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Sodium- and chloride-dependent betaine transporter (BGT-1) (Na( )/Cl(-) betaine/GABA transporter) (Solute carrier family 6 member 12)

 S6A12_HUMAN             Reviewed;         614 AA.
P48065; A0AV52; B2R992; D3DUN8;
01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
01-SEP-2009, sequence version 2.
12-SEP-2018, entry version 155.
RecName: Full=Sodium- and chloride-dependent betaine transporter;
AltName: Full=BGT-1;
AltName: Full=Na(+)/Cl(-) betaine/GABA transporter;
AltName: Full=Solute carrier family 6 member 12;
Name=SLC6A12;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-10.
TISSUE=Kidney;
PubMed=7589472; DOI=10.1016/0014-5793(95)01052-G;
Rasola A., Galietta L.J.V., Barone V., Romeo G., Bagnasco S.;
"Molecular cloning and functional characterization of a GABA/betaine
transporter from human kidney.";
FEBS Lett. 373:229-233(1995).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Corpus striatum;
PubMed=7861179;
Borden L.A., Smith K.E., Gustafson E.L., Branchek T.A.,
Weinshank R.L.;
"Cloning and expression of a betaine/GABA transporter from human
brain.";
J. Neurochem. 64:977-984(1995).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-10.
TISSUE=Fetal brain;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
TISSUE=Corpus striatum;
PubMed=16541075; DOI=10.1038/nature04569;
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
Kucherlapati R., Weinstock G., Gibbs R.A.;
"The finished DNA sequence of human chromosome 12.";
Nature 440:346-351(2006).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-10.
TISSUE=Cerebellum;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
-!- FUNCTION: Transports betaine and GABA. May have a role in
regulation of GABAergic transmission in the brain through the
reuptake of GABA into presynaptic terminals, as well as in osmotic
regulation.
-!- SUBUNIT: Interacts with LIN7C. {ECO:0000250}.
-!- INTERACTION:
Q04864:REL; NbExp=3; IntAct=EBI-3843589, EBI-307352;
Q14160:SCRIB; NbExp=2; IntAct=EBI-3843589, EBI-357345;
-!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
-!- TISSUE SPECIFICITY: Liver, heart, skeletal muscle, placenta, and a
widespread distribution in the brain.
-!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF)
(TC 2.A.22) family. SLC6A12 subfamily. {ECO:0000305}.
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EMBL; U27699; AAA87029.1; -; mRNA.
EMBL; L42300; AAA66574.1; -; mRNA.
EMBL; AK313690; BAG36439.1; -; mRNA.
EMBL; AC007406; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; CH471116; EAW88975.1; -; Genomic_DNA.
EMBL; CH471116; EAW88976.1; -; Genomic_DNA.
EMBL; CH471116; EAW88977.1; -; Genomic_DNA.
EMBL; CH471116; EAW88978.1; -; Genomic_DNA.
EMBL; BC126215; AAI26216.1; -; mRNA.
EMBL; BC126217; AAI26218.1; -; mRNA.
CCDS; CCDS8501.1; -.
PIR; S68236; S68236.
RefSeq; NP_001116319.1; NM_001122847.2.
RefSeq; NP_001116320.1; NM_001122848.2.
RefSeq; NP_001193860.1; NM_001206931.1.
RefSeq; NP_003035.3; NM_003044.4.
RefSeq; XP_011519312.1; XM_011521010.1.
UniGene; Hs.437174; -.
UniGene; Hs.737267; -.
ProteinModelPortal; P48065; -.
SMR; P48065; -.
BioGrid; 112430; 2.
IntAct; P48065; 3.
MINT; P48065; -.
STRING; 9606.ENSP00000352702; -.
BindingDB; P48065; -.
ChEMBL; CHEMBL3715; -.
DrugBank; DB08848; Guvacine.
GuidetoPHARMACOLOGY; 932; -.
TCDB; 2.A.22.3.1; the neurotransmitter:sodium symporter (nss) family.
PhosphoSitePlus; P48065; -.
BioMuta; SLC6A12; -.
DMDM; 257050987; -.
MaxQB; P48065; -.
PaxDb; P48065; -.
PeptideAtlas; P48065; -.
PRIDE; P48065; -.
ProteomicsDB; 55859; -.
DNASU; 6539; -.
Ensembl; ENST00000359674; ENSP00000352702; ENSG00000111181.
Ensembl; ENST00000397296; ENSP00000380464; ENSG00000111181.
Ensembl; ENST00000424061; ENSP00000399136; ENSG00000111181.
Ensembl; ENST00000536824; ENSP00000444268; ENSG00000111181.
GeneID; 6539; -.
KEGG; hsa:6539; -.
UCSC; uc001qhz.4; human.
CTD; 6539; -.
DisGeNET; 6539; -.
