S6A19_HUMAN
ID S6A19_HUMAN Reviewed; 634 AA.
AC Q695T7; A8K446;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Sodium-dependent neutral amino acid transporter B(0)AT1;
DE AltName: Full=Solute carrier family 6 member 19;
DE AltName: Full=System B(0) neutral amino acid transporter AT1;
GN Name=SLC6A19; Synonyms=B0AT1;
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], FUNCTION, TRANSPORTER ACTIVITY, TISSUE
RP SPECIFICITY, VARIANT HND CYS-57, AND CHARACTERIZATION OF VARIANT HND
RP CYS-57.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, TISSUE
RP SPECIFICITY, VARIANTS HND ASN-173; GLN-240; PRO-242 AND LYS-501,
RP CHARACTERIZATION OF VARIANTS HND ASN-173; GLN-240; PRO-242 AND LYS-501,
RP VARIANTS GLN-240 AND ILE-252, AND CHARACTERIZATION OF VARIANT ILE-252.
RX PubMed=15286788; DOI=10.1038/ng1406;
RA Seow H.F., Broeer S., Broeer A., Bailey C.G., Potter S.J., Cavanaugh J.A.,
RA Rasko J.E.J.;
RT "Hartnup disorder is caused by mutations in the gene encoding the neutral
RT amino acid transporter SLC6A19.";
RL Nat. Genet. 36:1003-1007(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
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 [5]
RP INVOLVEMENT IN HG AND 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).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND CHARACTERIZATION OF
RP VARIANT HND GLN-240.
RX PubMed=18424768; DOI=10.1096/fj.08-107300;
RA Kowalczuk S., Broeer A., Tietze N., Vanslambrouck J.M., Rasko J.E.,
RA Broeer S.;
RT "A protein complex in the brush-border membrane explains a Hartnup disorder
RT allele.";
RL FASEB J. 22:2880-2887(2008).
RN [7]
RP VARIANTS HND ARG-66; ARG-93; ASN-173; 178-ARG--TYR-634 DEL; GLN-240;
RP ARG-284; CYS-328; LYS-405 AND GLY-517, CHARACTERIZATION OF VARIANTS HND
RP ARG-66; ARG-93; 178-ARG--TYR-634 DEL; ARG-284; CYS-328; LYS-405 AND
RP GLY-517, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18484095; DOI=10.1002/humu.20777;
RA Azmanov D.N., Kowalczuk S., Rodgers H., Auray-Blais C., Giguere R.,
RA Rasko J.E., Broeer S., Cavanaugh J.A.;
RT "Further evidence for allelic heterogeneity in Hartnup disorder.";
RL Hum. Mutat. 29:1217-1221(2008).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANTS HND THR-69; ARG-93; LEU-265 AND
RP LEU-579, CHARACTERIZATION OF VARIANTS HND CYS-57; THR-69; ARG-93; PRO-242
RP AND LYS-501 AND PRO-579, AND CHARACTERIZATION OF VARIANTS GLN-240 AND
RP ILE-252.
RX PubMed=19185582; DOI=10.1053/j.gastro.2008.10.055;
RA Camargo S.M., Singer D., Makrides V., Huggel K., Pos K.M., Wagner C.A.,
RA Kuba K., Danilczyk U., Skovby F., Kleta R., Penninger J.M., Verrey F.;
RT "Tissue-specific amino acid transporter partners ACE2 and collectrin
RT differentially interact with hartnup mutations.";
RL Gastroenterology 136:872-882(2009).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [10] {ECO:0007744|PDB:6M18, ECO:0007744|PDB:6M1D}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 2-634, AND INTERACTION
RP WITH ACE2.
RX PubMed=32132184; DOI=10.1126/science.abb2762;
RA Yan R., Zhang Y., Li Y., Xia L., Guo Y., Zhou Q.;
RT "Structural basis for the recognition of the SARS-CoV-2 by full-length
RT human ACE2.";
RL Science 367:1444-1448(2020).
