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FLASH GENE

Symbol

AGTR2

contributors: mct - updated : 06-04-2020

HGNC name	angiotensin II receptor, type 2
HGNC id	338

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MRX88 mental retardation, 88
Location	Xq23      Physical location : 115.301.957 - 115.306.223
Synonym name	angiotensin receptor 2
Synonym symbol(s)	AT2, ATGR2, AT2R, MRX88

DNA

TYPE	like-sequence
STRUCTURE	4.27 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000686 3 - 2906 NP_000677 - 363 - 2007 17630322

EXPRESSION

Type	restricted

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Homo sapiens Nervous brain hindbrain cerebellum       brain basal nuclei striatum     Homo sapiens   ganglia sensory ganglia dorsal root     Rattus norvegicus Fetal   ganglia sensory ganglia dorsal root     Rattus norvegicus Adult Urinary kidney tubule       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular smouth uterus myometrium   Muscular striatum cardiac     Homo sapiens Muscular striatum skeletal     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Homo sapiens Cardiovascular endothelial cell Homo sapiens Digestive hepatocyte Homo sapiens Muscular myocyte Homo sapiens Urinary tubular cell Homo sapiens

cell lineage
cell lines
fluid/secretion	in human semen

at STAGE

physiological period

embryo, fetal

Text	abundantly during embryonic development in fetal tissues (kidney, intestine, brain)

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	seven transmembrane segments (7TM) receptor
	structures revealed an active-like conformation of the seven-transmembrane (7TM) helical bundle with a non-canonical positioning of the amphipathic helix VIII, potentially blocking recruitment of intracellular signaling partners

HOMOLOGY

interspecies

ortholog to murine Agtr2

Homologene

FAMILY

G-protein coupled receptor 1 family

CATEGORY

signaling hormone , receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,membrane
text	localization of AGTR2 in the mitochondrial inner membrane

basic FUNCTION	involved in blood pressure regulation
	involved in the activation of dephosphorylating enzymes
	stimulating a phosphotyrosine phosphatase which inhibits guanylate cyclase
	involved in brain development and in trophic maintenance of cerebral neuronal connections
	protecting from severe acute lung injury induced by acid aspiration or sepsis
	AGTR1 and AGTR2, in the striatum exert an opposite effect on the modulation of dopamine synthesis rather than dopamine release
	potential role in the cerebellar function
	modulate mitochondrial respiration
	AGTR1 and AGTR2 reciprocally regulate basal perfusion of muscle microvasculature
	AGTR2 activity is required for normal microvascular responses to insulin
	opposing effects of AGTR1 and AGTR2 on VEGF-driven angiogenesis converge on the regulation of activity of RHOA-ROCK-dependent endothelial cells migration
	induce production of nitric oxide (NO), which may interact with ROS and modulate AGTR1 signaling
	AGTR2-mediated effects may be implicated in the physiological maturation process of the heart
	plays an important role in arterial pressure regulation and may modulate T cell activation and renal cytokine production during pregnancy
	AGTR2 signaling positively regulates myoblast differentiation and potentiates skeletal muscle regenerative potential
	may be involved in the control of sperm motility
	plays a functional role in foetal development
	AGTR2 on peripheral macrophages is a critical trigger for pain sensitization at the site of nerve injury
	translocate to mitochondria and can contribute to reno-protective effects at early stages of diabetes
	role of AGTR2 in improving lipid metabolism and preventing adiposity

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

cardiovascular , nervous system

PATHWAY

metabolism

signaling

hormonal

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with NR1H4 (upregulates AGTR2 expression at a transcriptional level and play a role in the NR1H4-mediated inhibition of ERK activation via upregulation of PTPN6)
	plays a significant role in T3-induced cardioprotection
	AGTR2 inhibits ligand-induced AGTR1 signaling through the PKC-dependent pathway
	AGTR2 regulates TGFBR2 expression and function via the nitric oxide pathway, which may be important in the control of renal tubulointerstitial fibrosis
	IRF1 is one of the key transcriptional factors for the prevention of neointimal formation involving AGTR1, AGTR2
	DPP4, AGTR2, SLC4A1, KREMEN1, ASGR1, ANP, TMEM30A, CLEC4G, and LDLRAD3, along with ACE2 facilitate SARS-CoV-2. virus entry and transmission

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

MRX88

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       in mental retardation constitutional     --over   reduces enhanced collagen accumulation, MMP expression and activity in atherosclerotic regions via inhibition of pro-oxidant signals constitutional     --over   moderate cardiac-selective overexpression of AGTR2 protects heart function from ischaemic injury, which may be mediated, at least in part, through modulation of components of the cardiac renin-angiotensin system and collagen levels in the myocardium constitutional   deletion     in blood cells has a harmful effect on ischemic brain injury constitutional     --over   represents an endogenous protective pathway against vascular calcificationand its stimulation may efficiently reduce adverse cardiovascular events in patients with chronic kidney disease constitutional     --other   altered expression of AGTR1 and AGTR2 with aging may induce mitochondrial dysfunction, the main risk factor for neurodegeneration

Susceptibility

to preeclampsia

Variant & Polymorphism	increasing the risk of preeclampsia
	gender-specific association between AGTR2 polymorphism, kidney function and premature aging of the arterial tree in patients with type I diabetes

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed diabete type 1   targeted AGTR2 overexpression in renal cells may open new avenues to develop novel types of drugs preventing diabetic nephropathy miscelleaneous pain   AGTR2 antagonist showed effective analgesia for neuropathic pain immunology inflammatory   AT2R agonism might represent a novel therapeutic strategy for patients with rheumatoid arthritis cancer urinary   is a promising novel target gene for Bldder cancer gene therapy psychiatry     AGTR2 stimulation may be a new therapeutic approach to improve eating disorder associated with dopamine resistance

ANIMAL & CELL MODELS

	deletion of Agtr2 accelerates adipogenesis in murine mesenchymal stem cells via Wnt10b/beta-catenin signaling
	in female mice via potentially regulating estrogen may have protective role against Body weight gain and impaired glucose tolerance and lipid metabolism