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FLASH GENE
Symbol AGTR1 contributors: mct - updated : 10-11-2017
HGNC name angiotensin II receptor, type 1
HGNC id 336
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel     Homo sapiens
Nervousbrainbasal nucleicaudate nucleus   Homo sapiens
 brainbasal nucleistriatum   Homo sapiens
Reproductivefemale systemplacenta    Homo sapiens
Urinarykidney     Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularsmoothvessel highly Homo sapiens
Muscularstriatum    Homo sapiens
Muscularstriatumcardiac   Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticmonocyte Homo sapiens
Cardiovascularendothelial cell Homo sapiens
Digestivehepatocyte Homo sapiens
Muscularmyocyte Homo sapiens
Urinarymesenchymal cell
Urinarytubular 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
  • 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
  • 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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