ID   SC6A5_MOUSE             Reviewed;         799 AA.
AC   Q761V0; Q8CFM5; Q91ZQ2;
DT   27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   08-NOV-2023, entry version 124.
DE   RecName: Full=Sodium- and chloride-dependent glycine transporter 2;
DE            Short=GlyT-2;
DE            Short=GlyT2;
DE   AltName: Full=Solute carrier family 6 member 5;
GN   Name=Slc6a5 {ECO:0000312|MGI:MGI:105090};
GN   Synonyms=Glyt2 {ECO:0000312|EMBL:AAN11408.1};
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] {ECO:0000305, ECO:0000312|EMBL:BAD16781.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), AND TISSUE SPECIFICITY.
RC   STRAIN=129/Sv {ECO:0000312|EMBL:BAD16781.1};
RX   PubMed=15081419; DOI=10.1016/j.bbrc.2004.03.125;
RA   Ebihara S., Yamamoto T., Obata K., Yanagawa Y.;
RT   "Gene structure and alternative splicing of the mouse glycine transporter
RT   type-2.";
RL   Biochem. Biophys. Res. Commun. 317:857-864(2004).
RN   [2] {ECO:0000305, ECO:0000312|EMBL:AAL17054.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC   STRAIN=BALB/cJ {ECO:0000312|EMBL:AAL17054.1};
RC   TISSUE=Brain {ECO:0000312|EMBL:AAL17054.1};
RA   Liu Q.-R., Li Q.-F.;
RT   "Cloning and expression of mouse sodium-dependent glycine transporter 2
RT   (Glyt2).";
RL   Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-59 AND SER-86, 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).
CC   -!- FUNCTION: Sodium- and chloride-dependent glycine transporter.
CC       Terminates the action of glycine by its high affinity sodium-dependent
CC       reuptake into presynaptic terminals. May be responsible for the
CC       termination of neurotransmission at strychnine-sensitive glycinergic
CC       synapses (By similarity). {ECO:0000250|UniProtKB:P58295}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + glycine(out) + 3 Na(+)(out) = chloride(in) +
CC         glycine(in) + 3 Na(+)(in); Xref=Rhea:RHEA:70695, ChEBI:CHEBI:17996,
CC         ChEBI:CHEBI:29101, ChEBI:CHEBI:57305;
CC         Evidence={ECO:0000250|UniProtKB:P58295};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9Y345};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=a {ECO:0000269|PubMed:15081419};
CC         IsoId=Q761V0-1; Sequence=Displayed;
CC       Name=b {ECO:0000269|PubMed:15081419};
CC         IsoId=Q761V0-2; Sequence=VSP_051603;
CC   -!- TISSUE SPECIFICITY: [Isoform a]: Expressed at high levels in brain stem
CC       and spinal cord and is also expressed in the cerebellum.
CC       {ECO:0000269|PubMed:15081419}.
CC   -!- TISSUE SPECIFICITY: [Isoform b]: Expressed at high levels in brain stem
CC       and spinal cord. {ECO:0000269|PubMed:15081419}.
CC   -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9Y345}.
CC   -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF)
CC       (TC 2.A.22) family. SLC6A5 subfamily. {ECO:0000305}.
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DR   EMBL; AB118159; BAD16781.1; -; mRNA.
DR   EMBL; AF411042; AAL17054.1; -; mRNA.
DR   EMBL; AY147186; AAN11408.1; -; mRNA.
DR   CCDS; CCDS21308.1; -. [Q761V0-2]
DR   AlphaFoldDB; Q761V0; -.
DR   SMR; Q761V0; -.
DR   STRING; 10090.ENSMUSP00000058699; -.
DR   TCDB; 2.A.22.2.6; the neurotransmitter:sodium symporter (nss) family.
DR   GlyCosmos; Q761V0; 5 sites, No reported glycans.
DR   GlyGen; Q761V0; 7 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q761V0; -.
DR   PhosphoSitePlus; Q761V0; -.
DR   MaxQB; Q761V0; -.
DR   PaxDb; 10090-ENSMUSP00000058699; -.
DR   ProteomicsDB; 255350; -. [Q761V0-1]
DR   ProteomicsDB; 255351; -. [Q761V0-2]
DR   UCSC; uc012fle.1; mouse. [Q761V0-1]
DR   AGR; MGI:105090; -.
DR   MGI; MGI:105090; Slc6a5.
DR   eggNOG; KOG3660; Eukaryota.
DR   InParanoid; Q761V0; -.
DR   PhylomeDB; Q761V0; -.
DR   Reactome; R-MMU-442660; Na+/Cl- dependent neurotransmitter transporters.
DR   PRO; PR:Q761V0; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q761V0; Protein.
DR   GO; GO:0031045; C:dense core granule; ISO:MGI.
