Protein / target
Melatonin receptor type 1A
Protein at a glance
Biological role
G protein-coupled receptor activity
Strongest disease association
insomnia
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
4 approved · 1 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
High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity. Possibly involved in sleep induction, by melatonin activation of the potassium channel KCNMA1/BK and the dissociation of G-beta and G-gamma subunits, thereby decreasing synaptic transmission (By similarity)
Subcellular location
Domains and Gene Ontology detail (9)Hide
Gene Ontology
- Cplasma membrane
- Creceptor complex
- FG protein-coupled receptor activity
- Fhormone binding
- Fmelatonin receptor activity
- Padenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- Pcircadian rhythm
- PG protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- Pmating behavior
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
- ·G protein-coupled receptor activity
- ·adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- ·G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messen…
Synaptic signalling
- ·High affinity receptor for melatonin. Likely to mediate the reproductive and circadian a…
View underlying pathways (2)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.
Melatonin receptor agonist
Appears in clinical studies involving insomnia, autism, Sleep disturbance, insomnia
Melatonin receptor agonist
Appears in clinical studies involving major depressive disorder, treatment resistant depression, obsessive-compulsive disorder, depressive disorder
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 609 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 · 5 total
insomnia · autism · Sleep disturbance
major depressive disorder · treatment resistant depression · obsessive-compulsive disorder
Alzheimer disease · dementia · Alzheimer disease
Chromosomal anomaly · sleep-wake disorder · insomnia
insomnia · bipolar I disorder · depressive disorder
Tractability
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.
- Trial status changed
The Effect of Preoperative Oral Melatonin on Postoperative Pain Control After Cesarean Section: A Dose Comparison Study
- New publicationSTAT3 Signaling Mediates Agomelatine Restoration of Prefrontal Cortex Synaptic Plasticity in Chronic Social Defeat Stress Mice.
- New publicationMolecular Links Between Circadian Rhythm Disruption, Melatonin, and Neurodegenerative Diseases: An Updated Review.
- New publicationDysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment.
- New publicationMelatonin Regulates Neuronal Synaptic Plasticity in the Supramammillary Nucleus and Attenuates Methamphetamine-Induced Conditioned Place Preference and Sensitization in Mice.
- New publicationTranscriptomic Plasticity of the Circadian Clock in Response to Photoperiod: A Study in Male Melatonin-Competent Mice.
- New publicationThe Role of Gut Microbiome in Sleep Quality and Health: Dietary Strategies for Microbiota Support.
- New publicationPresence of melatonin in foods of daily consumption: The benefit of this hormone for health.
- New publicationMelatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration.
- New publicationThe European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.
- New publicationThe role of Neurochemicals, Stress Hormones and Immune System in the Positive Feedback Loops between Diabetes, Obesity and Depression.
- Regulatory approval
Approval: Melatonin Neurim (EMA)
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.