GLRA1_HUMAN
ID GLRA1_HUMAN Reviewed; 457 AA.
AC P23415; B2R6T3; Q14C77; Q6DJV9;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Glycine receptor subunit alpha-1;
DE AltName: Full=Glycine receptor 48 kDa subunit;
DE AltName: Full=Glycine receptor strychnine-binding subunit;
DE Flags: Precursor;
GN Name=GLRA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, SUBCELLULAR LOCATION, AND
RP ACTIVITY REGULATION.
RX PubMed=2155780; DOI=10.1002/j.1460-2075.1990.tb08172.x;
RA Grenningloh G., Schmieden V., Schofield P.R., Seeburg P.H., Siddique T.,
RA Mohandas T.K., Becker C.-M., Betz H.;
RT "Alpha subunit variants of the human glycine receptor: primary structures,
RT functional expression and chromosomal localization of the corresponding
RT genes.";
RL EMBO J. 9:771-776(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ALA-80.
RX PubMed=7920629; DOI=10.1038/ng0694-131;
RA Ryan S.G., Buckwalter M.S., Lynch J.W., Handford C.A., Segura L.,
RA Shiang R., Wasmuth J.J., Camper S.A., Schofield P., O'Connell P.;
RT "A missense mutation in the gene encoding the alpha 1 subunit of the
RT inhibitory glycine receptor in the spasmodic mouse.";
RL Nat. Genet. 7:131-135(1994).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION WITH GLRB.
RX PubMed=14551753; DOI=10.1007/s00249-003-0286-y;
RA Mohammadi B., Krampfl K., Cetinkaya C., Moschref H., Grosskreutz J.,
RA Dengler R., Bufler J.;
RT "Kinetic analysis of recombinant mammalian alpha(1) and alpha(1)beta
RT glycine receptor channels.";
RL Eur. Biophys. J. 32:529-536(2003).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP HIS-137; GLU-220; ASP-222 AND HIS-243.
RX PubMed=16144831; DOI=10.1074/jbc.m508303200;
RA Miller P.S., Da Silva H.M., Smart T.G.;
RT "Molecular basis for zinc potentiation at strychnine-sensitive glycine
RT receptors.";
RL J. Biol. Chem. 280:37877-37884(2005).
RN [8]
RP DISULFIDE BONDS.
RX PubMed=19861413; DOI=10.1074/jbc.m109.043448;
RA Vogel N., Kluck C.J., Melzer N., Schwarzinger S., Breitinger U., Seeber S.,
RA Becker C.M.;
RT "Mapping of disulfide bonds within the amino-terminal extracellular domain
RT of the inhibitory glycine receptor.";
RL J. Biol. Chem. 284:36128-36136(2009).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, INTERACTION WITH GLRB,
RP AND SUBUNIT STOICHIOMETRY.
RX PubMed=22715885; DOI=10.1021/bi300063m;
RA Yang Z., Taran E., Webb T.I., Lynch J.W.;
RT "Stoichiometry and subunit arrangement of alpha1beta glycine receptors as
RT determined by atomic force microscopy.";
RL Biochemistry 51:5229-5231(2012).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GLRB, AND SUBUNIT
RP STOICHIOMETRY.
RX PubMed=22973015; DOI=10.1523/jneurosci.2050-12.2012;
RA Durisic N., Godin A.G., Wever C.M., Heyes C.D., Lakadamyali M., Dent J.A.;
RT "Stoichiometry of the human glycine receptor revealed by direct subunit
RT counting.";
RL J. Neurosci. 32:12915-12920(2012).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25973519; DOI=10.1111/acer.12735;
RA Horani S., Stater E.P., Corringer P.J., Trudell J.R., Harris R.A.,
RA Howard R.J.;
RT "Ethanol modulation is quantitatively determined by the transmembrane
RT domain of human alpha1 glycine receptors.";
RL Alcohol. Clin. Exp. Res. 39:962-968(2015).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=25445488; DOI=10.1016/j.neuropharm.2014.10.026;
RA Zhang Y., Dixon C.L., Keramidas A., Lynch J.W.;
RT "Functional reconstitution of glycinergic synapses incorporating defined
RT glycine receptor subunit combinations.";
RL Neuropharmacology 89:391-397(2015).
RN [13]
RP STRUCTURE BY NMR OF 277-304.
RX PubMed=12667090; DOI=10.1021/bi026767g;
RA Yushmanov V.E., Mandal P.K., Liu Z., Tang P., Xu Y.;
RT "NMR structure and backbone dynamics of the extended second transmembrane
RT domain of the human neuronal glycine receptor alpha1 subunit.";
RL Biochemistry 42:3989-3995(2003).
RN [14]
RP STRUCTURE BY NMR OF 278-337.
RX PubMed=15952785; DOI=10.1021/bi050256n;
RA Ma D., Liu Z., Li L., Tang P., Xu Y.;
RT "Structure and dynamics of the second and third transmembrane domains of
RT human glycine receptor.";
RL Biochemistry 44:8790-8800(2005).
RN [15]
RP STRUCTURE BY NMR OF 244-453, ELECTRON MICROSCOPY, FUNCTION, ACTIVITY
RP REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, AND DOMAIN.
