involved in direct contacts with ERp57 [20].
  • Under experimental conditions when the intermediate compartment marker p58 was retained in peripheral sites, endomannosidase was redistributed to the Golgi apparatus [21].
  • These were heat shock proteins, HSP-60 and HSP-70, protein disulfide isomerase, and protein disulfide isomerase isozyme Q-2 [22].
  • Apolipoprotein B is intracellularly associated with an ER-60 protease homologue in HepG2 cells [23].
  • Among the hepatic proteins affected by ethanol, the concomitant supplementation with folic acid to alcoholic mother rats prevented EF-2, RhoGDI-1, ER-60 protease, and gelsolin depletion [24].

Analytical, diagnostic and therapeutic context of Pdia3

  • Isothermal titration microcalorimetry (ITC) now showed affinity of this fragment for ERp57 similar to that of the intact P-domain, demonstrating that CRT(221-256) may be used as a low molecular mass mimic of CRT for further investigations of the interaction with ERp57 [20].
  • The recombinant ER-60 protease was obtained in a water-soluble form and purified through four sequential chromatographies [1].
  • Evidence from co-immunoprecipitation and cross-linking experiments appear to suggest that the ER-60 homologue in HepG2 cells is associated with apoB intracellularly [23].
  • Cross-linking and immunoblotting experiments suggested the association of the 78-kDa BiP with both the 58-kDa ER-60 homologue as well as the 550-kDa apoB [23].
  • Immunofluorescence microscopy of normal rat kidney (NRK) and mouse myeloma cells showed the association of the protein with the Golgi complex and peripheral sites where it colocalized with p58, a pre- and cis-Golgi marker protein [25].