CC -!- FUNCTION: Transporter that mediates resorption of neutral amino acids
CC across the apical membrane of renal and intestinal epithelial cells
CC (PubMed:15286787, PubMed:15286788, PubMed:18424768, PubMed:18484095,
CC PubMed:19185582, PubMed:26240152). This uptake is sodium-dependent and
CC chloride-independent (PubMed:15286787, PubMed:19185582,
CC PubMed:15286788). Requires CLTRN in kidney or ACE2 in intestine for
CC cell surface expression and amino acid transporter activity
CC (PubMed:19185582, PubMed:18424768). {ECO:0000269|PubMed:15286787,
CC ECO:0000269|PubMed:15286788, ECO:0000269|PubMed:18424768,
CC ECO:0000269|PubMed:18484095, ECO:0000269|PubMed:19185582,
CC ECO:0000269|PubMed:26240152}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-alanine(in) + Na(+)(in) = L-alanine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:29283, ChEBI:CHEBI:29101, ChEBI:CHEBI:57972;
CC Evidence={ECO:0000269|PubMed:15286787, ECO:0000269|PubMed:15286788};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-cysteine(in) + Na(+)(in) = L-cysteine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:68232, ChEBI:CHEBI:29101, ChEBI:CHEBI:35235;
CC Evidence={ECO:0000269|PubMed:15286787};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutamine(in) + Na(+)(in) = L-glutamine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:68236, ChEBI:CHEBI:29101, ChEBI:CHEBI:58359;
CC Evidence={ECO:0000269|PubMed:15286787, ECO:0000269|PubMed:15286788};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycine(in) + Na(+)(in) = glycine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:68228, ChEBI:CHEBI:29101, ChEBI:CHEBI:57305;
CC Evidence={ECO:0000269|PubMed:15286787};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-isoleucine(in) + Na(+)(in) = L-isoleucine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:29275, ChEBI:CHEBI:29101, ChEBI:CHEBI:58045;
CC Evidence={ECO:0000269|PubMed:15286787};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-leucine(in) + Na(+)(in) = L-leucine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:29263, ChEBI:CHEBI:29101, ChEBI:CHEBI:57427;
CC Evidence={ECO:0000269|PubMed:15286787, ECO:0000269|PubMed:15286788};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-methionine(in) + Na(+)(in) = L-methionine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:68240, ChEBI:CHEBI:29101, ChEBI:CHEBI:57844;
CC Evidence={ECO:0000269|PubMed:15286787};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-phenylalanine(in) + Na(+)(in) = L-phenylalanine(out) +
CC Na(+)(out); Xref=Rhea:RHEA:68244, ChEBI:CHEBI:29101,
CC ChEBI:CHEBI:58095; Evidence={ECO:0000269|PubMed:15286787,
CC ECO:0000269|PubMed:15286788};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-serine(in) + Na(+)(in) = L-serine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:29575, ChEBI:CHEBI:29101, ChEBI:CHEBI:33384;
CC Evidence={ECO:0000269|PubMed:15286787};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tryptophan(in) + Na(+)(in) = L-tryptophan(out) + Na(+)(out);
CC Xref=Rhea:RHEA:68252, ChEBI:CHEBI:29101, ChEBI:CHEBI:57912;
CC Evidence={ECO:0000269|PubMed:15286787};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tyrosine(in) + Na(+)(in) = L-tyrosine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:68248, ChEBI:CHEBI:29101, ChEBI:CHEBI:58315;
CC Evidence={ECO:0000269|PubMed:15286787};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-valine(in) + Na(+)(in) = L-valine(out) + Na(+)(out);
CC Xref=Rhea:RHEA:29267, ChEBI:CHEBI:29101, ChEBI:CHEBI:57762;
CC Evidence={ECO:0000269|PubMed:15286787};
CC -!- SUBUNIT: Interacts in a tissue-specific manner with ACE2 in small
CC intestine and with CLTRN in the kidney (By similarity). Interacts with
CC CLTRN; this interaction is required for trafficking of SLC6A19 to the
CC plasma membrane and for its catalytic activation in kidneys (By
CC similarity). Interacts with ACE2; this interaction is required for
CC trafficking of SLC6A19 to the plasma membrane and for its catalytic
CC activation in intestine (PubMed:32132184). Interacts with ANPEP; the
CC interaction positively regulates its amino acid transporter activity
CC (By similarity). {ECO:0000250|UniProtKB:Q9D687,
CC ECO:0000269|PubMed:32132184}.
