Glycine receptor subunit alpha-1

Details

Name
Glycine receptor subunit alpha-1
Synonyms
  • Glycine receptor 48 kDa subunit
  • Glycine receptor strychnine-binding subunit
Gene Name
GLRA1
UniProtKB Entry
P23415Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0000863|Glycine receptor subunit alpha-1
MYSFNTLRLYLWETIVFFSLAASKEAEAARSAPKPMSPSDFLDKLMGRTSGYDARIRPNF
KGPPVNVSCNIFINSFGSIAETTMDYRVNIFLRQQWNDPRLAYNEYPDDSLDLDPSMLDS
IWKPDLFFANEKGAHFHEITTDNKLLRISRNGNVLYSIRITLTLACPMDLKNFPMDVQTC
IMQLESFGYTMNDLIFEWQEQGAVQVADGLTLPQFILKEEKDLRYCTKHYNTGKFTCIEA
RFHLERQMGYYLIQMYIPSLLIVILSWISFWINMDAAPARVGLGITTVLTMTTQSSGSRA
SLPKVSYVKAIDIWMAVCLLFVFSALLEYAAVNFVSRQHKELLRFRRKRRHHKSPMLNLF
QEDEAGEGRFNFSAYGMGPACLQAKDGISVKGANNSNTTNPPPAPSKSPEEMRKLFIQRA
KKIDKISRIGFPMAFLIFNMFYWIIYKIVRREDVHNQ
Number of residues
457
Molecular Weight
52623.35
Theoretical pI
9.04
GO Classification
Functions
extracellularly glycine-gated chloride channel activity / identical protein binding / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / neurotransmitter receptor activity / transmembrane signaling receptor activity / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / zinc ion binding
Processes
cellular response to amino acid stimulus / cellular response to ethanol / cellular response to zinc ion / monoatomic ion transport / neuronal action potential / regulation of respiratory gaseous exchange by nervous system process / response to alcohol
Components
dendrite / glycinergic synapse / membrane / neuronal cell body / perikaryon / transmembrane transporter complex
General Function
Glycine receptors are ligand-gated chloride channels (PubMed:23994010, PubMed:25730860). Channel opening is triggered by extracellular glycine (PubMed:14551753, PubMed:16144831, PubMed:2155780, PubMed:22715885, PubMed:22973015, PubMed:25973519, PubMed:7920629, PubMed:9009272). Channel opening is also triggered by taurine and beta-alanine (PubMed:16144831, PubMed:9009272). Channel characteristics depend on the subunit composition; heteropentameric channels are activated by lower glycine levels and display faster desensitization (PubMed:14551753). Plays an important role in the down-regulation of neuronal excitability (PubMed:8298642, PubMed:9009272). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Channel activity is potentiated by ethanol (PubMed:25973519). Potentiation of channel activity by intoxicating levels of ethanol contribute to the sedative effects of ethanol (By similarity)
Specific Function
Extracellularly glycine-gated chloride channel activity
Pfam Domain Function
Signal Regions
1-28
Transmembrane Regions
251-272 278-298 310-330 426-446
Cellular Location
Postsynaptic cell membrane
Gene sequence
>lcl|BSEQ0016090|Glycine receptor subunit alpha-1 (GLRA1)
ATGTACAGCTTCAATACTCTTCGACTCTACCTTTGGGAGACCATTGTATTCTTCAGCCTT
GCTGCTTCTAAGGAGGCTGAAGCTGCTCGCTCCGCACCCAAGCCTATGTCACCCTCGGAT
TTCCTGGATAAGCTAATGGGGAGAACCTCCGGATATGATGCCAGGATCAGGCCCAATTTT
AAAGGTCCCCCAGTGAACGTGAGCTGCAACATTTTCATCAACAGCTTTGGTTCCATTGCT
GAGACAACCATGGACTATAGGGTCAACATCTTCCTGCGGCAGCAATGGAACGACCCCCGC
CTGGCCTATAATGAATACCCTGACGACTCTCTGGACCTGGACCCATCCATGCTGGACTCC
ATCTGGAAACCTGACCTGTTCTTTGCCAACGAGAAGGGGGCCCACTTCCATGAGATCACC
ACAGACAACAAATTGCTAAGGATCTCCCGGAATGGGAATGTCCTCTACAGCATCAGAATC
