Angiotensin II receptor type 2

Angiotensin II receptor, type 2
Identifiers
Symbols	AGTR2 ; AT2; ATGR2; MRX88
External IDs	OMIM: 300034 MGI: 87966 HomoloGene: 20172 IUPHAR: 35 ChEMBL: 4607 GeneCards: AGTR2 Gene
Gene ontology Molecular function • angiotensin type II receptor activity • protein binding • transcription factor binding • peptide hormone binding • receptor antagonist activity Cellular component • extracellular region • plasma membrane • integral component of plasma membrane • perinuclear region of cytoplasm Biological process • blood vessel remodeling • regulation of systemic arterial blood pressure by circulatory renin-angiotensin • renin-angiotensin regulation of aldosterone production • vasodilation by angiotensin involved in regulation of systemic arterial blood pressure • brain renin-angiotensin system • cellular sodium ion homeostasis • inflammatory response • cell surface receptor signaling pathway • G-protein coupled receptor signaling pathway • G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger • nitric oxide mediated signal transduction • brain development • regulation of blood pressure • positive regulation of cell proliferation • response to organonitrogen compound • negative regulation of heart rate • negative regulation of norepinephrine secretion • cerebellar cortex development • negative regulation of cell growth • negative regulation of icosanoid secretion • positive regulation of phosphoprotein phosphatase activity • intracellular signal transduction • regulation of metanephros size • exploration behavior • positive regulation of renal sodium excretion • aldosterone secretion • angiotensin-activated signaling pathway • dopamine biosynthetic process • regulation of transcription factor import into nucleus • negative regulation of blood vessel endothelial cell migration • positive regulation of nitric oxide biosynthetic process • positive regulation of transcription, DNA-templated • positive regulation of vasodilation • negative regulation of fibroblast proliferation • positive regulation of cytokine secretion • positive regulation of nitric-oxide synthase activity • negative regulation of neurotrophin TRK receptor signaling pathway • cell growth involved in cardiac muscle cell development • cellular response to dexamethasone stimulus • positive regulation of metanephric glomerulus development • positive regulation of branching involved in ureteric bud morphogenesis • extracellular negative regulation of signal transduction • positive regulation of extrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	186	11609
Ensembl	ENSG00000180772	ENSMUSG00000068122
UniProt	P50052	P35374
RefSeq (mRNA)	NM_000686	NM_007429
RefSeq (protein)	NP_000677	NP_031455
Location (UCSC)	Chr X: 116.17 – 116.17 Mb	Chr X: 21.48 – 21.49 Mb
PubMed search

Angiotensin II receptor type 2, also known as the AT₂ receptor is a protein that in humans is encoded by the AGTR2 gene.^[1]

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). 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.^[1]

Stimulation of AT₂ by the selective agonist CGP 42112A increases mucosal nitric oxide production.^[2]

Model organisms

Agtr2 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Eye Histopathology	Normal
All tests and analysis from[3][4]

Model organisms have been used in the study of AGTR2 function. A conditional knockout mouse line, called Agtr2^{tm1a(EUCOMM)Wtsi[5][6]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.^[7][8][9]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[3][10] Twenty one tests were carried out on mutant mice, but no significant abnormalities were observed.^[3]

Interactions

Angiotensin II receptor type 2 has been shown to interact with MTUS1.^[11]

See also

• Angiotensin II receptor

References

1. "Entrez Gene: AGTR2 angiotensin II receptor, type 2".
2. Ewert S, Laesser M, Johansson B, Holm M, Aneman A, Fandriks L (March 2003). "The angiotensin II receptor type 2 agonist CGP 42112A stimulates NO production in the porcine jejunal mucosa". BMC Pharmacol. 3: 2. doi:10.1186/1471-2210-3-2. PMC 153509. PMID 12689346.
3. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
4. Mouse Resources Portal, Wellcome Trust Sanger Institute.
5. "International Knockout Mouse Consortium".
6. "Mouse Genome Informatics".
7. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
8. Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
9. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
10. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
11. Nouet S, Amzallag N, Li JM, Louis S, Seitz I, Cui TX, Alleaume AM, Di Benedetto M, Boden C, Masson M, Strosberg AD, Horiuchi M, Couraud PO, Nahmias C (July 2004). "Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP". J. Biol. Chem. 279 (28): 28989–97. doi:10.1074/jbc.M403880200. PMID 15123706.

External links

• "Angiotensin Receptors: AT₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

Further reading

• de Gasparo M, Catt KJ, Inagami T, "", et al. (2000). "International union of pharmacology. XXIII. The angiotensin II receptors". Parmacol Rev. 52 (3): 415–472. PMID 10977869.
• D'Amore A, Black MJ, Thomas WG (2005). "The angiotensin II type 2 receptor causes constituative growth of cardiomyocytes and does not antagonize angiotensin II type 1 receptor-mediated hypertrophy". Hypertension 46 (6): 1347–1354. doi:10.1161/01.HYP.0000193504.51489.cf. PMID 16286564.

