Angiotensin II receptor type 1: Difference between revisions

AGTR1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4YAY, 4ZUD
Identifiers
Aliases	AGTR1, AG2S, AGTR1B, AT1, AT1AR, AT1B, AT1BR, AT1R, AT2R1, HAT1R, angiotensin II receptor type 1
External IDs	OMIM: 106165; MGI: 87964; HomoloGene: 3556; GeneCards: AGTR1; OMA:AGTR1 - orthologs
Gene location (Human)
Chr.	Chromosome 3 (human)
End	148,743,008 bp
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)
End	30,566,850 bp
RNA expression pattern
	Top expressed in
	skin of hip; ; placenta; ; subcutaneous adipose tissue; ; liver; ; right lobe of liver; ; right adrenal gland; ; left adrenal gland; ; adrenal cortex; ; left adrenal cortex; ; right adrenal cortex;
	Top expressed in
	adrenal gland; ; interventricular septum; ; left lobe of liver; ; lumbar spinal ganglion; ; prostate; ; myocardium of ventricle; ; human kidney; ; lobe of prostate; ; right kidney; ; sciatic nerve;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	G protein-coupled receptor activity; angiotensin type II receptor activity; angiotensin type I receptor activity; signal transducer activity; bradykinin receptor binding; protein binding; protein heterodimerization activity;
Cellular component	integral component of membrane; membrane; plasma membrane; integral component of plasma membrane; intracellular anatomical structure;
Biological process	positive regulation of protein metabolic process; positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; positive regulation of inflammatory response; maintenance of blood vessel diameter homeostasis by renin-angiotensin; positive regulation of phospholipase A2 activity; regulation of renal sodium excretion; kidney development; positive regulation of cholesterol esterification; phospholipase C-activating angiotensin-activated signaling pathway; positive regulation of cytosolic calcium ion concentration; angiotensin-activated signaling pathway; renin-angiotensin regulation of aldosterone production; phospholipase C-activating G protein-coupled receptor signaling pathway; positive regulation of macrophage derived foam cell differentiation; positive regulation of reactive oxygen species metabolic process; regulation of vasoconstriction; low-density lipoprotein particle remodeling; regulation of cell population proliferation; regulation of cell growth; Rho protein signal transduction; positive regulation of NAD(P)H oxidase activity; regulation of inflammatory response; cell chemotaxis; regulation of systemic arterial blood pressure by renin-angiotensin; calcium-mediated signaling; signal transduction; blood vessel diameter maintenance; G protein-coupled receptor signaling pathway; positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; inflammatory response;
	Sources:Amigo / QuickGO
Orthologs
	185
	11607
	ENSG00000144891
	ENSMUSG00000049115
	P30556
	P29754
NM_032049; NM_000685; NM_004835; NM_009585; NM_031850;
	NM_001382736; NM_001382737
	NM_177322
NP_000676; NP_004826; NP_033611; NP_114038; NP_114438;
	NP_001369665; NP_001369666
	NP_796296
	Wikidata
View/Edit Human	View/Edit Mouse

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Latest revision as of 15:50, 24 January 2024

Angiotensin II receptor type 1 (AT1) is a G_q/11-coupled G protein-coupled receptor (GPCR) and the best characterized angiotensin receptor. It is encoded in humans by the AGTR1 gene. AT1 has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. Angiotensin II receptor blockers are drugs indicated for hypertension, diabetic nephropathy and congestive heart failure.

Signaling cascade

The angiotensin receptor is activated by the vasoconstricting peptide angiotensin II. The activated receptor in turn couples to G_q/11 and thus activates phospholipase C and increases the cytosolic Ca²⁺ concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C. Activated receptor also inhibits adenylate cyclase in hepatocytes and activates various tyrosine kinases.^[5]

Function

The AT1 receptor mediates the major cardiovascular effects of angiotensin II. Effects include vasoconstriction, aldosterone synthesis and secretion, increased vasopressin secretion, cardiac hypertrophy, augmentation of peripheral noradrenergic activity, vascular smooth muscle cells proliferation, decreased renal blood flow, renal renin inhibition, renal tubular sodium reuptake, modulation of central sympathetic nervous system activity, cardiac contractility, central osmocontrol and extracellular matrix formation.^[6] The main function of angiotensin II in the brain is to stimulate drinking behavior, an effect that is mediated by the AT1 receptor.^[7]^[8]

Clinical significance

Due to the hemodynamic pressure and volume effects mediated by AT1 receptors, AT1 receptor antagonists are widely prescribed drugs in the management of hypertension and stable heart failure.^[9]

Animal studies

Elements of the renin-angiotensin system have been widely studied in a large variety of vertebrate animals including amphibians, reptiles, birds, and mammals.^[10]

AT1 receptor blockers have been shown to reduce fear memory recall in mice, but the reliability and relevance of this finding are to be determined.^[11]^[12]

Gene

It was previously thought that a related gene, denoted as AGTR1B, existed; however, it is now believed that there is only one type 1 receptor gene in humans. At least four transcript variants have been described for this gene. Additional variants have been described but their full-length nature has not been determined. The entire coding sequence is contained in the terminal exon and is present in all transcript variants.^[13]

A huge number of polymorphisms is reported in the databases for AT1R which provide an avenue to explore these polymorphisms for their implications in protein structure, function and drug efficacy. Methods In the current study all the SNPs (10234) reported in NCBI were analyzed and SNPs which were important in protein structure and drug interactions were identified. Structures of these polymorphic forms were modeled and in silico drug interaction studies were carried out. Results Result of the interaction studies with polymorphism was in correlation with the reported case. Two SNP mutated structures of AT1R i.e. rs780860717 (G288T), rs868647200 (A182C) shows considerably less binding affinities in case of all angiotensin receptor blockers (ARBs).^[14]

