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Gene Review

AGTR2  -  angiotensin II receptor, type 2

Homo sapiens

Synonyms: AT2, ATGR2, Angiotensin II type-2 receptor, MRX88, Type-2 angiotensin II receptor
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Disease relevance of AGTR2


Psychiatry related information on AGTR2

  • Identification of two AGTR2 mutations in male patients with non-syndromic mental retardation [2].
  • In addition, the marked increase in the levels of angiotensin AT2 receptor recognition sites in temporal cortex from patients with Alzheimer's disease correlates with some other markers associated with the renin-angiotensin system previously investigated in tissue from patients with this neurological disease [6].
  • In brain tissue homogenates from patients with Huntington's disease, the angiotensin AT1 receptor recognition site levels were decreased by approximately 30% in putamen relative to the control patients whilst angiotensin AT2 receptor levels were increased by some 90% in the caudate nucleus relative to the control patients [6].
  • Déjà vu, a warm sensation, an indescribable strange sensation, a cephalic sensation, and fear were associated with an abnormal AT2 [7].

High impact information on AGTR2

  • AT1 receptors mediate most known functions of angiotensin II, while AT2 receptors may be important developmentally [8].
  • AGTR2, therefore, has a significant ontogenic role for the kidney and urinary tract system [9].
  • Studies of the human type 2 receptor (AGTR2) gene in two independent cohorts found that a significant association exists between CAKUT and a nucleotide transition within the lariat branchpoint motif of intron 1, which perturbs AGTR2 mRNA splicing efficiency [9].
  • Quantitative receptor autoradiography using the nonselective radioligand [125I]ANG II and subtype-selective competing compounds demonstrated the presence of both ANG II receptor (AT)1 and AT2 receptor recognition sites [10].
  • These observations also suggest, for the first time, the existence of a cross-talk between AT1 or AT2 receptors in trophoblast and that the reduction in placental AT1 receptors in IUGR may, in part, account for poor placental function in this disorder [10].

Chemical compound and disease context of AGTR2


Biological context of AGTR2


Anatomical context of AGTR2

  • These results indicate that human myometrium contains almost exclusively the AT2 receptor subtype [18].
  • Association and dissociation studies performed with 125I-AII on human myometrium membranes revealed that AII had a very high affinity for AT2 receptors, with a Kd of 0.01 nM (association rate constant K1 = 1.056 x 10(12) mol-1 min-1; dissociation rate constant K2 = 0.003 min-1) [18].
  • The uterus expresses the AT2 receptor abundantly even in adults, suggesting its role in reproduction [5].
  • In their amino-terminal portion, ATIP polypeptides exhibit distinct motifs for localisation in the cytosol, nucleus or cell membrane, suggesting that MTUS1 gene products may be involved in a variety of intracellular functions in an AT2-dependent and independent manner [19].
  • All components could additionally be demonstrated at mRNA level in cultured primary keratinocytes, melanocytes, dermal fibroblasts and dermal microvascular endothelial cells, except for AT2 receptors in melanocytes [20].

Associations of AGTR2 with chemical compounds

  • Two angiotensin II (Ang II)-specific receptors, AGTR1 and AGTR2, are expressed in the mammalian brain [3].
  • There are very few data regarding the regulation of the subtype AT2, indicating modulation by a number of growth factors and by Ang II [21].
  • In nonpregnant myometrium (n = 5), receptor density [maximum binding capacity (Bmax)] and dissociation constant (Kd) for AT2-selective CGP42112A were 287 +/- 46 fmol/mg protein and 0.48 +/- 0.09 nM, respectively [5].
  • Autoradiography of the polyacrylamide gel revealed a single band, of 68 kDa, and the labeling of this band was completely abolished in the presence of 1 microM PD 123319, indicating selective labeling of the AT2 receptor subtype [18].
  • [125I]-Ang IV binding was not modified by nonpeptide AT1 (losartan) or AT2 (PD123177) antagonists [22].

