WORKLIST ENTRIES (1): GLYRBETA View alignment Glycine receptor beta subunit signature Type of fingerprint: COMPOUND with 4 elements Links: PRINTS; PR00252 NRIONCHANNEL MIM; 138492 Creation date 14-MAR-2002 1.LOPEZ-CORCUERA, B., GEERLINGS, A. AND ARAGON, C. Glycine neurotransmitter transporters: an update. MOL.MEMBR.BIOL. 18 13-20 (2001). 2. ASHCROFT, F.M. Glycine receptors. IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.313-324. 3. LEGENDRE, P. The glycinergic inhibitory synapse. CELL.MOL.LIFE SCI. 58 760-793 (2001). 4. LEITE, J.F. AND CASCIO, M. Structure of ligand-gated ion channels: critical assessment of biochemical data supports novel topology. MOL.CELL.NEUROSCI. 17 777-792 (2001). 5. BETZ, H., KUHSE, J., SCHMIEDEN, J., LAUBE, B., KIRSCH, J. AND HARVEY, R.J. Structure and functions of inhibitory and excitatory glycine receptors. ANN.N.Y.ACAD.SCI. 868 667-676 (1999). Glycine is a majory inhibitory neurotransmitter (NT) in the adult vertebrate central nervous system (CNS). Glycinergic synapses have a well-established role in the processing of motor and sensory information that controls movement, vision and audition . This action of glycine is mediated through its interaction with the glycine receptor (GlyR): an intrinsic chloride channel is opened in reponse to agonist binding. The subsequent influx of anions prevents membrane depolarisation and neuronal firing induced by exitatory NTs. Strychnine acts as a competitive antagonist of glycine binding, thereby reducing the activity of inhibitory neurones. Poisoning with strychnine is characterised by over-excitation, muscle spasms and convulsions. Whilst glycine is the principal physiological agonsist at GlyRs, taurine and beta-alanine also behave as agonists . Compounds that modulate GlyR activity include zinc, some alcohols and anaesthetics, picrotoxin, cocaine and some anticonvulsants. GlyRs were thought for some time to be localised exclusively in the brain stem and spinal cord, but have since been found to be expressed more widely, including the cochlear nuclei, cerebellar cortex and forebrain . GlyRs belong to the ligand-gated ion channel family, which also includes the inhibitory gamma-aminobutyric acid type A (GABAA) and excitatory nicotinic acetylcholine (nACh) and serotonin type 3 (5-HT3) receptors . Affinity-purified GlyR was found to contain two glycosylated membrane proteins of 48kDa and 56kDa, corresponding to alpha and beta subunits, respectively. Four genes encoding alpha subunits have been identified (GLRA1 to 4), together with a single beta polypeptide (GLRB). The heterogeneity of alpha subunits is further increased by alternative exon splicing, yielding two isoforms of GLRA1 to 3 . The characteristics of different GlyR subtypes, therefore, can be largely explained by their GLRA content. GlyRs are generally believed to adopt a pentameric structure in vivo: five subunits assemble to form a ring structure with a central pore. Typically, a stoichiometry of 3:2 (alpha:beta) is observed . GlyR subunits share a high overall level of sequence similarity both with themselves and with the subunits of the GABAA and nACh receptors. Four highly conserved segments have been proposed to correspond to transmembrane (TM) alpha helices (TM1-4), the second of which is thought to contribute to the pore wall . A long extracellular N-terminal segment preceeds TM1 and a long cytoplasmic loop links TM3 and 4. Short cytoplasmic and extracellular loops join TM1-2 and TM2-3, respectively, and a short C-terminal sequence follows TM4. Studies using radiolabelled strychnine have shown the alpha subunit to be responsible for ligand binding, the critical residues for this interaction lying within the N-terminal domain . The beta subunit plays a structural role, contributing one of its TM domains to the pore wall as well as playing a putative role in postsynaptic clustering of the receptor . In several mammalian species, defects in glycinergic transmission are associated with complex motor disorders. Mutations in the gene encoding GLRA1 give rise to hyperplexia, or startle disease . This is characterised by muscular spasms in response to unexpected light or noise stimuli, similar to the symptoms of sublethal doses of