Protein-coding gene in the species Homo sapiens
| AVPR2 |
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| Available structures |
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| PDB | Ortholog search: PDBe RCSB |
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| Identifiers |
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| Aliases | AVPR2, ADHR, DI1, DIR, DIR3, NDI, V2R, arginine vasopressin receptor 2, NDI1 |
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| External IDs | OMIM: 300538; MGI: 88123; HomoloGene: 20064; GeneCards: AVPR2; OMA:AVPR2 - orthologs |
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| Gene location (Human) |
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 | | Chr. | X chromosome (human)[1] |
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| | Band | Xq28 | Start | 153,902,531 bp[1] |
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| End | 153,907,166 bp[1] |
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| Gene location (Mouse) |
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 | | Chr. | X chromosome (mouse)[2] |
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| | Band | X A7.3|X 37.46 cM | Start | 72,935,708 bp[2] |
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| End | 72,939,108 bp[2] |
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| RNA expression pattern |
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| Bgee | | Human | Mouse (ortholog) |
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| Top expressed in | - apex of heart
- subcutaneous adipose tissue
- left ventricle
- granulocyte
- vena cava
- human kidney
- muscle of thigh
- left uterine tube
- gastrocnemius muscle
- right auricle
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| | Top expressed in | - right kidney
- granulocyte
- human kidney
- medullary collecting duct
- embryo
- choroid plexus of fourth ventricle
- Ileal epithelium
- CA3 field
- thymus
- primary motor cortex
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| | More reference expression data |
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| BioGPS | |
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| Gene ontology |
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| Molecular function | - G protein-coupled receptor activity
- peptide binding
- signal transducer activity
- protein binding
- vasopressin receptor activity
| | Cellular component | - integral component of membrane
- endosome
- Golgi apparatus
- membrane
- plasma membrane
- integral component of plasma membrane
- endoplasmic reticulum
- clathrin-coated vesicle membrane
| | Biological process | - hemostasis
- excretion
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway
- regulation of systemic arterial blood pressure by vasopressin
- activation of adenylate cyclase activity
- response to peptide
- cellular response to hormone stimulus
- positive regulation of vasoconstriction
- renal water homeostasis
- positive regulation of protein ubiquitination
- signal transduction
- membrane organization
- G protein-coupled receptor signaling pathway
- positive regulation of gene expression
- positive regulation of systemic arterial blood pressure
- I-kappaB kinase/NF-kappaB signaling
- positive regulation of cell population proliferation
- telencephalon development
- response to cytokine
- negative regulation of urine volume
- negative regulation of renal sodium excretion
- positive regulation of blood pressure
| | Sources:Amigo / QuickGO |
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| Orthologs |
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| Species | Human | Mouse |
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| Entrez | | |
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| Ensembl | | |
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| UniProt | | |
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| RefSeq (mRNA) | | |
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NM_001276298
NM_001276299
NM_019404 |
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| RefSeq (protein) | | |
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NP_001263227
NP_001263228
NP_062277 |
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| Location (UCSC) | Chr X: 153.9 – 153.91 Mb | Chr X: 72.94 – 72.94 Mb |
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| PubMed search | [3] | [4] |
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| Wikidata |
| View/Edit Human | View/Edit Mouse |
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Vasopressin receptor 2 (V2R), or arginine vasopressin receptor 2 (officially called AVPR2), is a protein that acts as receptor for vasopressin.[5] AVPR2 belongs to the subfamily of G-protein-coupled receptors. Its activity is mediated by the Gs type of G proteins, which stimulate adenylate cyclase.
