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FLASH GENE

Symbol

AGTR1

contributors: mct - updated : 10-11-2017

HGNC name	angiotensin II receptor, type 1
HGNC id	336

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	RTD3 renal tubular dysgenesis 3
Location	3q24      Physical location : 148.415.657 - 148.460.788
Synonym name	type 1B angiotensin 2 receptor
	angiotensin receptor 1B
Synonym symbol(s)	AGTR, AT1R, AT1A, AT1B, AT2R1, AG2S, AGTR1A, AGTR1B

DNA

TYPE	functioning gene
STRUCTURE	45.27 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000685 3 splicing 2362 41.1 359 liver,lung,adrenal and adrenocortical adenomas 1992 1378723 NM_004835 3 splicing 2336 41.1 359 liver,lung,adrenal and adrenocortical adenomas 1992 1378723 NM_009585 2 splicing 2278 41.1 359 liver,lung,adrenal and adrenocortical adenomas 1992 1378723 pC1 NM_032049 3 splicing 2236 41.1 359 liver, lung, adrenal and adrenocortical adenomas 1992 1378723 pC4 NM_031850 4 - 2420 44.1 359 - 1992 1378723 pC3

EXPRESSION

Type

widely

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 vessel         Homo sapiens Nervous brain basal nuclei caudate nucleus     Homo sapiens   brain basal nuclei striatum     Homo sapiens Reproductive female system placenta       Homo sapiens Urinary kidney         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular smooth vessel   highly Homo sapiens Muscular striatum       Homo sapiens Muscular striatum cardiac     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 mesenchymal cell Urinary tubular cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	seven transmembrane domains that provide structural support for the formation of the ligand-binding pocket
	two distinct calmodulin binding sites within AGTR1, at juxtamembrane regions of the N-terminus of the third intracellular loop (AAs 214-231) and carboxyl tail (AA 302-317)
	C-terminus (CT) of AGTR1 directly and strongly bound to tubulin and the binding domains were mapped to two consecutive Lys residues at positions 310 and 311 in the CT membrane-proximal region of AGTR1 and the acidic CT of tubulin

mono polymer

heteromer , dimer

HOMOLOGY

interspecies

ortholog to murine Agtr1

Homologene

FAMILY

rhodopsin family

CATEGORY

signaling hormone , receptor

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	major blood pressure regulator (activation of vascular growth)
	activating phospholipase C and A2 inhibiting adenylate cyclase
	fundamental role for AGT/AGTR1 in age-induced vascular dysfunction
	may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions
	G alpha(q/11)-coupled G protein-coupled receptor, inducing membrane blebbing by coupling to RHOA, Rho kinase, and myosin light chain kinase
	AGTR1 and AGTR2, in the striatum exert an opposite effect on the modulation of dopamine synthesis rather than dopamine release
	AGTR1 and AGTR2 reciprocally regulate basal perfusion of muscle microvasculature
	AGTR1 activity restrains muscle metabolic responses to insulin via decreased microvascular recruitment and insulin delivery
	opposing effects of AGTR1 and AGTR2 on VEGF-driven angiogenesis converge on the regulation of activity of RHOA-ROCK-dependent endothelial cells migration
	role for AGTR1 on T lymphocytes to protect the kidney in the setting of hypertension by favorably modulating CD4(+) T helper cell differentiation
	plays a pivotal role in the development of chronic heart failure (CHF), and is upregulated in a number of tissues owing, in part, to transcription factor nuclear factor kappa B (NFKB)
	important role of the microtubule network in the cell surface transport of AGTR1
	may be of crucial importance for the modulation of intestinal epithelial cells apoptosis
	has a central role in the regulation of blood pressure
	AGTR1 and APLNR are mechanosensitive GPCRs in the heart, playing vital roles in cardiac physiological adaptation to changes in mechanical load

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

hormonal

a component

AGTR1–APLNR heterodimers activate distinct signaling pathways compared to monomeric receptors, or the multiple reported downstream pathways of AGTR1 and APLNR may be partially dependent on the activation of the heterodimeric receptor

INTERACTION

DNA

RNA

small molecule

protein	interaction with DRD5 (mediates AGTR1 degradation via a ubiquitin-proteasome pathway)
	ARAP1 may serve as a local modulator of vascular AGTR1 function
	AGTRAP is a molecule specifically interacting with the carboxyl- terminal domain of AGTR1
	stimulation of the AGTR1 on catecholaminergic cells is required for the full development of angiotensin-dependent hypertension
	GRK4, via regulation of arterial AGTR1 expression and function, participates in the pathogenesis of conduit vessel abnormalities in hypertension
	NFKB and CREB1 are required for angiotensin II type 1 (AGTR1) receptor upregulation in neurons
	SND1 increases angiotensin II type 1 receptor (AGTR1) levels by increasing AGTR1 mRNA stability
	regulatory role of DRD4 on AGTR1 expression and function in in the vascular smooth muscle cell (VSMC)
	AGTR2 inhibits ligand-induced AGTR1 signaling through the PKC-dependent pathway
	AGTR1 is an ouabain-associating protein
	IRF1 is one of the key transcriptional factors for the prevention of neointimal formation involving AGTR1, AGTR2
	dysregulated (RGS5-mediated) AGTR1 signaling could likely contribute to excessive vasoconstriction in hypertension
	AGT regulates ARHGDIA stability by SUMOylation and ubiquitination via AT1R activation and thus affects VSMC proliferation and vascular remodeling

cell & other

REGULATION

activated by

increased circulating AGT (this acivations are important mediators in the pathophysiology of several diseases characterized by sympatho-excitation)

repressed by

SIRT1 (downregulates AGTR1 expression in vascular smooth muscle cells)

ASSOCIATED DISORDERS

corresponding disease(s)

RTD3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in benign prostatic hyperplasia tumoral     --other   AGT plays a role in the growth of AGTR1-positive breast cancer cells through PI3-kinase/Akt pathway activation constitutional       gain of function of EDNRB and AGTR1 in vascular smooth muscle cells in ischemic heart disease constitutional     --other   altered expression of AGTR1 and AGTR2 with aging may induce mitochondrial dysfunction, the main risk factor for neurodegeneration

Susceptibility

contributing in association with ACE to the risk of coronary disease, to diabetic nephropathy and essential hypertension to development of retinopathy of prematurity (ROP) to fetal growth restriction syndrome to pediatric hypertrophic cardiomyopathy with poor outcome

Variant & Polymorphism SNP , repeat , other	increasing the risk of fetal growth restriction syndrome
	associated with progressive septal hypertrophy and left ventricular outflow tract obstruction in children with hypertrophic cardiomyopathy
	association between SNPs and the development of ROP

Candidate gene
Marker
Therapy target	therapy for hypertension might be optimized by designing compounds that can target the AGTR1 and DRD5
	targeting AGT/AGTR1 signaling could be a novel therapeutic for breast cancer

ANIMAL & CELL MODELS