SC6A9_MOUSE
ID SC6A9_MOUSE Reviewed; 692 AA.
AC P28571; B1ASI9; Q8VC47;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Sodium- and chloride-dependent glycine transporter 1;
DE Short=GlyT-1;
DE Short=GlyT1;
DE AltName: Full=Solute carrier family 6 member 9;
GN Name=Slc6a9; Synonyms=Glyt1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GLYT-1A), FUNCTION (ISOFORM GLYT-1A),
RP TRANSPORTER ACTIVITY (ISOFORM GLYT-1A), TISSUE SPECIFICITY (ISOFORM
RP GLYT-1A), AND BIOPHYSICOCHEMICAL PROPERTIES (ISOFORM GLYT-1A).
RC TISSUE=Brain;
RX PubMed=1618338; DOI=10.1016/0014-5793(92)80875-h;
RA Liu Q.-R., Nelson H., Mandiyan S., Lopez-Corcuera B., Nelson N.;
RT "Cloning and expression of a glycine transporter from mouse brain.";
RL FEBS Lett. 305:110-114(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS GLYT-1A; GLYT-1B AND GLYT-1C),
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, ALTERNATIVE PROMOTER USAGE, AND
RP ALTERNATIVE SPLICING.
RC STRAIN=NMRI;
RX PubMed=7891186; DOI=10.1523/jneurosci.15-03-02524.1995;
RA Adams R.H., Sato K., Shimada S., Tohyama M., Puschel A.W., Betz H.;
RT "Gene structure and glial expression of the glycine transporter GlyT1 in
RT embryonic and adult rodents.";
RL J. Neurosci. 15:2524-2532(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GLYT-1A).
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-117 (ISOFORMS GLYT-1A AND GLYT-1B), AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8226790; DOI=10.1016/s0021-9258(18)41598-0;
RA Liu Q.-R., Lopez-Corcuera B., Mandiyan S., Nelson H., Nelson N.;
RT "Cloning and expression of a spinal cord- and brain-specific glycine
RT transporter with novel structural features.";
RL J. Biol. Chem. 268:22802-22808(1993).
RN [6]
RP FUNCTION, TRANSPORTER ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=14622582; DOI=10.1016/s0896-6273(03)00672-x;
RA Gomeza J., Huelsmann S., Ohno K., Eulenburg V., Szoeke K., Richter D.,
RA Betz H.;
RT "Inactivation of the glycine transporter 1 gene discloses vital role of
RT glial glycine uptake in glycinergic inhibition.";
RL Neuron 40:785-796(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-657 AND SER-659, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=27773429; DOI=10.1016/j.ajhg.2016.09.004;
RA Kurolap A., Armbruster A., Hershkovitz T., Hauf K., Mory A., Paperna T.,
RA Hannappel E., Tal G., Nijem Y., Sella E., Mahajnah M., Ilivitzki A.,
RA Hershkovitz D., Ekhilevitch N., Mandel H., Eulenburg V., Baris H.N.;
RT "Loss of Glycine Transporter 1 Causes a Subtype of Glycine Encephalopathy
RT with Arthrogryposis and Mildly Elevated Cerebrospinal Fluid Glycine.";
RL Am. J. Hum. Genet. 99:1172-1180(2016).
CC -!- FUNCTION: Sodium- and chloride-dependent glycine transporter which is
CC essential for regulating glycine concentrations at inhibitory
CC glycinergic synapses. {ECO:0000269|PubMed:14622582}.
CC -!- FUNCTION: [Isoform GlyT-1A]: Sodium- and chloride-dependent glycine
CC transporter. {ECO:0000269|PubMed:1618338}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(out) + glycine(out) + 2 Na(+)(out) = chloride(in) +
CC glycine(in) + 2 Na(+)(in); Xref=Rhea:RHEA:70691, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:29101, ChEBI:CHEBI:57305;
CC Evidence={ECO:0000269|PubMed:14622582};
CC -!- CATALYTIC ACTIVITY: [Isoform GlyT-1A]:
CC Reaction=chloride(out) + glycine(out) + 2 Na(+)(out) = chloride(in) +
CC glycine(in) + 2 Na(+)(in); Xref=Rhea:RHEA:70691, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:29101, ChEBI:CHEBI:57305;
CC Evidence={ECO:0000269|PubMed:1618338};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform GlyT-1A]:
CC Kinetic parameters:
CC KM=20 uM for glycine {ECO:0000269|PubMed:1618338};
CC -!- SUBUNIT: Interacts with EXOC1; interaction increases the transporter
CC capacity of SLC6A9 probably by promoting its insertion into the cell
CC membrane (By similarity). Interacts with EXOC3 and EXOC4 (By
CC similarity). {ECO:0000250|UniProtKB:P28572}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P28572};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Name=GlyT-1C; Synonyms=GLYT1c;
CC IsoId=P28571-3; Sequence=Displayed;
CC Name=GlyT-1A; Synonyms=GLYT1a;
CC IsoId=P28571-1; Sequence=VSP_006272;
CC Name=GlyT-1B; Synonyms=GLYT1b;
CC IsoId=P28571-2; Sequence=VSP_039241;
CC -!- TISSUE SPECIFICITY: Expressed in the brain (at protein level)
CC (PubMed:27773429). At 11 dpc, expressed in the ventral part of the
CC ventricular zone. At 15 dpc, also expressed in adjacent mantle tissue
CC and the meninges. Strongly expressed in 12 dpc and 15 dpc liver.