RX PubMed=23994010; DOI=10.1016/j.str.2013.07.014;
RA Mowrey D.D., Cui T., Jia Y., Ma D., Makhov A.M., Zhang P., Tang P., Xu Y.;
RT "Open-channel structures of the human glycine receptor alpha1 full-length
RT transmembrane domain.";
RL Structure 21:1897-1904(2013).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 246-338 AND 418-446, FUNCTION,
RP ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY,
RP CHARACTERIZATION OF VARIANTS HKPX1 GLU-254; THR-278; GLN-299 AND MET-308,
RP AND MUTAGENESIS OF GLY-282 AND LYS-304.
RX PubMed=25730860; DOI=10.1073/pnas.1417864112;
RA Moraga-Cid G., Sauguet L., Huon C., Malherbe L., Girard-Blanc C.,
RA Petres S., Murail S., Taly A., Baaden M., Delarue M., Corringer P.J.;
RT "Allosteric and hyperekplexic mutant phenotypes investigated on an alpha1
RT glycine receptor transmembrane structure.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:2865-2870(2015).
RN [17]
RP VARIANTS HKPX1 LEU-299 AND GLN-299.
RX PubMed=8298642; DOI=10.1038/ng1293-351;
RA Shiang R., Ryan S.G., Zhu Y.-Z., Hahn A.F., O'Connell P., Wasmuth J.J.;
RT "Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause
RT the dominant neurologic disorder, hyperekplexia.";
RL Nat. Genet. 5:351-357(1993).
RN [18]
RP VARIANT HKPX1 CYS-307.
RA Shiang R., Ryan S.G., Zhu Y.-Z., O'Connell P., Wasmuth J.J.;
RT "Mutational and haplotype analysis of the aplha1 subunit of the glycine
RT receptor in hyperekplexia patients.";
RL Am. J. Hum. Genet. 55:A242-A242(1994).
RN [19]
RP CHARACTERIZATION OF VARIANTS HKPX1 LEU-299 AND GLN-299, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=7925268; DOI=10.1002/j.1460-2075.1994.tb06742.x;
RA Langosch D., Laube B., Runstroem N., Schmieden V., Bormann J., Betz H.;
RT "Decreased agonist affinity and chloride conductance of mutant glycine
RT receptors associated with human hereditary hyperekplexia.";
RL EMBO J. 13:4223-4228(1994).
RN [20]
RP VARIANT HKPX1 LEU-299.
RX PubMed=7981700; DOI=10.1093/hmg/3.7.1201;
RA Schorderet D.F., Pescia G., Bernasconi A., Regli F.;
RT "An additional family with Startle disease and a G1192A mutation at the
RT alpha 1 subunit of the inhibitory glycine receptor gene.";
RL Hum. Mol. Genet. 3:1201-1201(1994).
RN [21]
RP VARIANT HKPX1 ASN-272.
RX PubMed=7881416; DOI=10.1093/hmg/3.12.2175;
RA Rees M.I., Andrew M., Jawad S., Owen M.J.;
RT "Evidence for recessive as well as dominant forms of startle disease
RT (hyperekplexia) caused by mutations in the alpha 1 subunit of the
RT inhibitory glycine receptor.";
RL Hum. Mol. Genet. 3:2175-2179(1994).
RN [22]
RP VARIANT HKPX1 CYS-307.
RX PubMed=7611730; DOI=10.1002/ana.410380115;
RA Shiang R., Ryan S.G., Zhu Y.-Z., Fielder T.J., Allen R.J., Fryer A.,
RA Yamashita S., O'Connell P., Wasmuth J.J.;
RT "Mutational analysis of familial and sporadic hyperekplexia.";
RL Ann. Neurol. 38:85-91(1995).
RN [23]
RP VARIANT HKPX1 HIS-294.
RX PubMed=8571969;
RA Milani N., Dalpra L., del Prete A., Zanini R., Larizza L.;
RT "A novel mutation (Gln266-->His) in the alpha 1 subunit of the inhibitory
RT glycine-receptor gene (GLRA1) in hereditary hyperekplexia.";
RL Am. J. Hum. Genet. 58:420-422(1996).
RN [24]
RP VARIANT HKPX1 GLU-304.
RX PubMed=8733061; DOI=10.1136/jmg.33.5.435;
RA Elmslie F.V., Hutchings S.M., Spencer V., Curtis A., Covanis T.,
RA Gardiner R.M., Rees M.;
RT "Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel
RT mutation in a family cosegregating for hyperekplexia and spastic
RT paraparesis.";
RL J. Med. Genet. 33:435-436(1996).
RN [25]
RP CHARACTERIZATION OF VARIANTS HKPX1 ASN-272; LEU-299; GLN-299; GLU-304 AND
RP CYS-307, FUNCTION, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9009272; DOI=10.1093/emboj/16.1.110;
RA Lynch J.W., Rajendra S., Pierce K.D., Handford C.A., Barry P.H.,
RA Schofield P.R.;
RT "Identification of intracellular and extracellular domains mediating signal
RT transduction in the inhibitory glycine receptor chloride channel.";
RL EMBO J. 16:110-120(1997).
