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FLASH GENE
Symbol AGTR1 contributors: mct - updated : 10-11-2014
HGNC name angiotensin II receptor, type 1
HGNC id 336
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
    Physical map
    ZIC4 3q24 Zic family member 4 ZIC1 3q24 Zic family member 1 (odd-paired homolog, Drosophila) LOC339899 3q24 hypothetical LOC339899 LOC391586 3 similar to nucleophosmin 1; nucleolar phosphoprotein B23; numatrin; nucleophosmin/nucleoplasmin family, member 1 LOC344741 3q24 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP-1) (Topoisomerase-inhibitor suppressed) LOC389159 3 LOC389159 RPL38P1 3q21-q25 ribosomal protein L38 pseudogene 1 AGTR1 3q21-q25 angiotensin II receptor, type 1 CPB1 7p14-p13 carboxypeptidase B1 (tissue) CPA3 3q21-q25 carboxypeptidase A3 (mast cell) LOC285329 3q24 similar to Ataxin-1 ubiquitin-like interacting protein GYG 3q24 glycogenin SMARCA3 3q25.1-q26.1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 3 HPS3 3q24-q25.1 Hermansky-Pudlak syndrome 3 CP 3q23-q25 ceruloplasmin (ferroxidase) LOC389160 3 LOC389160 LOC116441 3q24 hypothetical protein BC014339 TM4SF1 3q21-q25 transmembrane 4 superfamily member 1 TM4SF4 3q25 transmembrane 4 superfamily member 4 TAZ Xq28 tafazzin (cardiomyopathy, dilated 3A (X-linked); endocardial fibroelastosis 2; Barth syndrome) LOC51122 3q25.1 HSPC042 protein LOC389161 3 hypothetical gene supported by AK027233 LOC389162 3 LOC389162 LOC389163 3 hypothetical gene supported by AK098078 RNF13 3q25.1 ring finger protein 13 PFN2 3q25.1-q25.2 profilin 2 LOC389164 3 similar to Chromosome 1 open reading frame 37 LOC391587 3 similar to peptidyl-Pro cis trans isomerase LOC389165 3 hypothetical gene supported by AF090923; AK023388; BC002719 LOC389166 3 LOC389166 KIAA0669 3q25.1-q25.2 LOC389166
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 splicing 2362 41.1 359 liver,lung,adrenal and adrenocortical adenomas 1992 1378723
    3 splicing 2336 41.1 359 liver,lung,adrenal and adrenocortical adenomas 1992 1378723
    2 splicing 2278 41.1 359 liver,lung,adrenal and adrenocortical adenomas 1992 1378723
  • pC1
  • 3 splicing 2236 41.1 359 liver, lung, adrenal and adrenocortical adenomas 1992 1378723
  • pC4
  • 4 - 2420 44.1 359 - 1992 1378723
  • pC3
  • 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
  • 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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling hormonal
    a component
    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
  • 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
    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