Sodium- and chloride-dependent glycine transporter 2

Sodium- and chloride-dependent glycine transporter 2, also known as glycine transporter 2 (GlyT2), is a protein that in humans is encoded by the SLC6A5 gene.

SLC6A5
Identifiers
Aliases	SLC6A5, GLYT-2, GLYT2, HKPX3, NET1, Glycine transporter 2, solute carrier family 6 member 5
External IDs	OMIM: 604159; MGI: 105090; HomoloGene: 37901; GeneCards: SLC6A5; OMA:SLC6A5 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11p15.1 Start 20,599,594 bp End 20,659,285 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7|7 B4 Start 49,559,894 bp End 49,613,604 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte testicle superior vestibular nucleus metencephalon cerebellum spinal cord cerebellar cortex cerebellar hemisphere right hemisphere of cerebellum left testis Top expressed in medial vestibular nucleus pontine nuclei spinal cord Gray matter of spinal cord anterior horn of spinal cord deep cerebellar nuclei lumbar subsegment of spinal cord posterior horn of spinal cord gray matter layer of cerebellum neural layer of retina More reference expression data BioGPS More reference expression data
Gene ontology Molecular function neurotransmitter:sodium symporter activity symporter activity glycine:sodium symporter activity metal ion binding glycine transmembrane transporter activity Cellular component integral component of membrane plasma membrane integral component of plasma membrane membrane glycinergic synapse integral component of presynaptic membrane Biological process synaptic transmission, glycinergic neurotransmitter transport chemical synaptic transmission glycine transport glycine import across plasma membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9152 104245 Ensembl ENSG00000165970 ENSMUSG00000039728 UniProt Q9Y345 Q761V0 RefSeq (mRNA) NM_004211 NM_001318369 NM_001146013 NM_148931 RefSeq (protein) NP_001305298 NP_004202 n/a Location (UCSC) Chr 11: 20.6 – 20.66 Mb Chr 7: 49.56 – 49.61 Mb PubMed search
Wikidata
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The glycine transporter 2 is a membrane protein which recaptures glycine, a major inhibitory transmitter in the spinal cord and brainstem. GlyT2 is a specific marker of glycinergic neurons and a member of the Na⁺ and Cl⁻-coupled transporter family SLC6. Glycine uptake mediated by GlyT2 is electrogenic, coupled to three Na⁺ and one Cl⁻ (i.e. two positive charges per glycine). In humans, GlyT2 is encoded by the SLC6A5 gene. Inactivation of GlyT2 in knockout mice is lethal during the second post-natal week as the absence of GlyT2 disrupts inhibitory transmission by reducing glycine release. Mutations in SLC6A5 gene are responsible for a presynaptic form of hyperekplexia, a genetic disease causing increased startle reflex. GlyT2 main physiological role is to recapture glycine released in the synaptic cleft and to maintain high glycine concentration in the presynaptic neuron. Therefore, chronic inhibition of GlyT2 will deplete intracellular storage of glycine and limit its accumulation in synaptic vesicles.

Inhibitors

• Amoxapine
• Ethanol
• N-Arachidonylglycine (NAGly)
• Opiranserin (VVZ-149)
• ORG-25543
• VVZ-368

See also

• Sodium:neurotransmitter symporter
• Solute carrier family

Further reading

• López-Corcuera B, Aragón C, Geerlings A (2002). "Regulation of glycine transporters". Biochem. Soc. Trans. 29 (Pt 6): 742–5. doi:10.1042/BST0290742. PMID 11709067.
• Gallagher MJ, Burgess LH, Brunden KR (1999). "Characterization of multiple forms of the human glycine transporter type-2". Brain Res. Mol. Brain Res. 70 (1): 101–15. doi:10.1016/S0169-328X(99)00135-7. PMID 10381548.
• 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. S2CID 21445629.
• Martínez-Maza R, Poyatos I, López-Corcuera B, et al. (2001). "The role of N-glycosylation in transport to the plasma membrane and sorting of the neuronal glycine transporter GLYT2". J. Biol. Chem. 276 (3): 2168–73. doi:10.1074/jbc.M006774200. PMID 11036075.
• 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. S2CID 22855247.
• Baliova M, Betz H, Jursky F (2004). "Calpain-mediated proteolytic cleavage of the neuronal glycine transporter, GlyT2". J. Neurochem. 88 (1): 227–32. doi:10.1046/j.1471-4159.2003.02192.x. PMID 14675166. S2CID 26788320.
• Jamra RA, Villela AW, Klein K, et al. (2006). "No association between genetic variants at the GLYT2 gene and bipolar affective disorder and schizophrenia". Psychiatr. Genet. 16 (3): 91. doi:10.1097/01.ypg.0000199450.07786.ab. PMID 16691125.
• Rees MI, Harvey K, Pearce BR, et al. (2006). "Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease". Nat. Genet. 38 (7): 801–6. doi:10.1038/ng1814. PMC 3204411. PMID 16751771.
• Roux M, Supplisson S (2000). "Neuronal and glial glycine transporters have different stoichiometries". Neuron. 25 (2): 373–83. doi:10.1016/s0896-6273(00)80901-0. PMID 10719892.
• Aubrey K, Rossi FM, et al. (2007). "The transporters GlyT2 and VIAAT cooperate to determine the vesicular glycinergic phenotype" (PDF). J. Neurosci. 27 (23): 6273–81. doi:10.1523/JNEUROSCI.1024-07.2007. PMC 6672136. PMID 17554001.
• Rousseau F, Aubrey KR, Supplisson S (2008). "The glycine transporter GlyT2 controls the dynamics of synaptic vesicle refilling in inhibitory spinal cord neurons." J. Neurosci. 28 (39): 9755–68. doi:10.1523/JNEUROSCI.0509-08.2008. PMC 6671229. PMID 18815261.
• Eulenburg V, Becker K, Gomeza J, et al. (2006). "Mutations within the human GLYT2 (SLC6A5) gene associated with hyperekplexia". Biochem. Biophys. Res. Commun. 348 (2): 400–5. doi:10.1016/j.bbrc.2006.07.080. PMID 16884688. S2CID 27350533.