Interactions

Angiotensin II receptor type 1 has been shown to interact with Zinc finger and BTB domain-containing protein 16.^[15] The protein's mRNA has been reported to interact with Mir-132 microRNA as part of an RNA silencing mechanism that reduces receptor expression.^[16]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000144891 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000049115 – 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.
^ Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S (April 2007). "Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology". Clinical Science. 112 (8): 417–428. doi:10.1042/CS20060342. PMID 17346243. S2CID 27624282.
^ Catt KJ, Mendelsohn FA, Millan MA, Aguilera G (1984). "The role of angiotensin II receptors in vascular regulation". Journal of Cardiovascular Pharmacology. 6 (Suppl 4): S575–S586. doi:10.1097/00005344-198406004-00004. PMID 6083400.
^ Barbella Y, Cierco M, Israel A (April 1993). "Effect of Losartan, a nonpeptide angiotensin II receptor antagonist, on drinking behavior and renal actions of centrally administered renin". Proceedings of the Society for Experimental Biology and Medicine. 202 (4): 401–406. doi:10.3181/00379727-202-43551. PMID 8456103. S2CID 38235497.
^ Malvin RL, Mouw D, Vander AJ (July 1977). "Angiotensin: physiological role in water-deprivation-induced thirst of rats". Science. 197 (4299): 171–173. Bibcode:1977Sci...197..171M. doi:10.1126/science.877549. PMID 877549.
^ "Angiotensin II receptor blocker", Wikipedia, 2022-07-26, retrieved 2022-08-10
^ Wilson JX (1984). "The renin-angiotensin system in nonmammalian vertebrates". Endocrine Reviews. 5 (1): 45–61. doi:10.1210/edrv-5-1-45. PMID 6368215.
^ Marvar PJ, Goodman J, Fuchs S, Choi DC, Banerjee S, Ressler KJ (June 2014). "Angiotensin type 1 receptor inhibition enhances the extinction of fear memory". Biological Psychiatry. 75 (11): 864–872. doi:10.1016/j.biopsych.2013.08.024. PMC 3975818. PMID 24094510.
^ Hurt RC, Garrett JC, Keifer OP, Linares A, Couling L, Speth RC, et al. (September 2015). "Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear". Genes, Brain and Behavior. 14 (7): 526–533. doi:10.1111/gbb.12235. PMC 4573765. PMID 26257395.
^ "Entrez Gene: AGTR1 angiotensin II receptor, type 1".
^ Sharma B, Jaiswal V, Khan MA (October 2020). "In silico Approach for Exploring the Role of AT1R Polymorphism on its Function, Structure and Drug Interactions". Current Computer-Aided Drug Design. 17 (7): 927–935. doi:10.2174/1573409916666201023113709. PMID 33100208. S2CID 225071659.
^ Senbonmatsu T, Saito T, Landon EJ, Watanabe O, Price E, Roberts RL, et al. (December 2003). "A novel angiotensin II type 2 receptor signaling pathway: possible role in cardiac hypertrophy". The EMBO Journal. 22 (24): 6471–6482. doi:10.1093/emboj/cdg637. PMC 291832. PMID 14657020.
^ Elton TS, Kuhn DE, Malana GE, Martin MM, Nuovo GJ, Pleister AP, Feldman DS (2007). "MiR-132 Regulates Angiotensin II Type 1 Receptor Expression Through a Protein Coding Region Binding Site". Circulation. 118 (18): S513.

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

External links

"Angiotensin Receptors: AT₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2014-02-28. Retrieved 2008-11-25.
Human AGTR1 genome location and AGTR1 gene details page in the UCSC Genome Browser.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000144891 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000049115 – 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.

[pmid17346243-5] Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S (April 2007). "Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology". Clinical Science. 112 (8): 417–428. doi:10.1042/CS20060342. PMID 17346243. S2CID 27624282.

[pmid6083400-6] Catt KJ, Mendelsohn FA, Millan MA, Aguilera G (1984). "The role of angiotensin II receptors in vascular regulation". Journal of Cardiovascular Pharmacology. 6 (Suppl 4): S575–S586. doi:10.1097/00005344-198406004-00004. PMID 6083400.

[7] Barbella Y, Cierco M, Israel A (April 1993). "Effect of Losartan, a nonpeptide angiotensin II receptor antagonist, on drinking behavior and renal actions of centrally administered renin". Proceedings of the Society for Experimental Biology and Medicine. 202 (4): 401–406. doi:10.3181/00379727-202-43551. PMID 8456103. S2CID 38235497.

[8] Malvin RL, Mouw D, Vander AJ (July 1977). "Angiotensin: physiological role in water-deprivation-induced thirst of rats". Science. 197 (4299): 171–173. Bibcode:1977Sci...197..171M. doi:10.1126/science.877549. PMID 877549.

[9] "Angiotensin II receptor blocker", Wikipedia, 2022-07-26, retrieved 2022-08-10

[10] Wilson JX (1984). "The renin-angiotensin system in nonmammalian vertebrates". Endocrine Reviews. 5 (1): 45–61. doi:10.1210/edrv-5-1-45. PMID 6368215.

[11] Marvar PJ, Goodman J, Fuchs S, Choi DC, Banerjee S, Ressler KJ (June 2014). "Angiotensin type 1 receptor inhibition enhances the extinction of fear memory". Biological Psychiatry. 75 (11): 864–872. doi:10.1016/j.biopsych.2013.08.024. PMC 3975818. PMID 24094510.

