5-hydroxytryptamine receptor 1F

Function

G protein-coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Receptor for lasmiditan, a drug for the treatment of acute migraine. 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. HTR1F is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity.

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

5HT1F_rcpt, 5HT_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 1

• 7EXD EM 3.40A

A predicted model is available from AlphaFold.

Gene Ontology · 12

• 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:0051378 serotonin binding
• 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

Drugs targeting this protein · 7

• ALMOTRIPTAN MALATE agonist
• ELETRIPTAN HYDROBROMIDE agonist
• DEXFENFLURAMINE HYDROCHLORIDE agonist
• ZIMELDINE HYDROCHLORIDE antagonist
• AMISULPRIDE antagonist
• LASMIDITAN agonist
• LASMIDITAN SUCCINATE agonist

Related proteins · sequence + function similarity

• 5-hydroxytryptamine receptor 1F 1.00
• 5-hydroxytryptamine receptor 1F 1.00
• 5-hydroxytryptamine receptor 1F 1.00
• 5-hydroxytryptamine receptor 1F 0.99
• 5-hydroxytryptamine receptor 1E 0.96
• 5-hydroxytryptamine receptor 1E 0.96
• 5-hydroxytryptamine receptor 1E 0.96
• 5-hydroxytryptamine receptor 1D 0.95
• 5-hydroxytryptamine receptor 1A-beta 0.94
• 5-hydroxytryptamine receptor 1D 0.93
• 5-hydroxytryptamine receptor 1B 0.93
• 5-hydroxytryptamine receptor 1B 0.93

Co-cited proteins · studied together in the literature

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

Literature · 9 cited papers

• Structural insights into the ligand binding and Gi coupling of serotonin receptor 5-HT5A. Cell Discov. · 2022
• Structural basis for recognition of anti-migraine drug lasmiditan by the serotonin receptor 5-HT1F-G protein complex. Cell Res. · 2021
• Toward selective drug development for the human 5-hydroxytryptamine 1E receptor: a comparison of 5-hydroxytryptamine 1E and 1F receptor structure-affinity relationships. J. Pharmacol. Exp. Ther. · 2011
• Serotonin receptors - from molecular biology to clinical applications. Physiol. Res. · 2011
• Serotonin receptors. Chem. Rev. · 2008
• The DNA sequence, annotation and analysis of human chromosome 3. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes. Proc. Natl. Acad. Sci. U.S.A. · 1993
• Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc. Natl. Acad. Sci. U.S.A. · 1993