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PKD1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1B4R
Identifiers
Aliases	PKD1, PBP, Pc-1, TRPP1, polycystin 1, transient receptor potential channel interacting, PC1
External IDs	OMIM: 601313; MGI: 97603; HomoloGene: 250; GeneCards: PKD1; OMA:PKD1 - orthologs
Gene location (Human) Chr. Chromosome 16 (human) Band 16p13.3 Start 2,088,708 bp End 2,135,898 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17 A3.3|17 12.4 cM Start 24,549,834 bp End 24,596,508 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum anterior pituitary right frontal lobe gastric mucosa ascending aorta Descending thoracic aorta muscle layer of sigmoid colon body of uterus right coronary artery popliteal artery Top expressed in cerebellar cortex layer of retina neural layer of retina primary visual cortex Hypothalamus superior frontal gyrus islet of Langerhans uterus olfactory bulb striatum of neuraxis More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transmembrane transporter binding protein domain specific binding calcium channel activity protein binding protein kinase binding carbohydrate binding Cellular component cytoplasm integral component of membrane Golgi apparatus cell projection lateral plasma membrane membrane Golgi membrane plasma membrane integral component of plasma membrane cilium cell surface basolateral plasma membrane ciliary membrane Golgi-associated vesicle membrane extracellular exosome nucleus polycystin complex motile cilium Biological process calcium-independent cell-matrix adhesion calcium ion transport regulation of proteasomal protein catabolic process mesonephric tubule development renal system development receptor signaling pathway via JAK-STAT metanephric distal tubule morphogenesis regulation of mitotic spindle organization mesonephric duct development kidney development cytoplasmic sequestering of transcription factor positive regulation of cytosolic calcium ion concentration anatomical structure morphogenesis placenta blood vessel development embryonic placenta development in utero embryonic development response to fluid shear stress genitalia development metanephric ascending thin limb development metanephric proximal tubule development heart development cartilage development regulation of cell adhesion nitrogen compound metabolic process blood vessel development calcium ion transmembrane transport peptidyl-serine phosphorylation lymph vessel morphogenesis neural tube development protein export from nucleus detection of mechanical stimulus establishment of cell polarity spinal cord development metanephric collecting duct development liver development positive regulation of protein binding digestive tract development cell-matrix adhesion lung epithelium development branching morphogenesis of an epithelial tube cartilage condensation positive regulation of transcription by RNA polymerase II skin development homophilic cell adhesion via plasma membrane adhesion molecules cell-cell adhesion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5310 18763 Ensembl ENSG00000008710 ENSMUSG00000032855 UniProt P98161 O08852 RefSeq (mRNA) NM_000296 NM_001009944 NM_013630 RefSeq (protein) NP_000287 NP_001009944 NP_038658 Location (UCSC) Chr 16: 2.09 – 2.14 Mb Chr 17: 24.55 – 24.6 Mb PubMed search
Wikidata
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Polycystin 1 (PC1) is a protein that in humans is encoded by the PKD1 gene. Mutations of PKD1 are associated with most cases of autosomal dominant polycystic kidney disease, 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 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 Ca-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 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

1. ^ GRCh38: Ensembl release 89: ENSG00000008710 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000032855 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millán JL, Gamble V, Harris PC (June 1995). "The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains". Nature Genetics. 10 (2): 151–60. doi:10.1038/ng0695-151. PMID 7663510. S2CID 20636101.
6. "Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium". Cell. 81 (2): 289–98. April 1995. doi:10.1016/0092-8674(95)90339-9. PMID 7736581. S2CID 11114706.
7. Torres VE, Harris PC, Pirson Y (April 2007). "Autosomal dominant polycystic kidney disease". Lancet. 369 (9569): 1287–301. doi:10.1016/S0140-6736(07)60601-1. PMID 17434405. S2CID 1700992.
8. ^ Zhou J (2009). "Polycystins and primary cilia: primers for cell cycle progression". Annual Review of Physiology. 71: 83–113. doi:10.1146/annurev.physiol.70.113006.100621. PMID 19572811.
9. Dalagiorgou G, Basdra EK, Papavassiliou AG (October 2010). "Polycystin-1: function as a mechanosensor". The International Journal of Biochemistry & Cell Biology. 42 (10): 1610–3. doi:10.1016/j.biocel.2010.06.017. PMID 20601082.
10. Trudel M, Yao Q, Qian F (January 2016). "The Role of G-Protein-Coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kidney Disease". Cells. 5 (1): 3. doi:10.3390/cells5010003. PMC 4810088. PMID 26805887.
11. Chauvet V, Tian X, Husson H, Grimm DH, Wang T, Hiesberger T, Hieseberger T, Igarashi P, Bennett AM, Ibraghimov-Beskrovnaya O, Somlo S, Caplan MJ (November 2004). "Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus". The Journal of Clinical Investigation. 114 (10): 1433–43. doi:10.1172/JCI21753. PMC 1052027. PMID 15545994.
12. Low SH, Vasanth S, Larson CH, Mukherjee S, Sharma N, Kinter MT, Kane ME, Obara T, Weimbs T (January 2006). "Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease". Developmental Cell. 10 (1): 57–69. doi:10.1016/j.devcel.2005.12.005. PMID 16399078.
13. Lal M, Song X, Pluznick JL, Di Giovanni V, Merrick DM, Rosenblum ND, Chauvet V, Gottardi CJ, Pei Y, Caplan MJ (October 2008). "Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical Wnt signaling". Human Molecular Genetics. 17 (20): 3105–17. doi:10.1093/hmg/ddn208. PMC 2722884. PMID 18632682.
14. Shi Y, Mei C, Zhou Q, Wang T, Yu S, Lei J, Ge X, Hu F, Su Q (2018-09-07). "Structure of the human PKD1-PKD2 complex". Science. 361 (6406): eaat9819. doi:10.1126/science.aat9819. ISSN 0036-8075. PMID 30093605.
15. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J (February 2003). "Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells". Nature Genetics. 33 (2): 129–37. doi:10.1038/ng1076. PMID 12514735. S2CID 23149223.
16. "Entrez Gene: PKD1 polycystic kidney disease 1 (autosomal dominant)".

External links

• GeneReviews/NIH/NCBI/UW entry on Polycystic Kidney Disease, Autosomal Dominant

• Genes on human chromosome 16
• EF-hand-containing proteins
• Ion channels