ACCCTGACACTGGCCTGCCCCATGGACTTGAAGAATTTCCCCATGGATGTCCAGACATGT
ATCATGCAACTGGAAAGCTTTGGATATACGATGAATGACCTCATCTTTGAGTGGCAGGAA
CAGGGAGCCGTGCAGGTAGCAGATGGACTAACTCTGCCCCAGTTTATCTTGAAGGAAGAG
AAGGACTTGAGATACTGCACCAAGCACTACAACACAGGTAAATTCACCTGCATTGAGGCC
CGGTTCCACCTGGAGCGGCAGATGGGTTACTACCTGATTCAGATGTATATTCCCAGCCTG
CTCATTGTCATCCTCTCATGGATCTCCTTCTGGATCAACATGGATGCTGCACCTGCTCGT
GTGGGCCTAGGCATCACCACTGTGCTCACCATGACCACCCAGAGCTCCGGCTCTCGAGCA
TCTCTGCCCAAGGTGTCCTATGTGAAAGCCATTGACATTTGGATGGCAGTTTGCCTGCTC
TTTGTGTTCTCAGCCCTATTAGAATATGCTGCCGTTAACTTTGTGTCTCGGCAACATAAG
GAGCTGCTCCGATTCAGGAGGAAGCGGAGACATCACAAGGAGGATGAAGCTGGAGAAGGC
CGCTTTAACTTCTCTGCCTATGGGATGGGCCCAGCCTGTCTACAGGCCAAGGATGGCATC
TCAGTCAAGGGCGCCAACAACAGTAACACCACCAACCCCCCTCCTGCACCATCTAAGTCC
CCAGAGGAGATGCGAAAACTCTTCATCCAGAGGGCCAAGAAGATCGACAAAATATCCCGC
ATTGGCTTCCCCATGGCCTTCCTCATTTTCAACATGTTCTACTGGATCATCTACAAGATT
GTCCGTAGAGAGGACGTCCACAACCAGTGA
Chromosome Location
5
Locus
5q33.1
External Identifiers
ResourceLink
UniProtKB IDP23415
UniProtKB Entry NameGLRA1_HUMAN
GenBank Protein ID31851
GenBank Gene IDX52009
GeneCard IDGLRA1
GenAtlas IDGLRA1
HGNC IDHGNC:4326
PDB ID(s)1MOT, 1VRY, 2M6B, 2M6I, 4X5T, 8DN2, 8DN3, 8DN4, 8DN5
KEGG IDhsa:2741
IUPHAR/Guide To Pharmacology ID423
NCBI Gene ID2741
General References
  1. Grenningloh G, Schmieden V, Schofield PR, Seeburg PH, Siddique T, Mohandas TK, Becker CM, Betz H: Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. EMBO J. 1990 Mar;9(3):771-6. [Article]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Vogel N, Kluck CJ, Melzer N, Schwarzinger S, Breitinger U, Seeber S, Becker CM: Mapping of disulfide bonds within the amino-terminal extracellular domain of the inhibitory glycine receptor. J Biol Chem. 2009 Dec 25;284(52):36128-36. doi: 10.1074/jbc.M109.043448. Epub 2009 Oct 27. [Article]
  5. Durisic N, Godin AG, Wever CM, Heyes CD, Lakadamyali M, Dent JA: Stoichiometry of the human glycine receptor revealed by direct subunit counting. J Neurosci. 2012 Sep 12;32(37):12915-20. doi: 10.1523/JNEUROSCI.2050-12.2012. [Article]
  6. Yushmanov VE, Mandal PK, Liu Z, Tang P, Xu Y: NMR structure and backbone dynamics of the extended second transmembrane domain of the human neuronal glycine receptor alpha1 subunit. Biochemistry. 2003 Apr 8;42(13):3989-95. [Article]
  7. Ma D, Liu Z, Li L, Tang P, Xu Y: Structure and dynamics of the second and third transmembrane domains of human glycine receptor. Biochemistry. 2005 Jun 21;44(24):8790-800. [Article]
  8. Shiang R, Ryan SG, Zhu YZ, Hahn AF, O'Connell P, Wasmuth JJ: Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nat Genet. 1993 Dec;5(4):351-8. [Article]
  9. Langosch D, Laube B, Rundstrom N, Schmieden V, Bormann J, Betz H: Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia. EMBO J. 1994 Sep 15;13(18):4223-8. [Article]
  10. Schorderet DF, Pescia G, Bernasconi A, Regli F: An additional family with Startle disease and a G1192A mutation at the alpha 1 subunit of the inhibitory glycine receptor gene. Hum Mol Genet. 1994 Jul;3(7):1201. [Article]
  11. Rees MI, Andrew M, Jawad S, Owen MJ: Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the alpha 1 subunit of the inhibitory glycine receptor. Hum Mol Genet. 1994 Dec;3(12):2175-9. [Article]
