5-hydroxytryptamine receptor 2A
Also known as: HTR2, HTR2A
Function
G protein-coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. HTR2A is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction (By similarity).
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- 5HT2A_rcpt, 5HT_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
- Functional cluster
- Membrane Transporters & GPCRs
Experimental structures · PDB · 37
- 6A93 X-ray 3.00A
- 6A94 X-ray 2.90A
- 6WGT X-ray 3.40A
- 6WH4 X-ray 3.40A
- 6WHA EM 3.36A
- 7RAN EM 3.45A
- 7VOD X-ray 3.30A
- 7VOE X-ray 2.90A
- 7WC4 X-ray 3.20A
- 7WC5 X-ray 3.20A
- 7WC6 X-ray 2.60A
- 7WC7 X-ray 2.60A
- … and 25 more
A predicted model is available from AlphaFold.
Gene Ontology · 55
- GO:0030424 axon
- GO:0005901 caveola
- GO:0070852 cell body fiber
- GO:0031410 cytoplasmic vesicle
- GO:0030425 dendrite
- GO:0043198 dendritic shaft
- GO:0098666 G protein-coupled serotonin receptor complex
- GO:0098978 glutamatergic synapse
- GO:0005883 neurofilament
- GO:0043025 neuronal cell body
- GO:0005886 plasma membrane
- GO:0045211 postsynaptic membrane
- GO:0042734 presynaptic membrane
- GO:0071886 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
- GO:0004993 G protein-coupled serotonin receptor activity
- GO:0001587 Gq/11-coupled serotonin receptor activity
- GO:0042802 identical protein binding
- GO:0030594 neurotransmitter receptor activity
- GO:0030296 protein tyrosine kinase activator activity
- GO:0044877 protein-containing complex binding
- GO:0051378 serotonin binding
- GO:0099589 serotonin receptor activity
- GO:0001618 virus receptor activity
- GO:0014824 artery smooth muscle contraction
- GO:0048148 behavioral response to cocaine
- GO:0007268 chemical synaptic transmission
- GO:0050966 detection of mechanical stimulus involved in sensory perception of pain
- GO:0050965 detection of temperature stimulus involved in sensory perception of pain
- GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- GO:0098664 G protein-coupled serotonin receptor signaling pathway
- GO:0006874 intracellular calcium ion homeostasis
- GO:0007613 memory
- GO:0043267 negative regulation of potassium ion transport
- GO:0051967 negative regulation of synaptic transmission, glutamatergic
- GO:0007208 phospholipase C-activating serotonin receptor signaling pathway
- GO:0008284 positive regulation of cell population proliferation
- GO:0002720 positive regulation of cytokine production involved in immune response
- GO:0007204 positive regulation of cytosolic calcium ion concentration
- GO:2000573 positive regulation of DNA biosynthetic process
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:1900119 positive regulation of execution phase of apoptosis
- GO:0031652 positive regulation of heat generation
- GO:0050729 positive regulation of inflammatory response
- GO:0043525 positive regulation of neuron apoptotic process
- GO:0010513 positive regulation of phosphatidylinositol biosynthetic process
- GO:1901731 positive regulation of platelet aggregation
- GO:0045907 positive regulation of vasoconstriction
- GO:0099171 presynaptic modulation of chemical synaptic transmission
- GO:0014059 regulation of dopamine secretion
- GO:0051209 release of sequestered calcium ion into cytosol
- GO:0009410 response to xenobiotic stimulus
- GO:0046960 sensitization
- GO:0007210 serotonin receptor signaling pathway
- GO:0001659 temperature homeostasis
- GO:0014832 urinary bladder smooth muscle contraction
Drugs targeting this protein · 63
- TEMANOGREL inverse agonist
- DROPERIDOL antagonist
- ARIPIPRAZOLE antagonist
- MOLINDONE HYDROCHLORIDE antagonist
- PROMAZINE HYDROCHLORIDE antagonist
- NEFAZODONE HYDROCHLORIDE antagonist
- CYCLOBENZAPRINE HYDROCHLORIDE antagonist
- TRAZODONE HYDROCHLORIDE antagonist
- THIORIDAZINE HYDROCHLORIDE antagonist
- TRIMIPRAMINE MALEATE antagonist
- HALOPERIDOL DECANOATE antagonist
- THIOTHIXENE antagonist
