S6A12_HUMAN
ID S6A12_HUMAN Reviewed; 614 AA.
AC P48065; A0AV52; B2R992; D3DUN8;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Sodium- and chloride-dependent betaine transporter;
DE AltName: Full=BGT-1;
DE AltName: Full=Na(+)/Cl(-) betaine/GABA transporter;
DE AltName: Full=Solute carrier family 6 member 12;
GN Name=SLC6A12;
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], AND VARIANT ARG-10.
RC TISSUE=Kidney;
RX PubMed=7589472; DOI=10.1016/0014-5793(95)01052-g;
RA Rasola A., Galietta L.J.V., Barone V., Romeo G., Bagnasco S.;
RT "Molecular cloning and functional characterization of a GABA/betaine
RT transporter from human kidney.";
RL FEBS Lett. 373:229-233(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Corpus striatum;
RX PubMed=7861179; DOI=10.1046/j.1471-4159.1995.64030977.x;
RA Borden L.A., Smith K.E., Gustafson E.L., Branchek T.A., Weinshank R.L.;
RT "Cloning and expression of a betaine/GABA transporter from human brain.";
RL J. Neurochem. 64:977-984(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-10.
RC TISSUE=Fetal 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC TISSUE=Corpus striatum;
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-10.
RC TISSUE=Cerebellum;
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: Transports betaine and GABA. May have a role in regulation of
CC GABAergic transmission in the brain through the reuptake of GABA into
CC presynaptic terminals, as well as in osmotic regulation.
CC -!- SUBUNIT: Interacts with LIN7C. {ECO:0000250}.
CC -!- INTERACTION:
CC P48065; P11912: CD79A; NbExp=3; IntAct=EBI-3843589, EBI-7797864;
CC P48065; Q04864: REL; NbExp=3; IntAct=EBI-3843589, EBI-307352;
CC P48065; Q14160: SCRIB; NbExp=2; IntAct=EBI-3843589, EBI-357345;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Liver, heart, skeletal muscle, placenta, and a
CC widespread distribution in the brain.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A12 subfamily. {ECO:0000305}.
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DR EMBL; U27699; AAA87029.1; -; mRNA.
DR EMBL; L42300; AAA66574.1; -; mRNA.
DR EMBL; AK313690; BAG36439.1; -; mRNA.
DR EMBL; AC007406; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CH471116; EAW88975.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88976.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88977.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88978.1; -; Genomic_DNA.
DR EMBL; BC126215; AAI26216.1; -; mRNA.
DR EMBL; BC126217; AAI26218.1; -; mRNA.
DR CCDS; CCDS8501.1; -.
DR PIR; S68236; S68236.
DR RefSeq; NP_001116319.1; NM_001122847.2.
DR RefSeq; NP_001116320.1; NM_001122848.2.
DR RefSeq; NP_001193860.1; NM_001206931.1.
DR RefSeq; NP_003035.3; NM_003044.4.
DR RefSeq; XP_011519312.1; XM_011521010.1.
DR AlphaFoldDB; P48065; -.
DR SMR; P48065; -.
DR BioGRID; 112430; 3.
DR IntAct; P48065; 3.
DR MINT; P48065; -.
DR STRING; 9606.ENSP00000399136; -.
DR BindingDB; P48065; -.
DR ChEMBL; CHEMBL3715; -.
DR DrugBank; DB08848; Guvacine.
DR DrugCentral; P48065; -.
DR GuidetoPHARMACOLOGY; 932; -.
DR TCDB; 2.A.22.3.1; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; P48065; 2 sites.
DR iPTMnet; P48065; -.
DR PhosphoSitePlus; P48065; -.
DR BioMuta; SLC6A12; -.
DR DMDM; 257050987; -.
DR MassIVE; P48065; -.
DR MaxQB; P48065; -.
DR PaxDb; P48065; -.
DR PeptideAtlas; P48065; -.
DR PRIDE; P48065; -.
DR ProteomicsDB; 55859; -.
DR Antibodypedia; 22038; 158 antibodies from 30 providers.
DR DNASU; 6539; -.
DR Ensembl; ENST00000359674.8; ENSP00000352702.4; ENSG00000111181.13.
DR Ensembl; ENST00000397296.6; ENSP00000380464.2; ENSG00000111181.13.
DR Ensembl; ENST00000424061.6; ENSP00000399136.2; ENSG00000111181.13.
DR Ensembl; ENST00000536824.5; ENSP00000444268.1; ENSG00000111181.13.
