SC6A9_RAT
ID SC6A9_RAT Reviewed; 638 AA.
AC P28572; A1A5N0; Q63322; Q63323;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 165.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=1353889; DOI=10.1073/pnas.89.15.7189;
RA Guastella J., Brecha N., Weigmann C., Lester H.A., Davidson N.;
RT "Cloning, expression, and localization of a rat brain high-affinity glycine
RT transporter.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7189-7193(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, TISSUE SPECIFICITY, TRANSPORTER ACTIVITY, AND ACTIVITY
RP REGULATION.
RC TISSUE=Brain;
RX PubMed=1534013; DOI=10.1016/0896-6273(92)90207-t;
RA Smith K.E., Borden L.A., Hartig P.R., Branchek T.A., Weinshank R.L.;
RT "Cloning and expression of a glycine transporter reveal colocalization with
RT NMDA receptors.";
RL Neuron 8:927-935(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Blood;
RX PubMed=8494645; DOI=10.1016/0896-6273(93)90201-2;
RA Borowsky B., Mezey E., Hoffman B.J.;
RT "Two glycine transporter variants with distinct localization in the CNS and
RT peripheral tissues are encoded by a common gene.";
RL Neuron 10:851-863(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [GENOMIC DNA] OF 1-67 (ISOFORMS 1 AND 2), AND
RP ALTERNATIVE PROMOTER USAGE.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=9786914; DOI=10.1074/jbc.273.44.29077;
RA Borowsky B., Hoffman B.J.;
RT "Analysis of a gene encoding two glycine transporter variants reveals
RT alternative promoter usage and a novel gene structure.";
RL J. Biol. Chem. 273:29077-29085(1998).
RN [6]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH EXOC1; EXCO3 AND EXOC4.
RX PubMed=16181645; DOI=10.1016/j.neuropharm.2005.07.021;
RA Cubelos B., Gimenez C., Zafra F.;
RT "The glycine transporter GLYT1 interacts with Sec3, a component of the
RT exocyst complex.";
RL Neuropharmacology 49:935-944(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-603 AND SER-605, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Sodium- and chloride-dependent glycine transporter
CC (PubMed:1534013, PubMed:16181645). Essential for regulating glycine
CC concentrations at inhibitory glycinergic synapses (By similarity).
CC {ECO:0000250|UniProtKB:P28571, ECO:0000269|PubMed:1534013,
CC ECO:0000269|PubMed:16181645}.
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:1534013, ECO:0000269|PubMed:16181645};
CC -!- ACTIVITY REGULATION: Inhibited by sarcosine.
CC {ECO:0000269|PubMed:1534013}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=123 uM for glycine {ECO:0000269|PubMed:1534013};
CC KM=185 uM for glycine {ECO:0000269|PubMed:16181645};
CC Vmax=28 nmol/min/mg enzyme with glycine as substrate
CC {ECO:0000269|PubMed:1534013, ECO:0000269|PubMed:16181645};
CC -!- SUBUNIT: Interacts with EXOC1; interaction increases the transporter
CC capacity of SLC6A9 probably by promoting its insertion into the cell
CC membrane (PubMed:16181645). Interacts with EXOC3 and EXOC4
CC (PubMed:16181645). {ECO:0000269|PubMed:16181645}.
CC -!- INTERACTION:
CC P28572; P31016: Dlg4; NbExp=2; IntAct=EBI-848783, EBI-375655;
CC P28572-2; P31016: Dlg4; NbExp=4; IntAct=EBI-848796, EBI-375655;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16181645};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1; Synonyms=GlyT-1B, GlyT-1;
CC IsoId=P28572-2; Sequence=Displayed;
CC Name=2; Synonyms=GlyT-1A, GlyT-2;
CC IsoId=P28572-1; Sequence=VSP_039239;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Found only in the white matter of the
CC CNS. {ECO:0000269|PubMed:1534013}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Found in the gray matter of CNS as
CC well as in macrophages and mast cells in peripheral tissues.
CC {ECO:0000269|PubMed:1353889, ECO:0000269|PubMed:8494645}.
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; M95413; AAA41256.1; -; mRNA.
DR EMBL; M88595; AAA41257.1; -; mRNA.
DR EMBL; L13600; AAA73557.1; -; mRNA.
DR EMBL; BC128732; AAI28733.1; -; mRNA.
DR EMBL; U28975; AAC71066.1; -; Genomic_DNA.
DR EMBL; U28975; AAC71067.1; -; Genomic_DNA.
DR PIR; I58140; I58140.
DR PIR; JH0673; JH0673.
DR RefSeq; NP_446270.1; NM_053818.2. [P28572-1]
DR RefSeq; XP_006238687.1; XM_006238625.3. [P28572-2]
DR AlphaFoldDB; P28572; -.
DR SMR; P28572; -.
DR BioGRID; 250476; 1.
DR IntAct; P28572; 2.
DR STRING; 10116.ENSRNOP00000040252; -.