RN [26]
RP VARIANT HKPX1 GLU-304.
RX PubMed=9067762;
RX DOI=10.1002/(sici)1098-1004(1997)9:2<185::aid-humu14>3.0.co;2-z;
RA Seri M., Bolino A., Galietta L.J.V., Lerone M., Silengo M., Romeo G.;
RT "Startle disease in an Italian family by mutation (K276E): the alpha-
RT subunit of the inhibiting glycine receptor.";
RL Hum. Mutat. 9:185-187(1997).
RN [27]
RP VARIANTS HKPX1 HIS-280 AND HIS-428.
RX PubMed=10514101;
RX DOI=10.1002/1531-8249(199910)46:4<634::aid-ana12>3.0.co;2-9;
RA Vergouwe M.N., Tijssen M.A., Peters A.C., Wielaard R., Frants R.R.;
RT "Hyperekplexia phenotype due to compound heterozygosity for GLRA1 gene
RT mutations.";
RL Ann. Neurol. 46:634-638(1999).
RN [28]
RP VARIANT HKPX1 THR-278.
RX PubMed=9920650; DOI=10.1523/jneurosci.19-03-00869.1999;
RA Saul B., Kuner T., Sobetzko D., Brune W., Hanefeld F., Meinck H.-M.,
RA Becker C.-M.;
RT "Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an
RT intracellular determinant of glycine receptor channel gating.";
RL J. Neurosci. 19:869-877(1999).
RN [29]
RP VARIANTS HKPX1 TRP-93; CYS-100; TRP-246; GLU-254; SER-258; PRO-319 AND
RP ALA-424, CHARACTERIZATION OF VARIANTS HKPX1 TRP-93; CYS-100; TRP-246;
RP GLU-254; SER-258; HIS-280; MET-308; PRO-319; ALA-424 AND HIS-450, FUNCTION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=24108130; DOI=10.1074/jbc.m113.509240;
RA Bode A., Wood S.E., Mullins J.G., Keramidas A., Cushion T.D., Thomas R.H.,
RA Pickrell W.O., Drew C.J., Masri A., Jones E.A., Vassallo G., Born A.P.,
RA Alehan F., Aharoni S., Bannasch G., Bartsch M., Kara B., Krause A.,
RA Karam E.G., Matta S., Jain V., Mandel H., Freilinger M., Graham G.E.,
RA Hobson E., Chatfield S., Vincent-Delorme C., Rahme J.E., Afawi Z.,
RA Berkovic S.F., Howell O.W., Vanbellinghen J.F., Rees M.I., Chung S.K.,
RA Lynch J.W.;
RT "New hyperekplexia mutations provide insight into glycine receptor
RT assembly, trafficking, and activation mechanisms.";
RL J. Biol. Chem. 288:33745-33759(2013).
CC -!- FUNCTION: Glycine receptors are ligand-gated chloride channels
CC (PubMed:23994010, PubMed:25730860). Channel opening is triggered by
CC extracellular glycine (PubMed:2155780, PubMed:7920629, PubMed:14551753,
CC PubMed:16144831, PubMed:22715885, PubMed:22973015, PubMed:25973519,
CC PubMed:9009272). Channel opening is also triggered by taurine and beta-
CC alanine (PubMed:16144831, PubMed:9009272). Channel characteristics
CC depend on the subunit composition; heteropentameric channels are
CC activated by lower glycine levels and display faster desensitization
CC (PubMed:14551753). Plays an important role in the down-regulation of
CC neuronal excitability (PubMed:8298642, PubMed:9009272). Contributes to
CC the generation of inhibitory postsynaptic currents (PubMed:25445488).
CC Channel activity is potentiated by ethanol (PubMed:25973519).
CC Potentiation of channel activity by intoxicating levels of ethanol
CC contribute to the sedative effects of ethanol (By similarity).
CC {ECO:0000250|UniProtKB:Q64018, ECO:0000269|PubMed:14551753,
CC ECO:0000269|PubMed:16144831, ECO:0000269|PubMed:2155780,
CC ECO:0000269|PubMed:22715885, ECO:0000269|PubMed:22973015,
CC ECO:0000269|PubMed:23994010, ECO:0000269|PubMed:25445488,
CC ECO:0000269|PubMed:25730860, ECO:0000269|PubMed:25973519,
CC ECO:0000269|PubMed:7920629, ECO:0000269|PubMed:7925268,
CC ECO:0000269|PubMed:9009272, ECO:0000305|PubMed:8298642}.
CC -!- ACTIVITY REGULATION: Channel activity is potentiated by nanomolar
CC concentrations of Zn(2+); half-maximal activation is observed with 37
CC nM Zn(2+) (PubMed:16144831). Inhibited by higher Zn(2+) levels; haf-
CC maximal inhibition occurs at 20 uM Zn(2+) (PubMed:16144831). Inhibited
CC by strychnine (PubMed:2155780, PubMed:16144831, PubMed:25445488).
