S6A18_HUMAN
ID S6A18_HUMAN Reviewed; 628 AA.
AC Q96N87;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Inactive sodium-dependent neutral amino acid transporter B(0)AT3;
DE AltName: Full=Sodium- and chloride-dependent transporter XTRP2;
DE AltName: Full=Solute carrier family 6 member 18;
DE AltName: Full=System B(0) neutral amino acid transporter AT3;
GN Name=SLC6A18; Synonyms=XTRP2;
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 [LARGE SCALE MRNA], AND VARIANTS ILE-32 AND LEU-478.
RC TISSUE=Kidney;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=15286787; DOI=10.1038/ng1405;
RA Kleta R., Romeo E., Ristic Z., Ohura T., Stuart C., Arcos-Burgos M.,
RA Dave M.H., Wagner C.A., Camargo S.R.M., Inoue S., Matsuura N.,
RA Helip-Wooley A., Bockenhauer D., Warth R., Bernardini I., Visser G.,
RA Eggermann T., Lee P., Chairoungdua A., Jutabha P., Babu E.,
RA Nilwarangkoon S., Anzai N., Kanai Y., Verrey F., Gahl W.A., Koizumi A.;
RT "Mutations in SLC6A19, encoding B(0)AT1, cause Hartnup disorder.";
RL Nat. Genet. 36:999-1002(2004).
RN [5]
RP POLYMORPHISM, AND LACK OF ASSOCIATION WITH HYPERTENSION.
RX PubMed=16340170; DOI=10.1620/tjem.208.25;
RA Eslami B., Kinboshi M., Inoue S., Harada K., Inoue K., Koizumi A.;
RT "A nonsense polymorphism (Y319X) of the solute carrier family 6 member 18
RT (SLC6A18) gene is not associated with hypertension and blood pressure in
RT Japanese.";
RL Tohoku J. Exp. Med. 208:25-31(2006).
RN [6]
RP LACK OF AMINO ACID TRANSPORTER ACTIVITY.
RX PubMed=26240152; DOI=10.1074/jbc.m115.648519;
RA Fairweather S.J., Broeer A., Subramanian N., Tumer E., Cheng Q.,
RA Schmoll D., O'Mara M.L., Broeer S.;
RT "Molecular basis for the interaction of the mammalian amino acid
RT transporters B0AT1 and B0AT3 with their ancillary protein collectrin.";
RL J. Biol. Chem. 290:24308-24325(2015).
RN [7]
RP VARIANTS SER-79; LEU-478 AND ARG-496, AND POSSIBLE INVOLVEMENT IN HG AND
RP IG.
RX PubMed=19033659; DOI=10.1172/jci36625;
RA Broer S., Bailey C.G., Kowalczuk S., Ng C., Vanslambrouck J.M., Rodgers H.,
RA Auray-Blais C., Cavanaugh J.A., Broer A., Rasko J.E.;
RT "Iminoglycinuria and hyperglycinuria are discrete human phenotypes
RT resulting from complex mutations in proline and glycine transporters.";
RL J. Clin. Invest. 118:3881-3892(2008).
CC -!- FUNCTION: Does not show neutral amino acid transporter activity.
CC {ECO:0000269|PubMed:26240152}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Abundantly expressed in kidney, but not in
CC intestine. {ECO:0000269|PubMed:15286787}.
CC -!- POLYMORPHISM: Genetic variation in SLC6A18 is not a significant
CC predictor for elevated systolic or diastolic blood pressure and is not
CC associated with hypertension in the Japanese population
CC (PubMed:16340170). {ECO:0000269|PubMed:16340170}.
CC -!- DISEASE: Note=Genetic variations in SLC6A18 might contribute to the
CC disease phentotype in some individuals with iminoglycinuria or
CC hyperglycinuria, that carry variants in SLC36A2, SLC6A19 or SLC6A20
CC (PubMed:19033659). {ECO:0000269|PubMed:19033659}.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A18 subfamily. {ECO:0000305}.
CC -!- CAUTION: The mouse ortholog protein is an active neutral amino acid
CC transporter. {ECO:0000269|PubMed:26240152}.
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DR EMBL; AK055798; BAB71018.1; -; mRNA.
DR EMBL; AC114291; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC056757; AAH56757.1; -; mRNA.
DR CCDS; CCDS3860.1; -.
DR RefSeq; NP_872438.2; NM_182632.2.
DR AlphaFoldDB; Q96N87; -.
DR SMR; Q96N87; -.
DR STRING; 9606.ENSP00000323549; -.
DR TCDB; 2.A.22.6.4; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; Q96N87; 4 sites.
DR iPTMnet; Q96N87; -.
DR PhosphoSitePlus; Q96N87; -.
DR BioMuta; SLC6A18; -.
DR DMDM; 313104185; -.
DR PaxDb; Q96N87; -.
DR PeptideAtlas; Q96N87; -.
DR PRIDE; Q96N87; -.
DR ProteomicsDB; 77484; -.
DR Antibodypedia; 1938; 78 antibodies from 23 providers.
DR DNASU; 348932; -.
DR Ensembl; ENST00000324642.4; ENSP00000323549.3; ENSG00000164363.10.
DR GeneID; 348932; -.
DR KEGG; hsa:348932; -.