  1. Functions of characteristic Cys-Gly-His-Cys (CGHC) and Gln-Glu-Asp-Leu (QEDL) motifs of microsomal ER-60 protease. Urade, R., Oda, T., Ito, H., Moriyama, T., Utsumi, S., Kito, M. J. Biochem. (1997) [Pubmed]
  2. Sequential coupling between COPII and COPI vesicle coats in endoplasmic reticulum to Golgi transport. Aridor, M., Bannykh, S.I., Rowe, T., Balch, W.E. J. Cell Biol. (1995) [Pubmed]
  3. Antibody against p58 surface antigen of RA-2 rat rhabdomyosarcoma cells inhibits their metastatic activity. Guzhova, I.V., Margulis, B.A., Kaminskaya, E.V. Int. J. Cancer (1992) [Pubmed]
  4. GABAA receptor function in developing rat thalamic reticular neurons: whole cell recordings of GABA-mediated currents and modulation by clonazepam. Gibbs, J.W., Schroder, G.B., Coulter, D.A. J. Neurophysiol. (1996) [Pubmed]
  5. HIP-70: a protein induced by estrogen in the brain and LH-RH in the pituitary. Mobbs, C.V., Fink, G., Pfaff, D.W. Science (1990) [Pubmed]
  6. Ca2+-dependent redox modulation of SERCA 2b by ERp57. Li, Y., Camacho, P. J. Cell Biol. (2004) [Pubmed]
  7. p53/58 binds COPI and is required for selective transport through the early secretory pathway. Tisdale, E.J., Plutner, H., Matteson, J., Balch, W.E. J. Cell Biol. (1997) [Pubmed]
  8. Macromolecular interactions in the nucleoporin p62 complex of rat nuclear pores: binding of nucleoporin p54 to the rod domain of p62. Buss, F., Stewart, M. J. Cell Biol. (1995) [Pubmed]
  9. gp74 a membrane glycoprotein of the cis-Golgi network that cycles through the endoplasmic reticulum and intermediate compartment. Alcalde, J., Egea, G., Sandoval, I.V. J. Cell Biol. (1994) [Pubmed]
  10. Competition for access to the rat major histocompatibility complex class I peptide-loading complex reveals optimization of peptide cargo in the absence of transporter associated with antigen processing (TAP) association. Ford, S., Antoniou, A., Butcher, G.W., Powis, S.J. J. Biol. Chem. (2004) [Pubmed]
  11. Molecular cloning and sequencing of a 58-kDa membrane- and microfilament-associated protein from ascites tumor cell microvilli with sequence similarities to retroviral Gag proteins. Juang, S.H., Huang, J., Li, Y., Salas, P.J., Fregien, N., Carraway, C.A., Carraway, K.L. J. Biol. Chem. (1994) [Pubmed]
  12. Characterization of a 58 kDa cis-Golgi protein in pancreatic exocrine cells. Lahtinen, U., Dahllöf, B., Saraste, J. J. Cell. Sci. (1992) [Pubmed]
  13. Evidence for phosphorylation of rat liver glucose-regulated protein 58, GRP58/ERp57/ER-60, induced by fasting and leptin. Kita, K., Okumura, N., Takao, T., Watanabe, M., Matsubara, T., Nishimura, O., Nagai, K. FEBS Lett. (2006) [Pubmed]
  14. Mixed-disulfide folding intermediates between thyroglobulin and endoplasmic reticulum resident oxidoreductases ERp57 and protein disulfide isomerase. Di Jeso, B., Park, Y.N., Ulianich, L., Treglia, A.S., Urbanas, M.L., High, S., Arvan, P. Mol. Cell. Biol. (2005) [Pubmed]
  15. Purification and characterization of a new isozyme of thiol:protein-disulfide oxidoreductase from rat hepatic microsomes. Relationship of this isozyme to cytosolic phosphatidylinositol-specific phospholipase C form 1A. Srivastava, S.P., Chen, N.Q., Liu, Y.X., Holtzman, J.L. J. Biol. Chem. (1991) [Pubmed]
  16. Inhibition by acidic phospholipids of protein degradation by ER-60 protease, a novel cysteine protease, of endoplasmic reticulum. Urade, R., Kito, M. FEBS Lett. (1992) [Pubmed]
  17. Isolation of subcellular agonist-sensitive calcium stores from the pancreatic acinar cell. Pandol, S.J., Fitzsimmons, T., Schoeffield-Payne, M., Carlile, G.W., Evans, W.H. Cell Calcium (1995) [Pubmed]
  18. Protein degradation by ERp72 from rat and mouse liver endoplasmic reticulum. Urade, R., Takenaka, Y., Kito, M. J. Biol. Chem. (1993) [Pubmed]
  19. The thiol-dependent reductase ERp57 interacts specifically with N-glycosylated integral membrane proteins. Elliott, J.G., Oliver, J.D., High, S. J. Biol. Chem. (1997) [Pubmed]
  20. NMR structures of 36 and 73-residue fragments of the calreticulin P-domain. Ellgaard, L., Bettendorff, P., Braun, D., Herrmann, T., Fiorito, F., Jelesarov, I., Güntert, P., Helenius, A., Wüthrich, K. J. Mol. Biol. (2002) [Pubmed]
  21. Golgi apparatus immunolocalization of endomannosidase suggests post-endoplasmic reticulum glucose trimming: implications for quality control. Zuber, C., Spiro, M.J., Guhl, B., Spiro, R.G., Roth, J. Mol. Biol. Cell (2000) [Pubmed]
  22. Components of the protein synthesis and folding machinery are induced in vascular smooth muscle cells by hypertrophic and hyperplastic agents. Identification by comparative protein phenotyping and microsequencing. Patton, W.F., Erdjument-Bromage, H., Marks, A.R., Tempst, P., Taubman, M.B. J. Biol. Chem. (1995) [Pubmed]
  23. Apolipoprotein B is intracellularly associated with an ER-60 protease homologue in HepG2 cells. Adeli, K., Macri, J., Mohammadi, A., Kito, M., Urade, R., Cavallo, D. J. Biol. Chem. (1997) [Pubmed]
  24. Effect of prenatal exposure to ethanol on hepatic elongation factor-2 and proteome in 21 d old rats: protective effect of folic acid. García-Rodríguez, S., Argüelles, S., Llopis, R., Murillo, M.L., Machado, A., Carreras, O., Ayala, A. Free Radic. Biol. Med. (2003) [Pubmed]
  25. Localization of the small GTP-binding protein rab1p to early compartments of the secretory pathway. Saraste, J., Lahtinen, U., Goud, B. J. Cell. Sci. (1995) [Pubmed]
WikiGenes - Universities