[PKD1_HUMAN] Involved in renal tubulogenesis. Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). Acts as a regulator of cilium length, together with PKD2 (By similarity). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (By similarity). May be an ion-channel regulator. Involved in adhesive protein-protein and protein-carbohydrate interactions.[35]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Most cases of autosomal dominant polycystic kidney disease (ADPKD) are the result of mutations in the PKD1 gene. The PKD1 gene codes for a large cell-surface glycoprotein, polycystin-1, of unknown function, which, based on its predicted domain structure, may be involved in protein-protein and protein-carbohydrate interactions. Approximately 30% of polycystin-1 consists of 16 copies of a novel protein module called the PKD domain. Here we show that this domain has a beta-sandwich fold. Although this fold is common to a number of cell-surface modules, the PKD domain represents a distinct protein family. The tenth PKD domain of human and Fugu polycystin-1 show extensive conservation of surface residues suggesting that this region could be a ligand-binding site. This structure will allow the likely effects of missense mutations in a large part of the PKD1 gene to be determined.
The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease.,Bycroft M, Bateman A, Clarke J, Hamill SJ, Sandford R, Thomas RL, Chothia C EMBO J. 1999 Jan 15;18(2):297-305. PMID:9889186[36]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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↑Qian F, Boletta A, Bhunia AK, Xu H, Liu L, Ahrabi AK, Watnick TJ, Zhou F, Germino GG. Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16981-6. Epub 2002 Dec 13. PMID:12482949 doi:10.1073/pnas.252484899
↑Bycroft M, Bateman A, Clarke J, Hamill SJ, Sandford R, Thomas RL, Chothia C. The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease. EMBO J. 1999 Jan 15;18(2):297-305. PMID:9889186 doi:10.1093/emboj/18.2.297