CC {ECO:0000269|PubMed:27773429, ECO:0000269|PubMed:7891186,
CC ECO:0000269|PubMed:8226790}.
CC -!- TISSUE SPECIFICITY: [Isoform GlyT-1A]: Expressed in the brain.
CC {ECO:0000269|PubMed:1618338}.
CC -!- DEVELOPMENTAL STAGE: Expression is present at low levels as early as 9
CC dpc and 10 dpc, but strongly increases at 13 dpc and remains at high
CC levels up to 15 dpc. Also expressed in adult.
CC {ECO:0000269|PubMed:7891186}.
CC -!- DISRUPTION PHENOTYPE: Mice show severe motor and respiration deficits
CC at birth and die during the first postnatal day (PubMed:14622582).
CC Accumulation of glycine in the synaptic cleft results in over-
CC activation of postsynaptic glycine receptors and death of the newborn
CC animals due to respiratory and feeding problem (PubMed:14622582).
CC {ECO:0000269|PubMed:14622582}.
CC -!- MISCELLANEOUS: [Isoform GlyT-1C]: Produced by alternative promoter
CC usage.
CC -!- MISCELLANEOUS: [Isoform GlyT-1A]: Produced by alternative promoter
CC usage. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform GlyT-1B]: Produced by alternative splicing of
CC isoform GlyT-1C. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A9 subfamily. {ECO:0000305}.
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DR EMBL; X67056; CAA47440.1; -; mRNA.
DR EMBL; X82567; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X82568; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X82569; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X82570; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X82571; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X82572; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL627128; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021828; AAH21828.1; -; mRNA.
DR CCDS; CCDS18538.1; -. [P28571-1]
DR PIR; E46027; E46027.
DR PIR; S23151; S23151.
DR RefSeq; NP_032161.2; NM_008135.4. [P28571-1]
DR AlphaFoldDB; P28571; -.
DR SMR; P28571; -.
DR BioGRID; 199958; 1.
DR STRING; 10090.ENSMUSP00000030269; -.
DR BindingDB; P28571; -.
DR ChEMBL; CHEMBL1075303; -.
DR iPTMnet; P28571; -.
DR PhosphoSitePlus; P28571; -.
DR MaxQB; P28571; -.
DR PaxDb; P28571; -.
DR PRIDE; P28571; -.
DR ProteomicsDB; 255352; -. [P28571-3]
DR ProteomicsDB; 255353; -. [P28571-1]
DR ProteomicsDB; 255354; -. [P28571-2]
DR Antibodypedia; 2813; 73 antibodies from 12 providers.
DR DNASU; 14664; -.
DR Ensembl; ENSMUST00000030269; ENSMUSP00000030269; ENSMUSG00000028542. [P28571-1]
DR Ensembl; ENSMUST00000063857; ENSMUSP00000066102; ENSMUSG00000028542. [P28571-1]
DR GeneID; 14664; -.
DR KEGG; mmu:14664; -.
DR UCSC; uc008uiy.1; mouse. [P28571-1]
DR CTD; 6536; -.
DR MGI; MGI:95760; Slc6a9.
DR VEuPathDB; HostDB:ENSMUSG00000028542; -.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000157263; -.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; P28571; -.
DR OMA; IWQAAAG; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; P28571; -.
DR TreeFam; TF343812; -.
DR Reactome; R-MMU-442660; Na+/Cl- dependent neurotransmitter transporters.
DR BioGRID-ORCS; 14664; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Slc6a9; mouse.
DR PRO; PR:P28571; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P28571; protein.
DR Bgee; ENSMUSG00000028542; Expressed in retinal neural layer and 237 other tissues.
DR ExpressionAtlas; P28571; baseline and differential.
DR Genevisible; P28571; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0032279; C:asymmetric synapse; ISO:MGI.
DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0031045; C:dense core granule; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IC:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:MGI.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0015187; F:glycine transmembrane transporter activity; IDA:MGI.