[Hurt_2015-12] Hurt RC, Garrett JC, Keifer OP, Linares A, Couling L, Speth RC, et al. (September 2015). "Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear". Genes, Brain and Behavior. 14 (7): 526–533. doi:10.1111/gbb.12235. PMC 4573765. PMID 26257395.

[entrez-13] "Entrez Gene: AGTR1 angiotensin II receptor, type 1".

[pmid_33100208-14] Sharma B, Jaiswal V, Khan MA (October 2020). "In silico Approach for Exploring the Role of AT1R Polymorphism on its Function, Structure and Drug Interactions". Current Computer-Aided Drug Design. 17 (7): 927–935. doi:10.2174/1573409916666201023113709. PMID 33100208. S2CID 225071659.

[pmid14657020-15] Senbonmatsu T, Saito T, Landon EJ, Watanabe O, Price E, Roberts RL, et al. (December 2003). "A novel angiotensin II type 2 receptor signaling pathway: possible role in cardiac hypertrophy". The EMBO Journal. 22 (24): 6471–6482. doi:10.1093/emboj/cdg637. PMC 291832. PMID 14657020.

[IDSN=389ON-16] Elton TS, Kuhn DE, Malana GE, Martin MM, Nuovo GJ, Pleister AP, Feldman DS (2007). "MiR-132 Regulates Angiotensin II Type 1 Receptor Expression Through a Protein Coding Region Binding Site". Circulation. 118 (18): S513.

