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
Organism
Humans
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
extracellular-glycine-gated chloride channel activity / glycine binding / taurine binding / transmitter-gated ion channel activity
Processes
acrosome reaction / action potential / adult walking behavior / chloride transmembrane transport / chloride transport / inhibitory postsynaptic potential / ion transmembrane transport / ion transport / muscle contraction / negative regulation of transmission of nerve impulse / neuromuscular process controlling posture / neuropeptide signaling pathway / positive regulation of acrosome reaction / regulation of membrane potential / regulation of respiratory gaseous exchange by neurological system process / response to amino acid / righting reflex / startle response / synaptic transmission, glycinergic / transmembrane transport / visual perception
Components
cell junction / chloride channel complex / external side of plasma membrane / inhibitory synapse / integral component of membrane / integral component of plasma membrane / intracellular membrane-bounded organelle / neuron projection / plasma membrane / postsynaptic membrane / synapse
General Function
Transmitter-gated ion channel activity
Specific Function
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Pfam Domain Function
Transmembrane Regions
248-274 281-298 313-336 429-446
Cellular Location
Cell junction
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
5q32
External Identifiers
ResourceLink
UniProtKB IDP23415
UniProtKB Entry NameGLRA1_HUMAN
GenBank Protein ID31851
GenBank Gene IDX52009
GenAtlas IDGLRA1
HGNC IDHGNC:4326
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. [PubMed:2155780]
  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. [PubMed:14702039]
  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. [PubMed:15489334]
  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. [PubMed:19861413]
  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. [PubMed:22973015]
  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. [PubMed:12667090]
  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. [PubMed:15952785]
  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. [PubMed:8298642]
  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. [PubMed:7925268]
  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. [PubMed:7981700]
  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. [PubMed:7881416]
  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. [PubMed:7611730]
  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. [PubMed:8571969]
  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. [PubMed:8733061]
  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. [PubMed:9067762]
  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. [PubMed:10514101]
  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. [PubMed:9920650]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00145Glycineapproved, nutraceutical, vet_approvedunknownDetails
DB00753Isofluraneapproved, vet_approvedyesagonistDetails
DB00898EthanolapprovedyesagonistDetails
DB01028Methoxyfluraneapproved, investigational, vet_approvedyesagonistDetails
DB01159Halothaneapproved, vet_approvedunknownallosteric modulatorDetails
DB01189DesfluraneapprovedyesagonistDetails
DB01236Sevofluraneapproved, vet_approvedyesagonistDetails
DB03929D-Serineapproved, experimentalunknownDetails
DB05417GW 468816investigationalunknownDetails
DB01381Ginkgo bilobaapproved, investigational, nutraceuticalunknownantagonistDetails
DB00431Lindaneapproved, withdrawnunknownantagonistDetails
DB11582ThiocolchicosideexperimentalunknownantagonistDetails
DB00572Atropineapproved, vet_approvedunknownantagonistDetails
DB00466PicrotoxinexperimentalunknownantagonistDetails
DB01956Taurineapproved, nutraceuticalunknownagonistDetails
DB09130Copperapproved, investigationalunknownDetails
DB01593Zincapproved, investigationalunknownDetails
DB09061Cannabidiolapproved, investigationalunknownDetails
DB14011NabiximolsinvestigationalunknownDetails
DB14009Medical Cannabisexperimental, investigationalunknownDetails
DB14487Zinc acetateapproved, investigationalunknownDetails
DB14533Zinc chlorideapproved, investigationalunknownDetails
DB00228Enfluraneapproved, investigational, vet_approvedyesagonistDetails
DB05885SeletracetaminvestigationalunknownbindingDetails
DB09061Cannabidiolapproved, investigationalunknownallosteric modulatorDetails
DB14011NabiximolsinvestigationalunknownDetails
DB14009Medical Cannabisexperimental, investigationalunknownDetails
DB01043Memantineapproved, investigationalunknowninhibitorDetails