5-hydroxytryptamine receptor 2C
Also known as: HTR1C, HTR2C
Function
G protein-coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 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. HTR2C 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. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelanocortin neurons and the release of CRH that then regulates the release of corticosterone (By similarity). Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress (By similarity). Plays a role in insulin sensitivity and glucose homeostasis (By similarity).
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- 5HT2C_rcpt, 5HT_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
- Functional cluster
- Membrane Transporters & GPCRs
Experimental structures · PDB · 7
- 6BQG X-ray 3.00A
- 6BQH X-ray 2.70A
- 8DPF EM 2.84A
- 8DPG EM 3.60A
- 8DPH EM 3.20A
- 8DPI EM 3.40A
- 8ZMF X-ray 3.60A
A predicted model is available from AlphaFold.
Gene Ontology · 27
- GO:0030425 dendrite
- GO:0098666 G protein-coupled serotonin receptor complex
- GO:0005886 plasma membrane
- GO:0045202 synapse
- 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:0051378 serotonin binding
- GO:0099589 serotonin receptor activity
- GO:0001662 behavioral fear response
- GO:0007268 chemical synaptic transmission
- GO:0007631 feeding behavior
- 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:0007626 locomotory behavior
- GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
- GO:0007208 phospholipase C-activating serotonin receptor signaling pathway
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0010513 positive regulation of phosphatidylinositol biosynthetic process
- GO:0032098 regulation of appetite
- GO:0043397 regulation of corticotropin-releasing hormone secretion
- GO:0031644 regulation of nervous system process
- GO:0051209 release of sequestered calcium ion into cytosol
- GO:0007210 serotonin receptor signaling pathway
Drugs targeting this protein · 34
- AGOMELATINE antagonist
- METHIXENE HYDROCHLORIDE antagonist
- NEFAZODONE HYDROCHLORIDE antagonist
- CYCLOBENZAPRINE HYDROCHLORIDE antagonist
- TRAZODONE HYDROCHLORIDE antagonist
- THIORIDAZINE HYDROCHLORIDE antagonist
- METHYSERGIDE MALEATE antagonist
- TRIMIPRAMINE MALEATE antagonist
- LOXAPINE HYDROCHLORIDE antagonist
- LOXAPINE SUCCINATE antagonist
- TRIFLUOPERAZINE HYDROCHLORIDE antagonist
- SERTINDOLE antagonist
- MINAPRINE HYDROCHLORIDE antagonist
- ZIPRASIDONE HYDROCHLORIDE antagonist
- DEXFENFLURAMINE HYDROCHLORIDE agonist
- LORCASERIN HYDROCHLORIDE agonist
- TEDATIOXETINE antagonist
- VABICASERIN HYDROCHLORIDE agonist
- FENFLURAMINE HYDROCHLORIDE agonist
- ESMIRTAZAPINE MALEATE antagonist
- ZIMELDINE HYDROCHLORIDE antagonist
- CARPHENAZINE MALEATE antagonist
- AMISULPRIDE antagonist
- MINAPRINE antagonist
- CLOTHIAPINE antagonist
- QUETIAPINE FUMARATE antagonist
- OLANZAPINE PAMOATE antagonist
- ZIPRASIDONE MESYLATE antagonist
- THIORIDAZINE antagonist
- MIRTAZAPINE antagonist
- OLANZAPINE antagonist
- LOXAPINE antagonist
- RISPERIDONE antagonist
- CHLORPROTHIXENE antagonist
Related proteins · sequence + function similarity
- 5-hydroxytryptamine receptor 2C 1.00
- 5-hydroxytryptamine receptor 2C 0.99
- 5-hydroxytryptamine receptor 2C 0.99
- 5-hydroxytryptamine receptor 2C 0.99
- 5-hydroxytryptamine receptor 2A 0.88
- 5-hydroxytryptamine receptor 2A 0.88
- 5-hydroxytryptamine receptor 2A 0.88
- 5-hydroxytryptamine receptor 2B 0.88
- 5-hydroxytryptamine receptor 2A 0.88
- 5-hydroxytryptamine receptor 2A 0.86
- 5-hydroxytryptamine receptor 2B 0.86
- 5-hydroxytryptamine receptor 2A 0.86
Co-cited proteins · studied together in the literature
- 5-hydroxytryptamine receptor 2A 7 shared papers
- 5-hydroxytryptamine receptor 2B 4 shared papers
- 5-hydroxytryptamine receptor 2C 1 shared papers
- MAGUK p55 subfamily member 3 2 shared papers
- Beta-arrestin-2 1 shared papers
- Multiple PDZ domain protein 1 shared papers
- Peroxiredoxin-6 1 shared papers
- Multiple PDZ domain protein 1 shared papers
- 5-hydroxytryptamine receptor 1D 1 shared papers
- 5-hydroxytryptamine receptor 1F 1 shared papers
- 5-hydroxytryptamine receptor 1E 1 shared papers
- 5-hydroxytryptamine receptor 2A 1 shared papers
Literature · 21 cited papers
- 5-HT2C receptor structures reveal the structural basis of GPCR polypharmacology. Cell · 2018
- The N-terminal region of the human 5-HT(2)C receptor has as a cleavable signal peptide. Eur. J. Pharmacol. · 2012
- 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
- Opposite effects of PSD-95 and MPP3 PDZ proteins on serotonin 5-hydroxytryptamine2C receptor desensitization and membrane stability. Mol. Biol. Cell · 2006
- A beta-arrestin binding determinant common to the second intracellular loops of rhodopsin family G protein-coupled receptors. J. Biol. Chem. · 2006
- The DNA sequence of the human X chromosome. Nature · 2005
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of PDZ proteins. J. Biol. Chem. · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy. Br. J. Pharmacol. · 2003
- … and 9 more in the literature graph