Group X - Polycystin
Polycystin-1 is a unique, ubiquitously-expressed CTLD-containing protein with 11 predicted transmembrane segments. The N-terminal extracellular portion of polycystin-1 is composed of three tandem leucine-rich repeats flanked by cysteine-rich domains, followed by a WSC (yeast cell wall integrity and stress response component) domain, an immunoglobulin-like polycystic kidney disease (PKD) repeat (first described in this protein), a CTLD, 15 further PKD repeats, a REJ (receptor for egg jelly) domain, and a GPS (G protein-coupled receptor proteolytic site) domain. Cleavage within the last domain leaves the extracellular region tethered at the cell surface and is probably involved in biological activity. The cytoplasmic tail has been implicated in multiple signalling pathways and also features a coiled-coil domain that binds to polycystin-2, a member of the transient receptor potential (TRP) family of cation channels. Heterodimers of polycystin-1 and polycystin-2 function as mechanosensitive calcium channels. Mechanical stimuli also promote intracellular cleavage of polycystin-1, which releases a polypeptide that enters the nucleus and regulates transcription.
Polycystin-1 regulates the cell cycle and the transcription of differentiation-related genes. It is found in cell adhesion and junctional complexes and interacts with extracellular matrix proteins, cell adhesion molecules and cytoskeletal proteins. It is essential during development and probably has a widespread role in cell-cell interactions and in establishing and maintaining epithelial cell differentiation, organization and polarization. In autosomal dominant polycystic kidney disease (ADPKD), a mutation is inherited in one copy of the gene for polycystin-1 (or less commonly polycystin-2), and then loss of heterozygosity occurs in multiple independent somatic mutation events in kidney and other epithelial cells. Each somatic mutation results in the formation of a fluid-filled cyst, but it is not clear how loss of functional polycystin heterodimers leads to cell proliferation.
It is not known if carbohydrate recognition has a role in the function of polycystin-1.
Protein Data Bank structure ID: 1B4R.