CC Inhibited by lindane (PubMed:25445488). Inhibited by picrotoxin
CC (PubMed:22715885, PubMed:23994010, PubMed:25730860). Strychnine binding
CC locks the channel in a closed conformation and prevents channel opening
CC in response to extracellular glycine (By similarity).
CC {ECO:0000250|UniProtKB:O93430, ECO:0000269|PubMed:16144831,
CC ECO:0000269|PubMed:2155780, ECO:0000269|PubMed:22715885,
CC ECO:0000269|PubMed:23994010, ECO:0000269|PubMed:25445488,
CC ECO:0000269|PubMed:25730860}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=A concentration of about 0.02 mM glycine results in half-maximal
CC channel conductance for homopentamers. A concentration of 0.018 mM
CC glycine results in half-maximal channel conductance for homopentamers
CC upon heterologous expression in cultured human embryonic kidney cells
CC (PubMed:9009272). A concentration of 0.027 mM glycine results in
CC half-maximal channel conductance for homopentamers upon heterologous
CC expression in cultured human embryonic kidney cells (PubMed:7920629).
CC {ECO:0000269|PubMed:7920629, ECO:0000269|PubMed:9009272};
CC -!- SUBUNIT: Homopentamer (in vitro) (PubMed:22715885, PubMed:22973015,
CC PubMed:23994010, PubMed:25730860). Interacts with GLRB to form
CC heteropentameric channels; this is probably the predominant form in
CC vivo (PubMed:22715885, PubMed:22973015, PubMed:25445488).
CC Heteropentamer composed of two GLRA1 and three GLRB (PubMed:22715885).
CC Heteropentamer composed of three GLRA1 and two GLRB (PubMed:22973015).
CC Both homopentamers and heteropentamers form functional ion channels,
CC but their characteristics are subtly different (PubMed:14551753,
CC PubMed:22715885, PubMed:22973015, PubMed:25445488, PubMed:23994010,
CC PubMed:25730860). {ECO:0000269|PubMed:14551753,
CC ECO:0000269|PubMed:22715885, ECO:0000269|PubMed:22973015,
CC ECO:0000269|PubMed:23994010, ECO:0000269|PubMed:25445488,
CC ECO:0000269|PubMed:25730860}.
CC -!- INTERACTION:
CC P23415; Q9Y5V3: MAGED1; NbExp=3; IntAct=EBI-12020340, EBI-716006;
CC P23415; O60504: SORBS3; NbExp=3; IntAct=EBI-12020340, EBI-741237;
CC P23415-1; P23415-1: GLRA1; NbExp=2; IntAct=EBI-16072009, EBI-16072009;
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q64018}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q64018}. Synapse {ECO:0000250|UniProtKB:Q64018}.
CC Perikaryon {ECO:0000250|UniProtKB:Q64018}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q64018}. Cell membrane
CC {ECO:0000269|PubMed:14551753, ECO:0000269|PubMed:16144831,
CC ECO:0000269|PubMed:2155780, ECO:0000269|PubMed:22715885,
CC ECO:0000269|PubMed:22973015, ECO:0000269|PubMed:24108130,
CC ECO:0000269|PubMed:25445488, ECO:0000269|PubMed:25730860,
CC ECO:0000269|PubMed:25973519, ECO:0000269|PubMed:7920629,
CC ECO:0000269|PubMed:7925268, ECO:0000269|PubMed:9009272}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:23994010,
CC ECO:0000269|PubMed:25730860, ECO:0000305|PubMed:2155780}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=P23415-1; Sequence=Displayed;
CC Name=b;
CC IsoId=P23415-2; Sequence=VSP_021142;
CC -!- DOMAIN: The channel pore is formed by pentameric assembly of the second
CC transmembrane domain from all five subunits. In the absence of the
CC extracellular domain, the channel is in a constitutively open
CC conformation (PubMed:23994010). Channel opening is effected by an
CC outward rotation of the transmembrane domains that increases the
CC diameter of the pore (By similarity). {ECO:0000250|UniProtKB:O93430,
CC ECO:0000269|PubMed:23994010}.
CC -!- DISEASE: Hyperekplexia 1 (HKPX1) [MIM:149400]: A neurologic disorder
CC characterized by muscular rigidity of central nervous system origin,
CC particularly in the neonatal period, and by an exaggerated startle
CC response to unexpected acoustic or tactile stimuli.
CC {ECO:0000269|PubMed:10514101, ECO:0000269|PubMed:24108130,
CC ECO:0000269|PubMed:25730860, ECO:0000269|PubMed:7611730,
CC ECO:0000269|PubMed:7881416, ECO:0000269|PubMed:7925268,
CC ECO:0000269|PubMed:7981700, ECO:0000269|PubMed:8298642,
CC ECO:0000269|PubMed:8571969, ECO:0000269|PubMed:8733061,
CC ECO:0000269|PubMed:9009272, ECO:0000269|PubMed:9067762,
CC ECO:0000269|PubMed:9920650, ECO:0000269|Ref.18}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The alpha subunit binds strychnine.
CC {ECO:0000269|PubMed:2155780}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Glycine receptor (TC 1.A.9.3) subfamily. GLRA1 sub-subfamily.
