Biology:Angiotensin II receptor type 2

Short description: Protein-coding gene in humans

Generic protein structure example

Angiotensin II receptor type 2, also known as the AT₂ receptor is a protein that in humans is encoded by the AGTR2 gene.

Function

Angiotensin II is a potent pressor hormone and a primary regulator of aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. It acts through at least two types of receptors termed AT₁ and AT₂. AGTR2 belongs to a family 1 of G protein-coupled receptors. It is an integral membrane protein. It plays a role in the central nervous system and cardiovascular functions that are mediated by the renin–angiotensin system. This receptor mediates programmed cell death (apoptosis). Consistent with its apoptotic function, angiotensin II receptor type II also opposes cell proliferation, as demonstrated by its antagonism of MAPK activity in cardiac fibroblasts during interstitial fibrosis. In adults, it is highly expressed in myometrium with lower levels in adrenal gland and fallopian tube. It is highly expressed in fetal kidney and intestine. The human AGTR2 gene is composed of three exons and spans at least 5 kb. Exons 1 and 2 encode for 5' untranslated mRNA sequence and exon 3 harbors the entire uninterrupted open reading frame.

Stimulation of AT₂ by the selective agonist CGP 42112A increases mucosal nitric oxide production.

Gene

Angiotensin II receptor type 2 (AGTR2) gene is a protein coding gene responsible for encoding AGTR2, the integral membrane protein that binds to two different G-protein coupled receptors. AGTR2 has recently been discovered to play a role in modifying lung disease. This receptor functions to mediate signaling in lung fibrosis and regulate nitric oxide synthase expression in pulmonary endothelium. AGTR2 has recently been prescribed as a target for lung inflammation therapy in cases of cystic fibrosis (CF). The X-chromosome region associated with CF lung disease is located in a non-coding region 3′ of the AGTR2 gene. The modification effect is likely due to variation in gene regulation rather than a change in protein coding sequence.

Variants at the X-chromosome locus containing AGTR2 gene were identified as significantly associating with lung function in patients with cystic fibrosis. Genetically modified mouse studies determined that absence of the AGTR2 gene normalized pulmonary function indicators in two independent CF mouse models. Furthermore, pharmacological antagonism of AGTR2 signaling improved lung function in CF mice to near wild-type levels. Manipulation of the angiotensin-signaling pathway to reduce AGTR2 signaling may be translatable for the treatment or prevention of CF.

Interactions

Angiotensin II receptor type 2 has been shown to interact with MTUS1.

See also

• Angiotensin II receptor

References

• This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Further reading

• "International union of pharmacology. XXIII. The angiotensin II receptors". Pharmacological Reviews 52 (3): 415–72. September 2000. PMID 10977869. 
• "The angiotensin II type 2 receptor causes constitutive growth of cardiomyocytes and does not antagonize angiotensin II type 1 receptor-mediated hypertrophy". Hypertension 46 (6): 1347–54. December 2005. doi:10.1161/01.HYP.0000193504.51489.cf. PMID 16286564. 
• "Subtype 2 and atypical angiotensin receptors in the human heart". Basic Research in Cardiology 91 (Suppl 2): 73–7. 1997. doi:10.1007/bf00795366. PMID 8957548. 
• "Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide". American Journal of Physiology. Heart and Circulatory Physiology 281 (6): H2337–65. December 2001. doi:10.1152/ajpheart.2001.281.6.H2337. PMID 11709400. 
• "Molecular cloning, sequence analysis and expression of a cDNA encoding human type-1 angiotensin II receptor". Biochemical and Biophysical Research Communications 183 (2): 910–6. March 1992. doi:10.1016/0006-291X(92)90570-B. PMID 1550596. 
• "Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice". Nature 377 (6551): 744–7. October 1995. doi:10.1038/377744a0. PMID 7477266. 
• "Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor". Nature 377 (6551): 748–50. October 1995. doi:10.1038/377748a0. PMID 7477267. Bibcode: 1995Natur.377..748I. 
• "Molecular characterization and chromosome localization of a human angiotensin II AT2 receptor gene highly expressed in fetal tissues". Receptors & Channels 2 (4): 271–80. 1995. PMID 7719706. 
• "The sequence and genomic organization of the human type 2 angiotensin II receptor". Biochemical and Biophysical Research Communications 209 (2): 554–62. April 1995. doi:10.1006/bbrc.1995.1537. PMID 7733925. 
• "Assignment of the human angiotensin II type 2 receptor gene (AGTR2) to chromosome Xq22-q23 by fluorescence in situ hybridization". Genomics 25 (2): 601–3. January 1995. doi:10.1016/0888-7543(95)80072-T. PMID 7790004. 
• "Human type 2 angiotensin II receptor gene: cloned, mapped to the X chromosome, and its mRNA is expressed in the human lung". Biochemical and Biophysical Research Communications 203 (3): 1842–50. September 1994. doi:10.1006/bbrc.1994.2402. PMID 7945336. 
• "Molecular cloning of the human angiotensin II type 2 receptor cDNA". Biochemical and Biophysical Research Communications 205 (1): 645–51. November 1994. doi:10.1006/bbrc.1994.2714. PMID 7999093. 
• "Molecular cloning and expression of the gene encoding human angiotensin II type 2 receptor". Biochemical and Biophysical Research Communications 200 (3): 1449–54. May 1994. doi:10.1006/bbrc.1994.1613. PMID 8185599. 
• "Photoaffinity labeling of subtype 2 angiotensin receptor of human myometrium". Molecular Pharmacology 43 (5): 677–83. May 1993. PMID 8502225. 
• "Angiotensin II type 2 receptor mediates programmed cell death". Proceedings of the National Academy of Sciences of the United States of America 93 (1): 156–60. January 1996. doi:10.1073/pnas.93.1.156. PMID 8552595. Bibcode: 1996PNAS...93..156Y. 
• "The AT2 receptor selectively associates with Gialpha2 and Gialpha3 in the rat fetus". The Journal of Biological Chemistry 271 (25): 15026–33. June 1996. doi:10.1074/jbc.271.25.15026. PMID 8663053. 
• "Genomic organization and polymorphism of human angiotensin II type 2 receptor: no evidence for its gene mutation in two families of human premature ovarian failure syndrome". Molecular and Cellular Endocrinology 127 (2): 221–8. March 1997. doi:10.1016/S0303-7207(97)04011-2. PMID 9099917. 
• "Expression of the AT2 receptor developmentally programs extracellular signal-regulated kinase activity and influences fetal vascular growth". The Journal of Clinical Investigation 103 (1): 63–71. January 1999. doi:10.1172/JCI5182. PMID 9884335. 
• "Analysis of functional domains of angiotensin II type 2 receptor involved in apoptosis". Molecular Endocrinology 13 (7): 1051–60. July 1999. doi:10.1210/me.13.7.1051. PMID 10406457. 
• "Identification of an interaction between the angiotensin II receptor sub-type AT2 and the ErbB3 receptor, a member of the epidermal growth factor receptor family". Regulatory Peptides 87 (1–3): 73–82. February 2000. doi:10.1016/S0167-0115(99)00111-1. PMID 10710290. 
• "Functional reconstitution of the angiotensin II type 2 receptor and G(i) activation". Circulation Research 87 (9): 753–9. October 2000. doi:10.1161/01.res.87.9.753. PMID 11055978. 

External links

• "Angiotensin Receptors: AT₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2202. 
• Human AGTR2 genome location and AGTR2 gene details page in the UCSC Genome Browser.