Angiotensin II receptor type 2

Angiotensin II receptor type 2, also known as the AT₂ receptor is a protein that in humans is encoded by the AGTR2 gene.[5]

AGTR2
Identifiers
Aliases	AGTR2, AT2, ATGR2, MRX88, Angiotensin II receptor type 2
External IDs	OMIM: 300034 MGI: 87966 HomoloGene: 20172 GeneCards: AGTR2
Gene location (Human) Chr. X chromosome (human)[1] Band Xq23 Start 116,170,744 bp[1] End 116,174,974 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X A2|X 16.71 cM Start 21,484,544 bp[2] End 21,489,164 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • signal transducer activity • receptor antagonist activity • peptide hormone binding • G-protein coupled receptor activity • GO:0001948 protein binding • angiotensin type II receptor activity • transcription factor binding Cellular component • integral component of membrane • membrane • perinuclear region of cytoplasm • cell membrane • integral component of plasma membrane • extracellular region Biological process • regulation of metanephros size • positive regulation of metanephric glomerulus development • GO:0007243 intracellular signal transduction • kidney morphogenesis • regulation of apoptotic process • positive regulation of cytokine secretion • positive regulation of branching involved in ureteric bud morphogenesis • positive regulation of nitric-oxide synthase activity • signal transduction • dopamine biosynthetic process • positive regulation of nitric oxide biosynthetic process • negative regulation of norepinephrine secretion • cellular sodium ion homeostasis • renin-angiotensin regulation of aldosterone production • cellular response to dexamethasone stimulus • brain development • angiotensin-mediated vasodilation involved in regulation of systemic arterial blood pressure • brain renin-angiotensin system • regulation of blood pressure • kidney development • negative regulation of icosanoid secretion • positive regulation of extrinsic apoptotic signaling pathway • regulation of systemic arterial blood pressure by circulatory renin-angiotensin • aldosterone secretion • G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger • positive regulation of cell proliferation • positive regulation of transcription, DNA-templated • negative regulation of blood vessel endothelial cell migration • negative regulation of neurotrophin TRK receptor signaling pathway • response to organonitrogen compound • cerebellar cortex development • negative regulation of fibroblast proliferation • blood vessel remodeling • cell growth involved in cardiac muscle cell development • negative regulation of heart rate • negative regulation of cell growth • positive regulation of phosphoprotein phosphatase activity • exploration behavior • inflammatory response • positive regulation of renal sodium excretion • cell surface receptor signaling pathway • nitric oxide mediated signal transduction • angiotensin-activated signaling pathway • extracellular negative regulation of signal transduction • vasodilation • regulation of blood vessel diameter • positive regulation of blood vessel diameter • G-protein coupled receptor signaling pathway • regulation of protein import into nucleus • negative regulation of receptor activity Sources:Amigo / QuickGO
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	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[5]

Stimulation of AT₂ by the selective agonist CGP 42112A increases mucosal nitric oxide production.[6]

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[7][8]

Model organisms have been used in the study of AGTR2 function. A conditional knockout mouse line, called Agtr2^{tm1a(EUCOMM)Wtsi}[9][10] 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.[11][12][13]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][14] Twenty one tests were carried out on mutant mice, but no significant abnormalities were observed.[7]

Interactions

Angiotensin II receptor type 2 has been shown to interact with MTUS1.[15]

See also

• Angiotensin II receptor

References

1. GRCh38: Ensembl release 89: ENSG00000180772 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000068122 - 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. "Entrez Gene: AGTR2 angiotensin II receptor, type 2".
6. 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 Pharmacology. 3: 2. doi:10.1186/1471-2210-3-2. PMC 153509. PMID 12689346.
7. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248): 0. doi:10.1111/j.1755-3768.2010.4142.x.
8. Mouse Resources Portal, Wellcome Trust Sanger Institute.
9. "International Knockout Mouse Consortium".
10. "Mouse Genome Informatics".
11. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
12. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
13. 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.
14. van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
15. 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". The Journal of Biological Chemistry. 279 (28): 28989–97. doi:10.1074/jbc.M403880200. PMID 15123706.

