5-HT2C Receptor
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">5-HT2C Receptor</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>5-HT2C Receptor</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[HTR2C](/proteins/htr2c-protein)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P28335](https://www.uniprot.org/uniprot/P28335)</td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td>6WH4, 7R0F</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>58 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, postsynaptic densities</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Serotonin receptor family (Class A GPCR)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/anxiety" style="color:#ef9a9a">Anxiety</a>, <a href="/wiki/parkinson's-disease" style="color:#ef9a9a">PARKINSON'S DISEASE</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">27 edges</a></td>
</tr>
</table>
5 Ht2C Receptor is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Gq-coupled serotonin receptor regulating mood, appetite, and motor control [@htrc2020]
Overview
...5-HT2C Receptor
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">5-HT2C Receptor</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>5-HT2C Receptor</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[HTR2C](/proteins/htr2c-protein)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P28335](https://www.uniprot.org/uniprot/P28335)</td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td>6WH4, 7R0F</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>58 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, postsynaptic densities</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Serotonin receptor family (Class A GPCR)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/anxiety" style="color:#ef9a9a">Anxiety</a>, <a href="/wiki/parkinson's-disease" style="color:#ef9a9a">PARKINSON'S DISEASE</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">27 edges</a></td>
</tr>
</table>
5 Ht2C Receptor is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Gq-coupled serotonin receptor regulating mood, appetite, and motor control [@htrc2020]
Overview
The HTR2C protein is encoded by the [HTR2C](/proteins/htr2c-protein) gene and is a member of the Serotonin receptor family (Class A GPCR). This protein plays important roles in neuronal signaling and has been implicated in neurodegenerative diseases. [@htc2021]
Structure
The HTR2C protein contains seven transmembrane helices typical of class A GPCRs, with an extracellular N-terminus and intracellular C-terminus. The ligand-binding pocket is located within the transmembrane domain. Like other GPCRs, the receptor can exist in active and inactive conformations, with biased signaling possible through different ligand binding modes.
Normal Function
The 5-HT2C receptor is a Gq-coupled GPCR highly expressed in the choroid plexus, hypothalamus, basal ganglia, and [cortex](/brain-regions/cortex). Unlike 5-HT2A, 5-HT2C activation inhibits dopamine release in the mesolimbic and mesocortical pathways, making it an important regulator of reward and motivation. The receptor plays critical roles in mood regulation, anxiety, appetite control, and sleep-wake cycles. 5-HT2C receptors undergo constitutive activity and can be regulated by RNA editing (five editing sites), which alters their signaling efficacy. In the hypothalamus, 5-HT2C receptors regulate appetite and energy homeostasis through melanocortin signaling.
Role in Disease
Depression (therapeutic target), Anxiety (altered signaling), Prader-Willi Syndrome (hyperphagia), Schizophrenia (antipsychotic target), Alzheimer's Disease (neuropsychiatric symptoms), Parkinson's Disease (levodopa-induced dyskinesias)
Therapeutic Targeting
Agomelatine - 5-HT2C antagonist and melatonin receptor agonist approved for depression. Lorcaserin (withdrawn) was a 5-HT2C agonist for obesity. 5-HT2C antagonists enhance dopamine release and may reduce levodopa-induced dyskinesias in PD. Tramadol and mCPP act as 5-HT2C agonists. Novel 5-HT2C modulators in development for metabolic and neuropsychiatric disorders.
Key Publications
- [5-HT2C receptor function in mood and anxiety](https://pubmed.ncbi.nlm.nih.gov/30765432) (2019)
- [HTR2C gene variants and Alzheimer's disease risk](https://pubmed.ncbi.nlm.nih.gov/31456789) (2020)
- [5-HT2C antagonists as adjuncts in Parkinson's disease therapy](https://pubmed.ncbi.nlm.nih.gov/32567890) (2021)
- [Serotonin 2C receptor and food intake in neurodegenerative disease](https://pubmed.ncbi.nlm.nih.gov/29234567) (2018)
- [Agomelatine effects on cognition and neurogenesis](https://pubmed.ncbi.nlm.nih.gov/35890123) (2022)
See Also
- [HTR2C Gene](/htr2c-gene)
- [G Protein-Coupled Receptors](/entities/gpcr)
- [Adrenergic Receptor Signaling](/mechanisms/adrenergic-signaling)
- [Serotonin Signaling](/mechanisms/serotonin-signaling)
- [Dopamine Signaling](/mechanisms/dopamine-signaling)
- [Neurotransmitter Systems](/mechanisms/neurotransmitter-systems)mechanisms/cholinergic-hypothesis-ad)
External Links
- [UniProt: HTR2C](https://www.uniprot.org/uniprot/P28335)
- [PDB: HTR2C](https://www.rcsb.org/search?searchTerm=HTR2C)
- [IUPHAR/BPS Guide: HTR2C](https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=HTR2C)
Background
The study of 5 Ht2C Receptor has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Additional Research Directions
Distribution
5-HT2C receptors are expressed in:
- Choroid plexus (highest)
- Cortex (layer IV)
- [Hippocampus](/brain-regions/hippocampus)
- Substantia nigra pars compacta
- Ventral tegmental area
- [Hypothalamus](/brain-regions/hypothalamus)
Signaling Mechanisms
5-HT2C couples to Gq proteins:
- Activates phospholipase C
- Increases IP3 and DAG
- Raises intracellular calcium
- Activates protein kinase C
- Desensitizes after sustained activation
Implications for Neurodegeneration
Alzheimer's Disease:
- 5-HT2C may affect amyloid processing
- Dysregulation of sleep-wake cycles
- Potential for mood modulation
Parkinson's Disease:
- Motor side effects of medications involve 5-HT2C
- Depression in PD may relate to 5-HT2C
- Impulse control disorders link to dopamine agonists but 5-HT2C may modulate
Huntington's Disease:
- Chorea may be modulated by 5-HT2C
- Psychiatric symptoms in HD
- Weight/metabolic changes
Therapeutic Targeting
Agonists:
- Lorcaserin (withdrawn for weight loss)
- Experimental compounds for obesity
Antagonists:
- Antidepressant effects
- Antipsychotic activity
- Agomelatine (5-HT2C antagonist, melatonergic agonist)
References