DR Ensembl; ENST00000684302.1; ENSP00000508194.1; ENSG00000111181.13.
DR GeneID; 6539; -.
DR KEGG; hsa:6539; -.
DR MANE-Select; ENST00000684302.1; ENSP00000508194.1; NM_001122848.3; NP_001116320.1.
DR UCSC; uc001qhz.4; human.
DR CTD; 6539; -.
DR DisGeNET; 6539; -.
DR GeneCards; SLC6A12; -.
DR HGNC; HGNC:11045; SLC6A12.
DR HPA; ENSG00000111181; Tissue enhanced (brain, kidney, liver).
DR MIM; 603080; gene.
DR neXtProt; NX_P48065; -.
DR OpenTargets; ENSG00000111181; -.
DR PharmGKB; PA35908; -.
DR VEuPathDB; HostDB:ENSG00000111181; -.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000161075; -.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; P48065; -.
DR OMA; QDPQVWM; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; P48065; -.
DR TreeFam; TF343812; -.
DR PathwayCommons; P48065; -.
DR Reactome; R-HSA-352230; Amino acid transport across the plasma membrane.
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; P48065; -.
DR SIGNOR; P48065; -.
DR BioGRID-ORCS; 6539; 16 hits in 1064 CRISPR screens.
DR ChiTaRS; SLC6A12; human.
DR GenomeRNAi; 6539; -.
DR Pharos; P48065; Tchem.
DR PRO; PR:P48065; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P48065; protein.
DR Bgee; ENSG00000111181; Expressed in metanephros cortex and 106 other tissues.
DR ExpressionAtlas; P48065; baseline and differential.
DR Genevisible; P48065; HS.
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:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0005332; F:gamma-aminobutyric acid:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0006865; P:amino acid transport; TAS:Reactome.
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:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002983; Na/ntran_symport_betaine.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR01198; BETTRANSPORT.
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 Disulfide bond; Glycoprotein; Membrane; Neurotransmitter transport;
KW Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..614
FT /note="Sodium- and chloride-dependent betaine transporter"
FT /id="PRO_0000214788"
FT TOPO_DOM 1..44
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..65
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 73..92
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..210
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 211..229
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..255
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 291..308
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 320..341
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 374..393
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..441
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 458..478
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 499..518
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 538..556
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 557..614
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 576..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 157..166
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT VARIANT 10
FT /note="C -> R (in dbSNP:rs557881)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:7589472"
FT /id="VAR_058704"
FT CONFLICT 10
FT /note="C -> Y (in Ref. 2; AAA66574)"
FT /evidence="ECO:0000305"
FT CONFLICT 571..572
FT /note="QL -> HV (in Ref. 1; AAA87029)"
FT /evidence="ECO:0000305"
FT CONFLICT 576
FT /note="D -> N (in Ref. 3; BAG36439)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 614 AA; 69368 MW; D8FE8D259CE64B62 CRC64;
MDGKVAVQEC GPPAVSWVPE EGEKLDQEDE DQVKDRGQWT NKMEFVLSVA GEIIGLGNVW
RFPYLCYKNG GGAFFIPYFI FFFVCGIPVF FLEVALGQYT SQGSVTAWRK ICPLFQGIGL
ASVVIESYLN VYYIIILAWA LFYLFSSFTS ELPWTTCNNF WNTEHCTDFL NHSGAGTVTP
FENFTSPVME FWERRVLGIT SGIHDLGSLR WELALCLLLA WVICYFCIWK GVKSTGKVVY
FTATFPYLML VILLIRGVTL PGAYQGIIYY LKPDLFRLKD PQVWMDAGTQ IFFSFAICQG
CLTALGSYNK YHNNCYKDCI ALCFLNSATS FVAGFVVFSI LGFMSQEQGV PISEVAESGP
GLAFIAFPKA VTMMPLSQLW SCLFFIMLIF LGLDSQFVCV ECLVTASIDM FPRQLRKSGR
RELLILTIAV MCYLIGLFLV TEGGMYIFQL FDYYASSGIC LLFLSLFEVV CISWVYGADR
FYDNIEDMIG YRPWPLVKIS WLFLTPGLCL ATFLFSLSKY TPLKYNNVYV YPPWGYSIGW
FLALSSMVCV PLFVVITLLK TRGPFRKRLR QLITPDSSLP QPKQHPCLDG SAGRNFGPSP
TREGLIAGEK ETHL