CC -!- INTERACTION:
CC Q695T7; Q9BYF1: ACE2; NbExp=4; IntAct=EBI-25475705, EBI-7730807;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19185582,
CC ECO:0000269|PubMed:26240152}; Multi-pass membrane protein
CC {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:18424768};
CC Multi-pass membrane protein {ECO:0000255}. Note=Colocalizes with ACE2
CC on the apical membrane of cells lining villi of the jejunum, ileum and
CC on kidney proximal tubules. {ECO:0000269|PubMed:18424768}.
CC -!- TISSUE SPECIFICITY: Robust expression in kidney and small intestine,
CC with minimal expression in pancreas (PubMed:18424768, PubMed:15286787).
CC Also expressed in stomach, liver, duodenum, ileocecum, colon and
CC prostate. Not detected in testis, whole brain, cerebellum, fetal liver,
CC spleen, skeletal muscle, uterus, heart or lung.
CC {ECO:0000269|PubMed:15286787, ECO:0000269|PubMed:15286788,
CC ECO:0000269|PubMed:18424768}.
CC -!- DISEASE: Hartnup disorder (HND) [MIM:234500]: Autosomal recessive
CC abnormality of renal and gastrointestinal neutral amino acid transport
CC noted for its clinical variability. First described in 1956, HND is
CC characterized by increases in the urinary and intestinal excretion of
CC neutral amino acids. Individuals with typical Hartnup aminoaciduria may
CC be asymptomatic, some develop a photosensitive pellagra-like rash,
CC attacks of cerebellar ataxia and other neurological or psychiatric
CC features. Although the definition of HND was originally based on
CC clinical and biochemical abnormalities, its marked clinical
CC heterogeneity has led to it being known as a disorder with a consistent
CC pathognomonic neutral hyperaminoaciduria. {ECO:0000269|PubMed:15286787,
CC ECO:0000269|PubMed:15286788, ECO:0000269|PubMed:18424768,
CC ECO:0000269|PubMed:18484095, ECO:0000269|PubMed:19185582}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hyperglycinuria (HG) [MIM:138500]: A condition characterized
CC by excess of glycine in the urine. In some cases it is associated with
CC renal colic and renal oxalate stones. {ECO:0000269|PubMed:19033659}.
CC Note=The disease may be caused by variants affecting the gene
CC represented in this entry. SLC6A19 deficiency combined with
CC haploinsufficiency of SLC6A20 or partially inactivating mutations in
CC SLC36A2, can be responsible for hyperglycinuria.
CC -!- DISEASE: Iminoglycinuria (IG) [MIM:242600]: A disorder of renal tubular
CC reabsorption of glycine and imino acids (proline and hydroxyproline),
CC marked by excessive levels of all three substances in the urine.
CC {ECO:0000269|PubMed:19033659}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry. SLC6A19
CC deficiency combined with haploinsufficiency of SLC6A20 or partially
CC inactivating mutations in SLC36A2, can be responsible for
CC iminoglycinuria. Additional polymorphisms and mutations in SLC6A18 can
CC contribute to the IG phenotype in some families.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A19 subfamily. {ECO:0000305}.
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DR EMBL; AY596807; AAT42127.1; -; mRNA.
DR EMBL; AY591756; AAT66171.1; -; mRNA.
DR EMBL; AK290811; BAF83500.1; -; mRNA.
DR EMBL; CH471102; EAX08175.1; -; Genomic_DNA.
DR CCDS; CCDS34130.1; -.
DR RefSeq; NP_001003841.1; NM_001003841.2.
DR PDB; 6M17; EM; 2.90 A; A/C=2-634.
DR PDB; 6M18; EM; 2.90 A; A/C=2-634.
DR PDB; 6M1D; EM; 4.50 A; A/C=2-634.
DR PDB; 7DWX; EM; 8.30 A; A/C=2-634.
DR PDBsum; 6M17; -.
DR PDBsum; 6M18; -.
DR PDBsum; 6M1D; -.
DR PDBsum; 7DWX; -.
DR AlphaFoldDB; Q695T7; -.
