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Angiotensin II receptor type 2

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AGTR2
Identifiers
AliasesAGTR2, AT2, ATGR2, MRX88, Angiotensin II receptor type 2
External IDsOMIM: 300034; MGI: 87966; HomoloGene: 20172; GeneCards: AGTR2; OMA:AGTR2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

186

11609

Ensembl

ENSG00000180772

ENSMUSG00000068122

UniProt

P50052

P35374

RefSeq (mRNA)

NM_000686
NM_001385624

NM_007429

RefSeq (protein)

NP_000677

NP_031455

Location (UCSC)Chr X: 116.17 – 116.17 MbChr X: 21.35 – 21.36 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

Function

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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). Consistent with its apoptotic function, angiotensin II receptor type II also opposes cell proliferation, as demonstrated by its antagonism of MAPK activity in cardiac fibroblasts during interstitial fibrosis.[6] 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.[7]

Gene

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Angiotensin II receptor type 2 (AGTR2) gene is a protein coding gene responsible for encoding AGTR2, the integral membrane protein that binds to two different G-protein coupled receptors. AGTR2 has recently been discovered to play a role in modifying lung disease. This receptor functions to mediate signaling in lung fibrosis and regulate nitric oxide synthase expression in pulmonary endothelium. [8] AGTR2 has recently been prescribed as a target for lung inflammation therapy in cases of cystic fibrosis (CF). The X-chromosome region associated with CF lung disease is located in a non-coding region 3′ of the AGTR2 gene. The modification effect is likely due to variation in gene regulation rather than a change in protein coding sequence.

Variants at the X-chromosome locus containing AGTR2 gene were identified as significantly associating with lung function in patients with cystic fibrosis. Genetically modified mouse studies determined that absence of the AGTR2 gene normalized pulmonary function indicators in two independent CF mouse models. Furthermore, pharmacological antagonism of AGTR2 signaling improved lung function in CF mice to near wild-type levels. Manipulation of the angiotensin-signaling pathway to reduce AGTR2 signaling may be translatable for the treatment or prevention of CF.[9]

Interactions

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Angiotensin II receptor type 2 has been shown to interact with MTUS1.[10]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000180772 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "Entrez Gene: AGTR2 angiotensin II receptor, type 2".
  6. ^ Tsutsumi Y, Matsubara H, Ohkubo N, Mori Y, Nozawa Y, Murasawa S, et al. (November 1998). "Angiotensin II type 2 receptor is upregulated in human heart with interstitial fibrosis, and cardiac fibroblasts are the major cell type for its expression". Circulation Research. 83 (10): 1035–1046. doi:10.1161/01.RES.83.10.1035. PMID 9815151.
  7. ^ 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.
  8. ^ Darrah RJ, Jacono FJ, Joshi N, Mitchell AL, Sattar A, Campanaro CK, et al. (January 2019). "AGTR2 absence or antagonism prevents cystic fibrosis pulmonary manifestations". Journal of Cystic Fibrosis. 18 (1): 127–134. doi:10.1016/j.jcf.2018.05.013. PMC 6830504. PMID 29937318.
  9. ^ Corvol H, Blackman SM, Boëlle PY, Gallins PJ, Pace RG, Stonebraker JR, et al. (September 2015). "Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis". Nature Communications. 6 (1): 8382. Bibcode:2015NatCo...6.8382C. doi:10.1038/ncomms9382. PMC 4589222. PMID 26417704.
  10. ^ 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.


Further reading

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