5-hydroxytryptamine receptor 6

Function

G protein-coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen. Also has a high affinity for tricyclic psychotropic drugs (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. HTR6 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity. Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of mTOR signaling.

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

5HT6_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 3

• 7XTB EM 3.30A
• 7YS6 EM 3.00A
• 8JLZ EM 3.09A

A predicted model is available from AlphaFold.

Gene Ontology · 13

• GO:0005929 cilium
• GO:0030425 dendrite
• GO:0005886 plasma membrane
• GO:0045202 synapse
• GO:0004993 G protein-coupled serotonin receptor activity
• GO:0004969 histamine receptor activity
• GO:0030594 neurotransmitter receptor activity
• GO:0007192 adenylate cyclase-activating serotonin receptor signaling pathway
• GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway
• GO:0021795 cerebral cortex cell migration
• GO:0007268 chemical synaptic transmission
• GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• GO:0032008 positive regulation of TOR signaling

Drugs targeting this protein · 8

• INTEPIRDINE antagonist
• DEXFENFLURAMINE HYDROCHLORIDE agonist
• CERLAPIRDINE antagonist
• ZIMELDINE HYDROCHLORIDE antagonist
• AMISULPRIDE antagonist
• IDALOPIRDINE antagonist
• PF-05212377 antagonist
• MASUPIRDINE antagonist

Related proteins · sequence + function similarity

• 5-hydroxytryptamine receptor 6 1.00
• 5-hydroxytryptamine receptor 6 0.99
• 5-hydroxytryptamine receptor 6 0.97
• Beta-3 adrenergic receptor 0.95
• Beta-3 adrenergic receptor 0.94
• Beta-3 adrenergic receptor 0.94
• Beta-3 adrenergic receptor 0.94
• Beta-3 adrenergic receptor 0.94
• Beta-3 adrenergic receptor 0.94
• D(4) dopamine receptor 0.93
• D(4) dopamine receptor 0.92
• Beta-3 adrenergic receptor 0.92

Co-cited proteins · studied together in the literature

• Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 3 shared papers
• Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 3 shared papers
• 5-hydroxytryptamine receptor 4 1 shared papers
• 5-hydroxytryptamine receptor 1E 1 shared papers
• 5-hydroxytryptamine receptor 2B 1 shared papers
• 5-hydroxytryptamine receptor 4 2 shared papers
• 5-hydroxytryptamine receptor 6 1 shared papers
• 5-hydroxytryptamine receptor 7 1 shared papers
• 5-hydroxytryptamine receptor 2A 1 shared papers
• 5-hydroxytryptamine receptor 4 1 shared papers
• Neurofibromin 1 shared papers
• Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 2 shared papers

Literature · 8 cited papers

• Structural insight into the selective agonist ST1936 binding of serotonin receptor 5-HT6. Biochem. Biophys. Res. Commun. · 2023
• Structural insights into constitutive activity of 5-HT6 receptor. Proc. Natl. Acad. Sci. U.S.A. · 2023
• GPCRs steer Gi and Gs selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors. Mol. Cell · 2022
• 5-HT(6) receptor recruitment of mTOR as a mechanism for perturbed cognition in schizophrenia. EMBO Mol. Med. · 2012
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. J. Neurochem. · 1996
• Expression of serotonin receptor mRNAs in blood vessels. FEBS Lett. · 1995