Structure, chromosomal assignment, and expression of the gene for proteinase-3. The Wegener's granulomatosis autoantigen.

摘要: Proteinase-3 (PR-3) is a neutral serine proteinase present in the azurophil granules of human polymorphonuclear leukocytes. It degrades variety extracellular matrix proteins including elastin vitro and causes emphysema when administered by tracheal insufflation to hamsters. identical target autoantigen (c-ANCA) associated with Wegener's granulomatosis myeloblastin, first identified HL-60 leukemia cells. In this study, gene encoding PR-3 was cloned sequenced. The spans approximately 6.5 kilobase pairs consists five exons four introns. genomic organization similar that other proteinases expressed hemopoietic Each residue catalytic triad located on separate exon, positions residues within are those leukocyte elastase cathepsin G. phase placement introns also 400-base pair (bp) 5‘-flanking sequence contains TATA box at position 379. There no CAAT promoter element. 3‘-untranslated region 200 bp, extending from TGA stop codon site polyadenylation 10 bp after canonical AATAAA signal. Amplification human/hamster hybrid cell line localizes chromosome 19. Evidence Northern analysis suggests expression primarily confined promyelocytic/myelocytic stage bone marrow development.