ID   S620A_MOUSE             Reviewed;         592 AA.
AC   Q8VDB9; Q3USE2;
DT   01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   24-JAN-2024, entry version 135.
DE   RecName: Full=Sodium- and chloride-dependent transporter XTRP3A;
DE   AltName: Full=IMINO-B;
DE   AltName: Full=Solute carrier family 6 member 20A;
DE   AltName: Full=X transporter protein 3 similar 1;
GN   Name=Slc6a20a {ECO:0000312|MGI:MGI:2143217};
GN   Synonyms=Slc6a20 {ECO:0000312|EMBL:CAI80736.1}, Xt3s1
GN   {ECO:0000303|PubMed:15689184}, Xtm3s1 {ECO:0000303|PubMed:12461651},
GN   Xtrp3s1 {ECO:0000312|EMBL:CAD20989.1, ECO:0000312|MGI:MGI:2143217};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1] {ECO:0000312|EMBL:CAD20989.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ {ECO:0000312|EMBL:CAD20989.1};
RX   PubMed=12461651; DOI=10.1007/s00335-002-3037-y;
RA   Kiss H., Darai E., Kiss C., Kost-Alimova M., Klein G., Dumanski J.P.,
RA   Imreh S.;
RT   "Comparative human/murine sequence analysis of the common eliminated region
RT   1 from human 3p21.3.";
RL   Mamm. Genome 13:646-655(2002).
RN   [2] {ECO:0000305, ECO:0000312|EMBL:CAI80736.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND TRANSPORTER
RP   ACTIVITY.
RC   STRAIN=C57BL/6J {ECO:0000312|EMBL:CAI80736.1};
RX   PubMed=15689184; DOI=10.1042/bj20050100;
RA   Kowalczuk S., Broeer A., Munzinger M., Tietze N., Klingel K., Broeer S.;
RT   "Molecular cloning of the mouse IMINO system: an Na(+)- and Cl(-)-dependent
RT   proline transporter.";
RL   Biochem. J. 386:417-422(2005).
RN   [3] {ECO:0000312|EMBL:BAE24391.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE24391.1};
RC   TISSUE=Medulla oblongata {ECO:0000312|EMBL:BAE24391.1};
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4] {ECO:0000312|EMBL:AAI18934.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [5]
RP   DEVELOPMENTAL STAGE.
RX   PubMed=15632147; DOI=10.1074/jbc.m413027200;
RA   Takanaga H., Mackenzie B., Suzuki Y., Hediger M.A.;
RT   "Identification of mammalian proline transporter SIT1 (SLC6A20) with
RT   characteristics of classical system imino.";
RL   J. Biol. Chem. 280:8974-8984(2005).
RN   [6] {ECO:0000305}
RP   SUBCELLULAR LOCATION.
RX   PubMed=16174864; DOI=10.1152/ajprenal.00286.2005;
RA   Romeo E., Dave M.H., Bacic D., Ristic Z., Camargo S.M.R., Loffing J.,
RA   Wagner C.A., Verrey F.;
RT   "Luminal kidney and intestine SLC6 amino acid transporters of B0AT-cluster
RT   and their tissue distribution in Mus musculus.";
RL   Am. J. Physiol. 290:F376-F383(2006).
RN   [7]
RP   FUNCTION, TISSUE SPECIFICITY, TRANSPORTER ACTIVTITY, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=33428810; DOI=10.15252/emmm.202012632;
RA   Bae M., Roh J.D., Kim Y., Kim S.S., Han H.M., Yang E., Kang H., Lee S.,
RA   Kim J.Y., Kang R., Jung H., Yoo T., Kim H., Kim D., Oh H., Han S., Kim D.,
RA   Han J., Bae Y.C., Kim H., Ahn S., Chan A.M., Lee D., Kim J.W., Kim E.;
RT   "SLC6A20 transporter: a novel regulator of brain glycine homeostasis and
RT   NMDAR function.";
RL   EMBO Mol. Med. 13:e12632-e12632(2021).
CC   -!- FUNCTION: Mediates the Na(+)- and Cl(-)-dependent uptake of imino acids
CC       such as L-proline, N-methyl-L-proline and pipecolate as well as N-
CC       methylated amino acids (PubMed:15689184). Also transports glycine,
CC       regulates proline and glycine homeostasis in the brain playing a role
CC       in the modulation of NMDAR currents (PubMed:33428810).
