Polycystin 1: Difference between revisions
Jump to navigation
Jump to search
m (Bot: HTTP→HTTPS) |
m (Open access bot: add pmc identifier to citation with #oabot.) |
||
| Line 1: | Line 1: | ||
{{Infobox_gene | {{#invoke:Infobox_gene|getTemplateData|QID=Q14914567}} | ||
== | '''Polycystin 1''' (often abbreviated to '''PC1''') is a [[protein]] that in [[Human|humans]] is encoded by the ''PKD1'' [[gene]] <ref name="pmid7663510">{{cite journal | vauthors = Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millán JL, Gamble V, Harris PC | title = The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains | journal = Nature Genetics | volume = 10 | issue = 2 | pages = 151–60 | date = June 1995 | pmid = 7663510 | doi = 10.1038/ng0695-151 }}</ref><ref name="pmid7736581">{{cite journal | vauthors = | title = Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium | journal = Cell | volume = 81 | issue = 2 | pages = 289–98 | date = April 1995 | pmid = 7736581 | doi = 10.1016/0092-8674(95)90339-9 }}</ref>. Mutations of ''PKD1'' are associated with most cases of [[autosomal dominant polycystic kidney disease]], a severe [[hereditary disorder]] of the [[Kidney|kidneys]] characterised by the development of renal cysts and severe kidney dysfunction <ref name="TP-150518-E20">{{cite journal | vauthors = Torres VE, Harris PC, Pirson Y | title = Autosomal dominant polycystic kidney disease | journal = Lancet | volume = 369 | issue = 9569 | pages = 1287–301 | date = April 2007 | pmid = 17434405 | doi = 10.1016/S0140-6736(07)60601-1 }}</ref>. | ||
== Protein Structure and Function == | |||
[[File:PKD1PKD2 en.png|thumb|150px|left|PC1 interacts with [[polycystin 2]] via a cytoplasmic coiled-coil domain.]] | |||
PC1 is a membrane-bound protein 4303 [[Amino acid|amino acids]] in length expressed largely upon the [[primary cilium]], as well as apical [[Cell membrane|membranes]], [[Adherens junction|adherens junctions]], and [[Desmosome|desmosomes]] <ref name=":0">{{cite journal | vauthors = Zhou J | title = Polycystins and primary cilia: primers for cell cycle progression | journal = Annual Review of Physiology | volume = 71 | pages = 83–113 | date = 2009 | pmid = 19572811 | doi = 10.1146/annurev.physiol.70.113006.100621 }}</ref>. It possesses eleven [[Transmembrane domain|transmembrane domains]], a large extracellular N-terminal domain, and a short (~200 amino acid) [[Cytoplasm|cytoplasmic]] C-terminal domain <ref name=":0" /><ref>{{cite journal | vauthors = Dalagiorgou G, Basdra EK, Papavassiliou AG | title = Polycystin-1: function as a mechanosensor | journal = The International Journal of Biochemistry & Cell Biology | volume = 42 | issue = 10 | pages = 1610–3 | date = October 2010 | pmid = 20601082 | doi = 10.1016/j.biocel.2010.06.017 | url = http://linkinghub.elsevier.com/retrieve/pii/S1357272510002268 }}</ref>. This intracellular domain contains a coiled-coil domain through which PC1 interacts with [[polycystin 2]] (PC2), a membrane-bound Ca<sup>2+</sup>-permeable [[ion channel]]. | |||
[[ | PC1 has been proposed to act as a [[G protein–coupled receptor]] <ref name=":0" /><ref>{{cite journal | vauthors = Trudel M, Yao Q, Qian F | title = The Role of G-Protein-Coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kidney Disease | journal = Cells | volume = 5 | issue = 1 | pages = 3 | date = January 2016 | pmid = 26805887 | doi = 10.3390/cells5010003 | url = http://www.mdpi.com/2073-4409/5/1/3 }}</ref>. 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 <ref>{{cite journal | vauthors = 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 | title = Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus | journal = The Journal of Clinical Investigation | volume = 114 | issue = 10 | pages = 1433–43 | date = November 2004 | pmid = 15545994 | doi = 10.1172/JCI21753 | pmc = 1052027 }}</ref>. 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 <ref>{{cite journal | vauthors = Low SH, Vasanth S, Larson CH, Mukherjee S, Sharma N, Kinter MT, Kane ME, Obara T, Weimbs T | title = Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease | journal = Developmental Cell | volume = 10 | issue = 1 | pages = 57–69 | date = January 2006 | pmid = 16399078 | doi = 10.1016/j.devcel.2005.12.005 }}</ref><ref>{{cite journal | vauthors = Lal M, Song X, Pluznick JL, Di Giovanni V, Merrick DM, Rosenblum ND, Chauvet V, Gottardi CJ, Pei Y, Caplan MJ | title = Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical Wnt signaling | journal = Human Molecular Genetics | volume = 17 | issue = 20 | pages = 3105–17 | date = October 2008 | pmid = 18632682 | pmc = 2722884 | doi = 10.1093/hmg/ddn208 }}</ref>. | ||