- MESORIDAZINE BESYLATE antagonist
- LOXAPINE HYDROCHLORIDE antagonist
- LOXAPINE SUCCINATE antagonist
- PRUVANSERIN antagonist
- TRIFLUOPERAZINE HYDROCHLORIDE antagonist
- SERTINDOLE antagonist
- MINAPRINE HYDROCHLORIDE antagonist
- ZIPRASIDONE HYDROCHLORIDE antagonist
- PIMOZIDE antagonist
- ILOPERIDONE antagonist
- LURASIDONE HYDROCHLORIDE antagonist
- PALIPERIDONE antagonist
- CHLORPROMAZINE HYDROCHLORIDE antagonist
- BLONANSERIN antagonist
- DEXFENFLURAMINE HYDROCHLORIDE agonist
- PSILOCYBIN agonist
- TEDATIOXETINE antagonist
- VABICASERIN HYDROCHLORIDE antagonist
- BREXPIPRAZOLE antagonist
- ESMIRTAZAPINE MALEATE antagonist
- PALIPERIDONE PALMITATE antagonist
- ARIPIPRAZOLE LAUROXIL antagonist
- ZIMELDINE HYDROCHLORIDE antagonist
- CARPHENAZINE MALEATE antagonist
- AMISULPRIDE antagonist
- PIMAVANSERIN TARTRATE inverse agonist
- EPLIVANSERIN antagonist
- MINAPRINE antagonist
- CLOTHIAPINE antagonist
- TRELANSERIN antagonist
- QUETIAPINE FUMARATE antagonist
- LUMATEPERONE antagonist
- ASENAPINE MALEATE antagonist
- IFERANSERIN antagonist
- OLANZAPINE PAMOATE antagonist
- THIOTHIXENE HYDROCHLORIDE antagonist
- ZIPRASIDONE MESYLATE antagonist
- CLOZAPINE antagonist
- HALOPERIDOL LACTATE antagonist
- THIORIDAZINE antagonist
- SARPOGRELATE antagonist
- SB-773812 antagonist
- HALOPERIDOL antagonist
- NELOTANSERIN inverse agonist
- MIRTAZAPINE antagonist
- CHLORPROMAZINE antagonist
- OLANZAPINE antagonist
- VOLINANSERIN antagonist
- LOXAPINE antagonist
- RISPERIDONE antagonist
- CHLORPROTHIXENE antagonist
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- 5-hydroxytryptamine receptor 2A 1.00
- 5-hydroxytryptamine receptor 2A 1.00
- 5-hydroxytryptamine receptor 2A 1.00
- 5-hydroxytryptamine receptor 2A 0.99
- 5-hydroxytryptamine receptor 2A 0.99
- 5-hydroxytryptamine receptor 2A 0.99
- 5-hydroxytryptamine receptor 2A 0.99
- 5-hydroxytryptamine receptor 2A 0.99
- 5-hydroxytryptamine receptor 2B 0.92
- 5-hydroxytryptamine receptor 2B 0.91
- 5-hydroxytryptamine receptor 2B 0.90
- 5-hydroxytryptamine receptor 2B 0.90
Co-cited proteins · studied together in the literature
- 5-hydroxytryptamine receptor 2C 7 shared papers
- 5-hydroxytryptamine receptor 2B 5 shared papers
- Metabotropic glutamate receptor 2 2 shared papers
- 5-hydroxytryptamine receptor 2A 3 shared papers
- Metabotropic glutamate receptor 2 1 shared papers
- 5-hydroxytryptamine receptor 1A 3 shared papers
- D(2) dopamine receptor 1 shared papers
- 5-hydroxytryptamine receptor 1D 2 shared papers
- Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 2 shared papers
- 5-hydroxytryptamine receptor 1F 2 shared papers
- 5-hydroxytryptamine receptor 1E 2 shared papers
- Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 2 shared papers
Literature · 25 cited papers
- Flexible scaffold-based cheminformatics approach for polypharmacological drug design. Cell · 2024
- Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity. Nature · 2022
- Structure-based discovery of nonhallucinogenic psychedelic analogs. Science · 2022
- Crystal structure of an LSD-bound human serotonin receptor. Cell · 2017
- Quantitative phosphoproteomics unravels biased phosphorylation of serotonin 2A receptor at Ser280 by hallucinogenic versus nonhallucinogenic agonists. Mol. Cell. Proteomics · 2014
- 5-HT2 receptors facilitate JC polyomavirus entry. J. Virol. · 2013
- Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades. Neuropharmacology · 2012
- Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology · 2011
- Serotonin receptors - from molecular biology to clinical applications. Physiol. Res. · 2011
- Pharmacological characterization of mitogen-activated protein kinase activation by recombinant human 5-HT2C, 5-HT2A, and 5-HT2B receptors. Naunyn Schmiedebergs Arch. Pharmacol. · 2009
- Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. Eur. J. Pharmacol. · 2008
- Serotonin receptors. Chem. Rev. · 2008
- … and 13 more in the literature graph