DR SMR; Q695T7; -.
DR BioGRID; 130985; 1.
DR ComplexPortal; CPX-5684; SARS-CoV-2 Spike - human ACE2-SLC6A19 complex.
DR IntAct; Q695T7; 1.
DR STRING; 9606.ENSP00000305302; -.
DR DrugCentral; Q695T7; -.
DR GuidetoPHARMACOLOGY; 939; -.
DR TCDB; 2.A.22.6.3; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; Q695T7; 5 sites.
DR iPTMnet; Q695T7; -.
DR PhosphoSitePlus; Q695T7; -.
DR BioMuta; SLC6A19; -.
DR DMDM; 73919285; -.
DR jPOST; Q695T7; -.
DR MassIVE; Q695T7; -.
DR PaxDb; Q695T7; -.
DR PeptideAtlas; Q695T7; -.
DR PRIDE; Q695T7; -.
DR ProteomicsDB; 66151; -.
DR Antibodypedia; 22313; 75 antibodies from 22 providers.
DR DNASU; 340024; -.
DR Ensembl; ENST00000304460.11; ENSP00000305302.10; ENSG00000174358.16.
DR GeneID; 340024; -.
DR KEGG; hsa:340024; -.
DR MANE-Select; ENST00000304460.11; ENSP00000305302.10; NM_001003841.3; NP_001003841.1.
DR UCSC; uc003jbw.5; human.
DR CTD; 340024; -.
DR DisGeNET; 340024; -.
DR GeneCards; SLC6A19; -.
DR HGNC; HGNC:27960; SLC6A19.
DR HPA; ENSG00000174358; Group enriched (intestine, kidney).
DR MalaCards; SLC6A19; -.
DR MIM; 138500; phenotype.
DR MIM; 234500; phenotype.
DR MIM; 242600; phenotype.
DR MIM; 608893; gene.
DR neXtProt; NX_Q695T7; -.
DR OpenTargets; ENSG00000174358; -.
DR Orphanet; 2116; Hartnup disease.
DR Orphanet; 42062; Iminoglycinuria.
DR PharmGKB; PA134968815; -.
DR VEuPathDB; HostDB:ENSG00000174358; -.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000154896; -.
DR HOGENOM; CLU_006855_7_2_1; -.
DR InParanoid; Q695T7; -.
DR OMA; SAKIQMS; -.
DR OrthoDB; 547281at2759; -.
DR PhylomeDB; Q695T7; -.
DR TreeFam; TF343812; -.
DR PathwayCommons; Q695T7; -.
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-5619044; Defective SLC6A19 causes Hartnup disorder (HND).
DR Reactome; R-HSA-5659735; Defective SLC6A19 causes Hartnup disorder (HND).
DR SignaLink; Q695T7; -.
DR BioGRID-ORCS; 340024; 14 hits in 1067 CRISPR screens.
DR ChiTaRS; SLC6A19; human.
DR GeneWiki; SLC6A19; -.
DR GenomeRNAi; 340024; -.
DR Pharos; Q695T7; Tchem.
DR PRO; PR:Q695T7; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q695T7; protein.
DR Bgee; ENSG00000174358; Expressed in ileal mucosa and 56 other tissues.
DR ExpressionAtlas; Q695T7; baseline and differential.
DR Genevisible; Q695T7; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; IDA:ARUK-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0015175; F:neutral amino acid transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0006865; P:amino acid transport; TAS:Reactome.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0019058; P:viral life cycle; IC:ComplexPortal.