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@@ Line 1: / Line 1: @@
+{{Short description|Protein-coding gene in the species Homo sapiens}}
+{{cs1 config|name-list-style=vanc}}
 {{Infobox gene}}
-'''Angiotensin II receptor type 1''' or '''AT<sub>1</sub> receptor''' is the best characterized [[angiotensin receptor]]. It has [[vasopressor]] effects and regulates [[aldosterone]] secretion. It is an important effector controlling [[blood pressure]] and [[blood volume|volume]] in the [[cardiovascular system]]. [[Angiotensin II receptor antagonist]]s are drugs indicated for [[hypertension]], [[diabetic nephropathy]] and [[congestive heart failure]].
+'''Angiotensin II receptor type 1''' '''(AT1)''' is a [[Gq alpha subunit|G<sub>q/11</sub>]]-coupled [[G protein-coupled receptor]] (GPCR) and the best characterized [[angiotensin receptor]]. It is encoded in humans by the ''AGTR1'' [[gene]]. AT1 has [[vasopressor]] effects and regulates [[aldosterone]] secretion. It is an important effector controlling [[blood pressure]] and [[blood volume|volume]] in the [[cardiovascular system]]. [[Angiotensin II receptor blocker]]s are drugs indicated for [[hypertension]], [[diabetic nephropathy]] and [[congestive heart failure]].
-== Function ==
+== Signaling cascade ==
-The AT<sub>1</sub> receptor mediates the major cardiovascular effects of angiotensin II. Effects include [[Vasoconstrictor|vasoconstriction]], [[aldosterone]] synthesis and secretion, increased [[vasopressin]] secretion, [[heart|cardiac]] [[Organ hypertrophy|hypertrophy]], augmentation of peripheral [[noradrenaline|noradrenergic activity]], [[blood vessel|vascular]] [[smooth muscle]] cells proliferation, decreased [[kidney|renal]] blood flow, renal [[renin]] inhibition, renal tubular [[sodium]] reuptake, modulation of central [[sympathetic nervous system]] activity, cardiac contractility, central [[osmoregulation|osmocontrol]] and [[extracellular matrix]] formation.<ref name="pmid6083400">{{cite journal | vauthors = Catt KJ, Mendelsohn FA, Millan MA, Aguilera G | title = The role of angiotensin II receptors in vascular regulation | journal = Journal of Cardiovascular Pharmacology | volume = 6 Suppl 4 | issue = Suppl 4 | pages = S575-86 | year = 1984 | pmid = 6083400 | doi = 10.1097/00005344-198406004-00004 }}</ref>
+The angiotensin receptor is activated by the [[vasoconstriction|vasoconstricting]] peptide [[angiotensin|angiotensin II]]. The activated receptor in turn couples to [[Gq alpha subunit|G<sub>q/11</sub>]] and thus activates [[phospholipase|phospholipase C]] and increases the cytosolic Ca<sup>2+</sup> concentrations, which in turn triggers cellular responses such as stimulation of [[protein kinase C]]. Activated receptor also inhibits [[adenylate cyclase]] in hepatocytes and activates various [[tyrosine kinase]]s.<ref name="pmid17346243">{{cite journal | vauthors = Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S | title = Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology | journal = Clinical Science | volume = 112 | issue = 8 | pages = 417–428 | date = April 2007 | pmid = 17346243 | doi = 10.1042/CS20060342 | s2cid = 27624282 }}</ref>
-== Mechanism ==
+== Function ==
+The AT1 receptor mediates the major cardiovascular effects of angiotensin II. Effects include [[Vasoconstrictor|vasoconstriction]], [[aldosterone]] synthesis and secretion, increased [[vasopressin]] secretion, [[heart|cardiac]] hypertrophy, augmentation of peripheral [[noradrenaline|noradrenergic activity]], [[blood vessel|vascular]] [[smooth muscle]] cells proliferation, decreased [[kidney|renal]] blood flow, renal [[renin]] inhibition, renal tubular [[sodium]] reuptake, modulation of central [[sympathetic nervous system]] activity, cardiac contractility, central [[osmoregulation|osmocontrol]] and [[extracellular matrix]] formation.<ref name="pmid6083400">{{cite journal | vauthors = Catt KJ, Mendelsohn FA, Millan MA, Aguilera G | title = The role of angiotensin II receptors in vascular regulation | journal = Journal of Cardiovascular Pharmacology | volume = 6 | issue = Suppl 4 | pages = S575–S586 | year = 1984 | pmid = 6083400 | doi = 10.1097/00005344-198406004-00004 | doi-access = free }}</ref> The main function of angiotensin II in the brain is to stimulate drinking behavior, an effect that is mediated by the AT1 receptor.<ref>{{cite journal | vauthors = Barbella Y, Cierco M, Israel A | title = Effect of Losartan, a nonpeptide angiotensin II receptor antagonist, on drinking behavior and renal actions of centrally administered renin | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 202 | issue = 4 | pages = 401–406 | date = April 1993 | pmid = 8456103 | doi = 10.3181/00379727-202-43551 | s2cid = 38235497 }}</ref><ref>{{cite journal | vauthors = Malvin RL, Mouw D, Vander AJ | title = Angiotensin: physiological role in water-deprivation-induced thirst of rats | journal = Science | volume = 197 | issue = 4299 | pages = 171–173 | date = July 1977 | pmid = 877549 | doi = 10.1126/science.877549 | bibcode = 1977Sci...197..171M }}</ref>
-The angiotensin receptor is activated by the [[vasoconstriction|vasoconstricting]] peptide [[angiotensin|angiotensin II]]. The activated receptor in turn couples to [[Gq alpha subunit|G<sub>q/11</sub>]] and thus activates [[phospholipase|phospholipase C]] and increases the cytosolic Ca<sup>2+</sup> concentrations, which in turn triggers cellular responses such as stimulation of [[protein kinase C]]. Activated receptor also inhibits [[adenylate cyclase]] and activates various [[tyrosine kinase]]s.<ref name="pmid17346243">{{cite journal | vauthors = Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S | title = Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology | journal = Clinical Science | volume = 112 | issue = 8 | pages = 417–28 | date = Apr 2007 | pmid = 17346243 | doi = 10.1042/CS20060342 }}</ref>