AVPR2 is expressed in the kidney tubule, predominantly in the membrane of cells of the distal convoluted tubule and collecting ducts, in fetal lung tissue and lung cancer, the last two being associated with alternative splicing. AVPR2 is also expressed outside the kidney in vascular endothelium.[6] Stimulation causes the release of von Willebrand factor and factor VIII from the endothelial cells.[6] Because von Willebrand factor helps stabilize circulating levels of factor VIII, the vasopressin analog desmopressin can be used to stimulate the AVPR2 receptor and increase levels of circulating factor VIII. This is useful in the treatment of hemophilia A as well as Von Willebrand disease.
In the kidney, AVPR2's primary property is to respond to arginine vasopressin by stimulating mechanisms that concentrate the urine and maintain water homeostasis in the organism. When the function of AVPR2 is lost, the disease nephrogenic diabetes insipidus (NDI) results.
Antagonists
Vasopressin receptor antagonists that are selective for the V2 receptor include:
Their main uses are in hyponatremia, such as that caused by syndrome of inappropriate antidiuretic hormone (SIADH) and heart failure, however these agents should be avoided in patients with cirrhosis.[7]
Demeclocycline and lithium carbonate act as indirect antagonists of renal vasopressin V2 receptors by inhibiting activation of the second messenger cascade of the receptors.[8][9]
Pharmacoperones
Vasopressin receptor 2 function has been shown to be deleteriously effected by point mutations in its gene. Some of these mutations, when expressed, cause the receptor to remain in the cytosol. An approach to rescue receptor function utilizes pharmacoperones or molecular chaperones, which are typically small molecules that rescue misfolded proteins to the cell surface. These interact with the receptor to restore cognate receptor function devoid of antagonist or agonist activity. This approach, when effective, should increase therapeutic reach. Pharmacoperones have been identified that restore function of V2R.[10][11][12][13]
Interactions
Arginine vasopressin receptor 2 has been shown to interact with C1QTNF1.[14]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000126895 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031390 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ van den Ouweland AM, Knoop MT, Knoers VV, Markslag PW, Rocchi M, Warren ST, Ropers HH, Fahrenholz F, Monnens LA, van Oost BA (Aug 1992). "Colocalization of the gene for nephrogenic diabetes insipidus (DIR) and the vasopressin type 2 receptor gene (AVPR2) in the Xq28 region". Genomics. 13 (4): 1350–2. doi:10.1016/0888-7543(92)90067-3. PMID 1324225.
- ^ a b Jackson EK (2018). "Drugs Affecting Renal Excretory Function". In: Brunton LL, Hilal-Dandan R, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e New York, NY: McGraw-Hill.
- ^ "SAMSCA (tolvaptan) prescribing information" (PDF). US Food and Drug Administration.
- ^ Ajay K. Singh, Gordon H. Williams (12 January 2009). Textbook of Nephro-Endocrinology. Academic Press. pp. 250–251. ISBN 978-0-08-092046-7.
- ^ L. Kovács, B. Lichardus (6 December 2012). Vasopressin: Disturbed Secretion and Its Effects. Springer Science & Business Media. pp. 179–180. ISBN 978-94-009-0449-1.
- ^ Janovick JA, Spicer TP, Bannister TD, Smith E, Ganapathy V, Scampavia L (September 2018). "Chemical validation and optimization of pharmacoperones targeting vasopressin type 2 receptor mutant". Biochemical Journal. 475 (18): 2941–2953. doi:10.1042/BCJ20180065. PMID 30068530. S2CID 51894840.
- ^ Janovick JA, Spicer TP, Smith E, Bannister T, Kenakin T, Scampavia L, Conn PM (October 2016). "Receptor antagonism/agonism can be uncoupled from pharmacoperone activity". Molecular and Cellular Endocrinology. 434: 176–185. doi:10.1016/j.mce.2016.07.003. PMC 4983495. PMID 27389877.
- ^ Smith E, Janovick JA, Bannister T, Shumate J, Scampavia L, Conn PM (September 2016). "Identification of Potential Pharmacoperones Capable of Rescuing the Functionality of Misfolded Vasopressin 2 Receptor Involved in Nephrogenic Diabetes Insipidus". SLAS Discovery. 21 (8): 824–831. doi:10.1177/1087057116653925. PMC 5594746. PMID 27280550.
