S6A11_HUMAN
ID S6A11_HUMAN Reviewed; 632 AA.
AC P48066; B2R6U6; Q8IYC9;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Sodium- and chloride-dependent GABA transporter 3;
DE Short=GAT-3;
DE AltName: Full=Solute carrier family 6 member 11;
GN Name=SLC6A11; Synonyms=GABT3, GAT3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TRANSPORTER ACTIVITY,
RP ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=7874447;
RA Borden L.A., Murali Dhar T.G., Smith K.E., Branchek T.A., Gluchowski C.,
RA Weinshank R.L.;
RT "Cloning of the human homologue of the GABA transporter GAT-3 and
RT identification of a novel inhibitor with selectivity for this site.";
RL Recept. Channels 2:207-213(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
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).
CC -!- FUNCTION: Mediates sodium- and chloride-dependent transport of gamma-
CC aminobutyric acid (GABA) (PubMed:7874447). Can also mediate transport
CC of beta-alanine and to a lower extent that of taurine and hypotaurine
CC (By similarity). {ECO:0000250|UniProtKB:P31650,
CC ECO:0000269|PubMed:7874447}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-aminobutanoate(out) + chloride(out) + 2 Na(+)(out) = 4-
CC aminobutanoate(in) + chloride(in) + 2 Na(+)(in);
CC Xref=Rhea:RHEA:70687, ChEBI:CHEBI:17996, ChEBI:CHEBI:29101,
CC ChEBI:CHEBI:59888; Evidence={ECO:0000269|PubMed:7874447};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70688;
CC Evidence={ECO:0000305|PubMed:7874447};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(out) + 2 Na(+)(out) + taurine(out) = chloride(in) + 2
CC Na(+)(in) + taurine(in); Xref=Rhea:RHEA:71223, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:29101, ChEBI:CHEBI:507393;
CC Evidence={ECO:0000250|UniProtKB:P31650};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71224;
CC Evidence={ECO:0000250|UniProtKB:P31650};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-alanine(out) + chloride(out) + 2 Na(+)(out) = beta-
CC alanine(in) + chloride(in) + 2 Na(+)(in); Xref=Rhea:RHEA:71247,
CC ChEBI:CHEBI:17996, ChEBI:CHEBI:29101, ChEBI:CHEBI:57966;
CC Evidence={ECO:0000250|UniProtKB:P31650};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71248;
CC Evidence={ECO:0000250|UniProtKB:P31650};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(out) + hypotaurine(out) + 2 Na(+)(out) = chloride(in)
CC + hypotaurine(in) + 2 Na(+)(in); Xref=Rhea:RHEA:71243,
CC ChEBI:CHEBI:17996, ChEBI:CHEBI:29101, ChEBI:CHEBI:57853;
CC Evidence={ECO:0000250|UniProtKB:P31650};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71244;
CC Evidence={ECO:0000250|UniProtKB:P31650};
CC -!- ACTIVITY REGULATION: GABA transport is inhibited by SNAP-5114.
CC {ECO:0000269|PubMed:7874447}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P31647};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P48066-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P48066-2; Sequence=VSP_056539;
CC -!- TISSUE SPECIFICITY: Widespread distribution in the brain.
CC {ECO:0000269|PubMed:7874447}.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A11 subfamily. {ECO:0000305}.
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DR EMBL; S75989; AAB33570.1; -; mRNA.
DR EMBL; AK312719; BAG35593.1; -; mRNA.
DR EMBL; AC018495; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC027128; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64086.1; -; Genomic_DNA.
DR EMBL; BC036083; AAH36083.1; -; mRNA.
DR CCDS; CCDS2602.1; -. [P48066-1]
DR CCDS; CCDS82734.1; -. [P48066-2]
DR RefSeq; NP_001304335.1; NM_001317406.1. [P48066-2]
DR RefSeq; NP_055044.1; NM_014229.2. [P48066-1]
DR AlphaFoldDB; P48066; -.
DR SMR; P48066; -.
DR IntAct; P48066; 3.
DR STRING; 9606.ENSP00000254488; -.
DR BindingDB; P48066; -.
DR ChEMBL; CHEMBL5208; -.
DR DrugBank; DB08848; Guvacine.
DR DrugCentral; P48066; -.
DR TCDB; 2.A.22.3.9; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; P48066; 3 sites.
DR iPTMnet; P48066; -.
DR PhosphoSitePlus; P48066; -.
DR BioMuta; SLC6A11; -.
DR DMDM; 1352531; -.
DR EPD; P48066; -.
DR MassIVE; P48066; -.
DR MaxQB; P48066; -.
DR PaxDb; P48066; -.
DR PeptideAtlas; P48066; -.
DR PRIDE; P48066; -.
