Human protein disulfide isomerase

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Isomerase

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536 231, 536 232, 536 235, 435 691, 4352523, 4353201, 530350, C12N 990, C07H 2102, C07H 2104, C12P 2106

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057982490

ABSTRACT:
The present invention provides a polynucleotide (pdih) the partial sequence for which was initially isolated from a lung cDNA library and which identifies and encodes a novel human protein disulfide isomerase (PDIH). The invention provides for genetically engineered expression vectors and host cells comprising the nucleic acid sequence encoding PDIH. The invention also provides for the use of purified PDIH and its agonists in the commercial production of recombinant proteins and in pharmaceutical compositions for the treatment of diseases associated with the abnormal expression of PDIH. Additionally, the invention provides for the use of antisense molecules to pdih or inhibitors of PDIH in pharmaceutical compositions for treatment of diseases resulting secretion of PDIH. The invention also describes diagnostic assays which utilize diagnostic compositions comprising the polynucleotide, fragments or the complement thereof, which hybridize with the genomic sequence or the transcript of pdih, or anti-PDIH antibodies which specifically bind to the polypeptide, PDIH.

REFERENCES:
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Tasanen, K., et al., "Promoter of the Gene for the Multifunctional Protein Disulfide Isomerase Polypeptide," The Journal of Biological Chemistry, 267(16):11513-11519 (1992).
LaMantia, M., et al., "Glycosylation site binding protein and protein disulfide isomerase are identical and essential for cell viability in yeast," Proc. Natl. Acad. Sci. USA, 88:4453-4457 (1991).
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Hayano, T., et al., "Molecular cloning of the cDNA encoding a novel protein disulfide isomerase-related protein (PDIR)," FEBS Letters, 372:210-214 (1995).
Wilson, R., et al., "2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans," Nature, 368;32-38 (1994) (GI 1086627).
Shorrosh, B., et al., "Molecular characterization and expression of an alfalfa protein with sequence similarity to mammalian ERp72, a glucose-regulated endoplasmic reticulum protein containing active site sequences of protein disulphide isomerase," The Plant Journal, 2(1)51-58 (1992) (GI 729442).
Hillier, L., et al. (GI 149007) GenBank Sequence Database (Accession N30487) National Center for Biotechnology Information, National Library of Medicine, Bethesda, Maryland 2084.
Edman, J., et al., "Sequence of protein disulphide isomerase and implications of its relationship to thioredoxin," Letters to Nature, 317:267-270 (1985).
Essex, D., et al., "Localization of Protein Disulfide Isomerase to the External Surface of the Platelet Plasma Membrane," Blood, 86(6)2168-2173 (1995).
Terada, K., et al., "Secretion, Surface Localization, Turnover, and Steady State Expression of Protein Disulfide Isomerase in Rat Hepatocytes," The Journal of Biological Chemistry, 270(35)20410-20416 (1995).

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