• Regitz-Zagrosek V, Neuss M, Warnecke C, et al. (1997). "Subtype 2 and atypical angiotensin receptors in the human heart". Basic Res. Cardiol. 91 Suppl 2: 73–7. doi:10.1007/bf00795366. PMID 8957548.
• Berry C, Touyz R, Dominiczak AF, et al. (2002). "Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide". Am. J. Physiol. Heart Circ. Physiol. 281 (6): H2337–65. PMID 11709400.
• Takayanagi R, Ohnaka K, Sakai Y, et al. (1992). "Molecular cloning, sequence analysis and expression of a cDNA encoding human type-1 angiotensin II receptor". Biochem. Biophys. Res. Commun. 183 (2): 910–6. doi:10.1016/0006-291X(92)90570-B. PMID 1550596.
• Hein L, Barsh GS, Pratt RE, et al. (1995). "Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice". Nature 377 (6551): 744–7. doi:10.1038/377744a0. PMID 7477266.
• Ichiki T, Labosky PA, Shiota C, et al. (1995). "Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor". Nature 377 (6551): 748–50. doi:10.1038/377748a0. PMID 7477267.
• Lazard D, Briend-Sutren MM, Villageois P, et al. (1995). "Molecular characterization and chromosome localization of a human angiotensin II AT2 receptor gene highly expressed in fetal tissues". Recept. Channels 2 (4): 271–80. PMID 7719706.
• Martin MM, Elton TS (1995). "The sequence and genomic organization of the human type 2 angiotensin II receptor". Biochem. Biophys. Res. Commun. 209 (2): 554–62. doi:10.1006/bbrc.1995.1537. PMID 7733925.
• Chassagne C, Beatty BG, Meloche S (1995). "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. doi:10.1016/0888-7543(95)80072-T. PMID 7790004.
• Koike G, Horiuchi M, Yamada T, et al. (1994). "Human type 2 angiotensin II receptor gene: cloned, mapped to the X chromosome, and its mRNA is expressed in the human lung". Biochem. Biophys. Res. Commun. 203 (3): 1842–50. doi:10.1006/bbrc.1994.2402. PMID 7945336.
• Martin MM, Su B, Elton TS (1995). "Molecular cloning of the human angiotensin II type 2 receptor cDNA". Biochem. Biophys. Res. Commun. 205 (1): 645–51. doi:10.1006/bbrc.1994.2714. PMID 7999093.
• Tsuzuki S, Ichiki T, Nakakubo H, et al. (1994). "Molecular cloning and expression of the gene encoding human angiotensin II type 2 receptor". Biochem. Biophys. Res. Commun. 200 (3): 1449–54. doi:10.1006/bbrc.1994.1613. PMID 8185599.
• Servant G, Boulay G, Bossé R, et al. (1993). "Photoaffinity labeling of subtype 2 angiotensin receptor of human myometrium". Mol. Pharmacol. 43 (5): 677–83. PMID 8502225.
• Yamada T, Horiuchi M, Dzau VJ (1996). "Angiotensin II type 2 receptor mediates programmed cell death". Proc. Natl. Acad. Sci. U.S.A. 93 (1): 156–60. doi:10.1073/pnas.93.1.156. PMC 40197. PMID 8552595.
• Zhang J, Pratt RE (1996). "The AT2 receptor selectively associates with Gialpha2 and Gialpha3 in the rat fetus". J. Biol. Chem. 271 (25): 15026–33. doi:10.1074/jbc.271.25.15026. PMID 8663053.
• Katsuya T, Horiuchi M, Minami S, et al. (1997). "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". Mol. Cell. Endocrinol. 127 (2): 221–8. doi:10.1016/S0303-7207(97)04011-2. PMID 9099917.
• Akishita M, Ito M, Lehtonen JY, et al. (1999). "Expression of the AT2 receptor developmentally programs extracellular signal-regulated kinase activity and influences fetal vascular growth". J. Clin. Invest. 103 (1): 63–71. doi:10.1172/JCI5182. PMC 407869. PMID 9884335.
• Lehtonen JY, Daviet L, Nahmias C, et al. (1999). "Analysis of functional domains of angiotensin II type 2 receptor involved in apoptosis". Mol. Endocrinol. 13 (7): 1051–60. doi:10.1210/me.13.7.1051. PMID 10406457.
• Knowle D, Ahmed S, Pulakat L (2000). "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". Regul. Pept. 87 (1–3): 73–82. doi:10.1016/S0167-0115(99)00111-1. PMID 10710290.
• Hansen JL, Servant G, Baranski TJ, et al. (2000). "Functional reconstitution of the angiotensin II type 2 receptor and G(i) activation". Circ. Res. 87 (9): 753–9. doi:10.1161/01.res.87.9.753. PMID 11055978.

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