- ^ Conn PM, Smith E, Hodder P, Janovick JA, Smithson D (September 2013). "High-throughput screen for pharmacoperones of the vasopressin type 2 receptor". SLAS Discovery. 18 (8): 930–937. doi:10.1177/1087057113483559. PMC 3735853. PMID 23640875.
- ^ Innamorati G, Whang MI, Molteni R, Le Gouill C, Birnbaumer M (Nov 2002). "GIP, a G-protein-coupled receptor interacting protein". Regulatory Peptides. 109 (1–3): 173–9. doi:10.1016/S0167-0115(02)00201-X. PMID 12409230. S2CID 30853177.
Further reading
- Birnbaumer M (Aug 2001). "The V2 vasopressin receptor mutations and fluid homeostasis". Cardiovascular Research. 51 (3): 409–15. doi:10.1016/S0008-6363(01)00337-6. PMID 11476731.
- Ishikawa SE (Feb 2002). "[Nephrogenic diabetes insipidus associated with mutations of vasopressin V2 receptors and aquaporin-2]". Nihon Rinsho. Japanese Journal of Clinical Medicine. 60 (2): 350–5. PMID 11857925.
- Thibonnier M, Coles P, Thibonnier A, Shoham M (2002). "Chapter 14 Molecular pharmacology and modeling of vasopressin receptors". Vasopressin and Oxytocin: From Genes to Clinical Applications. Progress in Brain Research. Vol. 139. pp. 179–96. doi:10.1016/S0079-6123(02)39016-2. ISBN 9780444509826. PMID 12436935.
- Bichet DG (Apr 2006). "Nephrogenic diabetes insipidus". Advances in Chronic Kidney Disease. 13 (2): 96–104. doi:10.1053/j.ackd.2006.01.006. PMID 16580609.
- Robben JH, Knoers NV, Deen PM (Aug 2006). "Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus" (PDF). American Journal of Physiology. Renal Physiology. 291 (2): F257–70. doi:10.1152/ajprenal.00491.2005. hdl:2066/50267. PMID 16825342. S2CID 15392.
- Pan Y, Metzenberg A, Das S, Jing B, Gitschier J (Oct 1992). "Mutations in the V2 vasopressin receptor gene are associated with X-linked nephrogenic diabetes insipidus". Nature Genetics. 2 (2): 103–6. doi:10.1038/ng1092-103. PMID 1303257. S2CID 26492862.
- van den Ouweland AM, Dreesen JC, Verdijk M, Knoers NV, Monnens LA, Rocchi M, van Oost BA (Oct 1992). "Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus". Nature Genetics. 2 (2): 99–102. doi:10.1038/ng1092-99. PMID 1303271. S2CID 9281694.
- van den Ouweland AM, Knoop MT, Knoers VV, Markslag PW, Rocchi M, Warren ST, Ropers HH, Fahrenholz F, Monnens LA, van Oost BA (Aug 1992). "Colocalization of the gene for nephrogenic diabetes insipidus (DIR) and the vasopressin type 2 receptor gene (AVPR2) in the Xq28 region". Genomics. 13 (4): 1350–2. doi:10.1016/0888-7543(92)90067-3. PMID 1324225.
- Rosenthal W, Seibold A, Antaramian A, Lonergan M, Arthus MF, Hendy GN, Birnbaumer M, Bichet DG (Sep 1992). "Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus". Nature. 359 (6392): 233–5. Bibcode:1992Natur.359..233R. doi:10.1038/359233a0. PMID 1356229. S2CID 4356664.
- Seibold A, Brabet P, Rosenthal W, Birnbaumer M (Nov 1992). "Structure and chromosomal localization of the human antidiuretic hormone receptor gene". American Journal of Human Genetics. 51 (5): 1078–83. PMC 1682836. PMID 1415251.
- Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, Antaramian A, Brabet P, Rosenthal W (May 1992). "Molecular cloning of the receptor for human antidiuretic hormone". Nature. 357 (6376): 333–5. Bibcode:1992Natur.357..333B. doi:10.1038/357333a0. PMID 1534149. S2CID 4271103.
- Lolait SJ, O'Carroll AM, McBride OW, Konig M, Morel A, Brownstein MJ (May 1992). "Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus". Nature. 357 (6376): 336–9. Bibcode:1992Natur.357..336L. doi:10.1038/357336a0. PMID 1534150. S2CID 4365214.
- Knoers N, van der Heyden H, van Oost BA, Monnens L, Willems J, Ropers HH (Apr 1989). "Three-point linkage analysis using multiple DNA polymorphic markers in families with X-linked nephrogenic diabetes insipidus". Genomics. 4 (3): 434–7. doi:10.1016/0888-7543(89)90352-2. PMID 2714800.
- Tsukaguchi H, Matsubara H, Taketani S, Mori Y, Seido T, Inada M (Oct 1995). "Binding-, intracellular transport-, and biosynthesis-defective mutants of vasopressin type 2 receptor in patients with X-linked nephrogenic diabetes insipidus". The Journal of Clinical Investigation. 96 (4): 2043–50. doi:10.1172/JCI118252. PMC 185843. PMID 7560098.
- Faà V, Ventruto ML, Loche S, Bozzola M, Podda R, Cao A, Rosatelli MC (Sep 1994). "Mutations in the vasopressin V2-receptor gene in three families of Italian descent with nephrogenic diabetes insipidus". Human Molecular Genetics. 3 (9): 1685–6. doi:10.1093/hmg/3.9.1685. PMID 7833930.
- Birnbaumer M, Gilbert S, Rosenthal W (Jul 1994). "An extracellular congenital nephrogenic diabetes insipidus mutation of the vasopressin receptor reduces cell surface expression, affinity for ligand, and coupling to the Gs/adenylyl cyclase system". Molecular Endocrinology. 8 (7): 886–94. doi:10.1210/mend.8.7.7984150. PMID 7984150.
- Wenkert D, Merendino JJ, Shenker A, Thambi N, Robertson GL, Moses AM, Spiegel AM (Aug 1994). "Novel mutations in the V2 vasopressin receptor gene of patients with X-linked nephrogenic diabetes insipidus". Human Molecular Genetics. 3 (8): 1429–30. doi:10.1093/hmg/3.8.1429. PMID 7987330.
- Oksche A, Dickson J, Schülein R, Seyberth HW, Müller M, Rascher W, Birnbaumer M, Rosenthal W (Nov 1994). "Two novel mutations in the vasopressin V2 receptor gene in patients with congenital nephrogenic diabetes insipidus". Biochemical and Biophysical Research Communications. 205 (1): 552–7. doi:10.1006/bbrc.1994.2700. PMID 7999078.
- Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S (Aug 1994). "Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus". American Journal of Human Genetics. 55 (2): 278–86. PMC 1918376. PMID 8037205.
- Yuasa H, Ito M, Oiso Y, Kurokawa M, Watanabe T, Oda Y, Ishizuka T, Tani N, Ito S, Shibata A (Aug 1994). "Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus". The Journal of Clinical Endocrinology and Metabolism. 79 (2): 361–5. doi:10.1210/jcem.79.2.8045948. PMID 8045948.
External links
- GeneReviews/NCBI/NIH/UW entry on Nephrogenic Diabetes Insipidus
- "Symbol Report: AVPR2". HUGO Gene Nomenclature Committee (HGNC).
- "Vasopressin and Oxytocin Receptors: V2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Human AVPR2 genome location and AVPR2 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P30518 (Vasopressin V2 receptor) at the PDBe-KB.
