Glycine receptor subunit alpha-1

Function

Subunit of heteromeric glycine-gated chloride channels. Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents. Channel activity is potentiated by ethanol. Potentiation of channel activity by intoxicating levels of ethanol contribute to the sedative effects of ethanol (By similarity).

Classification

Family (Pfam)

PF02931 Neur_chan_LBD, PF02932 Neur_chan_memb

InterPro

GABAA/Glycine_rcpt, Glycine_rcpt_A, Glycine_rcpt_A1, Neur_chan_lig-bd, Neur_chan_lig-bd_sf, Neur_channel, Neuro-gated_channel_TM_sf, Neuro_actylchol_rec, Neurotrans-gated_channel_TM, Neurotransmitter_ion_chnl_CS

Functional cluster

Cytochrome c Oxidase & Mito Import Proteins

Experimental structures · PDB · 9

• 1MOT NMR
• 1VRY NMR
• 2M6B NMR
• 2M6I NMR
• 4X5T X-ray 3.50A
• 8DN2 EM 3.90A
• 8DN3 EM 3.55A
• 8DN4 EM 4.10A
• 8DN5 EM 3.63A

A predicted model is available from AlphaFold.

Gene Ontology · 37

• GO:0034707 chloride channel complex
• GO:0030425 dendrite
• GO:0009897 external side of plasma membrane
• GO:0098690 glycinergic synapse
• GO:0060077 inhibitory synapse
• GO:0043231 intracellular membrane-bounded organelle
• GO:0016020 membrane
• GO:0043005 neuron projection
• GO:0043025 neuronal cell body
• GO:0043204 perikaryon
• GO:0005886 plasma membrane
• GO:0045211 postsynaptic membrane
• GO:0045202 synapse
• GO:0005231 excitatory extracellular ligand-gated monoatomic ion channel activity
• GO:0016934 extracellularly glycine-gated chloride channel activity
• GO:0016594 glycine binding
• GO:0042802 identical protein binding
• GO:0099507 ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
• GO:0030977 taurine binding
• GO:0004888 transmembrane signaling receptor activity
• GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
• GO:0008270 zinc ion binding
• GO:0071230 cellular response to amino acid stimulus
• GO:0071361 cellular response to ethanol
• GO:0071294 cellular response to zinc ion
• GO:1902476 chloride transmembrane transport
• GO:0006821 chloride transport
• GO:0060080 inhibitory postsynaptic potential
• GO:0006811 monoatomic ion transport
• GO:0006936 muscle contraction
• GO:0051970 negative regulation of transmission of nerve impulse
• GO:0007218 neuropeptide signaling pathway
• GO:2000344 positive regulation of acrosome reaction
• GO:0042391 regulation of membrane potential
• GO:0097305 response to alcohol
• GO:0001964 startle response
• GO:0060012 synaptic transmission, glycinergic

Disease associations

• hyperekplexia 1 MONDO:0007868

Drugs targeting this protein · 6

• SEVOFLURANE positive modulator
• DESFLURANE positive modulator
• ISOFLURANE positive modulator
• ENFLURANE positive modulator
• METHOXYFLURANE agonist
• HALOTHANE positive modulator

Related proteins · sequence + function similarity

• Glycine receptor subunit alpha-1 1.00
• Glycine receptor subunit alpha-1 1.00
• Glycine receptor subunit alpha-1 1.00
• Glycine receptor subunit alphaZ1 0.99
• Glycine receptor subunit alpha-2 0.98
• Glycine receptor subunit alpha-2 0.98
• Glycine receptor subunit alpha-2 0.98
• Glycine receptor subunit alpha-3 0.98
• Glycine receptor subunit alpha-3 0.98
• Glycine receptor subunit alpha-3 0.98
• Glycine receptor subunit alpha-2 0.97
• Glycine receptor subunit alpha-4 0.97

Co-cited proteins · studied together in the literature

• Glycine receptor subunit beta 7 shared papers
• Glycine receptor subunit alpha-2 3 shared papers
• Glycine receptor subunit alpha-1 1 shared papers
• Glycine receptor subunit alpha-1 1 shared papers
• Glycine receptor subunit alpha-3 1 shared papers
• Glycine receptor subunit beta 1 shared papers

Literature · 29 cited papers

• Asymmetric gating of a human hetero-pentameric glycine receptor. Nat. Commun. · 2023
• Clinical, genetic, and functional characterization of the glycine receptor beta-subunit A455P variant in a family affected by hyperekplexia syndrome. J. Biol. Chem. · 2022
• Ethanol modulation is quantitatively determined by the transmembrane domain of human alpha1 glycine receptors. Alcohol. Clin. Exp. Res. · 2015
• Allosteric and hyperekplexic mutant phenotypes investigated on an alpha1 glycine receptor transmembrane structure. Proc. Natl. Acad. Sci. U.S.A. · 2015
• Functional reconstitution of glycinergic synapses incorporating defined glycine receptor subunit combinations. Neuropharmacology · 2015
• New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms. J. Biol. Chem. · 2013
• Open-channel structures of the human glycine receptor alpha1 full-length transmembrane domain. Structure · 2013
• Stoichiometry of the human glycine receptor revealed by direct subunit counting. J. Neurosci. · 2012
• Stoichiometry and subunit arrangement of alpha1beta glycine receptors as determined by atomic force microscopy. Biochemistry · 2012
• Mapping of disulfide bonds within the amino-terminal extracellular domain of the inhibitory glycine receptor. J. Biol. Chem. · 2009
• Molecular basis for zinc potentiation at strychnine-sensitive glycine receptors. J. Biol. Chem. · 2005
• Structure and dynamics of the second and third transmembrane domains of human glycine receptor. Biochemistry · 2005
• … and 17 more in the literature graph