 == Clinical significance ==
+Due to the hemodynamic pressure and volume effects mediated by AT1 receptors, AT1 receptor antagonists are widely prescribed drugs in the management of hypertension and stable heart failure.<ref>{{Citation |title=Angiotensin II receptor blocker |date=2022-07-26 |url=https://en.wikipedia.org/w/index.php?title=Angiotensin_II_receptor_blocker&oldid=1100586375 |work=Wikipedia |language=en |access-date=2022-08-10}}</ref>
-The AT<sub>1</sub> receptor may play role in the generation of [[reperfusion arrhythmia]]s following restoration of blood flow to [[ischemic]] or [[infarcted]] myocardium.{{citation needed|date=November 2015}}
-The AT<sub>1</sub> receptor has also been implicated in [[post-traumatic stress disorder]],<ref>{{cite journal | vauthors = Khoury NM, Marvar PJ, Gillespie CF, Wingo A, Schwartz A, Bradley B, Kramer M, Ressler KJ | title = The renin-angiotensin pathway in posttraumatic stress disorder: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are associated with fewer traumatic stress symptoms | journal = The Journal of Clinical Psychiatry | volume = 73 | issue = 6 | pages = 849–55 | date = Jun 2012 | pmid = 22687631 | pmc = 4087173 | doi = 10.4088/JCP.11m07316 }}</ref>{{Unreliable medical source|date=October 2015|sure=y}}
 == Animal studies ==
+Elements of the renin-angiotensin system have been widely studied in a large variety of vertebrate animals including amphibians, reptiles, birds, and mammals.<ref>{{cite journal | vauthors = Wilson JX | title = The renin-angiotensin system in nonmammalian vertebrates | journal = Endocrine Reviews | volume = 5 | issue = 1 | pages = 45–61 | date = 1984 | pmid = 6368215 | doi = 10.1210/edrv-5-1-45 }}</ref>
-AT<sub>1</sub> receptor antagonists have been shown to reduce fear memory recall in mice.<ref>{{cite journal | vauthors = Marvar PJ, Goodman J, Fuchs S, Choi DC, Banerjee S, Ressler KJ | title = Angiotensin type 1 receptor inhibition enhances the extinction of fear memory | journal = Biological Psychiatry | volume = 75 | issue = 11 | pages = 864–72 | date = Jun 2014 | pmid = 24094510 | pmc = 3975818 | doi = 10.1016/j.biopsych.2013.08.024 }}</ref><ref name="Hurt 2015">{{cite journal | vauthors = Hurt RC, Garrett JC, Keifer OP, Linares A, Couling L, Speth RC, Ressler KJ, Marvar PJ | title = Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear(1) | journal = Genes, Brain, and Behavior | volume = 14 | issue = 7 | pages = 526–33 | date = Sep 2015 | pmid = 26257395 | doi = 10.1111/gbb.12235 | pmc = 4573765 }}</ref>
+AT1 receptor blockers have been shown to reduce fear memory recall in mice, but the reliability and relevance of this finding are to be determined.<ref>{{cite journal | vauthors = Marvar PJ, Goodman J, Fuchs S, Choi DC, Banerjee S, Ressler KJ | title = Angiotensin type 1 receptor inhibition enhances the extinction of fear memory | journal = Biological Psychiatry | volume = 75 | issue = 11 | pages = 864–872 | date = June 2014 | pmid = 24094510 | pmc = 3975818 | doi = 10.1016/j.biopsych.2013.08.024 }}</ref><ref name="Hurt 2015">{{cite journal | vauthors = Hurt RC, Garrett JC, Keifer OP, Linares A, Couling L, Speth RC, Ressler KJ, Marvar PJ | display-authors = 6 | title = Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear | journal = Genes, Brain and Behavior | volume = 14 | issue = 7 | pages = 526–533 | date = September 2015 | pmid = 26257395 | pmc = 4573765 | doi = 10.1111/gbb.12235 }}</ref>
 == Gene ==
-It was previously thought that a related gene, denoted as AGTR1B, existed; however, it is now believed that there is only one type 1 receptor gene in humans. At least four [[transcript variant]]s have been described for this gene. Additional variants have been described but their full-length nature has not been determined. The entire coding sequence is contained in the terminal exon and is present in all transcript variants.<ref name="entrez">{{cite web | title = Entrez Gene: AGTR1 angiotensin II receptor, type 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=185| accessdate = }}</ref>
+It was previously thought that a related gene, denoted as ''AGTR1B'', existed; however, it is now believed that there is only one type 1 receptor gene in humans. At least four [[transcript variant]]s have been described for this gene. Additional variants have been described but their full-length nature has not been determined. The entire coding sequence is contained in the terminal exon and is present in all transcript variants.<ref name="entrez">{{cite web | title = Entrez Gene: AGTR1 angiotensin II receptor, type 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=185}}</ref>
+A huge number of polymorphisms is reported in the databases for AT1R which provide an avenue to explore these polymorphisms for their implications in protein structure, function and drug efficacy. Methods In the current study all the SNPs (10234) reported in NCBI were analyzed and SNPs which were important in protein structure and drug interactions were identified. Structures of these polymorphic forms were modeled and in silico drug interaction studies were carried out. Results Result of the interaction studies with polymorphism was in correlation with the reported case. Two SNP mutated structures of AT1R i.e. rs780860717 (G288T), rs868647200 (A182C) shows considerably less binding affinities in case of all angiotensin receptor blockers (ARBs).<ref name="pmid 33100208">{{cite journal | vauthors = Sharma B, Jaiswal V, Khan MA | title = ''In silico'' Approach for Exploring the Role of AT1R Polymorphism on its Function, Structure and Drug Interactions | journal = Current Computer-Aided Drug Design | volume = 17 | issue = 7 | pages = 927–935 | date = October 2020 | pmid = 33100208 | doi = 10.2174/1573409916666201023113709 | s2cid = 225071659 }}</ref>