DR MANE-Select; ENST00000324642.4; ENSP00000323549.3; NM_182632.3; NP_872438.2.
DR UCSC; uc003jby.2; human.
DR CTD; 348932; -.
DR DisGeNET; 348932; -.
DR GeneCards; SLC6A18; -.
DR HGNC; HGNC:26441; SLC6A18.
DR HPA; ENSG00000164363; Tissue enriched (kidney).
DR MalaCards; SLC6A18; -.
DR MIM; 610300; gene.
DR neXtProt; NX_Q96N87; -.
DR OpenTargets; ENSG00000164363; -.
DR Orphanet; 42062; Iminoglycinuria.
DR PharmGKB; PA134982449; -.
DR VEuPathDB; HostDB:ENSG00000164363; -.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000158906; -.
DR HOGENOM; CLU_006855_7_2_1; -.
DR InParanoid; Q96N87; -.
DR OMA; IPIFHVE; -.
DR OrthoDB; 547281at2759; -.
DR PhylomeDB; Q96N87; -.
DR TreeFam; TF343812; -.
DR PathwayCommons; Q96N87; -.
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-5619079; Defective SLC6A18 may confer susceptibility to iminoglycinuria and/or hyperglycinuria.
DR Reactome; R-HSA-5659729; Defective SLC6A18 may confer susceptibility to iminoglycinuria and/or hyperglycinuria.
DR SignaLink; Q96N87; -.
DR BioGRID-ORCS; 348932; 14 hits in 1061 CRISPR screens.
DR GeneWiki; SLC6A18; -.
DR GenomeRNAi; 348932; -.
DR Pharos; Q96N87; Tbio.
DR PRO; PR:Q96N87; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q96N87; protein.
DR Bgee; ENSG00000164363; Expressed in adult mammalian kidney and 13 other tissues.
DR Genevisible; Q96N87; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0006865; P:amino acid transport; TAS:Reactome.
DR GO; GO:0006836; P:neurotransmitter transport; IEA:UniProtKB-KW.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR CDD; cd11517; SLC6sbd_B0AT3; 1.
DR InterPro; IPR042701; B0AT3_SLC6sbd.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002438; Neutral_aa_SLC6.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR00176; NANEUSMPORT.
DR PRINTS; PR01206; ORPHTRNSPORT.
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 Amino-acid transport; Glycoprotein; Membrane; Neurotransmitter transport;
KW Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..628
FT /note="Inactive sodium-dependent neutral amino acid
FT transporter B(0)AT3"
FT /id="PRO_0000214806"
FT TOPO_DOM 1..26
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 27..47
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 48..51
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 52..74
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 75..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 89..111
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..178
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..201
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..207
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 208..230
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..253
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 254..276
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..288
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 289..311
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 312..399
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 400..422
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 423..442
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 443..465
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 466..474
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 475..497
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 498..517
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 518..540
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 541..568
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 569..591
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 592..628
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 602..628
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 4
FT /note="A -> D (in dbSNP:rs34469326)"
FT /id="VAR_057210"
FT VARIANT 12
FT /note="C -> S (in dbSNP:rs7728667)"
FT /id="VAR_027975"
FT VARIANT 32
FT /note="T -> I (in dbSNP:rs7705355)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_027976"
FT VARIANT 79
FT /note="G -> S (in dbSNP:rs113861454)"
FT /evidence="ECO:0000269|PubMed:19033659"
FT /id="VAR_064796"
FT VARIANT 478
FT /note="P -> L (in dbSNP:rs4073918)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:19033659"
FT /id="VAR_027977"
FT VARIANT 496
FT /note="G -> R (in dbSNP:rs147278493)"
FT /evidence="ECO:0000269|PubMed:19033659"
FT /id="VAR_064797"
SQ SEQUENCE 628 AA; 70897 MW; DDFA217424060095 CRC64;
MAHAPEPDPA ACDLGDERPK WDNKAQYLLS CTGFAVGLGN IWRFPYLCQT YGGGAFLIPY
VIALVFEGIP IFHVELAIGQ RLRKGSVGVW TAISPYLSGV GLGCVTLSFL ISLYYNTIVA
WVLWYLLNSF QHPLPWSSCP PDLNRTGFVE ECQGSSAVSY FWYRQTLNIT ADINDSGSIQ
WWLLICLAAS WAVVYMCVIR GIETTGKVIY FTALFPYLVL TIFLIRGLTL PGATKGLIYL
FTPNMHILQN PRVWLDAATQ IFFSLSLAFG GHIAFASYNS PRNDCQKDAV VIALVNRMTS
LYASIAVFSV LGFKATNDYE HCLDRNILSL INDFDFPEQS ISRDDYPAVL MHLNATWPKR
VAQLPLKACL LEDFLDKSAS GPGLAFVVFT ETDLHMPGAP VWAMLFFGML FTLGLSTMFG
TVEAVITPLL DVGVLPRWVP KEALTGLVCL VCFLSATCFT LQSGNYWLEI FDNFAASPNL
LMLAFLEVVG VVYVYGMKRF CDDIAWMTGR RPSPYWRLTW RVVSPLLLTI FVAYIILLFW
KPLRYKAWNP KYELFPSRQE KLYPGWARAA CVLLSLLPVL WVPVAALAQL LTRRRRTWRD
RDARPDTDMR PDTDTRPDTD MRPDTDMR