CC {ECO:0000305}.
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DR EMBL; X52009; CAA36258.1; -; mRNA.
DR EMBL; AK312702; BAG35580.1; -; mRNA.
DR EMBL; CH471062; EAW61657.1; -; Genomic_DNA.
DR EMBL; BC074980; AAH74980.1; -; mRNA.
DR EMBL; BC114947; AAI14948.1; -; mRNA.
DR CCDS; CCDS4320.1; -. [P23415-2]
DR CCDS; CCDS54942.1; -. [P23415-1]
DR PIR; S12382; S12382.
DR RefSeq; NP_000162.2; NM_000171.3. [P23415-2]
DR RefSeq; NP_001139512.1; NM_001146040.1. [P23415-1]
DR PDB; 1MOT; NMR; -; A=277-304.
DR PDB; 1VRY; NMR; -; A=278-337.
DR PDB; 2M6B; NMR; -; A=244-453.
DR PDB; 2M6I; NMR; -; A/B/C/D/E=244-453.
DR PDB; 4X5T; X-ray; 3.50 A; A/B/C/D/E=246-338, A/B/C/D/E=418-446.
DR PDBsum; 1MOT; -.
DR PDBsum; 1VRY; -.
DR PDBsum; 2M6B; -.
DR PDBsum; 2M6I; -.
DR PDBsum; 4X5T; -.
DR AlphaFoldDB; P23415; -.
DR BMRB; P23415; -.
DR SMR; P23415; -.
DR BioGRID; 109003; 3.
DR CORUM; P23415; -.
DR DIP; DIP-48768N; -.
DR IntAct; P23415; 2.
DR STRING; 9606.ENSP00000411593; -.
DR BindingDB; P23415; -.
DR ChEMBL; CHEMBL5845; -.
DR DrugBank; DB00572; Atropine.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB03929; D-Serine.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB01381; Ginkgo biloba.
DR DrugBank; DB00145; Glycine.
DR DrugBank; DB05417; GW 468816.
DR DrugBank; DB01159; Halothane.
DR DrugBank; DB00753; Isoflurane.
DR DrugBank; DB00431; Lindane.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB01043; Memantine.
DR DrugBank; DB01028; Methoxyflurane.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB00466; Picrotoxin.
DR DrugBank; DB05885; Seletracetam.
DR DrugBank; DB01236; Sevoflurane.
DR DrugBank; DB01956; Taurine.
DR DrugBank; DB11582; Thiocolchicoside.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR DrugCentral; P23415; -.
DR GuidetoPHARMACOLOGY; 423; -.
DR TCDB; 1.A.9.3.1; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR GlyGen; P23415; 1 site.
DR iPTMnet; P23415; -.
DR PhosphoSitePlus; P23415; -.
DR BioMuta; GLRA1; -.
DR DMDM; 116242495; -.
DR MassIVE; P23415; -.
DR PaxDb; P23415; -.
DR PeptideAtlas; P23415; -.
DR PRIDE; P23415; -.
DR ProteomicsDB; 54089; -. [P23415-1]
DR ProteomicsDB; 54090; -. [P23415-2]
DR Antibodypedia; 3089; 418 antibodies from 36 providers.
DR DNASU; 2741; -.
DR Ensembl; ENST00000274576.9; ENSP00000274576.5; ENSG00000145888.11. [P23415-2]
DR Ensembl; ENST00000455880.2; ENSP00000411593.2; ENSG00000145888.11. [P23415-1]
DR GeneID; 2741; -.
DR KEGG; hsa:2741; -.
DR MANE-Select; ENST00000274576.9; ENSP00000274576.5; NM_000171.4; NP_000162.2. [P23415-2]
DR UCSC; uc003lur.4; human. [P23415-1]
DR CTD; 2741; -.
DR DisGeNET; 2741; -.
DR GeneCards; GLRA1; -.
DR GeneReviews; GLRA1; -.
DR HGNC; HGNC:4326; GLRA1.
DR HPA; ENSG00000145888; Tissue enriched (brain).
DR MalaCards; GLRA1; -.
DR MIM; 138491; gene.
DR MIM; 149400; phenotype.
DR neXtProt; NX_P23415; -.
DR OpenTargets; ENSG00000145888; -.
DR Orphanet; 3197; Hereditary hyperekplexia.
DR PharmGKB; PA28727; -.
DR VEuPathDB; HostDB:ENSG00000145888; -.
DR eggNOG; KOG3644; Eukaryota.
DR GeneTree; ENSGT00940000159047; -.
DR HOGENOM; CLU_010920_1_4_1; -.
DR InParanoid; P23415; -.
DR OMA; FNFAYGM; -.
DR OrthoDB; 614790at2759; -.
DR PhylomeDB; P23415; -.
DR TreeFam; TF315453; -.
DR PathwayCommons; P23415; -.
DR Reactome; R-HSA-112314; Neurotransmitter receptors and postsynaptic signal transmission.
DR SignaLink; P23415; -.
DR SIGNOR; P23415; -.
DR BioGRID-ORCS; 2741; 10 hits in 1068 CRISPR screens.
