Polycystin 1 (PC1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''PKD1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Mutations of ''PKD1'' are associated with most cases of

autosomal dominant polycystic kidney disease Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening Genetic disorder, inherited human disorders and the most common hereditary kidney disease. It is associated with large interfamilial and intrafamilia ...

, a severe hereditary disorder of the kidneys characterised by the development of renal cysts and severe kidney dysfunction.

Protein structure and function

PC1 is a membrane-bound protein 4303

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

in length expressed largely upon the primary cilium, as well as apical membranes, adherens junctions, and desmosomes. It has 11 transmembrane domains, a large extracellular N-terminal domain, and a short (about 200 amino acid) cytoplasmic C-terminal domain. This intracellular domain contains a coiled-coil domain through which PC1 interacts with polycystin 2 (PC2), a membrane-bound Ca²⁺-permeable ion channel. PC1 has been proposed to act as a G protein–coupled receptor. The C-terminal domain may be cleaved in a number of different ways. In one instance, a ~35 kDa portion of the tail has been found to accumulate in the

cell nucleus The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...

in response to decreased fluid flow in the mouse kidney. In another instance, a 15 kDa fragment may be yielded, interacting with transcriptional activator and co-activator STAT6 and p100, or components of the canonical Wnt signaling pathway in an inhibitory manner. The structure of the human PKD1-PKD2 complex has been solved by cryo-electron microscopy, which showed a 1:3 ratio of PKD1 and PKD2 in the structure. PKD1 consists of a voltage-gated ion channel fold that interacts with PKD2. PC1 mediates mechanosensation of fluid flow by the primary cilium in the renal epithelium and of mechanical deformation of articular cartilage.

Gene

Splice variants encoding different isoforms have been noted for ''PKD1''. The gene is closely linked to six pseudogenes in a known duplicated region on chromosome 16p.

References

External links

GeneReviews/NIH/NCBI/UW entry on Polycystic Kidney Disease, Autosomal Dominant
{{DEFAULTSORT:Pkd1 EF-hand-containing proteins Ion channels