Normal mammals generally excrete only small amounts of protein in the urine, thus avoiding major leakage of proteins from the body. Proteinuria is the most commonly recognized abnormality in renal disease. However, healthy domestic cats (Felis catus) excrete proteins at high concentrations (about 0.5mg/ml) in their urine. We investigated the possible cause of proteinuria in healthy cats, and discovered a 70kDa glycoprotein, which was excreted as a major urinary protein in cat urine, irrespective of gender. To elucidate the biochemical functions and the excretion mechanism of this protein, we cloned the cDNA for this protein from a cat kidney cDNA library. The deduced amino acid sequence shared 47% identity with the rat liver carboxylesterase (EC 126.96.36.199), and both the serine hydrolase active site and the carboxylesterase-specific sequence were conserved. Therefore we named this protein cauxin (carboxylesterase-like urinary excreted protein). In contrast to the mammalian carboxylesterases, most of which are localized within the cells of various organs, cauxin was expressed specifically in the epithelial cells of the distal tubules, and was secreted efficiently into the urine, probably because it lacked the endoplasmic reticulum retention sequence (HDEL). Based on our finding that cauxin is not expressed in the immature cat kidney, we conclude that cauxin is involved in physiological functions that are specific for mature cats. Recently, cauxin-like cDNAs were found from human brain and teratocarcinoma cells. These data suggest that cauxin and cauxin-like human proteins are categorized as a novel group of carboxylesterase multigene family.
- distal tubules
- urinary protein
The nucleotide sequences reported in this paper has been deposited in the DDBJ/EMBL/GenBank Database under the accession number, AB045377.
Abbreviations used: CBB, Coomassie Brilliant Blue R-250; DIG, digoxigenin; ER, endoplasmic reticulum; HRP, horseradish peroxidase; 1-NA, 1-naphthylacetate; p-NPA, p-nitrophenylacetate; ORF, open reading frame; RT-PCR, reverse transcriptase polymerase chain reaction.
- The Biochemical Society, London ©2003