Physical interactions of AGTR2

  • We report here that MTUS1 encodes a family of proteins whose leader member (ATIP1) was previously isolated in our laboratory as a novel interacting partner of the angiotensin II AT2 receptor involved in growth inhibition (Nouet, JBC 279: 28989-97, 2004) [19].
  • AT1 and AT2 receptor binding were determined with the AT1 receptor antagonist losartan [23].

Regulatory relationships of AGTR2

  • The inhibitory effect of Ang II on VEGF-induced migration of endothelial cells was mimicked by the specific AT2 receptor agonist CGP-42112A [24].
  • Recent evidence suggests that angiotensin II (Ang II) may promote growth through the AT1 and inhibit growth through the AT2 receptor subtypes [25].
  • Both the AT1 and AT2 ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO [26].
  • In the gastrointestinal tract, physiological quantities of ANG II stimulate the AT2 receptor releasing NO and cGMP leading to increased sodium and water absorption [27].
  • Furthermore, 10 of 23 (44%) patients with VUR and seven of 19 (42%) controls carried the AT2 receptor gene variation [28].

Other interactions of AGTR2


Analytical, diagnostic and therapeutic context of AGTR2

  • METHODS: ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls [1].
  • Northern blots revealed AT1 and AT2 receptor messenger RNA (mRNA) expressions in all samples examined; the former was much lower than the latter [5].
  • We first analyzed the AT2 mRNA splice pattern by RT-PCR in myocardial samples from 12 explanted human hearts and compared it with the respective genotypes [31].
  • Immunofluorescence studies demonstrated that stimulation with Ang II or CGP 42112 (an agonist of the AT2 receptor) strongly modified the actin network, now localized exclusively along the plasma membrane, with a predominance of labeling at the base of the bleb formation [33].
  • Single copies of two distinct acetyltransferase genes, designated AT1 and AT2, were detected in hamster DNA by Southern blot analysis using gene-specific hybridization probes for the 3' end of the AT coding regions [34].