 == Interactions ==
-Angiotensin II receptor type 1 has been shown to [[Protein-protein interaction|interact]] with [[Zinc finger and BTB domain-containing protein 16]].<ref name="pmid14657020">{{cite journal | vauthors = Senbonmatsu T, Saito T, Landon EJ, Watanabe O, Price E, Roberts RL, Imboden H, Fitzgerald TG, Gaffney FA, Inagami T | title = A novel angiotensin II type 2 receptor signaling pathway: possible role in cardiac hypertrophy | journal = The EMBO Journal | volume = 22 | issue = 24 | pages = 6471–82 | date = Dec 2003 | pmid = 14657020 | pmc = 291832 | doi = 10.1093/emboj/cdg637 }}</ref> The protein's mRNA has been reported to interact with [[Mir-132 microRNA]] as part of an RNA silencing mechanism that reduces receptor expression.<ref name="IDSN=389ON ">{{cite journal |vauthors =Elton TS, Kuhn DE, Malana GE, Martin MM, Nuovo GJ, Pleister AP, Feldman DS |title=MiR-132 Regulates Angiotensin II Type 1 Receptor Expression Through a Protein Coding Region Binding Site|journal=Circulation|volume=118 |issue=18 |pages=S513|year=2007|url=http://circ.ahajournals.org/cgi/content/meeting_abstract/118/18_MeetingAbstracts/S_513}}</ref>
+Angiotensin II receptor type 1 has been shown to [[Protein-protein interaction|interact]] with [[Zinc finger and BTB domain-containing protein 16]].<ref name="pmid14657020">{{cite journal | vauthors = Senbonmatsu T, Saito T, Landon EJ, Watanabe O, Price E, Roberts RL, Imboden H, Fitzgerald TG, Gaffney FA, Inagami T | display-authors = 6 | title = A novel angiotensin II type 2 receptor signaling pathway: possible role in cardiac hypertrophy | journal = The EMBO Journal | volume = 22 | issue = 24 | pages = 6471–6482 | date = December 2003 | pmid = 14657020 | pmc = 291832 | doi = 10.1093/emboj/cdg637 }}</ref> The protein's mRNA has been reported to interact with [[Mir-132 microRNA]] as part of an RNA silencing mechanism that reduces receptor expression.<ref name="IDSN=389ON ">{{cite journal |vauthors =Elton TS, Kuhn DE, Malana GE, Martin MM, Nuovo GJ, Pleister AP, Feldman DS |title=MiR-132 Regulates Angiotensin II Type 1 Receptor Expression Through a Protein Coding Region Binding Site|journal=Circulation|volume=118 |issue=18 |pages=S513|year=2007|url=http://circ.ahajournals.org/cgi/content/meeting_abstract/118/18_MeetingAbstracts/S_513}}</ref>
 == References ==
@@ Line 35: / Line 39: @@
 == Further reading ==
 {{refbegin|33em}}
-* {{cite journal | vauthors = Matsusaka T, Ichikawa I | title = Biological functions of angiotensin and its receptors | journal = Annual Review of Physiology | volume = 59 | issue =  | pages = 395–412 | year = 1997 | pmid = 9074770 | doi = 10.1146/annurev.physiol.59.1.395 }}
+* {{cite journal | vauthors = Matsusaka T, Ichikawa I | title = Biological functions of angiotensin and its receptors | journal = Annual Review of Physiology | volume = 59 | pages = 395–412 | year = 1997 | pmid = 9074770 | doi = 10.1146/annurev.physiol.59.1.395 }}
-* {{cite journal | vauthors = Allen AM, Moeller I, Jenkins TA, Zhuo J, Aldred GP, Chai SY, Mendelsohn FA | title = Angiotensin receptors in the nervous system | journal = Brain Research Bulletin | volume = 47 | issue = 1 | pages = 17–28 | date = Sep 1998 | pmid = 9766385 | doi = 10.1016/S0361-9230(98)00039-2 }}
+* {{cite journal | vauthors = Allen AM, Moeller I, Jenkins TA, Zhuo J, Aldred GP, Chai SY, Mendelsohn FA | title = Angiotensin receptors in the nervous system | journal = Brain Research Bulletin | volume = 47 | issue = 1 | pages = 17–28 | date = September 1998 | pmid = 9766385 | doi = 10.1016/S0361-9230(98)00039-2 | s2cid = 24936475 }}
-* {{cite journal | vauthors = Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG | title = Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 281 | issue = 6 | pages = H2337-65 | date = Dec 2001 | pmid = 11709400 | doi =  10.1152/ajpheart.2001.281.6.H2337}}
+* {{cite journal | vauthors = Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG | title = Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 281 | issue = 6 | pages = H2337–H2365 | date = December 2001 | pmid = 11709400 | doi = 10.1152/ajpheart.2001.281.6.H2337 | s2cid = 41296327 }}
-* {{cite journal | vauthors = Arima S, Ito S | title = New insights into actions of the renin-angiotensin system in the kidney: concentrating on the Ang II receptors and the newly described Ang-(1-7) and its receptor | journal = Seminars in Nephrology | volume = 21 | issue = 6 | pages = 535–43 | date = Nov 2001 | pmid = 11709801 | doi = 10.1053/snep.2001.26792 }}
+* {{cite journal | vauthors = Arima S, Ito S | title = New insights into actions of the renin-angiotensin system in the kidney: concentrating on the Ang II receptors and the newly described Ang-(1-7) and its receptor | journal = Seminars in Nephrology | volume = 21 | issue = 6 | pages = 535–543 | date = November 2001 | pmid = 11709801 | doi = 10.1053/snep.2001.26792 }}
-* {{cite journal | vauthors = Stowasser M, Gunasekera TG, Gordon RD | title = Familial varieties of primary aldosteronism | journal = Clinical and Experimental Pharmacology & Physiology | volume = 28 | issue = 12 | pages = 1087–90 | date = Dec 2001 | pmid = 11903322 | doi = 10.1046/j.1440-1681.2001.03574.x }}
+* {{cite journal | vauthors = Stowasser M, Gunasekera TG, Gordon RD | title = Familial varieties of primary aldosteronism | journal = Clinical and Experimental Pharmacology & Physiology | volume = 28 | issue = 12 | pages = 1087–1090 | date = December 2001 | pmid = 11903322 | doi = 10.1046/j.1440-1681.2001.03574.x | s2cid = 23091842 }}