DR ChiTaRS; GLRA1; human.
DR EvolutionaryTrace; P23415; -.
DR GeneWiki; Glycine_receptor,_alpha_1; -.
DR GenomeRNAi; 2741; -.
DR Pharos; P23415; Tclin.
DR PRO; PR:P23415; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P23415; protein.
DR Bgee; ENSG00000145888; Expressed in islet of Langerhans and 20 other tissues.
DR ExpressionAtlas; P23415; baseline and differential.
DR Genevisible; P23415; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0098690; C:glycinergic synapse; IEA:Ensembl.
DR GO; GO:0060077; C:inhibitory synapse; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0016934; F:extracellularly glycine-gated chloride channel activity; IDA:UniProtKB.
DR GO; GO:0016594; F:glycine binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0030977; F:taurine binding; IDA:UniProtKB.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IMP:UniProtKB.
DR GO; GO:0007340; P:acrosome reaction; IEA:Ensembl.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:UniProtKB.
DR GO; GO:0071361; P:cellular response to ethanol; IDA:UniProtKB.
DR GO; GO:0071294; P:cellular response to zinc ion; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006821; P:chloride transport; IDA:UniProtKB.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; ISS:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; IDA:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; IMP:UniProtKB.
DR GO; GO:0051970; P:negative regulation of transmission of nerve impulse; IMP:UniProtKB.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0050884; P:neuromuscular process controlling posture; IEA:Ensembl.
DR GO; GO:0019228; P:neuronal action potential; IEA:Ensembl.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:UniProtKB.
DR GO; GO:2000344; P:positive regulation of acrosome reaction; IMP:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:MGI.
DR GO; GO:0002087; P:regulation of respiratory gaseous exchange by nervous system process; IEA:Ensembl.
DR GO; GO:0097305; P:response to alcohol; ISS:UniProtKB.
DR GO; GO:0043200; P:response to amino acid; IBA:GO_Central.
DR GO; GO:0060013; P:righting reflex; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0001964; P:startle response; IMP:UniProtKB.
DR GO; GO:0060012; P:synaptic transmission, glycinergic; ISS:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:Ensembl.
DR Gene3D; 1.20.58.390; -; 1.
DR Gene3D; 2.70.170.10; -; 1.
DR InterPro; IPR006028; GABAA/Glycine_rcpt.
DR InterPro; IPR008127; Glycine_rcpt_A.
DR InterPro; IPR008128; Glycine_rcpt_A1.
DR InterPro; IPR006202; Neur_chan_lig-bd.
DR InterPro; IPR036734; Neur_chan_lig-bd_sf.
DR InterPro; IPR006201; Neur_channel.
DR InterPro; IPR036719; Neuro-gated_channel_TM_sf.
DR InterPro; IPR038050; Neuro_actylchol_rec.
DR InterPro; IPR006029; Neurotrans-gated_channel_TM.
DR InterPro; IPR018000; Neurotransmitter_ion_chnl_CS.
DR PANTHER; PTHR18945; PTHR18945; 1.
DR Pfam; PF02931; Neur_chan_LBD; 1.
DR Pfam; PF02932; Neur_chan_memb; 1.
DR PRINTS; PR00253; GABAARECEPTR.
DR PRINTS; PR01673; GLYRALPHA.
DR PRINTS; PR01674; GLYRALPHA1.
DR PRINTS; PR00252; NRIONCHANNEL.
DR SUPFAM; SSF63712; SSF63712; 1.
DR SUPFAM; SSF90112; SSF90112; 1.
DR TIGRFAMs; TIGR00860; LIC; 1.
DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Chloride; Chloride channel; Disease variant; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
KW Metal-binding; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Signal; Synapse; Transmembrane; Transmembrane helix; Transport; Zinc.