DR   GO; GO:0005768; C:endosome; ISO:MGI.
DR   GO; GO:0098690; C:glycinergic synapse; IDA:SynGO.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0042734; C:presynaptic membrane; ISO:MGI.
DR   GO; GO:0015187; F:glycine transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0015375; F:glycine:sodium symporter activity; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:1903804; P:glycine import across plasma membrane; ISO:MGI.
DR   GO; GO:0015816; P:glycine transport; ISO:MGI.
DR   GO; GO:0098810; P:neurotransmitter reuptake; IDA:SynGO.
DR   GO; GO:0001504; P:neurotransmitter uptake; IDA:SynGO.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0060012; P:synaptic transmission, glycinergic; ISO:MGI.
DR   CDD; cd11499; SLC6sbd_GlyT2; 1.
DR   InterPro; IPR000175; Na/ntran_symport.
DR   InterPro; IPR037272; SNS_sf.
DR   PANTHER; PTHR11616:SF315; SODIUM- AND CHLORIDE-DEPENDENT GLYCINE TRANSPORTER 2; 1.
DR   PANTHER; PTHR11616; SODIUM/CHLORIDE DEPENDENT TRANSPORTER; 1.
DR   Pfam; PF00209; SNF; 1.
DR   PRINTS; PR00176; NANEUSMPORT.
DR   SUPFAM; SSF161070; SNF-like; 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 splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW   Membrane; Metal-binding; Neurotransmitter transport; Phosphoprotein;
KW   Reference proteome; Sodium; Symport; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..799
FT                   /note="Sodium- and chloride-dependent glycine transporter
FT                   2"
FT                   /id="PRO_0000214763"
FT   TOPO_DOM        1..201
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        202..222
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        229..249
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        273..293
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        294..396
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        397..417
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        433..453
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        472..492
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        510..530
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        565..585
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        611..631
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        640..660
FT                   /note="Helical; Name=10"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        677..697
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        717..737
FT                   /note="Helical; Name=12"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        738..799
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..64
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          93..120
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        93..107
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         208
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         210
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         211
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         215
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         479
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         511
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         576
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   BINDING         579
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   MOD_RES         58
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P58295"
FT   MOD_RES         59
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         86
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   CARBOHYD        345
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        355
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        360
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        366
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        714
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        313..322
FT                   /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT   VAR_SEQ         1..8
FT                   /note="Missing (in isoform b)"
FT                   /evidence="ECO:0000303|PubMed:15081419, ECO:0000303|Ref.2"
FT                   /id="VSP_051603"
FT   CONFLICT        151
FT                   /note="V -> E (in Ref. 2; AAL17054/AAN11408)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   799 AA;  87861 MW;  92AC7750C7023D45 CRC64;
     MDCSAPKEMN KQPANILEAA VPGHRDSPRA PRTSPEQDLP AEAPAATVQP PRVPRSASTG
     AQTFQSADAR ACEAQQSGVG FCNLSSPRAQ ATSAALRDLS EGHSAQANPP SGPAGAGNAL
     HCKIPALRGP EEDANVSVGK GTLEHNNTPA VGWVNMSQST VVLGTDGIAS VLPGSVATTT
     IPEDEQGDEN KARGNWSSKL DFILSMVGYA VGLGNVWRFP YLAFQNGGGA FLIPYLMMLA
     LAGLPIFFLE VSLGQFASQG PVSVWKAIPA LQGCGIAMLI ISVLIAIYYN VIICYTLFYL
     FASFVSVLPW GSCNNPWNTP ECKDKTKLLL DSCVIGDHPK IQIKNSTFCM TAYPNLTMVN
     FTSQTNKTFV SGSEEYFKYF VLKISAGIEY PGEIRWPLAF CLFLAWVIVY ASLAKGIKSS
     GKVVYFTATF PYVVLVILLI RGVTLPGAGA GIWYFITPKW EKLTDATVWK DAATQIFFSL
     SAAWGGLITL SSYNKFHNNC YRDTLIVTCT NSATSIFAGF VIFSVIGFMA NERKVNIENV
     ADQGPGIAFV VYPEALTRLP LSPFWAIIFF LMLLTLGLDT MFATIETIVT SISDEFPKYL
     RTHKPVFTLG CCICFFIMGF PMITQGGIYM FQLVDTYAAS YALVIIAIFE LVGISYVYGL
     QRFCEDIEMM IGFKPNIFWK VCWAFVTPTI LTFILCFSFY QWEPMTYGSY RYPNWSMVLG
     WLMLACSVIW IPIMFVIKMY LAPGRFIERL KLVCSPQPDW GPFLAQHRGE RYKNMIDPLG
     TSSLGLKLPV KDLELGTQC
//