  1. Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis. Takemoto, Y., Sakatani, M., Takami, S., Tachibana, T., Higaki, J., Ogihara, T., Miki, T., Katsuya, T., Tsuchiyama, T., Yoshida, A., Yu, H., Tanio, Y., Ueda, E. Thorax (1998) [Pubmed]
  2. Identification of two AGTR2 mutations in male patients with non-syndromic mental retardation. Ylisaukko-oja, T., Rehnström, K., Vanhala, R., Tengström, C., Lähdetie, J., Järvelä, I. Hum. Genet. (2004) [Pubmed]
  3. AGTR2 mutations in X-linked mental retardation. Vervoort, V.S., Beachem, M.A., Edwards, P.S., Ladd, S., Miller, K.E., de Mollerat, X., Clarkson, K., DuPont, B., Schwartz, C.E., Stevenson, R.E., Boyd, E., Srivastava, A.K. Science (2002) [Pubmed]
  4. Haplotypes of the angiotensin II receptor genes AGTR1 and AGTR2 in women with normotensive pregnancy and women with preeclampsia. Plummer, S., Tower, C., Alonso, P., Morgan, L., Baker, P., Broughton-Pipkin, F., Kalsheker, N. Hum. Mutat. (2004) [Pubmed]
  5. Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy. Matsumoto, T., Sagawa, N., Mukoyama, M., Tanaka, I., Itoh, H., Goto, M., Itoh, H., Horiuchi, M., Dzau, V.J., Mori, T., Nakao, K. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  6. Alterations in angiotensin AT1 and AT2 receptor subtype levels in brain regions from patients with neurodegenerative disorders. Ge, J., Barnes, N.M. Eur. J. Pharmacol. (1996) [Pubmed]
  7. The amygdala and temporal lobe simple partial seizures: a prospective and quantitative MRI study. Van Paesschen, W., King, M.D., Duncan, J.S., Connelly, A. Epilepsia (2001) [Pubmed]
  8. Angiotensin receptors and their therapeutic implications. Griendling, K.K., Lassègue, B., Alexander, R.W. Annu. Rev. Pharmacol. Toxicol. (1996) [Pubmed]
  9. Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men. Nishimura, H., Yerkes, E., Hohenfellner, K., Miyazaki, Y., Ma, J., Hunley, T.E., Yoshida, H., Ichiki, T., Threadgill, D., Phillips, J.A., Hogan, B.M., Fogo, A., Brock, J.W., Inagami, T., Ichikawa, I. Mol. Cell (1999) [Pubmed]
  10. Cellular localization of AT1 receptor mRNA and protein in normal placenta and its reduced expression in intrauterine growth restriction. Angiotensin II stimulates the release of vasorelaxants. Li, X., Shams, M., Zhu, J., Khalig, A., Wilkes, M., Whittle, M., Barnes, N., Ahmed, A. J. Clin. Invest. (1998) [Pubmed]
  11. Angiotensin II regulates phosphoinositide 3 kinase/Akt cascade via a negative crosstalk between AT1 and AT2 receptors in skin fibroblasts of human hypertrophic scars. Liu, H.W., Cheng, B., Yu, W.L., Sun, R.X., Zeng, D., Wang, J., Liao, Y.X., Fu, X.B. Life Sci. (2006) [Pubmed]
  12. Immunohistochemical detection of angiotensin receptors AT1 and AT2 in normal rat pituitary gland, estrogen-induced rat pituitary tumor and human pituitary adenomas. Pawlikowski, M. Folia Histochem. Cytobiol. (2006) [Pubmed]
  13. Differentiation of NG108-15 neuroblastoma cells by serum starvation or dimethyl sulfoxide results in marked differences in angiotensin II receptor subtype expression. Seidman, K.J., Barsuk, J.H., Johnson, R.F., Weyhenmeyer, J.A. J. Neurochem. (1996) [Pubmed]
  14. AT1 receptor blockade regulates the local angiotensin II system in cerebral microvessels from spontaneously hypertensive rats. Zhou, J., Pavel, J., Macova, M., Yu, Z.X., Imboden, H., Ge, L., Nishioku, T., Dou, J., Delgiacco, E., Saavedra, J.M. Stroke (2006) [Pubmed]
  15. Genetic polymorphisms in the angiotensin II receptor gene and their association with open-angle glaucoma in a Japanese population. Hashizume, K., Mashima, Y., Fumayama, T., Ohtake, Y., Kimura, I., Yoshida, K., Ishikawa, K., Yasuda, N., Fujimaki, T., Asaoka, R., Koga, T., Kanamoto, T., Fukuchi, T., Miyaki, K. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  16. Assignment of the human angiotensin II type 2 receptor gene (AGTR2) to chromosome Xq22-q23 by fluorescence in situ hybridization. Chassagne, C., Beatty, B.G., Meloche, S. Genomics (1995) [Pubmed]
