Alpha-1A adrenergic receptor
Also known as: ADRA1A, ADRA1C
Function
Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11). Upon activation, they stimulate the phosphatidylinositol-calcium second messenger pathway, leading to calcium release from intracellular stores and activation of protein kinase C. ADRA1A binds the catecholamine ligands norepinephrine and epinephrine. Can also couple to G(14) protein (By similarity). Nuclear ADRA1A forms heterooligomers with ADRA1B to regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. At the plasma membrane, ADRA1A interacts with CAVIN4/MURC to regulates ERK activation in cardiomyocytes, contributing to the regulation of cardiac hypertrophy. Additionally, functions as a vasopressor in resistance arteries and plays a role in maintaining normal arterial blood pressure (By similarity).
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- ADR_fam, ADRA1A_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
- Functional cluster
- G Protein-Coupled Receptors
Experimental structures · PDB · 9
- 7YM8 EM 2.92A
- 7YMH EM 3.52A
- 7YMJ EM 3.35A
- 8HN1 EM 2.90A
- 8THK EM 2.60A
- 8THL EM 3.10A
- 9IQV EM 3.30A
- 9M4Q EM 2.99A
- 9M4T EM 3.19A
A predicted model is available from AlphaFold.
Gene Ontology · 32
- GO:0005901 caveola
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0031965 nuclear membrane
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0004937 alpha1-adrenergic receptor activity
- GO:0046982 protein heterodimerization activity
- GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway
- GO:0006915 apoptotic process
- GO:0007267 cell-cell signaling
- GO:0007186 G protein-coupled receptor signaling pathway
- GO:0035556 intracellular signal transduction
- GO:0008285 negative regulation of cell population proliferation
- GO:0150099 neuron-glial cell signaling
- GO:0001994 norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure
- GO:0071882 phospholipase C-activating adrenergic receptor signaling pathway
- GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
- GO:0097195 pilomotor reflex
- GO:0045760 positive regulation of action potential
- GO:0060452 positive regulation of cardiac muscle contraction
- GO:0010613 positive regulation of cardiac muscle hypertrophy
- GO:0007204 positive regulation of cytosolic calcium ion concentration
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0043410 positive regulation of MAPK cascade
- GO:0045987 positive regulation of smooth muscle contraction
- GO:0032230 positive regulation of synaptic transmission, GABAergic
- GO:0045907 positive regulation of vasoconstriction
- GO:0009725 response to hormone
- GO:0009410 response to xenobiotic stimulus
- GO:0007165 signal transduction
- GO:0006939 smooth muscle contraction
Drugs targeting this protein · 43
- LABETALOL HYDROCHLORIDE antagonist
- PHENYLEPHRINE HYDROCHLORIDE agonist
- TETRAHYDROZOLINE HYDROCHLORIDE agonist
- MIDODRINE HYDROCHLORIDE agonist
- DOXAZOSIN MESYLATE antagonist
- PHENYLPROPANOLAMINE HYDROCHLORIDE agonist
- HYDROXYAMPHETAMINE HYDROBROMIDE agonist
- PHENOXYBENZAMINE HYDROCHLORIDE antagonist
- OXYMETAZOLINE HYDROCHLORIDE agonist
- DIPIVEFRIN HYDROCHLORIDE agonist
- PHENTOLAMINE MESYLATE antagonist
- TAMSULOSIN HYDROCHLORIDE antagonist
- TRIMIPRAMINE MALEATE antagonist
- DAPIPRAZOLE HYDROCHLORIDE antagonist
- METHOXAMINE HYDROCHLORIDE agonist
- CARVEDILOL PHOSPHATE antagonist
- XYLOMETAZOLINE HYDROCHLORIDE agonist
- EPINEPHRINE BITARTRATE agonist
- SERTINDOLE antagonist
- NOREPINEPHRINE BITARTRATE agonist
- EPHEDRINE SULFATE agonist
- PRAZOSIN HYDROCHLORIDE antagonist
- MOXISYLYTE antagonist
- TOLAZOLINE HYDROCHLORIDE antagonist
- NAPHAZOLINE HYDROCHLORIDE agonist
- ALFUZOSIN HYDROCHLORIDE agonist
- BUNAZOSIN antagonist
- AVIPTADIL antagonist
- METARAMINOL BITARTRATE agonist
- PHENYLEPHRINE BITARTRATE agonist
- DROXIDOPA agonist
- TEDATIOXETINE antagonist
- BUCINDOLOL HYDROCHLORIDE antagonist
- EPHEDRINE HYDROCHLORIDE agonist
- ERGOLOID MESYLATES antagonist
- ERGOTAMINE TARTRATE agonist
- SILODOSIN antagonist
- DABUZALGRON partial agonist
- MEPHENTERMINE SULFATE agonist
- TERAZOSIN HYDROCHLORIDE antagonist
- ISOXSUPRINE HYDROCHLORIDE antagonist
- EPINEPHRINE agonist
- CARVEDILOL antagonist
Related proteins · sequence + function similarity
- Alpha-1A adrenergic receptor 0.99
- Alpha-1A adrenergic receptor 0.99
- Alpha-1A adrenergic receptor 0.99
- Alpha-1A adrenergic receptor 0.99
- Alpha-1A adrenergic receptor 0.99
- Alpha-1A adrenergic receptor 0.96
- Alpha-1A adrenergic receptor 0.92
- Beta-2 adrenergic receptor 0.90
- Beta-2 adrenergic receptor 0.90
- Alpha-1B adrenergic receptor 0.90
- D(1A) dopamine receptor 0.90
- Beta-2 adrenergic receptor 0.90
Co-cited proteins · studied together in the literature
- Alpha-1D adrenergic receptor 3 shared papers
- Alpha-1B adrenergic receptor 5 shared papers
- Alpha-1B adrenergic receptor 1 shared papers
- Alpha-1A adrenergic receptor 1 shared papers
- Alpha-1D adrenergic receptor 1 shared papers
- Erbin 1 shared papers
- 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 1 shared papers
- Guanine nucleotide-binding protein G(q) subunit alpha 1 shared papers
- Caveolae-associated protein 4 1 shared papers
- Caveolin-3 1 shared papers
- Caveolae-associated protein 4 1 shared papers
- Caveolin-3 1 shared papers
Literature · 18 cited papers
- Structural basis of agonist specificity of alpha1A-adrenergic receptor. Nat. Commun. · 2023
- MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by alpha1-adrenergic receptors. Proc. Natl. Acad. Sci. U.S.A. · 2014
- Nuclear localization drives alpha1-adrenergic receptor oligomerization and signaling in cardiac myocytes. Cell. Signal. · 2012
- Nuclear alpha1-adrenergic receptors signal activated ERK localization to caveolae in adult cardiac myocytes. Circ. Res. · 2008
- The consensus coding sequences of human breast and colorectal cancers. Science · 2006
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Alpha 1A-adrenergic receptor polymorphism and vascular response. Clin. Pharmacol. Ther. · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Truncated isoforms inhibit [3H]prazosin binding and cellular trafficking of native human alpha1A-adrenoceptors. Biochem. J. · 1999
- Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms. FEBS Lett. · 1998
- Alpha 1a-adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy. Br. J. Pharmacol. · 1996
- The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types. Br. J. Pharmacol. · 1995
- … and 6 more in the literature graph