DR GO; GO:0015375; F:glycine:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:1903804; P:glycine import across plasma membrane; IMP:ARUK-UCL.
DR GO; GO:0061537; P:glycine secretion, neurotransmission; IMP:MGI.
DR GO; GO:0015816; P:glycine transport; IDA:MGI.
DR GO; GO:1904782; P:negative regulation of NMDA glutamate receptor activity; IMP:ARUK-UCL.
DR GO; GO:0001504; P:neurotransmitter uptake; IMP:SynGO.
DR GO; GO:0070455; P:positive regulation of heme biosynthetic process; IMP:ARUK-UCL.
DR GO; GO:0046985; P:positive regulation of hemoglobin biosynthetic process; IMP:ARUK-UCL.
DR GO; GO:0060092; P:regulation of synaptic transmission, glycinergic; IMP:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR003028; Na/ntran_symport_glycine_GLY1.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR01204; GLY1TRNSPORT.
DR PRINTS; PR00176; NANEUSMPORT.
DR SUPFAM; SSF161070; SSF161070; 1.
DR PROSITE; PS00610; NA_NEUROTRAN_SYMP_1; 1.
DR PROSITE; PS00754; NA_NEUROTRAN_SYMP_2; 1.
DR PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1.
PE 1: Evidence at protein level;
KW Alternative promoter usage; Alternative splicing; Amino-acid transport;
KW Cell membrane; Membrane; Neurotransmitter transport; Phosphoprotein;
KW Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..692
FT /note="Sodium- and chloride-dependent glycine transporter
FT 1"
FT /id="PRO_0000214781"
FT TOPO_DOM 1..94
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 195..271
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..292
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 301..321
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 346..366
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 393..413
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 436..456
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 492..512
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 516..536
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 556..576
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 596..616
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 617..692
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 681..692
FT /note="Essential for interaction with EXOC1"
FT /evidence="ECO:0000250|UniProtKB:P28572"
FT MOD_RES 657
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48067"
FT VAR_SEQ 1..69
FT /note="MIGGDTRAASAHPGMASAQGPVATPSPEQPFPGTTSVSLARPVLRVWHGAHS
FT SGLLPNLIAQHSPAMAQ -> MVGKGAKGML (in isoform GlyT-1A)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1618338, ECO:0000303|PubMed:8226790"
FT /id="VSP_006272"
FT VAR_SEQ 29..69
FT /note="Missing (in isoform GlyT-1B)"
FT /evidence="ECO:0000303|PubMed:8226790"
FT /id="VSP_039241"
FT CONFLICT 341
FT /note="I -> Y (in Ref. 1; CAA47440 and 2; X82570)"
FT /evidence="ECO:0000305"
FT CONFLICT 393..394
FT /note="SV -> RL (in Ref. 1; CAA47440)"
FT /evidence="ECO:0000305"
FT CONFLICT 597
FT /note="A -> R (in Ref. 1; CAA47440 and 2; X82571)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 692 AA; 76544 MW; C4A78A6562DAB01E CRC64;
MIGGDTRAAS AHPGMASAQG PVATPSPEQP FPGTTSVSLA RPVLRVWHGA HSSGLLPNLI
AQHSPAMAQN GAVPSEATKK DQNLTRGNWG NQIEFVLTSV GYAVGLGNVW RFPYLCYRNG
GGAFMFPYFI MLIFCGIPLF FMELSFGQFA SQGCLGVWRI SPMFKGVGYG MMVVSTYIGI
YYNVVICIAF YYFFSSMTHV LPWAYCNNPW NTPDCAGVLD ASNLTNGSRP AALSGNLSHL
FNYTLQRTSP SEEYWRLYVL KLSDDIGNFG EVRLPLLGCL GVSWVVVFLC LIRGVKSSGK
VVYFTATFPY VVLTILFVRG VTLEGAFTGI MYYLTPQWDK ILEAKVWGDA ASQIFYSLGC
AWGGLITMAS YNKFHNNCYR DSVIISITNC ATSVYAGFVI FSILGFMANH LGVDVSRVAD
HGPGLAFVAY PEALTLLPIS PLWSLLFFFM LILLGLGTQF CLLETLVTAI VDEVGNEWIL
QKKTYVTLGV AVAGFLLGIP LTSQAGIYWL LLMDNYAASF SLVVISCIMC VSIMYIYGHR
NYFQDIQMML GFPPPLFFQI CWRFVSPAII FFILIFTVIQ YRPITYNHYQ YPGWAVAIGF
LMALSSVICI PLYALFQLCR TDGDTLLQRL KNATKPSRDW GPALLEHRTG RYAPTTTPSP
EDGFEVQPLH PDKAQIPIVG SNGSSRFQDS RI
