SC6A5_RAT
ID SC6A5_RAT Reviewed; 799 AA.
AC P58295; F1LNM6; Q6QDB3;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 2.
DT 03-AUG-2022, entry version 135.
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; Synonyms=Glyt2;
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 A), FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND 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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC STRAIN=Sprague-Dawley;
RA Liu Q.-R., Li Q.-F.;
RT "Isoforms of sodium dependent type 2 glycine transporter.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND IDENTIFICATION BY
RP 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:8226790). Terminates the action of glycine by its high affinity
CC sodium-dependent reuptake into presynaptic terminals (PubMed:8226790).
CC May be responsible for the termination of neurotransmission at
CC strychnine-sensitive glycinergic synapses (PubMed:8226790).
CC {ECO:0000269|PubMed:8226790}.
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:0000269|PubMed:8226790};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=17 uM for glycine {ECO:0000269|PubMed:8226790};
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;
CC IsoId=P58295-1; Sequence=Displayed;
CC Name=b;
CC IsoId=P58295-2; Sequence=VSP_011610;
CC -!- TISSUE SPECIFICITY: Specifically expressed in spinal cord, brain stem,
CC and to a lesser extent in the cerebellum. {ECO:0000269|PubMed:8226790}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9Y345}.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A5 subfamily. {ECO:0000305}.
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DR EMBL; L21672; AAS19315.1; -; mRNA.
DR EMBL; AY547309; AAS49497.1; -; mRNA.
DR EMBL; AC141159; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A48716; A48716.
DR RefSeq; NP_976079.1; NM_203334.1.
DR RefSeq; XP_017444218.1; XM_017588729.1. [P58295-2]
DR AlphaFoldDB; P58295; -.
DR SMR; P58295; -.
DR STRING; 10116.ENSRNOP00000043665; -.
DR BindingDB; P58295; -.
DR ChEMBL; CHEMBL3195; -.
DR GlyGen; P58295; 4 sites.
DR iPTMnet; P58295; -.
DR PhosphoSitePlus; P58295; -.
DR PaxDb; P58295; -.
DR Ensembl; ENSRNOT00000041950; ENSRNOP00000043665; ENSRNOG00000031662. [P58295-1]
DR GeneID; 171148; -.
DR KEGG; rno:171148; -.
DR UCSC; RGD:621824; rat. [P58295-1]
DR CTD; 9152; -.
DR RGD; 621824; Slc6a5.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000154963; -.
DR InParanoid; P58295; -.
DR OMA; GAPKEMN; -.
DR OrthoDB; 250396at2759; -.
DR TreeFam; TF343812; -.
DR Reactome; R-RNO-442660; Na+/Cl- dependent neurotransmitter transporters.
DR PRO; PR:P58295; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000031662; Expressed in cerebellum and 6 other tissues.
DR GO; GO:0031045; C:dense core granule; IDA:ARUK-UCL.
DR GO; GO:0005768; C:endosome; IDA:ARUK-UCL.
DR GO; GO:0098690; C:glycinergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0015187; F:glycine transmembrane transporter activity; IDA:RGD.
DR GO; GO:0015375; F:glycine:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1903804; P:glycine import across plasma membrane; ISO:RGD.
DR GO; GO:0015816; P:glycine transport; IDA:RGD.
DR GO; GO:0098810; P:neurotransmitter reuptake; ISO:RGD.
DR GO; GO:0001504; P:neurotransmitter uptake; IMP:SynGO.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0060012; P:synaptic transmission, glycinergic; ISO:RGD.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
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 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_0000214764"
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 230..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..395
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 396..414
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..440
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 476..493
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 505..526
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 559..578
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 606..624
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 640..660
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 681..700
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 719..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 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:0007744|PubMed:22673903"
FT MOD_RES 59
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q761V0"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q761V0"
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 DISULFID 313..322
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT VAR_SEQ 1..8
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_011610"
FT CONFLICT 139
FT /note="G -> A (in Ref. 1; AAS19315 and 2; AAS49497)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="A -> P (in Ref. 1; AAS19315 and 2; AAS49497)"
FT /evidence="ECO:0000305"
FT CONFLICT 399
FT /note="A -> P (in Ref. 1; AAS19315 and 2; AAS49497)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 799 AA; 87842 MW; 5F0D87B3D2DBE662 CRC64;
MDCSAPKEMN KPPTNILEAT VPGHRDSPRA PRTSPEQDLP AAAPAAAVQP PRVPRSASTG
AQTFQSADAR ACEAQRPGVG FCKLSSPQAQ ATSAALRDLS EGHSAQANPP SGAAGAGNAL
HCKIPALRGP EEDENVSVGK GTLEHNNTPA VGWVNMSQST VVLGTDGIAS VLPGSVATTT
IPEDEQGDEN KARGNWSSKL DFILSMVGYA VGLGNVWRFP YLAFQNGGGA FLIPYLMMLA
LAGLPIFFLE VSLGQFASQG PVSVWKAIPA LQGCGIAMLI ISVLIAIYYN VIICYTLFYL
FASFVSVLPW GSCNNPWNTP ECKDKTKLLL DSCVIGDHPK IQIKNSTFCM TAYPNLTMVN
FTSQANKTFV SGSEEYFKYF VLKISAGIEY PGEIRWPLAF CLFLAWVIVY ASLAKGIKTS
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 IGFQPNIFWK VCWAFVTPTI LTFILCFSFY QWEPMTYGSY RYPNWSMVLG
WLMLACSVIW IPIMFVIKMY LAPGRFIERL KLVCSPQPDW GPFLAQHRGE RYKNMIDPLG
TSSLGLKLPV KDLELGTQC