DR BindingDB; P28572; -.
DR ChEMBL; CHEMBL4556; -.
DR GuidetoPHARMACOLOGY; 935; -.
DR TCDB; 2.A.22.2.2; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; P28572; 4 sites.
DR iPTMnet; P28572; -.
DR PhosphoSitePlus; P28572; -.
DR PaxDb; P28572; -.
DR PRIDE; P28572; -.
DR Ensembl; ENSRNOT00000085527; ENSRNOP00000070161; ENSRNOG00000019484. [P28572-2]
DR GeneID; 116509; -.
DR KEGG; rno:116509; -.
DR CTD; 6536; -.
DR RGD; 621243; Slc6a9.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000157263; -.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; P28572; -.
DR OMA; IWQAAAG; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; P28572; -.
DR TreeFam; TF343812; -.
DR Reactome; R-RNO-442660; Na+/Cl- dependent neurotransmitter transporters.
DR SABIO-RK; P28572; -.
DR PRO; PR:P28572; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000019484; Expressed in cerebellum and 19 other tissues.
DR Genevisible; P28572; RN.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0032279; C:asymmetric synapse; IDA:SynGO.
DR GO; GO:0009925; C:basal plasma membrane; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0031045; C:dense core granule; IDA:ARUK-UCL.
DR GO; GO:0005768; C:endosome; IDA:ARUK-UCL.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:RGD.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0015187; F:glycine transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015375; F:glycine:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:1903804; P:glycine import across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0061537; P:glycine secretion, neurotransmission; ISO:RGD.
DR GO; GO:0015816; P:glycine transport; ISO:RGD.
DR GO; GO:1904782; P:negative regulation of NMDA glutamate receptor activity; ISO:RGD.
DR GO; GO:0001504; P:neurotransmitter uptake; ISO:RGD.
DR GO; GO:0070455; P:positive regulation of heme biosynthetic process; ISO:RGD.
DR GO; GO:0046985; P:positive regulation of hemoglobin biosynthetic process; ISO:RGD.
DR GO; GO:1904440; P:positive regulation of iron ion import across plasma membrane; ISO:RGD.
DR GO; GO:1904256; P:positive regulation of iron ion transmembrane transporter activity; ISO:RGD.
DR GO; GO:0060092; P:regulation of synaptic transmission, glycinergic; ISS: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; Amino-acid transport; Cell membrane;
KW Glycoprotein; Membrane; Neurotransmitter transport; Phosphoprotein;
KW Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..638
FT /note="Sodium- and chloride-dependent glycine transporter
FT 1"
FT /id="PRO_0000214782"
FT TOPO_DOM 1..40
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..61
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 120..140
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 141..217
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..238
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 247..267
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 292..312
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..359
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..458
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 462..482
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 502..522
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 542..562
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 563..638
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 627..638
FT /note="Essential for interaction with EXOC1"
FT /evidence="ECO:0000269|PubMed:16181645"
FT COMPBIAS 9..30
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 603
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 605
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 630
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48067"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..15
FT /note="MAVAHGPVATSSPEQ -> MVGKGAKGML (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1353889,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8494645"
FT /id="VSP_039239"
FT CONFLICT 50
FT /note="V -> W (in Ref. 5; AAC71066/AAC71067)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 638 AA; 71061 MW; AB43FCDE767F4AFA CRC64;
MAVAHGPVAT SSPEQNGAVP SEATKKDQNL TRGNWGNQIE FVLTSVGYAV GLGNVWRFPY
LCYRNGGGAF MFPYFIMLVF CGIPLFFMEL SFGQFASQGC LGVWRISPMF KGVGYGMMVV
STYIGIYYNV VICIAFYYFF SSMTHVLPWA YCNNPWNTPD CAGVLDASNL TNGSRPTALS
GNLSHLFNYT LQRTSPSEEY WRLYVLKLSD DIGDFGEVRL PLLGCLGVSW VVVFLCLIRG
VKSSGKVVYF TATFPYVVLT ILFVRGVTLE GAFTGIMYYL TPKWDKILEA KVWGDAASQI
FYSLGCAWGG LITMASYNKF HNNCYRDSVI ISITNCATSV YAGFVIFSIL GFMANHLGVD
VSRVADHGPG LAFVAYPEAL TLLPISPLWS LLFFFMLILL GLGTQFCLLE TLVTAIVDEV
GNEWILQKKT YVTLGVAVAG FLLGIPLTSQ AGIYWLLLMD NYAASFSLVV ISCIMCVSIM
YIYGHRNYFQ DIQMMLGFPP PLFFQICWRF VSPTIIFFIL IFTVIQYRPI TYNHYQYPGW
AVAIGFLMAL SSVICIPLYA LFQLCRTDGD TLLQRLKNAT KPSRDWGPAL LEHRTGRYAP
TTTPSPEDGF EVQPLHPDKA QIPIVGSNGS SRLQDSRI