CC       {ECO:0000269|PubMed:15689184, ECO:0000269|PubMed:33428810}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + L-proline(out) + 2 Na(+)(out) = chloride(in) +
CC         L-proline(in) + 2 Na(+)(in); Xref=Rhea:RHEA:71263, ChEBI:CHEBI:17996,
CC         ChEBI:CHEBI:29101, ChEBI:CHEBI:60039;
CC         Evidence={ECO:0000269|PubMed:15689184, ECO:0000269|PubMed:33428810};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4-hydroxy-L-proline(out) + chloride(out) + 2 Na(+)(out) = 4-
CC         hydroxy-L-proline + chloride(in) + 2 Na(+)(in); Xref=Rhea:RHEA:72223,
CC         ChEBI:CHEBI:17996, ChEBI:CHEBI:29101, ChEBI:CHEBI:58419;
CC         Evidence={ECO:0000269|PubMed:15689184};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-methyl-2-(methylamino)propanoate(out) + chloride(out) + 2
CC         Na(+)(out) = 2-methyl-2-(methylamino)propanoate(in) + chloride(in) +
CC         2 Na(+)(in); Xref=Rhea:RHEA:72235, ChEBI:CHEBI:17996,
CC         ChEBI:CHEBI:29101, ChEBI:CHEBI:192077;
CC         Evidence={ECO:0000269|PubMed:15689184};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + L-pipecolate(out) + 2 Na(+)(out) =
CC         chloride(in) + L-pipecolate(in) + 2 Na(+)(in); Xref=Rhea:RHEA:71267,
CC         ChEBI:CHEBI:17996, ChEBI:CHEBI:29101, ChEBI:CHEBI:61185;
CC         Evidence={ECO:0000269|PubMed:15689184};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + glycine betaine(out) + 2 Na(+)(out) =
CC         chloride(in) + glycine betaine(in) + 2 Na(+)(in);
CC         Xref=Rhea:RHEA:70735, ChEBI:CHEBI:17750, ChEBI:CHEBI:17996,
CC         ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:15689184};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + glycine(out) + 2 Na(+)(out) = chloride(in) +
CC         glycine(in) + 2 Na(+)(in); Xref=Rhea:RHEA:70691, ChEBI:CHEBI:17996,
CC         ChEBI:CHEBI:29101, ChEBI:CHEBI:57305;
CC         Evidence={ECO:0000269|PubMed:33428810};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=19.64 uM for proline {ECO:0000269|PubMed:33428810};
CC         KM=63.16 uM for glycine {ECO:0000269|PubMed:33428810};
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000269|PubMed:16174864}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:16174864}. Note=Located in the apical brush border
CC       membrane of kidney proximal tubule cells and in the apical membrane of
CC       enterocytes lining the intestinal villi. {ECO:0000269|PubMed:16174864}.
CC   -!- TISSUE SPECIFICITY: Expressed in brain, kidney, small intestine,
CC       thymus, spleen and lung. In the brain, expressed in cerebellum, cortex
CC       and brain stem. Not detected in liver, muscle or heart
CC       (PubMed:15689184). In brain, widespread in various regions, including
CC       the meninges, choroid plexus, cortex, hippocampus and thalamus
CC       (PubMed:33428810). {ECO:0000269|PubMed:15689184,
CC       ECO:0000269|PubMed:33428810}.
CC   -!- DEVELOPMENTAL STAGE: Expression in kidney is highly induced 3 days
CC       after birth. {ECO:0000269|PubMed:15632147}.
CC   -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF)
CC       (TC 2.A.22) family. SLC6A20 subfamily. {ECO:0000305}.
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DR   EMBL; AJ428067; CAD20989.1; -; mRNA.
DR   EMBL; AJ964961; CAI80736.1; -; mRNA.
DR   EMBL; AK140445; BAE24391.1; -; mRNA.
DR   EMBL; BC118933; AAI18934.1; -; mRNA.
DR   CCDS; CCDS40817.1; -.
DR   RefSeq; NP_631881.1; NM_139142.2.
DR   AlphaFoldDB; Q8VDB9; -.
DR   SMR; Q8VDB9; -.
DR   STRING; 10090.ENSMUSP00000047690; -.
DR   GlyCosmos; Q8VDB9; 1 site, No reported glycans.
DR   GlyGen; Q8VDB9; 1 site.
DR   iPTMnet; Q8VDB9; -.
DR   PhosphoSitePlus; Q8VDB9; -.
DR   jPOST; Q8VDB9; -.
DR   MaxQB; Q8VDB9; -.
DR   PaxDb; 10090-ENSMUSP00000047690; -.
DR   ProteomicsDB; 253387; -.
DR   DNASU; 102680; -.
DR   Ensembl; ENSMUST00000040960.13; ENSMUSP00000047690.7; ENSMUSG00000036814.14.
DR   GeneID; 102680; -.
DR   KEGG; mmu:102680; -.
DR   UCSC; uc009sgk.1; mouse.
DR   AGR; MGI:2143217; -.
DR   CTD; 102680; -.
DR   MGI; MGI:2143217; Slc6a20a.
DR   VEuPathDB; HostDB:ENSMUSG00000036814; -.
DR   eggNOG; KOG3659; Eukaryota.
DR   GeneTree; ENSGT00940000155873; -.
DR   HOGENOM; CLU_006855_7_2_1; -.
DR   InParanoid; Q8VDB9; -.
DR   OMA; FNNINHR; -.
DR   OrthoDB; 3084493at2759; -.
DR   PhylomeDB; Q8VDB9; -.
DR   TreeFam; TF343812; -.
