AGTR2 angiotensin II receptor type 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AGTR2provided by HGNC
Official Full Name: angiotensin II receptor type 2provided by HGNC
Primary source: HGNC:HGNC:338
See related: Ensembl:ENSG00000180772 MIM:300034
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AT2; ATGR2; MRX88
Summary: The protein encoded by this gene belongs to the G-protein coupled receptor 1 family, and functions as a receptor for angiotensin II. It is an intergral membrane protein that is highly expressed in fetus and in neonates, but scantily in adult tissues, except brain, adrenal medulla, and atretic ovary. This receptor has been shown to mediate programmed cell death and this apoptotic function may play an important role in developmental biology and pathophysiology. Mutations in this gene are been associated with X-linked cognitive disability. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and SARS-CoV-2 infection results in down-regulation of angiotensin converting enzyme-2 (ACE2) receptors, the effects of which, triggers serious inflammatory lesions in the tissues involved, primarily in the lungs. The inflammatory reaction appears to be mediated by angiotensin II derivatives, including the angiotensin AT2 receptor which has been found to be upregulated in bronchoalveolar lavage samples from Coronavirus disease 2019 (COVID19) patients. [provided by RefSeq, Jul 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for disease process.
Expression: Biased expression in lung (RPKM 5.8), endometrium (RPKM 4.4) and 2 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xq23

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
109.20210226	current	GRCh38.p13 (GCF_000001405.39)	X	NC_000023.11 (116170744..116174974)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (115301997..115306227)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The discovery of a new antibody for BRIL-fused GPCR structure determination.
Title: The discovery of a new antibody for BRIL-fused GPCR structure determination.
Brain Angiotensin Type-1 and Type-2 Receptors in Physiological and Hypertensive Conditions: Focus on Neuroinflammation.
Title: Brain Angiotensin Type-1 and Type-2 Receptors in Physiological and Hypertensive Conditions: Focus on Neuroinflammation.
Seminal levels of angiotensin II and angiotensin II type 2 receptor expression on spermatozoa in varicocele patients: Relation to fertility status.
Title: Seminal levels of angiotensin II and angiotensin II type 2 receptor expression on spermatozoa in varicocele patients: Relation to fertility status.
findings suggest that prior activation of AT2R is prophylactic in preventing LPS-induced renal immune cell infiltration and dysfunction, possibly via IL-10 pathway.
Title: Prevention of lipopolysaccharide-induced CD11b<sup>+</sup> immune cell infiltration in the kidney: role of AT<sub>2</sub> receptors.
High ATGR2 expression is associated with cardiomyocyte hypertrophy and hypercholesterolemia.
Title: Angiotensin II type 2 receptor mediates high fat diet-induced cardiomyocyte hypertrophy and hypercholesterolemia.
AT2R is not expressed in human dorsal root ganglia (DRG) sensory neurons. Expression/activation of AT2R on peripheral/skin macrophages constitutes a critical trigger of mouse and human DRG sensory neuron excitation.
Title: Angiotensin II Triggers Peripheral Macrophage-to-Sensory Neuron Redox Crosstalk to Elicit Pain.
AGT C/T and AT2 G/A polymorphisms were not significantly associated with aneurysmal subarachnoid hemorrhage (aSAH) after controlling for potential confounders. However, a strong trend was identified for a dominant effect of the G allele of the AT2 G/A SNP. Downregulation of the local RAS may contribute to the formation of cerebral aneurysms and subsequent presentation with aSAH.
Title: Association of renin-angiotensin system genetic polymorphisms and aneurysmal subarachnoid hemorrhage.
Both the ACE I/D polymorphism and the AT2 A/C single nucleotide polymorphism were associated with an age-dependent risk of delayed cerebral ischemia, whereas only the ACE I/D polymorphism was associated with poor clinical grade at presentation
Title: Associations of renin-angiotensin system genetic polymorphisms and clinical course after aneurysmal subarachnoid hemorrhage.
We have solved the crystal structure of AT2R binding the peptide ligand [Sar(1), Ile(8)]AngII and its specific antibody at 3.2-A resolution. [Sar(1), Ile(8)]AngII interacts with both the 'core' binding domain, where the small-molecule ligands of AT1R and AT2R bind, and the 'extended' binding domain, which is equivalent to the allosteric modulator binding site of muscarinic acetylcholine receptor.
Title: Crystal structure of the human angiotensin II type 2 receptor bound to an angiotensin II analog.
our study demonstrated that (i) AT2R is overexpressed in the inflamed RA synovial tissue, (ii) the expression of this receptor is strikingly modulated in FLS by pro-inflammatory stimuli, and (iii) exogenous AT2R activation with a selective agonist might represent a potential novel therapeutic strategy for dampening of synovial inflammation in RA.
Title: Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium.