  17. Altered transmission of maternal angiotensin II receptor haplotypes in fetal growth restriction. Tower, C., Chappell, S., Acharya, M., Crane, R., Szolin, S., Symonds, L., Chevins, H., Kalsheker, N., Baker, P., Morgan, L. Hum. Mutat. (2006) [Pubmed]
  18. Photoaffinity labeling of subtype 2 angiotensin receptor of human myometrium. Servant, G., Boulay, G., Bossé, R., Escher, E., Guillemette, G. Mol. Pharmacol. (1993) [Pubmed]
  19. Structural organization and expression of human MTUS1, a candidate 8p22 tumor suppressor gene encoding a family of angiotensin II AT2 receptor-interacting proteins, ATIP. Di Benedetto, M., Bièche, I., Deshayes, F., Vacher, S., Nouet, S., Collura, V., Seitz, I., Louis, S., Pineau, P., Amsellem-Ouazana, D., Couraud, P.O., Strosberg, A.D., Stoppa-Lyonnet, D., Lidereau, R., Nahmias, C. Gene (2006) [Pubmed]
  20. Human skin: source of and target organ for angiotensin II. Steckelings, U.M., Wollschläger, T., Peters, J., Henz, B.M., Hermes, B., Artuc, M. Exp. Dermatol. (2004) [Pubmed]
  21. Regulation of the angiotensin receptor subtypes in cell cultures, animal models and human diseases. Regitz-Zagrosek, V., Auch-Schwelk, W., Neuss, M., Fleck, E. Eur. Heart J. (1994) [Pubmed]
  22. Evidence for angiotensin IV receptors in human collecting duct cells. Czekalski, S., Chansel, D., Vandermeersch, S., Ronco, P., Ardaillou, R. Kidney Int. (1996) [Pubmed]
  23. Differential regulation of cardiac angiotensin converting enzyme binding sites and AT1 receptor density in the failing human heart. Zisman, L.S., Asano, K., Dutcher, D.L., Ferdensi, A., Robertson, A.D., Jenkin, M., Bush, E.W., Bohlmeyer, T., Perryman, M.B., Bristow, M.R. Circulation (1998) [Pubmed]
  24. Angiotensin II type 2 receptor inhibits vascular endothelial growth factor-induced migration and in vitro tube formation of human endothelial cells. Benndorf, R., Böger, R.H., Ergün, S., Steenpass, A., Wieland, T. Circ. Res. (2003) [Pubmed]
  25. Angiotensin II receptor subtype AT1 and AT2 expression after heart transplantation. Gullestad, L., Haywood, G., Aass, H., Ross, H., Yee, G., Ueland, T., Geiran, O., Kjekshus, J., Simonsen, S., Bishopric, N., Fowler, M. Cardiovasc. Res. (1998) [Pubmed]
  26. Interaction between arginine vasopressin and angiotensin II receptors in the central regulation of sodium balance. Saad, W.A., Camargo, L.A., Antunes-Rodrigues, J., Saad, W.A., Guarda, I.F., Guarda, R.S. Regul. Pept. (2005) [Pubmed]
  27. Nitric oxide: a physiological mediator of the type 2 (AT2) angiotensin receptor. Carey, R.M., Jin, X., Wang, Z., Siragy, H.M. Acta Physiol. Scand. (2000) [Pubmed]
  28. Angiotensin II, type 2 receptor in the development of vesico-ureteric reflux. Hohenfellner, K., Hunley, T.E., Yerkes, E., Habermehl, P., Hohenfellner, R., Kon, V. BJU international. (1999) [Pubmed]
  29. Angiotensin II regulates 11beta-hydroxysteroid dehydrogenase type 2 via AT2 receptors. Lanz, B., Kadereit, B., Ernst, S., Shojaati, K., Causevic, M., Frey, B.M., Frey, F.J., Mohaupt, M.G. Kidney Int. (2003) [Pubmed]
  30. Angiotensin gene polymorphism as a determinant of posttransplantation renal dysfunction and hypertension. Abdi, R., Tran, T.B., Zee, R., Brenner, B.M., Milford, E.L. Transplantation (2001) [Pubmed]
  31. Intronic ANG II type 2 receptor gene polymorphism 1675 G/A modulates receptor protein expression but not mRNA splicing. Warnecke, C., Mugrauer, P., Sürder, D., Erdmann, J., Schubert, C., Regitz-Zagrosek, V. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  32. Angiotensin II type 2 receptor-mediated gene expression profiling in human coronary artery endothelial cells. Falcón, B.L., Veerasingham, S.J., Sumners, C., Raizada, M.K. Hypertension (2005) [Pubmed]
  33. Involvement of the angiotensin II type 2 receptor in apoptosis during human fetal adrenal gland development. Chamoux, E., Breault, L., Lehoux, J.G., Gallo-Payet, N. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  34. Biochemical and genetic analysis of two acetyltransferases from hamster tissues that can metabolize aromatic amine derivatives. Land, S.J., Jones, R.F., King, C.M. Carcinogenesis (1994) [Pubmed]
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