EuPathDB; HostDB:ENSG00000111181.12; -.
GeneCards; SLC6A12; -.
H-InvDB; HIX0037041; -.
H-InvDB; HIX0201858; -.
HGNC; HGNC:11045; SLC6A12.
HPA; HPA034973; -.
MIM; 603080; gene.
neXtProt; NX_P48065; -.
OpenTargets; ENSG00000111181; -.
PharmGKB; PA35908; -.
eggNOG; KOG3659; Eukaryota.
eggNOG; COG0733; LUCA.
GeneTree; ENSGT00760000118857; -.
HOGENOM; HOG000116406; -.
HOVERGEN; HBG071421; -.
InParanoid; P48065; -.
KO; K05039; -.
OMA; NFTSPVM; -.
OrthoDB; EOG091G08PX; -.
PhylomeDB; P48065; -.
TreeFam; TF343812; -.
Reactome; R-HSA-352230; Amino acid transport across the plasma membrane.
Reactome; R-HSA-442660; Na+/Cl- dependent neurotransmitter transporters.
Reactome; R-HSA-71288; Creatine metabolism.
Reactome; R-HSA-888593; Reuptake of GABA.
SIGNOR; P48065; -.
ChiTaRS; SLC6A12; human.
GenomeRNAi; 6539; -.
PRO; PR:P48065; -.
Proteomes; UP000005640; Chromosome 12.
Bgee; ENSG00000111181; Expressed in 110 organ(s), highest expression level in cortex of kidney.
CleanEx; HS_SLC6A12; -.
ExpressionAtlas; P48065; baseline and differential.
Genevisible; P48065; HS.
GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0015171; F:amino acid transmembrane transporter activity; TAS:Reactome.
GO; GO:0005332; F:gamma-aminobutyric acid:sodium symporter activity; IEA:InterPro.
GO; GO:0005215; F:transporter activity; IBA:GO_Central.
GO; GO:0006865; P:amino acid transport; TAS:Reactome.
InterPro; IPR000175; Na/ntran_symport.
InterPro; IPR002983; Na/ntran_symport_betaine.
InterPro; IPR037272; SNS_sf.
PANTHER; PTHR11616; PTHR11616; 1.
Pfam; PF00209; SNF; 1.
PRINTS; PR01198; BETTRANSPORT.
PRINTS; PR00176; NANEUSMPORT.
SUPFAM; SSF161070; SSF161070; 1.
PROSITE; PS00610; NA_NEUROTRAN_SYMP_1; 1.
PROSITE; PS00754; NA_NEUROTRAN_SYMP_2; 1.
PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1.
1: Evidence at protein level;
Complete proteome; Disulfide bond; Glycoprotein; Membrane;
Neurotransmitter transport; Polymorphism; Reference proteome; Symport;
Transmembrane; Transmembrane helix; Transport.
CHAIN 1 614 Sodium- and chloride-dependent betaine
transporter.
/FTId=PRO_0000214788.
TOPO_DOM 1 44 Cytoplasmic. {ECO:0000255}.
TRANSMEM 45 65 Helical; Name=1. {ECO:0000255}.
TRANSMEM 73 92 Helical; Name=2. {ECO:0000255}.
TRANSMEM 117 137 Helical; Name=3. {ECO:0000255}.
TOPO_DOM 138 210 Extracellular. {ECO:0000255}.
TRANSMEM 211 229 Helical; Name=4. {ECO:0000255}.
TRANSMEM 238 255 Helical; Name=5. {ECO:0000255}.
TRANSMEM 291 308 Helical; Name=6. {ECO:0000255}.
TRANSMEM 320 341 Helical; Name=7. {ECO:0000255}.
TRANSMEM 374 393 Helical; Name=8. {ECO:0000255}.
TRANSMEM 423 441 Helical; Name=9. {ECO:0000255}.
TRANSMEM 458 478 Helical; Name=10. {ECO:0000255}.
TRANSMEM 499 518 Helical; Name=11. {ECO:0000255}.
TRANSMEM 538 556 Helical; Name=12. {ECO:0000255}.
TOPO_DOM 557 614 Cytoplasmic. {ECO:0000255}.
CARBOHYD 171 171 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 183 183 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 157 166 {ECO:0000250|UniProtKB:Q7K4Y6}.
VARIANT 10 10 C -> R (in dbSNP:rs557881).
{ECO:0000269|PubMed:14702039,
ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:7589472}.
/FTId=VAR_058704.
CONFLICT 10 10 C -> Y (in Ref. 2; AAA66574).
{ECO:0000305}.
CONFLICT 571 572 QL -> HV (in Ref. 1; AAA87029).
{ECO:0000305}.
CONFLICT 576 576 D -> N (in Ref. 3; BAG36439).
{ECO:0000305}.
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


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