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

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 amino 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 pre-propeptide. 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.