strychnine. The mutations result in amino acid substitutions within the TM1-2 and TM3-4 loops, suggesting that these regions are involved in the transduction of ligand binding into channel activation . By contrast with GLRA proteins, GLRB is expressed ubiquitously throughout the CNS, including areas where there is no evidence for GlyRs. The reason for such widepread expression is unclear, since GLRB is not believed to assemble with alpha subunits other than those of GlyRs . The GLRB subunit locus has been mapped to human chromosome 4q32. GlyRs are densely clustered within spinal cord neurons; this arrangement is thought to be mediated by gephyrin, a peripheral membrane protein of 93kDa that binds to both GLRB, via an 18-residue motif on the large cytoplasmic loop, and polymerised tubulin. It has been proposed that gephyrin acts as a GlyR-cytoskeleton linker protein . GLYRBETA is a 4-element fingerprint that provides a signature for glycine receptor beta (GLRB) subunits. The fingerprint was derived from an initial alignment of 4 sequences: the motifs were drawn from conserved regions spanning virtually the full alignment length, focusing on those sections that characterise GLRB subunits but distinguish them from the rest of the GlyR subunit family - motifs 1 and 2 lie within the N-terminal domain; and motifs 3 and 4 reside within the long cytoplasmic loop between TM domains 3 and 4. A single iteration on SPTR40_18f was required to reach convergence, no further sequences being identified beyond the starting set. SUMMARY INFORMATION 4 codes involving 4 elements 0 codes involving 3 elements 0 codes involving 2 elements COMPOSITE FINGERPRINT INDEX 4| 4 4 4 4 3| 0 0 0 0 2| 0 0 0 0 --+--------------------- | 1 2 3 4 True positives.. GRB_HUMAN Q9GJS9 GRB_RAT GRB_MOUSE PROTEIN TITLES GRB_HUMAN Glycine receptor beta chain precursor - Homo sapiens (Human) Q9GJS9 GLYCINE RECEPTOR BETA SUBUNIT - Bos taurus (Bovine). GRB_RAT Glycine receptor beta chain precursor (58 kDa) - Rattus norv GRB_MOUSE Glycine receptor beta chain precursor - Mus musculus (Mouse)
SCAN HISTORY SPTR40_18f 1 300 NSINGLE INITIAL MOTIF SETS GLYRBETA1 Length of motif = 30 Motif number = 1 Glycine receptor beta subunit motif I - 1 PCODE ST INT LCPSQQSAEDLARVPPNSTSNILNRLLVSY GRB_RAT 38 38 LCPSQQSPEDLARVPPNSTSNILNRLLVSY GRB_MOUSE 38 38 LCPSQQSAEDLARVPANSTSNILNRLLVSY Q9GJS9 38 38 LCPSQQSAEDLARVPANSTSNILNRLLVSY GRB_HUMAN 38 38 GLYRBETA2 Length of motif = 15 Motif number = 2 Glycine receptor beta subunit motif II - 1 PCODE ST INT LKLPSDFRGSDALTV GRB_RAT 116 48 LKLPSDFRGSDALTV GRB_MOUSE 116 48 LKLPSDFRGSDALTV Q9GJS9 116 48 LKLPSDFRGSDALTV GRB_HUMAN 116 48 GLYRBETA3 Length of motif = 23 Motif number = 3 Glycine receptor beta subunit motif III - 1 PCODE ST INT GETRCKKVCTSKSDLRSNDFSIV GRB_RAT 401 270 GETRCKKVCTSKSDLRSNDFSIV GRB_MOUSE 401 270 GETRCKKVCTSKSDLRSNDFSIV Q9GJS9 401 270 GETRCKKVCTSKSDLRSNDFSIV GRB_HUMAN 401 270 GLYRBETA4 Length of motif = 19 Motif number = 4 Glycine receptor beta subunit motif IV - 1 PCODE ST INT RDFELSNYDCYGKPIEVNN GRB_RAT 428 4 RDFELSNYDCYGKPIEVNN GRB_MOUSE 428 4 RDFELSNYDCYGKPIEVNN Q9GJS9 428 4 RDFELSNYDCYGKPIEVNN GRB_HUMAN 428 4 FINAL MOTIF SETS GLYRBETA1 Length of motif = 30 Motif number = 1 Glycine receptor beta subunit motif I - 1 PCODE ST INT LCPSQQSAEDLARVPANSTSNILNRLLVSY GRB_HUMAN 38 38 LCPSQQSAEDLARVPANSTSNILNRLLVSY Q9GJS9 38 38 LCPSQQSAEDLARVPPNSTSNILNRLLVSY GRB_RAT 38 38 LCPSQQSPEDLARVPPNSTSNILNRLLVSY GRB_MOUSE 38 38 GLYRBETA2 Length of motif = 15 Motif number = 2 Glycine receptor beta subunit motif II - 1 PCODE ST INT LKLPSDFRGSDALTV GRB_HUMAN 116 48 LKLPSDFRGSDALTV Q9GJS9 116 48 LKLPSDFRGSDALTV GRB_RAT 116 48 LKLPSDFRGSDALTV GRB_MOUSE 116 48 GLYRBETA3 Length of motif = 23 Motif number = 3 Glycine receptor beta subunit motif III - 1 PCODE ST INT GETRCKKVCTSKSDLRSNDFSIV GRB_HUMAN 401 270 GETRCKKVCTSKSDLRSNDFSIV Q9GJS9 401 270 GETRCKKVCTSKSDLRSNDFSIV GRB_RAT 401 270 GETRCKKVCTSKSDLRSNDFSIV GRB_MOUSE 401 270 GLYRBETA4 Length of motif = 19 Motif number = 4 Glycine receptor beta subunit motif IV - 1 PCODE ST INT RDFELSNYDCYGKPIEVNN GRB_HUMAN 428 4 RDFELSNYDCYGKPIEVNN Q9GJS9 428 4 RDFELSNYDCYGKPIEVNN GRB_RAT 428 4 RDFELSNYDCYGKPIEVNN GRB_MOUSE 428 4
User query: Display/Full Code "GLYRBETA"