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

Further reading

• de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T (September 2000). "International union of pharmacology. XXIII. The angiotensin II receptors". Pharmacological Reviews. 52 (3): 415–72. PMID 10977869.
• D'Amore A, Black MJ, Thomas WG (December 2005). "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. doi:10.1161/01.HYP.0000193504.51489.cf. PMID 16286564.
• Regitz-Zagrosek V, Neuss M, Warnecke C, Holzmeister J, Hildebrandt AG, Fleck E (1997). "Subtype 2 and atypical angiotensin receptors in the human heart". Basic Research in Cardiology. 91 Suppl 2: 73–7. doi:10.1007/bf00795366. PMID 8957548.
• Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG (December 2001). "Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide". American Journal of Physiology. Heart and Circulatory Physiology. 281 (6): H2337–65. doi:10.1152/ajpheart.2001.281.6.H2337. PMID 11709400.
• Takayanagi R, Ohnaka K, Sakai Y, Nakao R, Yanase T, Haji M, Inagami T, Furuta H, Gou DF, Nakamuta M (March 1992). "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. doi:10.1016/0006-291X(92)90570-B. PMID 1550596.
• Hein L, Barsh GS, Pratt RE, Dzau VJ, Kobilka BK (October 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, Okuyama S, Imagawa Y, Fogo A, Niimura F, Ichikawa I, Hogan BL, Inagami T (October 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, Mattei MG, Strosberg AD, Nahmias C (1995). "Molecular characterization and chromosome localization of a human angiotensin II AT2 receptor gene highly expressed in fetal tissues". Receptors & Channels. 2 (4): 271–80. PMID 7719706.
• Martin MM, Elton TS (April 1995). "The sequence and genomic organization of the human type 2 angiotensin II receptor". Biochemical and Biophysical Research Communications. 209 (2): 554–62. doi:10.1006/bbrc.1995.1537. PMID 7733925.
• Chassagne C, Beatty BG, Meloche S (January 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, Szpirer C, Jacob HJ, Dzau VJ (September 1994). "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. doi:10.1006/bbrc.1994.2402. PMID 7945336.
• Martin MM, Su B, Elton TS (November 1994). "Molecular cloning of the human angiotensin II type 2 receptor cDNA". Biochemical and Biophysical Research Communications. 205 (1): 645–51. doi:10.1006/bbrc.1994.2714. PMID 7999093.
• Tsuzuki S, Ichiki T, Nakakubo H, Kitami Y, Guo DF, Shirai H, Inagami T (May 1994). "Molecular cloning and expression of the gene encoding human angiotensin II type 2 receptor". Biochemical and Biophysical Research Communications. 200 (3): 1449–54. doi:10.1006/bbrc.1994.1613. PMID 8185599.
• Servant G, Boulay G, Bossé R, Escher E, Guillemette G (May 1993). "Photoaffinity labeling of subtype 2 angiotensin receptor of human myometrium". Molecular Pharmacology. 43 (5): 677–83. PMID 8502225.
• Yamada T, Horiuchi M, Dzau VJ (January 1996). "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. doi:10.1073/pnas.93.1.156. PMC 40197. PMID 8552595.
• Zhang J, Pratt RE (June 1996). "The AT2 receptor selectively associates with Gialpha2 and Gialpha3 in the rat fetus". The Journal of Biological Chemistry. 271 (25): 15026–33. doi:10.1074/jbc.271.25.15026. PMID 8663053.
• Katsuya T, Horiuchi M, Minami S, Koike G, Santoro NF, Hsueh AJ, Dzau VJ (March 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". Molecular and Cellular Endocrinology. 127 (2): 221–8. doi:10.1016/S0303-7207(97)04011-2. PMID 9099917.
• Akishita M, Ito M, Lehtonen JY, Daviet L, Dzau VJ, Horiuchi M (January 1999). "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. doi:10.1172/JCI5182. PMC 407869. PMID 9884335.
• Lehtonen JY, Daviet L, Nahmias C, Horiuchi M, Dzau VJ (July 1999). "Analysis of functional domains of angiotensin II type 2 receptor involved in apoptosis". Molecular Endocrinology. 13 (7): 1051–60. doi:10.1210/me.13.7.1051. PMID 10406457.
• Knowle D, Ahmed S, Pulakat L (February 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". Regulatory Peptides. 87 (1–3): 73–82. doi:10.1016/S0167-0115(99)00111-1. PMID 10710290.
• Hansen JL, Servant G, Baranski TJ, Fujita T, Iiri T, Sheikh SP (October 2000). "Functional reconstitution of the angiotensin II type 2 receptor and G(i) activation". Circulation Research. 87 (9): 753–9. 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.
• Human AGTR2 genome location and AGTR2 gene details page in the UCSC Genome Browser.