-* {{cite journal | vauthors = Padmanabhan N, Padmanabhan S, Connell JM | title = Genetic basis of cardiovascular disease--the renin-angiotensin-aldosterone system as a paradigm | journal = Journal of the Renin-Angiotensin-Aldosterone System | volume = 1 | issue = 4 | pages = 316–24 | date = Dec 2000 | pmid = 11967817 | doi = 10.3317/jraas.2000.060 }}
+* {{cite journal | vauthors = Padmanabhan N, Padmanabhan S, Connell JM | title = Genetic basis of cardiovascular disease--the renin-angiotensin-aldosterone system as a paradigm | journal = Journal of the Renin-Angiotensin-Aldosterone System | volume = 1 | issue = 4 | pages = 316–324 | date = December 2000 | pmid = 11967817 | doi = 10.3317/jraas.2000.060 | doi-access = free }}
-* {{cite journal | vauthors = Thibonnier M, Coles P, Thibonnier A, Shoham M | title = Molecular pharmacology and modeling of vasopressin receptors | journal = Progress in Brain Research | volume = 139 | issue =  | pages = 179–96 | year = 2002 | pmid = 12436935 | doi = 10.1016/S0079-6123(02)39016-2 | isbn = 978-0-444-50982-6 }}
+* {{cite book | vauthors = Thibonnier M, Coles P, Thibonnier A, Shoham M | chapter = Chapter 14 Molecular pharmacology and modeling of vasopressin receptors | title = Vasopressin and Oxytocin: From Genes to Clinical Applications | series = Progress in Brain Research | volume = 139 | pages = 179–96 | year = 2002 | pmid = 12436935 | doi = 10.1016/S0079-6123(02)39016-2 | isbn = 978-0-444-50982-6 }}
-* {{cite journal | vauthors = Elton TS, Martin MM | title = Alternative splicing: a novel mechanism to fine-tune the expression and function of the human AT1 receptor | journal = Trends in Endocrinology and Metabolism | volume = 14 | issue = 2 | pages = 66–71 | date = Mar 2003 | pmid = 12591176 | doi = 10.1016/S1043-2760(02)00038-3 }}
+* {{cite journal | vauthors = Elton TS, Martin MM | title = Alternative splicing: a novel mechanism to fine-tune the expression and function of the human AT1 receptor | journal = Trends in Endocrinology and Metabolism | volume = 14 | issue = 2 | pages = 66–71 | date = March 2003 | pmid = 12591176 | doi = 10.1016/S1043-2760(02)00038-3 | s2cid = 45146964 }}
-* {{cite journal | vauthors = Saavedra JM, Benicky J, Zhou J | title = Mechanisms of the Anti-Ischemic Effect of Angiotensin II AT( 1 ) Receptor Antagonists in the Brain | journal = Cellular and Molecular Neurobiology | volume = 26 | issue = 7–8 | pages = 1099–111 | year = 2007 | pmid = 16636899 | doi = 10.1007/s10571-006-9009-0 }}
+* {{cite journal | vauthors = Saavedra JM, Benicky J, Zhou J | title = Mechanisms of the Anti-Ischemic Effect of Angiotensin II AT( 1 ) Receptor Antagonists in the Brain | journal = Cellular and Molecular Neurobiology | volume = 26 | issue = 7–8 | pages = 1099–1111 | year = 2007 | pmid = 16636899 | doi = 10.1007/s10571-006-9009-0 | s2cid = 20245643 | url = https://zenodo.org/record/1232792 }}
-* {{cite journal | vauthors = Oliveira L, Costa-Neto CM, Nakaie CR, Schreier S, Shimuta SI, Paiva AC | title = The angiotensin II AT1 receptor structure-activity correlations in the light of rhodopsin structure | journal = Physiological Reviews | volume = 87 | issue = 2 | pages = 565–92 | date = Apr 2007 | pmid = 17429042 | doi = 10.1152/physrev.00040.2005 }}
+* {{cite journal | vauthors = Oliveira L, Costa-Neto CM, Nakaie CR, Schreier S, Shimuta SI, Paiva AC | title = The angiotensin II AT1 receptor structure-activity correlations in the light of rhodopsin structure | journal = Physiological Reviews | volume = 87 | issue = 2 | pages = 565–592 | date = April 2007 | pmid = 17429042 | doi = 10.1152/physrev.00040.2005 }}
-* {{cite journal | vauthors = Ariza AC, Bobadilla NA, Halhali A | title = [Endothelin 1 and angiotensin II in preeeclampsia] | journal = Revista De Investigación Clínica; Organo Del Hospital De Enfermedades De La Nutrición | volume = 59 | issue = 1 | pages = 48–56 | year = 2007 | pmid = 17569300 | doi =  }}
+* {{cite journal | vauthors = Ariza AC, Bobadilla NA, Halhali A | title = [Endothelin 1 and angiotensin II in preeeclampsia] | journal = Revista de Investigacion Clinica | volume = 59 | issue = 1 | pages = 48–56 | year = 2007 | pmid = 17569300 }}
-* {{cite journal | vauthors = Xia Y, Zhou CC, Ramin SM, Kellems RE | title = Angiotensin receptors, autoimmunity, and preeclampsia | journal = Journal of Immunology | volume = 179 | issue = 6 | pages = 3391–5 | date = Sep 2007 | pmid = 17785770 | pmc = 3262172 | doi = 10.4049/jimmunol.179.6.3391 }}
+* {{cite journal | vauthors = Xia Y, Zhou CC, Ramin SM, Kellems RE | title = Angiotensin receptors, autoimmunity, and preeclampsia | journal = Journal of Immunology | volume = 179 | issue = 6 | pages = 3391–3395 | date = September 2007 | pmid = 17785770 | pmc = 3262172 | doi = 10.4049/jimmunol.179.6.3391 }}
-* {{cite journal | vauthors = Mauzy CA, Hwang O, Egloff AM, Wu LH, Chung FZ | title = Cloning, expression, and characterization of a gene encoding the human angiotensin II type 1A receptor | journal = Biochemical and Biophysical Research Communications | volume = 186 | issue = 1 | pages = 277–84 | date = Jul 1992 | pmid = 1378723 | doi = 10.1016/S0006-291X(05)80804-6 }}
+* {{cite journal | vauthors = Mauzy CA, Hwang O, Egloff AM, Wu LH, Chung FZ | title = Cloning, expression, and characterization of a gene encoding the human angiotensin II type 1A receptor | journal = Biochemical and Biophysical Research Communications | volume = 186 | issue = 1 | pages = 277–284 | date = July 1992 | pmid = 1378723 | doi = 10.1016/S0006-291X(05)80804-6 }}
