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2.A.22.2.10
Sodium- and chloride-dependent glycine transporter 2 (GlyT-2) (GlyT2) (Solute carrier family 6 member 5). The stoichiometry is Na+:Cl-;Gly = 3:1:1 (Le Guellec et al. 2022). The STAS domain has been solved by x-ray crystalography (PDB# 3LLO).  Functions to remove and recycle synaptic glycine from inhibitory synapses.  Mutations in GlyT are a common cause of hyperakplexia or startle disease in humans. The ER chaparone, calnexin, facilitates GlyT processing (Arribas-González et al. 2013). An allosteric binding site on GlyT2, for bioactive lipid analgesics has been identified (Mostyn et al. 2019), and it is formed by a crevice between TMSs 5, 7, and 8, and extracellular loop 4. Membrane cholesterol binds to and modulates the function of various SLC6 neurotransmitter transporters, including stabilizing the outward-facing conformation of the dopamine and serotonin transporters. Frangos et al. 2023 investigated how cholesterol binds to GlyT2 (SLC6A5), modulates the glycine transport rate, and influences bioactive lipid inhibition of GlyT2.

Accession Number:Q9Y345
Protein Name:Sodium- and chloride-dependent glycine transporter 2
Length:797
Molecular Weight:87434.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate chloride, sodium(1+), glycine

Cross database links:

Entrez Gene ID: 9152   
Pfam: PF00209   
KEGG: hsa:9152   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0015375 F:glycine:sodium symporter activity
GO:0005328 F:neurotransmitter:sodium symporter activity
GO:0007268 P:synaptic transmission

References (7)

[1] “Molecular cloning and functional expression of the human glycine transporter GlyT2 and chromosomal localisation of the gene in the human genome.”  Morrow J.A.et.al.   9845349
[2] “Characterization of multiple forms of the human glycine transporter type-2.”  Gallagher M.J.et.al.   10381548
[3] “Cloning, functional characterisation and population analysis of a variant form of the human glycine type 2 transporter.”  Evans J.et.al.   10606742
[4] “Human chromosome 11 DNA sequence and analysis including novel gene identification.”  Taylor T.D.et.al.   16554811
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease.”  Rees M.I.et.al.   16751771
[7] “The consensus coding sequences of human breast and colorectal cancers.”  Sjoeblom T.et.al.   16959974

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence 
1:	MDCSAPKEMN KLPANSPEAA AAQGHPDGPC APRTSPEQEL PAAAAPPPPR VPRSASTGAQ 
61:	TFQSADARAC EAERPGVGSC KLSSPRAQAA SAALRDLREA QGAQASPPPG SSGPGNALHC 
121:	KIPFLRGPEG DANVSVGKGT LERNNTPVVG WVNMSQSTVV LATDGITSVL PGSVATVATQ 
181:	EDEQGDENKA RGNWSSKLDF ILSMVGYAVG LGNVWRFPYL AFQNGGGAFL IPYLMMLALA 
241:	GLPIFFLEVS LGQFASQGPV SVWKAIPALQ GCGIAMLIIS VLIAIYYNVI ICYTLFYLFA 
301:	SFVSVLPWGS CNNPWNTPEC KDKTKLLLDS CVISDHPKIQ IKNSTFCMTA YPNVTMVNFT 
361:	SQANKTFVSG SEEYFKYFVL KISAGIEYPG EIRWPLALCL FLAWVIVYAS LAKGIKTSGK 
421:	VVYFTATFPY VVLVILLIRG VTLPGAGAGI WYFITPKWEK LTDATVWKDA ATQIFFSLSA 
481:	AWGGLITLSS YNKFHNNCYR DTLIVTCTNS ATSIFAGFVI FSVIGFMANE RKVNIENVAD 
541:	QGPGIAFVVY PEALTRLPLS PFWAIIFFLM LLTLGLDTMF ATIETIVTSI SDEFPKYLRT 
601:	HKPVFTLGCC ICFFIMGFPM ITQGGIYMFQ LVDTYAASYA LVIIAIFELV GISYVYGLQR 
661:	FCEDIEMMIG FQPNIFWKVC WAFVTPTILT FILCFSFYQW EPMTYGSYRY PNWSMVLGWL 
721:	MLACSVIWIP IMFVIKMHLA PGRFIERLKL VCSPQPDWGP FLAQHRGERY KNMIDPLGTS 
781:	SLGLKLPVKD LELGTQC