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

• A dynamic multimolecular assembly termed the peptide-loading complex (PLC) participates in this process and is composed of MHC class I molecules, calreticulin, ERp57, and tapasin bound to the transporter associated with antigen processing (TAP) peptide transporter [10].
• Screening a MAT-C1 cDNA library with a degenerate oligonucleotide derived from the larger peptide and polymerase chain reaction amplification of cDNA ends permitted the isolation of overlapping cDNAs encoding the 427-amino acid open reading frame of p58 [11].
• 5. This size and charge heterogeneity of p58 did not appear to be due to acylation, glycosylation or phosphorylation [12].
• Evidence for phosphorylation of rat liver glucose-regulated protein 58, GRP58/ERp57/ER-60, induced by fasting and leptin [13].

Anatomical context of Pdia3

• Mixed-disulfide folding intermediates between thyroglobulin and endoplasmic reticulum resident oxidoreductases ERp57 and protein disulfide isomerase [14].
• Chromatography of solubilized hepatic microsomes on Mono Q yielded two peaks, Q-2 and Q-5, which contained all the thiol:protein-disulfide oxidoreductase activity [15].
• Although Q-2 was immunoreactive with a polyclonal antibody to guinea pig, uterine cytosolic PLC, partially purified PLCs from rat liver cytosol did not react to this antibody [15].
• With the use of protease inhibitors, ER-60 protease is shown to be a novel cysteine protease distinct from those of the cytosol and lysosomes [16].
• By Western blot analysis, all fractions contained calnexin, p58, sarcoplasmic reticulum type Ca(2+)-ATPase, and IP3 receptor [17].

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].

References