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; PS50267; NA_NEUROTRAN_SYMP_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid transport; Cell membrane; Disease variant;
KW Glycoprotein; Membrane; Phosphoprotein; Reference proteome; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..634
FT /note="Sodium-dependent neutral amino acid transporter
FT B(0)AT1"
FT /id="PRO_0000214809"
FT TOPO_DOM 1..41
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 42..62
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 63..67
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 89..120
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 121..141
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 142..192
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 193..213
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..221
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..268
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..304
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 305..325
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 326..413
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..434
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..456
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 457..477
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 478..490
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 491..511
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 512..531
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 532..552
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 553..581
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 582..602
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 603..634
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D687"
FT MOD_RES 627
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D687"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 57
FT /note="R -> C (in HND; no amino acid transport activity
FT when expressed alone or coexpressed with CLTRN or ACE2;
FT loss of surface expression when expressed alone or
FT coexpressed with CLTRN or ACE2; dbSNP:rs762989809)"
FT /evidence="ECO:0000269|PubMed:15286787,
FT ECO:0000269|PubMed:19185582"
FT /id="VAR_023314"
FT VARIANT 66
FT /note="G -> R (in HND; abolishes amino acid transport
FT activity; dbSNP:rs1251095994)"
FT /evidence="ECO:0000269|PubMed:18484095"
FT /id="VAR_081070"
FT VARIANT 69
FT /note="A -> T (in HND; increases cell membrane localization
FT in presence of ACE2 or CLTRN; does not affect interaction
FT with ACE2; amino acid transport activity is not activated
FT in presence of ACE2 or CLTRN)"
FT /evidence="ECO:0000269|PubMed:19185582"
FT /id="VAR_081071"
FT VARIANT 93
FT /note="G -> R (in HND; no amino acid transport activity
FT when expressed alone or coexpressed with CLTRN or ACE2;
FT increases surface cell expression when expressed alone or
FT coexpressed with CLTRN or ACE2; dbSNP:rs757679627)"
FT /evidence="ECO:0000269|PubMed:18484095,
FT ECO:0000269|PubMed:19185582"
FT /id="VAR_081072"
FT VARIANT 173
FT /note="D -> N (in HND; population allele frequency among
FT Europeans is 0.007; reduced transport activity by 50% but
FT does not completely inactivates the transporter;
FT coexpression with ACE2 increased the transport rate whereas
FT coexpression with CLTRN has the opposite effect; does not
FT affect interaction with ACE2; decreased cell membrane
FT localization in presence of CLTRN; dbSNP:rs121434346)"
FT /evidence="ECO:0000269|PubMed:15286788,
FT ECO:0000269|PubMed:18484095"
FT /id="VAR_023315"
FT VARIANT 178..634
FT /note="Missing (in HND; abolishes amino acid transport
FT activity)"
FT /evidence="ECO:0000269|PubMed:18484095"
FT /id="VAR_081073"
FT VARIANT 240
FT /note="R -> Q (in HND; does not affect amino acid transport
FT activity when expressed alone; decreases amino acid
FT transport activity in presence of ACE2 or CLTRN; decreased
FT surface cell expression when expressed with CLTRN or ACE2;
FT dbSNP:rs758492838)"
FT /evidence="ECO:0000269|PubMed:15286788,
FT ECO:0000269|PubMed:18424768, ECO:0000269|PubMed:18484095,
FT ECO:0000269|PubMed:19185582"
FT /id="VAR_023316"
FT VARIANT 242
FT /note="L -> P (in HND; no amino acid transport activity
FT when expressed alone or coexpressed with CLTRN or ACE2;
FT loss of surface expression when expressed coexpressed with
FT CLTRN or ACE2; dbSNP:rs200745023)"
FT /evidence="ECO:0000269|PubMed:15286788,
FT ECO:0000269|PubMed:19185582"
FT /id="VAR_023317"
FT VARIANT 252
FT /note="V -> I (does not affect cell membrane localization;
FT does not affect amino acid transport activity;
FT dbSNP:rs7732589)"
FT /evidence="ECO:0000269|PubMed:15286788,
FT ECO:0000269|PubMed:19185582"
FT /id="VAR_023318"
FT VARIANT 265
FT /note="P -> L (in HND; does not affect interaction with
FT ACE2; coexpression with ACE2 increased the transport rate
FT whereas coexpression with CLTRN has the opposite effect;
