Protein / target
Alpha-1A adrenergic receptor
Protein at a glance
Biological role
Alpha1-adrenergic receptor activity
Primary system
Nervous system
Strongest disease association
benign prostatic hyperplasia
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
58 approved · 5 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
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 (PubMed:37563160). ADRA1A binds the catecholamine ligands norepinephrine and epinephrine (PubMed:18802028, PubMed:37563160, PubMed:7815325, PubMed:8024574, PubMed:8183249, PubMed:8832064). 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 (PubMed:18802028, PubMed:22120526). At the plasma membrane, ADRA1A interacts with CAVIN4/MURC to regulates ERK activation in cardiomyocytes, contributing to the regulation of cardiac hypertrophy (PubMed:24567387). Additionally, functions as a vasopressor in resistance arteries and plays a role in maintaining normal arterial blood pressure (By similarity)
Subcellular location
Domains and Gene Ontology detail (32)Hide
Gene Ontology
- Ccaveola
- Ccytoplasm
- Ccytosol
- Cnuclear membrane
- Cnucleus
- Cplasma membrane
- Falpha1-adrenergic receptor activity
- Fprotein heterodimerization activity
- Padenylate cyclase-activating adrenergic receptor signaling pathway
- Papoptotic process
- Pcell-cell signaling
- PG protein-coupled receptor signaling pathway
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
G protein-coupled signalling
- ·Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that sig…
- ·G protein-coupled receptor signaling pathway
- ·phospholipase C-activating G protein-coupled receptor signaling pathway
Muscle contraction
- ·positive regulation of cardiac muscle contraction
- ·positive regulation of smooth muscle contraction
- ·smooth muscle contraction
Inhibitory neurotransmission
- ·positive regulation of synaptic transmission, GABAergic
Synaptic signalling
- ·positive regulation of synaptic transmission, GABAergic
Kinase signalling
- ·Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that sig…
Apoptosis & cell death
- ·apoptotic process
View underlying pathways (3)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Adrenergic receptor alpha-1 antagonist
Appears in clinical studies involving myocardial infarction, hypertensive disorder, heart failure, congestive heart failure
Adrenergic receptor agonist
Appears in clinical studies involving sudden cardiac arrest, asthma, sinusitis, septic shock
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 368 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 66 total
adrenal gland pheochromocytoma · erectile dysfunction · Pain
cardiovascular disorder · Sepsis · major depressive disorder
cardiovascular disorder · presbyopia · Reduced visual acuity
Nasal congestion · seasonal allergic rhinitis · common cold
Nasal congestion · eye allergy · common cold
cardiovascular disorder · hypertensive disorder · hypotensive disorder
Urinary incontinence
sudden cardiac arrest · asthma · sinusitis
benign prostatic hyperplasia · nephrolithiasis · ureterolithiasis
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Label change
Label change: EPINEPHRINE (NDA204640)
- Product recall
Recall (Class III): EPINEPHRINE
- Regulatory approval
Approval: Eurneffy (EMA)
- New publicationImpact of norepinephrine on immunity and oxidative metabolism in sepsis.
- New publicationMulticenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial.
- Label change
Label change: EPINEPHRINE (NDA204640)
- Supplemental approval
Supplemental approval: EPINEPHRINE (NDA204640)
- New publicationThe effect of topical epinephrine 1:1000 with and without infiltration of 1% lidocaine with epinephrine 1:100,000 on endoscopic surgical field visualization: a double-blind randomized controlled study.
- Indication expanded
Indication expansion: EPINEPHRINE (NDA204640)
- New publicationPulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial.
- Label change
Label change: EPINEPHRINE (NDA204640)
- Label change
Label change: EPINEPHRINE (NDA204640)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.