-* {{cite journal | vauthors = Curnow KM, Pascoe L, White PC | title = Genetic analysis of the human type-1 angiotensin II receptor | journal = Molecular Endocrinology | volume = 6 | issue = 7 | pages = 1113–8 | date = Jul 1992 | pmid = 1508224 | doi = 10.1210/me.6.7.1113 }}
+* {{cite journal | vauthors = Curnow KM, Pascoe L, White PC | title = Genetic analysis of the human type-1 angiotensin II receptor | journal = Molecular Endocrinology | volume = 6 | issue = 7 | pages = 1113–1118 | date = July 1992 | pmid = 1508224 | doi = 10.1210/mend.6.7.1508224 | doi-access = free }}
-* {{cite journal | vauthors = Furuta H, Guo DF, Inagami T | title = Molecular cloning and sequencing of the gene encoding human angiotensin II type 1 receptor | journal = Biochemical and Biophysical Research Communications | volume = 183 | issue = 1 | pages = 8–13 | date = Feb 1992 | pmid = 1543512 | doi = 10.1016/0006-291X(92)91600-U }}
+* {{cite journal | vauthors = Furuta H, Guo DF, Inagami T | title = Molecular cloning and sequencing of the gene encoding human angiotensin II type 1 receptor | journal = Biochemical and Biophysical Research Communications | volume = 183 | issue = 1 | pages = 8–13 | date = February 1992 | pmid = 1543512 | doi = 10.1016/0006-291X(92)91600-U }}
-* {{cite journal | vauthors = Takayanagi R, Ohnaka K, Sakai Y, Nakao R, Yanase T, Haji M, Inagami T, Furuta H, Gou DF, Nakamuta M | title = Molecular cloning, sequence analysis and expression of a cDNA encoding human type-1 angiotensin II receptor | journal = Biochemical and Biophysical Research Communications | volume = 183 | issue = 2 | pages = 910–6 | date = Mar 1992 | pmid = 1550596 | doi = 10.1016/0006-291X(92)90570-B }}
+* {{cite journal | vauthors = Takayanagi R, Ohnaka K, Sakai Y, Nakao R, Yanase T, Haji M, Inagami T, Furuta H, Gou DF, Nakamuta M | display-authors = 6 | title = Molecular cloning, sequence analysis and expression of a cDNA encoding human type-1 angiotensin II receptor | journal = Biochemical and Biophysical Research Communications | volume = 183 | issue = 2 | pages = 910–916 | date = March 1992 | pmid = 1550596 | doi = 10.1016/0006-291X(92)90570-B }}
-* {{cite journal | vauthors = Bergsma DJ, Ellis C, Kumar C, Nuthulaganti P, Kersten H, Elshourbagy N, Griffin E, Stadel JM, Aiyar N | title = Cloning and characterization of a human angiotensin II type 1 receptor | journal = Biochemical and Biophysical Research Communications | volume = 183 | issue = 3 | pages = 989–95 | date = Mar 1992 | pmid = 1567413 | doi = 10.1016/S0006-291X(05)80288-8 }}
+* {{cite journal | vauthors = Bergsma DJ, Ellis C, Kumar C, Nuthulaganti P, Kersten H, Elshourbagy N, Griffin E, Stadel JM, Aiyar N | display-authors = 6 | title = Cloning and characterization of a human angiotensin II type 1 receptor | journal = Biochemical and Biophysical Research Communications | volume = 183 | issue = 3 | pages = 989–995 | date = March 1992 | pmid = 1567413 | doi = 10.1016/S0006-291X(05)80288-8 | s2cid = 19816702 }}
-* {{cite journal | vauthors = Gemmill RM, Drabkin HA | title = Report of the Second International Workshop on Human Chromosome 3 mapping | journal = Cytogenetics and Cell Genetics | volume = 57 | issue = 4 | pages = 162–6 | year = 1992 | pmid = 1683828 | doi = 10.1159/000133138 }}
+* {{cite journal | vauthors = Gemmill RM, Drabkin HA | title = Report of the Second International Workshop on Human Chromosome 3 mapping | journal = Cytogenetics and Cell Genetics | volume = 57 | issue = 4 | pages = 162–166 | year = 1992 | pmid = 1683828 | doi = 10.1159/000133138 }}
-* {{cite journal | vauthors = Curnow KM, Pascoe L, Davies E, White PC, Corvol P, Clauser E | title = Alternatively spliced human type 1 angiotensin II receptor mRNAs are translated at different efficiencies and encode two receptor isoforms | journal = Molecular Endocrinology | volume = 9 | issue = 9 | pages = 1250–62 | date = Sep 1995 | pmid = 7491117 | doi = 10.1210/me.9.9.1250 }}
+* {{cite journal | vauthors = Curnow KM, Pascoe L, Davies E, White PC, Corvol P, Clauser E | title = Alternatively spliced human type 1 angiotensin II receptor mRNAs are translated at different efficiencies and encode two receptor isoforms | journal = Molecular Endocrinology | volume = 9 | issue = 9 | pages = 1250–1262 | date = September 1995 | pmid = 7491117 | doi = 10.1210/mend.9.9.7491117 | s2cid = 46112700 | doi-access = free }}
-* {{cite journal | vauthors = Marrero MB, Schieffer B, Paxton WG, Heerdt L, Berk BC, Delafontaine P, Bernstein KE | title = Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor | journal = Nature | volume = 375 | issue = 6528 | pages = 247–50 | date = May 1995 | pmid = 7746328 | doi = 10.1038/375247a0 }}
+* {{cite journal | vauthors = Marrero MB, Schieffer B, Paxton WG, Heerdt L, Berk BC, Delafontaine P, Bernstein KE | title = Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor | journal = Nature | volume = 375 | issue = 6528 | pages = 247–250 | date = May 1995 | pmid = 7746328 | doi = 10.1038/375247a0 | bibcode = 1995Natur.375..247M | s2cid = 4272223 }}
 {{refend}}
 == External links ==
-* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2200 | title = Angiotensin Receptors: AT<sub>1</sub>  | accessdate = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archiveurl = | archivedate = | quote = }}
+* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2200 | title = Angiotensin Receptors: AT<sub>1</sub> | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | access-date = 2008-11-25 | archive-date = 2014-02-28 | archive-url = https://web.archive.org/web/20140228203645/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2200 | url-status = dead }}
 * {{UCSC gene info|AGTR1}}