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Glycine transporter subfamily C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Two gene products, GlyT1 and GlyT2, are known that give rise to transporters that are predominantly located on glia and neurones, respectively. Five variants of GlyT1 (a,b,c,d & e) differing in their N- and C-termini are generated by alternative promoter usage and splicing, and three splice variants of GlyT2 (a,b & c) have also been identified (see [5,12,14,37] for reviews). GlyT1 transporter isoforms expressed in glia surrounding glutamatergic synapses regulate synaptic glycine concentrations influencing NMDA receptor-mediated neurotransmission [4,13], but also are important, in early neonatal life, for regulating glycine concentrations at inhibitory glycinergic synapses [15]. Homozygous mice engineered to totally lack GlyT1 exhibit severe respiratory and motor deficiencies due to hyperactive glycinergic signalling and die within the first postnatal day [15,38]. Disruption of GlyT1 restricted to forebrain neurones is associated with enhancement of EPSCs mediated by NMDA receptors and behaviours that are suggestive of a promnesic action [43]. GlyT2 transporters localised on the axons and boutons of glycinergic neurones appear crucial for efficient transmitter loading of synaptic vesicles but may not be essential for the termination of inhibitory neurotransmission [16,35]. Mice in which GlyT2 has been deleted develop a fatal hyperekplexia phenotype during the second postnatal week [16] and mutations in the human gene encoding GlyT2 (SLC6A5) have been identified in patients with hyperekplexia (reviewed by [17]). ATB0+ (SLC6A14) is a transporter for numerous dipolar and cationic amino acids and thus has a much broader substrate specificity than the glycine transporters alongside which it is grouped on the basis of structural similarity [10]. ATB0+ is expressed in various peripheral tissues [10]. By contrast PROT (SLC6A7), which is expressed only in brain in association with a subset of excitatory nerve terminals, shows specificity for the transport of L-proline.

Transporters

937
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GlyT1 / SLC6A9 C Show summary » More detailed page go icon to follow link

GlyT2 / SLC6A5 C Show summary »

ATB0,+ / SLC6A14 C Show summary »


Target Id 937
Nomenclature ATB0,+
Systematic nomenclature SLC6A14
Previous and unofficial names solute carrier family 6 (neurotransmitter transporter), member 14 | Atb0+ | colonic system B0+ amino acid transporter | neutral cationic amino acid transporter B0,+ | sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) | solute carrier family 6 (amino acid transporter), member 14 | solute carrier family 6 (neurotransmitter transporter)
Genes SLC6A14 (Hs), Slc6a14 (Mm), Slc6a14 (Rn)
Ensembl ID ENSG00000087916 (Hs), ENSMUSG00000031089 (Mm), ENSRNOG00000005687 (Rn)
UniProtKB AC Q9UN76 (Hs), Q9JMA9 (Mm)
Bioparadigms SLC Tables SLC6A14 (Hs)
Endogenous substrates L-isoleucine > L-leucine, L-methionine > L-phenylalanine > L-tryptophan > L-valine > L-serine  [36]
Endogenous substrates
β-alanine [1-2]
Substrates
1-methyltryptophan [22]
BCH
valganciclovir [39]
zwitterionic or cationic NOS inhibitors [18]
Selective inhibitors
α-methyl-D,L-tryptophan pIC50 3.6 [22]
Stoichiometry 2-3 Na+: 1 Cl-: 1 amino acid [36]

PROT / SLC6A7 C Show summary »

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: Transporters. Br J Pharmacol. 176 Issue S1: S397-S493.