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 27-MAR-2024, entry version 230. 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 INTERACTION WITH GLRB. RX PubMed=35526563; DOI=10.1016/j.jbc.2022.102018; RA Aboheimed G.I., AlRasheed M.M., Almudimeegh S., Pena-Guerra K.A., RA Cardona-Londono K.J., Salih M.A., Seidahmed M.Z., Al-Mohanna F., Colak D., RA Harvey R.J., Harvey K., Arold S.T., Kaya N., Ruiz A.J.; RT "Clinical, genetic, and functional characterization of the glycine receptor RT beta-subunit A455P variant in a family affected by hyperekplexia RT syndrome."; RL J. Biol. Chem. 298:102018-102018(2022). RN [14] 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 [15] 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 [16] RP STRUCTURE BY NMR OF 244-453, ELECTRON MICROSCOPY, FUNCTION, TRANSPORTER RP ACTIVITY, ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, AND RP 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 [17] RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 246-338 AND 418-446, FUNCTION, RP TRANSPORTER ACTIVITY, ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, RP TOPOLOGY, CHARACTERIZATION OF VARIANTS HKPX1 GLU-254; THR-278; GLN-299 AND RP MET-308, 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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 [29] 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 [30] 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 -!- CATALYTIC ACTIVITY: CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823, CC ChEBI:CHEBI:17996; Evidence={ECO:0000269|PubMed:23994010, CC ECO:0000269|PubMed:25730860}; 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). Interacts with GLRB (PubMed:35526563). CC {ECO:0000269|PubMed:14551753, ECO:0000269|PubMed:22715885, CC ECO:0000269|PubMed:22973015, ECO:0000269|PubMed:23994010, CC ECO:0000269|PubMed:25445488, ECO:0000269|PubMed:25730860, CC ECO:0000269|PubMed:35526563}. CC -!- INTERACTION: CC P23415; P48167: GLRB; NbExp=2; IntAct=EBI-12020340, EBI-11733190; 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.19}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8DN2; EM; 3.90 A; A/B/C/D=29-343, A/B/C/D=410-457. DR PDB; 8DN3; EM; 3.55 A; A/B/C/D=29-457. DR PDB; 8DN4; EM; 4.10 A; A/B/C/D=30-341, A/B/C/D=410-457. DR PDB; 8DN5; EM; 3.63 A; A/B/C/D=30-341, A/B/C/D=410-457. DR PDBsum; 1MOT; -. DR PDBsum; 1VRY; -. DR PDBsum; 2M6B; -. DR PDBsum; 2M6I; -. DR PDBsum; 4X5T; -. DR PDBsum; 8DN2; -. DR PDBsum; 8DN3; -. DR PDBsum; 8DN4; -. DR PDBsum; 8DN5; -. DR AlphaFoldDB; P23415; -. DR BMRB; P23415; -. DR EMDB; EMD-27552; -. DR EMDB; EMD-27553; -. DR EMDB; EMD-27554; -. DR EMDB; EMD-27555; -. DR SMR; P23415; -. DR BioGRID; 109003; 3. DR ComplexPortal; CPX-7841; Glycine receptor complex, GLRA1-GLRB. DR CORUM; P23415; -. DR DIP; DIP-48768N; -. DR IntAct; P23415; 3. DR MINT; P23415; -. 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 GlyCosmos; P23415; 1 site, No reported glycans. DR GlyGen; P23415; 1 site. DR iPTMnet; P23415; -. DR PhosphoSitePlus; P23415; -. DR BioMuta; GLRA1; -. DR DMDM; 116242495; -. DR MassIVE; P23415; -. DR PaxDb; 9606-ENSP00000411593; -. DR PeptideAtlas; P23415; -. DR ProteomicsDB; 54089; -. [P23415-1] DR ProteomicsDB; 54090; -. [P23415-2] DR Antibodypedia; 3089; 445 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 AGR; HGNC:4326; -. DR CTD; 2741; -. DR DisGeNET; 2741; -. DR GeneCards; GLRA1; -. DR GeneReviews; GLRA1; -. DR HGNC; HGNC:4326; GLRA1. DR HPA; ENSG00000145888; Tissue enriched (retina). 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; LVFWLEP; -. DR OrthoDB; 4265336at2759; -. 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; 11 hits in 1154 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 22 other cell types or tissues. DR ExpressionAtlas; P23415; baseline and differential. 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:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016020; C:membrane; NAS: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; IDA:HPA. DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. 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:0099507; F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IDA:SynGO. 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 monoatomic 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: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:0006811; P:monoatomic 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: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: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 CDD; cd19009; LGIC_ECD_GlyR_alpha; 1. DR CDD; cd19060; LGIC_TM_GlyR_alpha; 1. DR Gene3D; 2.70.170.10; Neurotransmitter-gated ion-channel ligand-binding domain; 1. DR Gene3D; 1.20.58.390; Neurotransmitter-gated ion-channel transmembrane domain; 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 NCBIfam; TIGR00860; LIC; 1. DR PANTHER; PTHR18945:SF213; GLYCINE RECEPTOR SUBUNIT ALPHA-1; 1. DR PANTHER; PTHR18945; NEUROTRANSMITTER GATED ION CHANNEL; 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; SSF90112; Neurotransmitter-gated ion-channel transmembrane pore; 1. DR SUPFAM; SSF63712; Nicotinic receptor ligand binding domain-like; 1. DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1. DR Genevisible; P23415; HS. 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.19" 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 //