Submit: New GeneRIF Correction See all GeneRIFs (155)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2. GeneReviews: Not available

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-05-10) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-05-10) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AGTR2 (e-PCR)
- UniSTS:498204

GDB:360300 (e-PCR)
- UniSTS:156714

AGTR2__4208 (e-PCR)
- UniSTS:462720

PMC153509P1 (e-PCR)
- UniSTS:271257

STS-U20860 (e-PCR)
- UniSTS:28413

Homology

Homologs of the AGTR2 gene: The AGTR2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 309 organisms have orthologs with human gene AGTR2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
G protein-coupled receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
angiotensin type II receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
angiotensin type II receptor activity	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
receptor antagonist activity	TAS Traceable Author Statement more info	PubMed
transcription factor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
G protein-coupled receptor signaling pathway	IC Inferred by Curator more info	PubMed
G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger	ISS Inferred from Sequence or Structural Similarity more info	PubMed
aldosterone secretion	IEA Inferred from Electronic Annotation more info
angiotensin-activated signaling pathway	IEA Inferred from Electronic Annotation more info
blood vessel remodeling	TAS Traceable Author Statement more info	PubMed
brain development	NAS Non-traceable Author Statement more info	PubMed
cell growth involved in cardiac muscle cell development	IEA Inferred from Electronic Annotation more info
cell surface receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
cellular response to dexamethasone stimulus	IEA Inferred from Electronic Annotation more info
cellular sodium ion homeostasis	IEA Inferred from Electronic Annotation more info
cerebellar cortex development	IEA Inferred from Electronic Annotation more info
dopamine biosynthetic process	IEA Inferred from Electronic Annotation more info
inflammatory response	IBA Inferred from Biological aspect of Ancestor more info	PubMed
intracellular signal transduction	ISS Inferred from Sequence or Structural Similarity more info	PubMed
kidney morphogenesis	IEA Inferred from Electronic Annotation more info
negative regulation of blood vessel endothelial cell migration	NAS Non-traceable Author Statement more info	PubMed
negative regulation of cell growth	TAS Traceable Author Statement more info	PubMed
negative regulation of fibroblast proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of heart rate	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of icosanoid secretion	IEA Inferred from Electronic Annotation more info
negative regulation of neurotrophin TRK receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of norepinephrine secretion	IEA Inferred from Electronic Annotation more info
negative regulation of signaling receptor activity	IEA Inferred from Electronic Annotation more info
nitric oxide mediated signal transduction	IC Inferred by Curator more info	PubMed
nitric oxide mediated signal transduction	TAS Traceable Author Statement more info	PubMed
positive regulation of branching involved in ureteric bud morphogenesis	IEA Inferred from Electronic Annotation more info
positive regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of nitric oxide biosynthetic process	IC Inferred by Curator more info	PubMed
positive regulation of nitric-oxide synthase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
positive regulation of phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of renal sodium excretion	IEA Inferred from Electronic Annotation more info
regulation of blood pressure	TAS Traceable Author Statement more info	PubMed
regulation of protein import into nucleus	IEA Inferred from Electronic Annotation more info
regulation of systemic arterial blood pressure by circulatory renin-angiotensin	ISS Inferred from Sequence or Structural Similarity more info
renin-angiotensin regulation of aldosterone production	IEA Inferred from Electronic Annotation more info
vasodilation	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
integral component of plasma membrane	IC Inferred by Curator more info	PubMed
perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: type-2 angiotensin II receptor

Names: angiotensin II type-2 receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016326.1 RefSeqGene

Range

5040..9270

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000686.5 → NP_000677.2 type-2 angiotensin II receptor isoform 1

See identical proteins and their annotated locations for NP_000677.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AI911273, AL732602, BC095504, CR738498, DA538369, U16957

Consensus CDS

CCDS14569.1

UniProtKB/Swiss-Prot

P50052

Related

ENSP00000360973.4, ENST00000371906.5

Conserved Domains (1) summary

cd15191
Location:45 → 329

7tmA_AT2R; type 2 angiotensin II receptor, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001385624.1 → NP_001372553.1 type-2 angiotensin II receptor isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the non-coding region compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AL732602

Related

ENSP00000505750.1, ENST00000681852.1

Conserved Domains (1) summary

cd15191
Location:45 → 329

7tmA_AT2R; type 2 angiotensin II receptor, member of the class A family of seven-transmembrane G protein-coupled receptors