Disease relevance of ERP29

• In human hepatoma cells, ERp29 mRNA expression was not increased by stresses (tunicamycin, calcium ionophore) that induced other reticuloplasmins [1].
• In in vitro experiments, ERp28 and calnexin precipitate with overexpressed, wild-type hepatitis B small surface antigen and with a mutated ER-retained form [2].
• We have demonstrated previously that ERp29 induces the local unfolding of polyomavirus in the ER, a step required for viral infection [3].

High impact information on ERP29

• These results indicate that dimerization of ERp29 is crucial for its protein unfolding function [3].
• Recently we characterised a novel 29 kDa endoplasmic reticulum protein that is widely expressed in rat tissues, and named it ERp29 [4].
• Consequent links established to human genome and proteome projects showed that ERp29 is encoded by a gene on chromosome 12 that is expressed universally in human tissues [4].
• Investigations of ERp29 function in human health and disease should benefit from the integrated links between genome, proteome and murine model organisms established here [4].
• Such characteristics of the promoter as GC-rich sequence, absence of TATA-box, multiple transcription start sites taken together with the ubiquitous gene expression, reaching maximum levels in the specialized secretory tissues, indicate that ERp29 belongs to the group of the constitutively expressed housekeeping genes [5].

Chemical compound and disease context of ERP29

• In rat hepatoma cells ERp29 was found to be associated with the abundant molecular chaperone/stress protein BiP/GRP78 and this interaction was significantly enhanced after treatment with tunicamycin and A23187 [6].
• ERp29 was induced to high levels in the rat hepatoma cells under metabolic stress conditions known to cause an aberrant accumulation of proteins in the ER [(e.g. culture in presence of the Ca2+ ionophore A23187, inhibitors of Ca2+-ATPase (thapsigargin), intracellular protein transport (brefeldin A), or protein N-glycosylation (tunicamycin)] [6].

Biological context of ERP29

• These clues indicated that the ERp29 precursor, perhaps related to secretory protein synthesis and absorbed by spermatozoa, may play a vital role in sperm maturation during the epididymal transit, particularly, in the sperm/organelle membrane [7].
• ERp29 shares a common predecessor with PDI; however in the course of divergent evolution it has lost a hallmark active site motif of redox enzymes but retained the characteristic structural fold in one of its domains [8].

Anatomical context of ERP29

• ERp29 is a soluble protein localized in the endoplasmic reticulum (ER) of eukaryotic cells, which is conserved in all mammalian species [5].
• ERp29 was localized exclusively to the ER/nuclear envelope of MDCK cells using confocal immunocytochemistry and comparative markers of the ER lumen, ER/Golgi membrane, nuclei, and mitochondria [9].
• Current work is an attempt to substantiate this assumption by answering the question whether the secretion of Tg can be regulated through the manipulation of ERp29 expression in the FRTL-5 rat thyroid cells [10].
• Identification and characterization of ERp29 in rat spermatozoa during epididymal transit [7].
• Furthermore, the results from immunofluorescence-stained epididymal frozen sections demonstrated that ERp29 was localized in cytoplasm of epididymal epithelia, and the fluorescence intensity was significantly higher in the caudal epididymis than in the caput [7].

Associations of ERP29 with chemical compounds

• In contrast to Ig-heavy-chain-binding protein, human ERp28 is not induced by metabolic stress (tunicamycin) [2].
• The effect of TSH on the ERp29 gene expression was specific, while other growth factors (transferrin, insulin and hydrocortisone) did not alter its expression [11].
• Ubiquinol-cytochrome C reductase complex core protein I, adenine phosphoribosyl transferase and endoplasmic reticulum protein hERp29 showed decreased levels after irradiation or arsenite treatment, but not after the combined exposure [12].

Other interactions of ERP29

• This indicates that ERp28, as calnexin, may be involved in the processing of secretory proteins within the ER [2].
• Thioredoxin fold as homodimerization module in the putative chaperone ERp29: NMR structures of the domains and experimental model of the 51 kDa dimer [13].

Analytical, diagnostic and therapeutic context of ERP29

• Molecular cloning of ERp29, a novel and widely expressed resident of the endoplasmic reticulum [1].
• ERp29 constitutes about 0.1% of the rat hepatic microsomal proteins and is constitutively expressed in all rat tissues examined, as evident from northern blot analysis [6].
• Western blot analysis also revealed that ERp29 precursor, from both whole spermatozoa and membrane proteins, increased significantly as the sperm underwent epididymal maturation [7].
• Its secondary structure was studied by circular dichroism (CD), Fourier transformed infrared spectroscopy (FTIR) and Raman spectroscopy and it was found that human ERp29 comprises significant alpha-helical structure [14].
• Finally, using indirect immunofluorescence, we demonstrated that localization of one of these seven proteins, the endoplasmic reticulum protein (ERp29) precursor, which was first reported in mammalian spermatozoa, was apparently up-regulated as the sperm underwent epididymal maturation and expressed mainly on caudal sperm [7].

References