FT dbSNP:rs148139045)"
FT /evidence="ECO:0000269|PubMed:19185582"
FT /id="VAR_081074"
FT VARIANT 284
FT /note="G -> R (in HND; abolishes amino acid transport
FT activity; dbSNP:rs200842846)"
FT /evidence="ECO:0000269|PubMed:18484095"
FT /id="VAR_081075"
FT VARIANT 328
FT /note="R -> C (in HND; abolishes amino acid transport
FT activity; dbSNP:rs142164435)"
FT /evidence="ECO:0000269|PubMed:18484095"
FT /id="VAR_081076"
FT VARIANT 405
FT /note="E -> K (in HND; abolishes amino acid transport
FT activity; dbSNP:rs765501634)"
FT /evidence="ECO:0000269|PubMed:18484095"
FT /id="VAR_081077"
FT VARIANT 501
FT /note="E -> K (in HND; no amino acid transport activity
FT when expressed alone or coexpressed with CLTRN or ACE2;
FT loss of surface expression when expressed alone or
FT coexpressed with CLTRN or ACE2; dbSNP:rs1236852017)"
FT /evidence="ECO:0000269|PubMed:15286788,
FT ECO:0000269|PubMed:19185582"
FT /id="VAR_023319"
FT VARIANT 517
FT /note="D -> G (in HND; abolishes amino acid transport
FT activity; dbSNP:rs745524993)"
FT /evidence="ECO:0000269|PubMed:18484095"
FT /id="VAR_081078"
FT VARIANT 579
FT /note="P -> L (in HND; no amino acid transport activity
FT when expressed alone or coexpressed with CLTRN or ACE2;
FT loss of surface expression when expressed alone or
FT coexpressed with CLTRN or ACE2; dbSNP:rs751554174)"
FT /evidence="ECO:0000269|PubMed:19185582"
FT /id="VAR_081079"
FT TURN 12..14
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 18..20
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 21..24
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 38..48
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 58..64
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 65..70
FT /evidence="ECO:0007829|PDB:6M18"
FT HELIX 71..80
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 82..96
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 101..104
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 109..112
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 113..141
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 157..162
FT /evidence="ECO:0007829|PDB:6M18"
FT HELIX 164..168
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 177..180
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:6M18"
FT HELIX 196..211
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 216..218
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 219..241
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 251..255
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 259..263
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 266..278
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 285..290
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 301..316
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 318..345
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 346..349
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 360..370
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 372..376
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 387..391
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 399..402
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 403..407
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 411..414
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 415..429
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 431..444
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 455..469
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 470..473
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 478..506
FT /evidence="ECO:0007829|PDB:6M17"
FT TURN 507..510
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 511..521
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 528..535
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 537..545
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 547..553
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 554..556
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 559..562
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 567..569
FT /evidence="ECO:0007829|PDB:6M17"
FT STRAND 574..577
FT /evidence="ECO:0007829|PDB:6M17"
FT HELIX 582..608
FT /evidence="ECO:0007829|PDB:6M17"
SQ SEQUENCE 634 AA; 71110 MW; B85EFB02F9D53BB9 CRC64;
MVRLVLPNPG LDARIPSLAE LETIEQEEAS SRPKWDNKAQ YMLTCLGFCV GLGNVWRFPY
LCQSHGGGAF MIPFLILLVL EGIPLLYLEF AIGQRLRRGS LGVWSSIHPA LKGLGLASML
TSFMVGLYYN TIISWIMWYL FNSFQEPLPW SDCPLNENQT GYVDECARSS PVDYFWYRET
LNISTSISDS GSIQWWMLLC LACAWSVLYM CTIRGIETTG KAVYITSTLP YVVLTIFLIR
GLTLKGATNG IVFLFTPNVT ELAQPDTWLD AGAQVFFSFS LAFGGLISFS SYNSVHNNCE
KDSVIVSIIN GFTSVYVAIV VYSVIGFRAT QRYDDCFSTN ILTLINGFDL PEGNVTQENF
VDMQQRCNAS DPAAYAQLVF QTCDINAFLS EAVEGTGLAF IVFTEAITKM PLSPLWSVLF
FIMLFCLGLS SMFGNMEGVV VPLQDLRVIP PKWPKEVLTG LICLGTFLIG FIFTLNSGQY
WLSLLDSYAG SIPLLIIAFC EMFSVVYVYG VDRFNKDIEF MIGHKPNIFW QVTWRVVSPL
LMLIIFLFFF VVEVSQELTY SIWDPGYEEF PKSQKISYPN WVYVVVVIVA GVPSLTIPGY
AIYKLIRNHC QKPGDHQGLV STLSTASMNG DLKY