DR ProteomicsDB; 55860; -. [P48066-1]
DR ProteomicsDB; 71155; -.
DR Antibodypedia; 26041; 133 antibodies from 26 providers.
DR DNASU; 6538; -.
DR Ensembl; ENST00000254488.7; ENSP00000254488.2; ENSG00000132164.10. [P48066-1]
DR Ensembl; ENST00000454147.1; ENSP00000404120.1; ENSG00000132164.10. [P48066-2]
DR GeneID; 6538; -.
DR KEGG; hsa:6538; -.
DR MANE-Select; ENST00000254488.7; ENSP00000254488.2; NM_014229.3; NP_055044.1.
DR UCSC; uc003bvy.2; human. [P48066-1]
DR CTD; 6538; -.
DR DisGeNET; 6538; -.
DR GeneCards; SLC6A11; -.
DR HGNC; HGNC:11044; SLC6A11.
DR HPA; ENSG00000132164; Tissue enriched (brain).
DR MIM; 607952; gene.
DR neXtProt; NX_P48066; -.
DR OpenTargets; ENSG00000132164; -.
DR PharmGKB; PA35907; -.
DR VEuPathDB; HostDB:ENSG00000132164; -.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000157569; -.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; P48066; -.
DR OMA; NERGMWN; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; P48066; -.
DR TreeFam; TF343812; -.
DR PathwayCommons; P48066; -.
DR Reactome; R-HSA-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-HSA-71288; Creatine metabolism.
DR Reactome; R-HSA-888593; Reuptake of GABA.
DR SignaLink; P48066; -.
DR SIGNOR; P48066; -.
DR BioGRID-ORCS; 6538; 7 hits in 1060 CRISPR screens.
DR ChiTaRS; SLC6A11; human.
DR GenomeRNAi; 6538; -.
DR Pharos; P48066; Tchem.
DR PRO; PR:P48066; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P48066; protein.
DR Bgee; ENSG00000132164; Expressed in medial globus pallidus and 108 other tissues.
DR Genevisible; P48066; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005332; F:gamma-aminobutyric acid:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0042165; F:neurotransmitter binding; IEA:Ensembl.
DR GO; GO:0005369; F:taurine:sodium symporter activity; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0051936; P:gamma-aminobutyric acid reuptake; TAS:Reactome.
DR GO; GO:0015718; P:monocarboxylic acid transport; IDA:ARUK-UCL.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR CDD; cd11508; SLC6sbd_GAT3; 1.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002982; Na/ntran_symport_GABA_GAT3.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR01197; GAT3TRNSPORT.
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 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Glycoprotein; Membrane;
KW Neurotransmitter transport; Phosphoprotein; Reference proteome; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..632
FT /note="Sodium- and chloride-dependent GABA transporter 3"
FT /id="PRO_0000214784"
FT TOPO_DOM 1..58
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 59..79
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..106
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..151
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 152..225
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..244
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 253..270
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..323
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 335..356
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..408
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..456
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 473..493
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 514..533
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 553..571
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 572..632
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31647"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 209..632
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056539"
FT CONFLICT 284
FT /note="F -> L (in Ref. 2; BAG35593)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 632 AA; 70606 MW; D75C5B988E983278 CRC64;
MTAEKALPLG NGKAAEEARE SEAPGGGCSS GGAAPARHPR VKRDKAVHER GHWNNKVEFV
LSVAGEIIGL GNVWRFPYLC YKNGGGAFLI PYVVFFICCG IPVFFLETAL GQFTSEGGIT
CWRKVCPLFE GIGYATQVIE AHLNVYYIII LAWAIFYLSN CFTTELPWAT CGHEWNTENC
VEFQKLNVSN YSHVSLQNAT SPVMEFWEHR VLAISDGIEH IGNLRWELAL CLLAAWTICY
FCIWKGTKST GKVVYVTATF PYIMLLILLI RGVTLPGASE GIKFYLYPDL SRLSDPQVWV
DAGTQIFFSY AICLGCLTAL GSYNNYNNNC YRDCIMLCCL NSGTSFVAGF AIFSVLGFMA
YEQGVPIAEV AESGPGLAFI AYPKAVTMMP LSPLWATLFF MMLIFLGLDS QFVCVESLVT
AVVDMYPKVF RRGYRRELLI LALSVISYFL GLVMLTEGGM YIFQLFDSYA ASGMCLLFVA
IFECICIGWV YGSNRFYDNI EDMIGYRPPS LIKWCWMIMT PGICAGIFIF FLIKYKPLKY
NNIYTYPAWG YGIGWLMALS SMLCIPLWIC ITVWKTEGTL PEKLQKLTTP STDLKMRGKL
GVSPRMVTVN DCDAKLKSDG TIAAITEKET HF