FT SIGNAL 1..28
FT /evidence="ECO:0000250|UniProtKB:P07727, ECO:0000255"
FT CHAIN 29..457
FT /note="Glycine receptor subunit alpha-1"
FT /id="PRO_0000000412"
FT TOPO_DOM 29..250
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 251..272
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:23994010,
FT ECO:0000269|PubMed:25730860"
FT TOPO_DOM 273..277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:23994010,
FT ECO:0000269|PubMed:25730860"
FT TRANSMEM 278..298
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:23994010,
FT ECO:0000269|PubMed:25730860"
FT TOPO_DOM 299..309
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:23994010,
FT ECO:0000269|PubMed:25730860"
FT TRANSMEM 310..330
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:23994010,
FT ECO:0000269|PubMed:25730860"
FT TOPO_DOM 331..425
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:23994010"
FT TRANSMEM 426..446
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:23994010"
FT TOPO_DOM 447..457
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT REGION 391..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 220
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:16144831"
FT BINDING 222
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:16144831"
FT BINDING 230..235
FT /ligand="strychnine"
FT /ligand_id="ChEBI:CHEBI:90700"
FT /evidence="ECO:0000250|UniProtKB:O93430"
FT BINDING 243
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:16144831"
FT SITE 289
FT /note="Important for obstruction of the ion pore in the
FT closed conformation"
FT /evidence="ECO:0000269|PubMed:25730860"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 166..180
FT /evidence="ECO:0000269|PubMed:19861413"
FT DISULFID 226..237
FT /evidence="ECO:0000269|PubMed:19861413"
FT VAR_SEQ 354..361
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:2155780"
FT /id="VSP_021142"
FT VARIANT 93
FT /note="R -> W (in HKPX1; impairs expression at the cell
FT membrane; requires much higher glycine levels for channel
FT activation; dbSNP:rs199547699)"
FT /evidence="ECO:0000269|PubMed:24108130"
FT /id="VAR_075418"
FT VARIANT 100
FT /note="R -> C (in HKPX1; abolishes expression at the cell
FT membrane; requires much higher glycine levels for channel
FT activation; dbSNP:rs1581623910)"
FT /evidence="ECO:0000269|PubMed:24108130"
FT /id="VAR_075419"
FT VARIANT 246
FT /note="R -> W (in HKPX1; abolishes expression at the cell
FT membrane; requires much higher glycine levels for channel
FT activation; dbSNP:rs751659671)"
FT /evidence="ECO:0000269|PubMed:24108130"
FT /id="VAR_075420"
FT VARIANT 254
FT /note="Q -> E (in HKPX1; strongly increases sensitivity to
FT extracellular glycine; high leak currents in the absence of
FT glycine due to spontaneous channel opening)"
FT /evidence="ECO:0000269|PubMed:24108130,
FT ECO:0000269|PubMed:25730860"
FT /id="VAR_075421"
FT VARIANT 258
FT /note="P -> S (in HKPX1; impairs expression at the cell
FT membrane; requires much higher glycine levels for channel
FT activation)"
FT /evidence="ECO:0000269|PubMed:24108130"
FT /id="VAR_075422"
FT VARIANT 272
FT /note="I -> N (in HKPX1; requires much higher glycine
FT levels for channel activation; dbSNP:rs121918409)"
FT /evidence="ECO:0000269|PubMed:7881416,
FT ECO:0000269|PubMed:9009272"
FT /id="VAR_000296"
FT VARIANT 278
FT /note="P -> T (in HKPX1; requires much higher glycine
FT levels for channel activation and displays an increased
FT rate of desensitization; dbSNP:rs121918413)"
FT /evidence="ECO:0000269|PubMed:25730860,
FT ECO:0000269|PubMed:9920650"
FT /id="VAR_010112"
FT VARIANT 280
FT /note="R -> H (in HKPX1; dbSNP:rs281864918)"
FT /evidence="ECO:0000269|PubMed:10514101"
FT /id="VAR_010113"
FT VARIANT 294
FT /note="Q -> H (in HKPX1; dbSNP:rs121918411)"
FT /evidence="ECO:0000269|PubMed:8571969"
FT /id="VAR_000297"
FT VARIANT 299
FT /note="R -> L (in HKPX1; requires much higher glycine
FT levels for channel activation; dbSNP:rs121918408)"
FT /evidence="ECO:0000269|PubMed:7925268,
FT ECO:0000269|PubMed:7981700, ECO:0000269|PubMed:8298642,
FT ECO:0000269|PubMed:9009272"
FT /id="VAR_000298"
FT VARIANT 299
FT /note="R -> Q (in HKPX1; decreases unitary channel
FT conductance and requires much higher glycine concentrations
FT for activation; dbSNP:rs121918408)"
FT /evidence="ECO:0000269|PubMed:25730860,
FT ECO:0000269|PubMed:7925268, ECO:0000269|PubMed:8298642,
FT ECO:0000269|PubMed:9009272"
FT /id="VAR_000299"
FT VARIANT 304
FT /note="K -> E (in HKPX1; requires much higher glycine
FT levels for channel activation; dbSNP:rs121918412)"
FT /evidence="ECO:0000269|PubMed:8733061,
FT ECO:0000269|PubMed:9009272, ECO:0000269|PubMed:9067762"
FT /id="VAR_000300"
FT VARIANT 307
FT /note="Y -> C (in HKPX1; requires much higher glycine
FT levels for channel activation; dbSNP:rs121918410)"
FT /evidence="ECO:0000269|PubMed:7611730,
FT ECO:0000269|PubMed:9009272, ECO:0000269|Ref.18"
FT /id="VAR_000301"
FT VARIANT 308
FT /note="V -> M (in HKPX1; high leak currents in the absence
FT of glycine due to spontaneous channel opening)"
FT /evidence="ECO:0000269|PubMed:24108130,
FT ECO:0000269|PubMed:25730860"
FT /id="VAR_075423"
FT VARIANT 319
FT /note="L -> P (in HKPX1; impairs expression at the cell
FT membrane; requires much higher glycine levels for channel
FT activation)"
FT /evidence="ECO:0000269|PubMed:24108130"
FT /id="VAR_075424"
FT VARIANT 424
FT /note="D -> A (in HKPX1; abolishes expression at the cell
FT membrane)"
FT /evidence="ECO:0000269|PubMed:24108130"
FT /id="VAR_075425"
FT VARIANT 428
FT /note="R -> H (in HKPX1; dbSNP:rs281864919)"
FT /evidence="ECO:0000269|PubMed:10514101"
FT /id="VAR_010114"
FT VARIANT 450
FT /note="R -> H (in HKPX1; displays leak currents in the
FT absence of glycine due to spontaneous channel opening;
FT dbSNP:rs200130685)"
FT /evidence="ECO:0000269|PubMed:24108130"
FT /id="VAR_075426"
FT MUTAGEN 80
FT /note="A->S: The mutant channel requires much higher
FT glycine concentrations for activation."
