Glycine transporter 1

Solute carrier family 6 (neurotransmitter transporter, glycine), member 9
Identifiers
Symbols	SLC6A9 ; GLYT1
External IDs	OMIM: 601019 MGI: 95760 HomoloGene: 5050 IUPHAR: 935 ChEMBL: 2337 GeneCards: SLC6A9 Gene
Gene ontology Molecular function • neurotransmitter:sodium symporter activity • glycine:sodium symporter activity Cellular component • plasma membrane • integral component of plasma membrane • membrane Biological process • transport • neurotransmitter transport • glycine transport • transmembrane transport • regulation of synaptic transmission, glycinergic • L-alpha-amino acid transmembrane transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6536	14664
Ensembl	ENSG00000196517	ENSMUSG00000028542
UniProt	P48067	P28571
RefSeq (mRNA)	NM_001024845	NM_008135
RefSeq (protein)	NP_001020016	NP_032161
Location (UCSC)	Chr 1: 43.99 – 44.03 Mb	Chr 4: 117.83 – 117.88 Mb
PubMed search

Sodium- and chloride-dependent glycine transporter 1 is a protein that in humans is encoded by the SLC6A9 gene.^[1][2][3]

Selective inhibitors

Elevation of extracellular synaptic glycine concentration by blockade of GlyT1 has been hypothesized to potentiate NMDA receptor function in vivo and to represent a rational approach for the treatment of schizophrenia and cognitive disorders. Several drug candidates have reached clinical trials.^[4]

• ASP2535^[5]
• Bitopertin (RG1678), which has entered phase II trials for the treatment of schizophrenia^[6]
• Org 25935
• PF-03463275 (in phase II trial)

See also

• Sodium:neurotransmitter symporter
• Solute carrier family

References

1. Kim KM, Kingsmore SF, Han H, Yang-Feng TL, Godinot N, Seldin MF, Caron MG, Giros B (Jun 1994). "Cloning of the human glycine transporter type 1: molecular and pharmacological characterization of novel isoform variants and chromosomal localization of the gene in the human and mouse genomes". Mol Pharmacol 45 (4): 608–17. PMID 8183239.
2. Jones EM, Fernald A, Bell GI, Le Beau MM (Nov 1995). "Assignment of SLC6A9 to human chromosome band 1p33 by in situ hybridization". Cytogenet Cell Genet 71 (3): 211. doi:10.1159/000134110. PMID 7587377.
3. "Entrez Gene: SLC6A9 solute carrier family 6 (neurotransmitter transporter, glycine), member 9".
4. "Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain". Nature Reviews Drug Discovery 12: 866–85. 31 October 2013. doi:10.1038/nrd3893. PMID 24172334.
5. Harada K, Nakato K, Yarimizu J, Yamazaki M, Morita M, Takahashi S, Aota M, Saita K, Doihara H, Sato Y, Yamaji T, Ni K, Matsuoka N (2012). "A novel glycine transporter-1 (GlyT1) inhibitor, ASP2535 (4-[3-isopropyl-5-(6-phenyl-3-pyridyl)-4H-1,2,4-triazol-4-yl]-2,1,3-benzoxadiazole), improves cognition in animal models of cognitive impairment in schizophrenia and Alzheimer's disease". European Journal of Pharmacology 685: 59–69. doi:10.1016/j.ejphar.2012.04.013. PMID 22542656.
6. Pinard E, Alanine A, Alberati D, Bender M, Borroni E, Bourdeaux P, Brom V, Burner S, Fischer H, Hainzl D, Halm R, Hauser N, Jolidon S, Lengyel J, Marty HP, Meyer T, Moreau JL, Mory R, Narquizian R, Nettekoven M, Norcross RD, Puellmann B, Schmid P, Schmitt S, Stalder H, Wermuth R, Wettstein JG, Zimmerli D (June 2010). "Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia". J. Med. Chem. 53 (12): 4603–14. doi:10.1021/jm100210p. PMID 20491477.

Further reading

• Olivares L, Aragón C, Giménez C, Zafra F (1995). "The role of N-glycosylation in the targeting and activity of the GLYT1 glycine transporter". J. Biol. Chem. 270 (16): 9437–42. doi:10.1074/jbc.270.16.9437. PMID 7721869.
• Borowsky B, Mezey E, Hoffman BJ (1993). "Two glycine transporter variants with distinct localization in the CNS and peripheral tissues are encoded by a common gene". Neuron 10 (5): 851–63. doi:10.1016/0896-6273(93)90201-2. PMID 8494645.
• Evans J, Herdon H, Cairns W, et al. (2000). "Cloning, functional characterisation and population analysis of a variant form of the human glycine type 2 transporter". FEBS Lett. 463 (3): 301–6. doi:10.1016/S0014-5793(99)01636-1. PMID 10606742.
• Hanley JG, Jones EM, Moss SJ (2000). "GABA receptor rho1 subunit interacts with a novel splice variant of the glycine transporter, GLYT-1". J. Biol. Chem. 275 (2): 840–6. doi:10.1074/jbc.275.2.840. PMID 10625616.
• Geerlings A, López-Corcuera B, Aragón C (2000). "Characterization of the interactions between the glycine transporters GLYT1 and GLYT2 and the SNARE protein syntaxin 1A". FEBS Lett. 470 (1): 51–4. doi:10.1016/S0014-5793(00)01297-7. PMID 10722844.
• Christie GR, Ford D, Howard A, et al. (2001). "Glycine supply to human enterocytes mediated by high-affinity basolateral GLYT1". Gastroenterology 120 (2): 439–48. doi:10.1053/gast.2001.21207. PMID 11159884.
• Reye P, Penfold P, Pow DV (2001). "Glyt-1 expression in cultured human Müller cells and intact retinae". Glia 34 (4): 311–5. doi:10.1002/glia.1064. PMID 11360303.
• Geerlings A, Núñez E, Rodenstein L, et al. (2002). "Glycine transporter isoforms show differential subcellular localization in PC12 cells". J. Neurochem. 82 (1): 58–65. doi:10.1046/j.1471-4159.2002.00930.x. PMID 12091465.
• Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
• Antonov SM, Brovtsyna NB, Mironova EV (2005). "The mechanism of allosteric interaction of cytoplasmic and extracellular Cl⁻ in the glial glycine transporter (hGlyTlb)". Dokl. Biol. Sci. 402: 163–6. doi:10.1007/s10630-005-0076-z. PMID 16121932.