InterPro domain: IPR013122

Polycystic kidney diseases (PKD) are disorders characterised by largenumbers of cysts distributed throughout grossly-enlarged kidneys. Cystdevelopment is associated with impairment of kidney function, and ultimatelykidney failure and death [ 1 ]. Most cases of autosomal dominant PKD result from mutations in the PKD1 gene that cause premature protein termination.

A second gene for autosomal dominant polycystic kidney disease has beenidentified by positional cloning [ 2 ]. The predicted 968-amino acid sequence of the PKD2 gene product (polycystin-2) contains 6 transmembrane domains, with intracellular N- and C-termini. Polycystin-2 shares some similarity with the family of voltage-activated calcium (and sodium) channels, and contains a potential calcium-binding domain.

Polycystin-2 is strongly expressed in ovary, foetal and adult kidney, testis, and small intestine. Polycystin-1 requires the presence of this protein for stable expression and is believed to interact with it via its C terminus. All mutations between exons 1 and 11 result in a truncated polycystin-2 that lacks a calcium-binding EF-hand domain and the cytoplasmic domains required for the interaction of polycystin-2 with polycystin-1 [ 3 ]. PKD2, although clinically milder than PKD1, has a deleterious impact on life expectancy.

This entry contains proteins belonging to the polycystin family including Mucolipin and Polycystin-1 and -2 (PKD1 and PKD2). The domain contains the cation channel region of PKD1 and PKD2 proteins. PKD1 and PKD2 may function through a common signalling pathway that is necessary for normal tubulogenesis. The PKD2 gene product has six transmembrane spans with intracellular amino- and carboxyl-termini [ 4 ].

Mucolipin is a cationic channel which probably plays a role in the endocytic pathway and in the control of membrane trafficking of proteins and lipids. It could play a major role in the calcium ion transport regulating lysosomal exocytosis [ 4 , 5 , 6 ].

1. Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney. Proc. Natl. Acad. Sci. U.S.A. 93, 1524-8
2. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272, 1339-42
3. A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2). Am. J. Hum. Genet. 61, 547-55
4. Cloning of the gene encoding a novel integral membrane protein, mucolipidin-and identification of the two major founder mutations causing mucolipidosis type IV. Am. J. Hum. Genet. 67, 1110-20
5. Identification and characterization of the single channel function of human mucolipin-1 implicated in mucolipidosis type IV, a disorder affecting the lysosomal pathway. FEBS Lett. 532, 183-7
6. Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel. Hum. Mol. Genet. 13, 617-27