Disease relevance of TINAG

• Tubulointerstitial nephritis antigen (TIN-Ag) is a recently described basement membrane glycoprotein reactive with autoantibodies in some forms of immunologically mediated human tubulointerstitial nephritis [1].
• Role of antibodies to tubulointerstitial nephritis antigen in human anti-tubular basement membrane nephritis associated with membranous nephropathy [2].
• Superinfection with retroviruses carrying wild-type or mutant forms of TIN2, a negative regulator of telomere length, created telomerase-positive, immortal populations with varying average telomere lengths [3].
• Northern blot analysis revealed a single TIN-ag-RP transcript of 2.4 kb in various tissues with the highest transcript levels detected in aorta, heart, placenta, skeletal muscle, kidney, and a colorectal adenocarcinoma cell line [4].

High impact information on TINAG

• Tubulointerstitial nephritis antigen (TIN-ag) is a 58-kDa basement membrane glycoprotein that is recognized by human autoantibodies in certain forms of tubulointerstitial nephritis [5].
• In this report the cDNA and predicted amino acid sequences of TIN-ag are presented [5].
• 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 [5].
• 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 [5].
• 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 [1].

Biological context of TINAG

• This report presents the complete cDNA and predicted amino acid sequences of two human TIN-Ag mRNA species referred to as TIN1 and TIN2 [1].
• Interestingly, uterine smooth muscle cells completely lacked TIN-ag-RP expression, implying a regulated gene expression [4].
• The TIN-ag-RP is encoded in ten exons with introns ranging from 83 bp to 4 kb [6].
• The 12 kb gene was mapped by fluorescence in situ hybridization to chromosome 1p34.2-3, a locus neither related to that of the human TIN-ag (6p11.2-12) nor to that of cathepsin B (8p22-23.1) [6].

Anatomical context of TINAG

• REceptors in proximal tubular epithelial cells for tubulointerstitial nephritis antigen [7].
• In more mature fetal tubules, TIN-ag expression closely resembles that of previously reported observations in mature tissue where it is present in high amounts in the basement membranes of proximal tubules, and to a lesser extent in Bowman's capsule and distal tubules [8].
• TIN-ag is first detected in basement membranes underlying the epithelium of Bowman's capsule of early capillary loop stage glomeruli and the primitive proximal tubule [8].
• TIN antigen is also present in interstitium between tubules and in the periarterial sheath, but not in glomerular basement membrane or mesangial matrix [9].
• Furthermore, human TIN-ag-RP tagged with the T7-epitope, was expressed in HeLa cells, and was found to be localized in vesicular compartments as well as secreted into the medium suggesting the involvement of the endosomal trafficking pathway [6].

Associations of TINAG with chemical compounds

• The EGF motif and part of the region that is homologous with the cysteine proteinase family are removed from the TIN2 cDNA [1].
• Tubulointerstitial nephritis antigen (TIN-ag) is a 58 kDa glycoprotein restricted within the kidney to basement membranes underlying the epithelium of Bowman's capsule and proximal and distal tubules [8].
• Tubulointerstitial nephritis antigen (TIN-ag) is expressed in distinct segments of the developing human nephron [8].
• Immunohistochemically, UUO is associated with increased interstitial collagens I and III, fibronectin, heparan sulfate proteoglycan and tubulointerstitial nephritis antigen [10].

Other interactions of TINAG

• Both approaches suggested that integrins alpha 3 beta 1 and alpha 5 beta 3 are crucial for the adhesion of proximal tubule epithelial cells on TIN-ag, and that they are probably using independent domains of TIN-ag for their action [7].
• BLAST searches revealed the highest degree of homology to several mammalian TIN-ag orthologues, and a weak homology to cathepsin B-like proteases [6].

Analytical, diagnostic and therapeutic context of TINAG

• Immunoprecipitation of in vitro generated recombinant protein using a TIN-ag-specific monoclonal antibody (A8), confirms the identity of the isolated TIN-ag cDNA [5].

References