Identification of two alternatively spliced forms of human tubulointerstitial nephritis antigen (TIN-Ag)

Bing Zhou, Todd R. Nelson, Clifford Kashtan, Bill Gleason, Alfred F. Michael, Metaxia Vlassi, Aristidis S. Charonis

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Tubulointerstitial nephritis antigen (TIN-Ag) is a recently described basement membrane glycoprotein reactive with autoantibodies in some forms of immunologically mediated human tubulointerstitial nephritis. This report presents the complete cDNA and predicted antino acid sequences of two human TIN-Ag mRNA species referred to as TIN1 and TIN2. Translation through the open reading frames of these clones indicates the presence of a signal peptide and putative prepropeptide. TIN1 additionally contains a characteristic laminin-like epidermal growth factor (EGF) motif and significant homology within the carboxy terminus with the cysteine proteinase family of enzymes. The EGF motif bears important similarities in the positions of cysteines with two motifs in the propeptide of von Willebrand factor. The EGF motif and part of the region that is homologous with the cysteine proteinase family are removed from the TIN2 cDNA. However, the rest of the sequence is identical in these two forms, indicating an alternatively spliced TIN-Ag mRNA product. Both forms contain putative calcium-binding sites. Secondary structure predictions strongly suggest differences between TIN1 and TIN2 leading to the hypothesis that these two forms of TIN-Ag may exhibit differences in their function. Expression studies with appropriate probes demonstrate expression mainly in the kidney and in the intestinal epithelium and lack of expression in other tissues. In the kidney, both TIN1 and TIN2 transcripts are detected, however, TIN1 appears to be the predominant form.

Original languageEnglish (US)
Pages (from-to)658-668
Number of pages11
JournalJournal of the American Society of Nephrology
Volume11
Issue number4
StatePublished - Apr 2000

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