Identification of a cDNA encoding tubulointerstitial nephritis antigen

T. R. Nelson, A. S. Charonis, R S Mc Ivor, R. J. Butkowski

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Tubulointerstitial nephritis antigen (TIN-ag) is a 58-kDa basement membrane glycoprotein that is recognized by human autoantibodies in certain forms of tubulointerstitial nephritis. To further characterize this macromolecule and isolate cDNAs encoding TIN-ag, amino acid sequences from tryptic peptides were used to design and synthesize primers in order to amplify a probe for screening a rabbit kidney cortex cDNA library. A cDNA encoding TIN-ag was cloned and sequenced. The predicted amino acid sequence deduced from this cDNA includes the chemically determined sequences of peptides derived from TIN-ag, supporting its authenticity. The predicted amino acid sequence also shows that the carboxyl-terminal region of the molecule exhibits a 30% homology with human preprocathepsin B, a member of the cysteine proteinase family of proteins. A domain in the amino-terminal region of TIN-ag contains an epidermal growth factor-like motif that shares homology with laminin A and S chains, α1 chain of type I collagen, von Willebrand's factor, and mucin, suggesting structural and perhaps functional similarities among these molecules. Immunoprecipitation of in vitro generated recombinant protein using a TIN-ag-specific monoclonal antibody (A8), confirms the identity of the isolated TIN-ag cDNA. In this report the cDNA and predicted amino acid sequences of TIN-ag are presented. Knowledge of the primary structure of TIN-ag will facilitate our understanding of the molecular structure of this novel basement membrane component and may provide clues toward understanding its functional role.

Original languageEnglish (US)
Pages (from-to)16265-16270
Number of pages6
JournalJournal of Biological Chemistry
Volume270
Issue number27
DOIs
StatePublished - 1995

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