5-hydroxytryptamine receptor 1A
Also known as: ADRB2RL1, ADRBRL1, HTR1A
Function
G protein-coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. HTR1A is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission: signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Beta-arrestin family members regulate signaling by mediating both receptor desensitization and resensitization processes. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- 5HT1A_rcpt, 5HT_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
- Functional cluster
- G Protein-Coupled Receptors
Experimental structures · PDB · 28
- 7E2X EM 3.00A
- 7E2Y EM 3.00A
- 7E2Z EM 3.10A
- 8FY8 EM 2.79A
- 8FYE EM 2.85A
- 8FYL EM 2.94A
- 8FYT EM 2.64A
- 8FYX EM 2.62A
- 8JSP EM 3.65A
- 8JT6 EM 3.00A
- 8PJK EM 2.40A
- 8PKM EM 2.90A
- … and 16 more
A predicted model is available from AlphaFold.
Gene Ontology · 23
- GO:0030425 dendrite
- GO:0005886 plasma membrane
- GO:0045202 synapse
- GO:0004993 G protein-coupled serotonin receptor activity
- GO:0001586 Gi/o-coupled serotonin receptor activity
- GO:0030594 neurotransmitter receptor activity
- GO:0090722 receptor-receptor interaction
- GO:0051378 serotonin binding
- GO:0099589 serotonin receptor activity
- GO:0007198 adenylate cyclase-inhibiting serotonin receptor signaling pathway
- GO:0001662 behavioral fear response
- GO:0007268 chemical synaptic transmission
- GO:0035640 exploration behavior
- GO:0007186 G protein-coupled receptor signaling pathway
- GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- GO:0008284 positive regulation of cell population proliferation
- GO:0050795 regulation of behavior
- GO:0042053 regulation of dopamine metabolic process
- GO:0046883 regulation of hormone secretion
- GO:0014062 regulation of serotonin secretion
- GO:0019229 regulation of vasoconstriction
- GO:0042428 serotonin metabolic process
- GO:0007210 serotonin receptor signaling pathway
Disease associations
- menstrual cycle-dependent periodic fever MONDO:0044660
Drugs targeting this protein · 29
- ARIPIPRAZOLE partial agonist
- BUSPIRONE HYDROCHLORIDE partial agonist
- METHYSERGIDE MALEATE partial agonist
- GEPIRONE HYDROCHLORIDE agonist
- XALIPRODEN agonist
- REPINOTAN agonist
- VILAZODONE HYDROCHLORIDE partial agonist
- ROBALZOTAN antagonist
- GSK163090 antagonist
- OSEMOZOTAN agonist
- DEXFENFLURAMINE HYDROCHLORIDE agonist
- NALUZOTAN agonist
- PARDOPRUNOX agonist
- BREXPIPRAZOLE partial agonist
- LECOZOTAN HYDROCHLORIDE antagonist
- VORTIOXETINE HYDROBROMIDE agonist
- SARIZOTAN HYDROCHLORIDE agonist
- BIFEPRUNOX partial agonist
- ADOPRAZINE agonist
- ARIPIPRAZOLE LAUROXIL partial agonist
- ERGOLOID MESYLATES agonist
- ZIMELDINE HYDROCHLORIDE antagonist
- AMISULPRIDE antagonist
- ALVERINE antagonist
- GEPIRONE agonist
- PICLOZOTAN agonist
- BEFIRADOL agonist
- ULOTARONT agonist
- DU 125530 antagonist
Related proteins · sequence + function similarity
- 5-hydroxytryptamine receptor 1A 1.00
- 5-hydroxytryptamine receptor 1A 1.00
- 5-hydroxytryptamine receptor 1A 0.99
- 5-hydroxytryptamine receptor 1A 0.99
- 5-hydroxytryptamine receptor 1A 0.99
- 5-hydroxytryptamine receptor 1A 0.99
- 5-hydroxytryptamine receptor 1A 0.99
- 5-hydroxytryptamine receptor 1A-alpha 0.97
- 5-hydroxytryptamine receptor 1A 0.96
- 5-hydroxytryptamine receptor 1A-beta 0.95
- 5-hydroxytryptamine receptor 1B 0.94
- 5-hydroxytryptamine receptor 1B 0.93
Co-cited proteins · studied together in the literature
- G protein-coupled receptor 39 1 shared papers
- Galanin receptor type 1 1 shared papers
- 5-hydroxytryptamine receptor 1E 4 shared papers
- 5-hydroxytryptamine receptor 1D 3 shared papers
- Corticotropin-releasing hormone receptor 1 1 shared papers
- 5-hydroxytryptamine receptor 1F 3 shared papers
- Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 5 shared papers
- 5-hydroxytryptamine receptor 1B 3 shared papers
- Guanine nucleotide-binding protein G(i) subunit alpha-1 5 shared papers
- Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 5 shared papers
- 5-hydroxytryptamine receptor 2A 3 shared papers
- Trace amine-associated receptor 1 2 shared papers
Literature · 21 cited papers
- Flexible scaffold-based cheminformatics approach for polypharmacological drug design. Cell · 2024
- Recognition of methamphetamine and other amines by trace amine receptor TAAR1. Nature · 2023
- Ligand recognition and G-protein coupling of trace amine receptor TAAR1. Nature · 2023
- Structural insights into the ligand binding and Gi coupling of serotonin receptor 5-HT5A. Cell Discov. · 2022
- Structural insights into the lipid and ligand regulation of serotonin receptors. Nature · 2021
- The zinc binding receptor GPR39 interacts with 5-HT1A and GalR1 to form dynamic heteroreceptor complexes with signaling diversity. Biochim. Biophys. Acta · 2015
- Post-synaptic density-95 (PSD-95) binding capacity of G-protein-coupled receptor 30 (GPR30), an estrogen receptor that can be identified in hippocampal dendritic spines. J. Biol. Chem. · 2013
- Role of glycosphingolipids in the function of human serotonin(1)A receptors. J. Neurochem. · 2012
- Menstrual cycle-dependent febrile episode mediated by sequence-specific repression of poly(ADP-ribose) polymerase-1 on the transcription of the human serotonin receptor 1A gene. Hum. Mutat. · 2012
- Serotonin receptors - from molecular biology to clinical applications. Physiol. Res. · 2011
- 5-HT1A receptor-regulated signal transduction pathways in brain. Cell. Signal. · 2010
- Serotonin receptors. Chem. Rev. · 2008
- … and 9 more in the literature graph