FT /evidence="ECO:0000269|PubMed:7920629"
FT MUTAGEN 137
FT /note="H->F: Abolishes sensitivity of channel activity to
FT potentiation or inhibition by Zn(2+); when associated with
FT K-222."
FT /evidence="ECO:0000269|PubMed:16144831"
FT MUTAGEN 137
FT /note="H->N: Strongly decreases sensitivity to inhibition
FT by Zn(2+)."
FT /evidence="ECO:0000269|PubMed:16144831"
FT MUTAGEN 220
FT /note="E->A: Abolishes potentiation of channel activity by
FT Zn(2+)."
FT /evidence="ECO:0000269|PubMed:16144831"
FT MUTAGEN 222
FT /note="D->A: Abolishes potentiation of channel activity by
FT Zn(2+)."
FT /evidence="ECO:0000269|PubMed:16144831"
FT MUTAGEN 222
FT /note="D->K: Abolishes sensitivity of channel activity to
FT potentiation or inhibition by Zn(2+); when associated with
FT F-137."
FT /evidence="ECO:0000269|PubMed:16144831"
FT MUTAGEN 243
FT /note="H->A: Strongly decreases potentiation of channel
FT activity by Zn(2+)."
FT /evidence="ECO:0000269|PubMed:16144831"
FT MUTAGEN 282
FT /note="G->A: Increased single-channel conductance. No
FT effect on glycine sensitivity, but decreased rate of
FT activation."
FT /evidence="ECO:0000269|PubMed:25730860"
FT MUTAGEN 304
FT /note="K->C: Decreases channel conductance; the mutant
FT channel requires much higher glycine concentrations for
FT activation."
FT /evidence="ECO:0000269|PubMed:25730860"
FT CONFLICT 12..14
FT /note="WET -> SGA (in Ref. 1; CAA36258)"
FT /evidence="ECO:0000305"
FT CONFLICT 33
FT /note="P -> T (in Ref. 1; CAA36258)"
FT /evidence="ECO:0000305"
FT TURN 246..248
FT /evidence="ECO:0007829|PDB:2M6B"
FT HELIX 249..254
FT /evidence="ECO:0007829|PDB:4X5T"
FT HELIX 256..267
FT /evidence="ECO:0007829|PDB:4X5T"
FT TURN 274..276
FT /evidence="ECO:0007829|PDB:2M6B"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:4X5T"
FT HELIX 281..284
FT /evidence="ECO:0007829|PDB:4X5T"
FT HELIX 286..289
FT /evidence="ECO:0007829|PDB:4X5T"
FT HELIX 291..297
FT /evidence="ECO:0007829|PDB:4X5T"
FT HELIX 299..301
FT /evidence="ECO:0007829|PDB:4X5T"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:4X5T"
FT HELIX 316..323
FT /evidence="ECO:0007829|PDB:4X5T"
FT HELIX 325..335
FT /evidence="ECO:0007829|PDB:4X5T"
FT HELIX 416..419
FT /evidence="ECO:0007829|PDB:2M6B"
FT HELIX 420..423
FT /evidence="ECO:0007829|PDB:4X5T"
FT TURN 424..426
FT /evidence="ECO:0007829|PDB:4X5T"
FT HELIX 427..446
FT /evidence="ECO:0007829|PDB:4X5T"
FT TURN 449..453
FT /evidence="ECO:0007829|PDB:2M6B"
SQ SEQUENCE 457 AA; 52624 MW; 5ED80AF62B06A3AA CRC64;
MYSFNTLRLY LWETIVFFSL AASKEAEAAR SAPKPMSPSD FLDKLMGRTS GYDARIRPNF
KGPPVNVSCN IFINSFGSIA ETTMDYRVNI FLRQQWNDPR LAYNEYPDDS LDLDPSMLDS
IWKPDLFFAN EKGAHFHEIT TDNKLLRISR NGNVLYSIRI TLTLACPMDL KNFPMDVQTC
IMQLESFGYT MNDLIFEWQE QGAVQVADGL TLPQFILKEE KDLRYCTKHY NTGKFTCIEA
RFHLERQMGY YLIQMYIPSL LIVILSWISF WINMDAAPAR VGLGITTVLT MTTQSSGSRA
SLPKVSYVKA IDIWMAVCLL FVFSALLEYA AVNFVSRQHK ELLRFRRKRR HHKSPMLNLF
QEDEAGEGRF NFSAYGMGPA CLQAKDGISV KGANNSNTTN PPPAPSKSPE EMRKLFIQRA
KKIDKISRIG FPMAFLIFNM FYWIIYKIVR REDVHNQ
