5-hydroxytryptamine receptor 1D

Function

G protein-coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other 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. HTR1D is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

5HT1D_rcpt, 5HT_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 1

• 7E32 EM 2.90A

A predicted model is available from AlphaFold.

Gene Ontology · 15

• 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:0099589 serotonin receptor activity
• GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• GO:0007198 adenylate cyclase-inhibiting serotonin receptor signaling pathway
• GO:0007268 chemical synaptic transmission
• GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• GO:0014827 intestine smooth muscle contraction
• GO:0050795 regulation of behavior
• GO:0040012 regulation of locomotion
• GO:0042310 vasoconstriction

Drugs targeting this protein · 17

• ZOLMITRIPTAN agonist
• DIHYDROERGOTAMINE MESYLATE agonist
• ALMOTRIPTAN MALATE agonist
• NARATRIPTAN HYDROCHLORIDE agonist
• ELETRIPTAN HYDROBROMIDE agonist
• RIZATRIPTAN BENZOATE agonist
• SUMATRIPTAN SUCCINATE agonist
• SUMATRIPTAN agonist
• GSK163090 antagonist
• DONITRIPTAN agonist
• DEXFENFLURAMINE HYDROCHLORIDE agonist
• FENFLURAMINE HYDROCHLORIDE agonist
• FROVATRIPTAN SUCCINATE agonist
• ZIMELDINE HYDROCHLORIDE antagonist
• AMISULPRIDE antagonist
• ERGOTAMINE TARTRATE agonist
• ELZASONAN HYDROCHLORIDE antagonist

Related proteins · sequence + function similarity

• 5-hydroxytryptamine receptor 1D 0.99
• 5-hydroxytryptamine receptor 1D 0.99
• 5-hydroxytryptamine receptor 1D 0.98
• 5-hydroxytryptamine receptor 1D 0.98
• 5-hydroxytryptamine receptor 1D 0.98
• 5-hydroxytryptamine receptor 1D 0.95
• 5-hydroxytryptamine receptor 1B 0.95
• 5-hydroxytryptamine receptor 1B 0.95
• 5-hydroxytryptamine receptor 1D 0.95
• 5-hydroxytryptamine receptor 1B 0.95
• 5-hydroxytryptamine receptor 1B 0.95
• 5-hydroxytryptamine receptor 1B 0.95

Co-cited proteins · studied together in the literature

• 5-hydroxytryptamine receptor 1B 4 shared papers
• 5-hydroxytryptamine receptor 1E 3 shared papers
• 5-hydroxytryptamine receptor 1A 3 shared papers
• 5-hydroxytryptamine receptor 1F 2 shared papers
• 5-hydroxytryptamine receptor 2B 2 shared papers
• 5-hydroxytryptamine receptor 2A 2 shared papers
• 5-hydroxytryptamine receptor 2C 1 shared papers
• Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 1 shared papers
• Guanine nucleotide-binding protein G(i) subunit alpha-1 1 shared papers
• Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 1 shared papers

Literature · 10 cited papers

• Structural insights into the lipid and ligand regulation of serotonin receptors. Nature · 2021
• Serotonin receptors - from molecular biology to clinical applications. Physiol. Res. · 2011
• Serotonin receptors. Chem. Rev. · 2008
• 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
• Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone and heterodimers when co-expressed. FEBS Lett. · 1999
• Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat. Genet. · 1999
• Postsynaptic localization of 5-HT1D receptor binding sites in human caudate. Exp. Neurol. · 1991
• Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol. Pharmacol. · 1991
• Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta. Proc. Natl. Acad. Sci. U.S.A. · 1992