{{ | Evidence suggests that PC1 mediates [[mechanosensation]] of fluid flow by the primary cilium in the renal epithelium and of mechanical deformation of articular cartilage <ref>{{cite journal | vauthors = Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J | title = Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells | language = En | journal = Nature Genetics | volume = 33 | issue = 2 | pages = 129–37 | date = February 2003 | pmid = 12514735 | doi = 10.1038/ng1076 | url = http://www.nature.com/articles/ng1076 }}</ref>. | ||
=== | == Gene == | ||
Splice variants encoding different isoforms have been noted for ''PKD1''. The gene is closely linked to six [[pseudogene]]s in a known duplicated region on chromosome 16p.<ref>{{cite web | title = Entrez Gene: PKD1 polycystic kidney disease 1 (autosomal dominant)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5310| access-date = }}</ref> | |||
== | == References == | ||
{{Reflist}} | {{Reflist}} | ||
== External links == | == External links == | ||
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=pkd-ad GeneReviews/NIH/NCBI/UW entry on Polycystic Kidney Disease, Autosomal Dominant] | * [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=pkd-ad GeneReviews/NIH/NCBI/UW entry on Polycystic Kidney Disease, Autosomal Dominant] | ||
| Line 38: | Line 25: | ||
{{Ciliary proteins}} | {{Ciliary proteins}} | ||
{{Transient receptor potential channel modulators}} | {{Transient receptor potential channel modulators}} | ||
{{DEFAULTSORT:Pkd1}} | {{DEFAULTSORT:Pkd1}} | ||
[[Category:EF-hand-containing proteins]] | [[Category:EF-hand-containing proteins]] | ||
[[Category:Ion channels]] | [[Category:Ion channels]] | ||
Revision as of 18:32, 15 May 2018
| VALUE_ERROR (nil) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Aliases | |||||||
| External IDs | GeneCards: [1] | ||||||
| Orthologs | |||||||
| Species | Human | Mouse | |||||
| Entrez |
|
| |||||
| Ensembl |
|
| |||||
| UniProt |
|
| |||||
| RefSeq (mRNA) |
|
| |||||
| RefSeq (protein) |
|
| |||||
| Location (UCSC) | n/a | n/a | |||||
| PubMed search | n/a | n/a | |||||
| Wikidata | |||||||
| |||||||
Polycystin 1 (often abbreviated to PC1) is a protein that in humans is encoded by the PKD1 gene [1][2]. 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 [3].
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 [4]. It possesses eleven transmembrane domains, a large extracellular N-terminal domain, and a short (~200 amino acid) cytoplasmic C-terminal domain [4][5]. 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 [4][6]. 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 [7]. 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 [8][9].
Evidence suggests that PC1 mediates mechanosensation of fluid flow by the primary cilium in the renal epithelium and of mechanical deformation of articular cartilage [10].
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.[11]
References
- ↑ 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.
- ↑ "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.
- ↑ 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.
- ↑ 4.0 4.1 4.2 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.
- ↑ 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.
- ↑ 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. PMID 26805887.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ "Entrez Gene: PKD1 polycystic kidney disease 1 (autosomal dominant)".