DR   Reactome; R-MMU-352230; Amino acid transport across the plasma membrane.
DR   Reactome; R-MMU-442660; Na+/Cl- dependent neurotransmitter transporters.
DR   BioGRID-ORCS; 102680; 5 hits in 79 CRISPR screens.
DR   ChiTaRS; Slc6a20a; mouse.
DR   PRO; PR:Q8VDB9; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; Q8VDB9; Protein.
DR   Bgee; ENSMUSG00000036814; Expressed in small intestine Peyer's patch and 121 other cell types or tissues.
DR   ExpressionAtlas; Q8VDB9; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0015171; F:amino acid transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0015199; F:amino-acid betaine transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0015193; F:L-proline transmembrane transporter activity; IDA:MGI.
DR   GO; GO:0015175; F:neutral L-amino acid transmembrane transporter activity; IDA:ARUK-UCL.
DR   GO; GO:0005298; F:proline:sodium symporter activity; IDA:UniProtKB.
DR   GO; GO:0015370; F:solute:sodium symporter activity; IDA:UniProtKB.
DR   GO; GO:0089718; P:amino acid import across plasma membrane; ISO:MGI.
DR   GO; GO:0006865; P:amino acid transport; IDA:UniProtKB.
DR   GO; GO:0015838; P:amino-acid betaine transport; IDA:MGI.
DR   GO; GO:1903804; P:glycine import across plasma membrane; IDA:UniProtKB.
DR   GO; GO:0015816; P:glycine transport; ISO:MGI.
DR   GO; GO:1904271; P:L-proline import across plasma membrane; IDA:UniProtKB.
DR   GO; GO:1905647; P:proline import across plasma membrane; IDA:ARUK-UCL.
DR   GO; GO:0035524; P:proline transmembrane transport; IDA:MGI.
DR   GO; GO:0015824; P:proline transport; ISO:MGI.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR   InterPro; IPR000175; Na/ntran_symport.
DR   InterPro; IPR002438; Neutral_aa_SLC6.
DR   InterPro; IPR037272; SNS_sf.
DR   PANTHER; PTHR11616:SF44; SODIUM- AND CHLORIDE-DEPENDENT TRANSPORTER XTRP3; 1.
DR   PANTHER; PTHR11616; SODIUM/CHLORIDE DEPENDENT TRANSPORTER; 1.
DR   Pfam; PF00209; SNF; 1.
DR   PRINTS; PR00176; NANEUSMPORT.
DR   PRINTS; PR01206; ORPHTRNSPORT.
DR   SUPFAM; SSF161070; SNF-like; 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.
DR   Genevisible; Q8VDB9; MM.
PE   1: Evidence at protein level;
KW   Amino-acid transport; Cell membrane; Glycoprotein; Membrane;
KW   Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..592
FT                   /note="Sodium- and chloride-dependent transporter XTRP3A"
FT                   /id="PRO_0000343522"
FT   TOPO_DOM        1..7
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        8..28
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        29..42
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        43..63
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        64..79
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        80..100
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        101..165
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        166..186
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        187..194
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        195..215
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        216..241
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        242..262
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        263..276
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        277..297
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        298..389
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        390..410
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        411..431
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        432..452
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        453..465
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        466..486
FT                   /note="Helical; Name=10"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        487..504
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        505..525
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        526..554
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        555..575
FT                   /note="Helical; Name=12"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        576..592
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        131
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        58
FT                   /note="L -> P (in Ref. 3; BAE24391)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   592 AA;  66178 MW;  547B9F8C0B7A99AA CRC64;
     MEKARPQWGH PLQFVFACIS YAVGLGNVWR FPYLCQMYGG GSFLVPYIIM LIVEGMPLLY
     LELAVGQRMR QGSIGAWRTI SPYLSGVGVA SVVVSFFLSM YYNVINAWGF WYLFHSFQDP
     LPWSVCPLNS NHTGYDEECE KASSTQYFWY RKTLNISPSI QENGGVQWEP ALCLTLAWLM
     VYLCILRGTE STGKVVYFTA SMPYCVLIIY LVRGLTLHGA TNGLMYMFTP KMEQLANPKA
     WINAATQIFF SLGLGFGSLI AFASYNEPSN NCQKHAIIVS IINSSTSIFA SIVTFSIYGF
     KATFNYENCL NKVILLLTNS FDLEDGFLTV SNLEEVKNYL ASTYPNKYSE VFPHIRNCSL
     ESELDTAVQG TGLAFIVYTE AIKNMEVSQL WSVLYFFMLL MLGIGSMLGN TAAILTPLTD
     SKVISSYLPK EAISGLVCLI NCAVGMVFTM EAGNYWFDIF NDYAATLSLL LIVLVETIAV
     CYVYGLKRFE SDLRAMTGRT LSWYWKVMWA FVSPLLIVGL FIFYLSDYIL TGTLQYQAWD
     ATQGQLVTKD YPPHALAVIG LLVASSTMCI PLVALGTFIR NRLKRGGSAP VA
//