  12. Shiang R, Ryan SG, Zhu YZ, Fielder TJ, Allen RJ, Fryer A, Yamashita S, O'Connell P, Wasmuth JJ: Mutational analysis of familial and sporadic hyperekplexia. Ann Neurol. 1995 Jul;38(1):85-91. [Article]
  13. Milani N, Dalpra L, del Prete A, Zanini R, Larizza L: A novel mutation (Gln266-->His) in the alpha 1 subunit of the inhibitory glycine-receptor gene (GLRA1) in hereditary hyperekplexia. Am J Hum Genet. 1996 Feb;58(2):420-2. [Article]
  14. Elmslie FV, Hutchings SM, Spencer V, Curtis A, Covanis T, Gardiner RM, Rees M: Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis. J Med Genet. 1996 May;33(5):435-6. [Article]
  15. Seri M, Bolino A, Galietta LJ, Lerone M, Silengo M, Romeo G: Startle disease in an Italian family by mutation (K276E): The alpha-subunit of the inhibiting glycine receptor. Hum Mutat. 1997;9(2):185-7. [Article]
  16. Vergouwe MN, Tijssen MA, Peters AC, Wielaard R, Frants RR: Hyperekplexia phenotype due to compound heterozygosity for GLRA1 gene mutations. Ann Neurol. 1999 Oct;46(4):634-8. [Article]
  17. Saul B, Kuner T, Sobetzko D, Brune W, Hanefeld F, Meinck HM, Becker CM: Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating. J Neurosci. 1999 Feb 1;19(3):869-77. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Glycine receptor subunit alpha-1 (Humans)protein
primary
Glycine receptor (alpha-1/beta) (Humans)protein
Glycine receptors (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Glycineapproved, nutraceutical, vet_approvedunknowntargetligandDetails
Isofluraneapproved, vet_approvedyestargetagonistDetails
EthanolapprovedyestargetagonistDetails
Methoxyfluraneapproved, investigational, vet_approved, withdrawnyestargetagonistDetails
Halothaneapproved, vet_approvedunknowntargetallosteric modulatorDetails
DesfluraneapprovedyestargetagonistDetails
Sevofluraneapproved, vet_approvedyestargetagonistDetails
D-Serineapproved, experimentalyestargetinhibitorDetails
GW 468816investigationalunknowntargetDetails
Ginkgo bilobaapproved, investigational, nutraceuticalunknowntargetantagonistDetails
Lindaneapproved, withdrawnunknowntargetantagonistDetails
ThiocolchicosideexperimentalunknowntargetantagonistDetails
Atropineapproved, vet_approvedunknowntargetantagonistDetails
PicrotoxinexperimentalunknowntargetantagonistDetails
Taurineapproved, nutraceuticalyestargetagonistDetails
Copperapproved, investigationalunknowntargetDetails
Zincapproved, investigationalunknowntargetDetails
Cannabidiolapproved, investigationalunknowntargetDetails
NabiximolsinvestigationalunknowntargetDetails
Medical Cannabisexperimental, investigationalunknowntargetDetails
Zinc acetateapproved, investigationalunknowntargetDetails
Zinc chlorideapproved, investigationalunknowntargetinhibitorDetails
Zinc sulfate, unspecified formapproved, experimentalunknowntargetinhibitorDetails
Enfluraneapproved, investigational, vet_approvedyestargetpotentiatorDetails
StrychnineexperimentalyestargetantagonistDetails
Ginkgolide AnutraceuticalyestargetinhibitorDetails
GavestinelinvestigationalyestargetmodulatorDetails
SeletracetaminvestigationalunknowntargetbindingDetails
Cannabidiolapproved, investigationalunknowntargetallosteric modulatorDetails
NabiximolsinvestigationalunknowntargetDetails
Medical Cannabisexperimental, investigationalunknowntargetDetails