S6A20_HUMAN
ID S6A20_HUMAN Reviewed; 592 AA.
AC Q9NP91; A1A4F2; O75590; Q8TF10; Q9NPQ2; Q9NQ77;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Sodium- and chloride-dependent transporter XTRP3;
DE AltName: Full=Sodium/imino-acid transporter 1;
DE AltName: Full=Solute carrier family 6 member 20;
DE AltName: Full=Transporter rB21A homolog;
GN Name=SLC6A20; Synonyms=SIT1, XT3, XTRP3;
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 [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RX PubMed=11352561; DOI=10.1006/geno.2000.6498;
RA Kiss H., Kedra D., Kiss C., Kost-Alimova M., Yang Y., Klein G., Imreh S.,
RA Dumanski J.P.;
RT "The LZTFL1 gene is a part of a transcriptional map covering 250 kb within
RT the common eliminated region 1 (C3CER1) in 3p21.3.";
RL Genomics 73:10-19(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhou Y., Yu L., Zhao S.Y.;
RT "Cloning of a new human cDNA similar to Rattus norvegicus neurotransmitter
RT transporter rB21a.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-315 (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9932288;
RA Nash S.R., Giros B., Kingsmore S.F., Kim K.M., El-Mestikawy S., Dong Q.,
RA Fumagalli F., Seldin M.F., Caron M.G.;
RT "Cloning, gene structure, and genomic localization of an orphan transporter
RT from mouse kidney with six alternatively-spliced isoforms.";
RL Recept. Channels 6:113-128(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 232-592.
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION.
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 [8]
RP FUNCTION, TISSUE SPECIFICITY, VARIANT MET-199, CHARACTERIZATION OF VARIANT
RP MET-199, AND 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).
CC -!- FUNCTION: Mediates the calcium-dependent uptake of imino acids such as
CC L-proline, N-methyl-L-proline and pipecolate as well as N-methylated
CC amino acids. Involved in the transport of glycine.
CC {ECO:0000269|PubMed:15632147, ECO:0000269|PubMed:19033659}.
CC -!- INTERACTION:
CC Q9NP91; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-10311198, EBI-10173507;
CC Q9NP91; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-10311198, EBI-3867333;
CC Q9NP91; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-10311198, EBI-11959885;
CC Q9NP91; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-10311198, EBI-10172150;
CC Q9NP91; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-10311198, EBI-10172290;
CC Q9NP91; P60410: KRTAP10-8; NbExp=6; IntAct=EBI-10311198, EBI-10171774;
CC Q9NP91; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-10311198, EBI-10172052;
CC Q9NP91; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10311198, EBI-945833;
CC Q9NP91; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-10311198, EBI-22310682;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000250}; Multi-pass
CC membrane protein {ECO:0000250}. Note=Located in the apical brush border
CC membrane of kidney proximal tubule cells. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=XT3;
CC IsoId=Q9NP91-1; Sequence=Displayed;
CC Name=2; Synonyms=XT3a;
CC IsoId=Q9NP91-2; Sequence=VSP_050002;
CC -!- TISSUE SPECIFICITY: Kidney and small intestine. Expressed in the S3
CC segment of the proximal tubule. {ECO:0000269|PubMed:19033659,
CC ECO:0000269|PubMed:9932288}.
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 is caused by variants affecting the gene represented
CC in this entry.
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 is caused by variants
CC affecting the gene represented in this entry. Haploinsufficiency of
CC SLC6A20 combined with deficiency of the neutral amino acid transporter
CC SLC6A19 or partially inactivating mutations in SLC36A2, is responsible
CC for iminoglycinuria. Additional polymorphisms and mutations in SLC6A18
CC can contribute to the IG phenotype in some families.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A20 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL75944.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ276207; CAB99310.1; -; mRNA.
DR EMBL; AJ276208; CAB99311.1; -; mRNA.
DR EMBL; AJ289880; CAB96872.1; -; Genomic_DNA.
DR EMBL; AF125107; AAL75944.1; ALT_INIT; mRNA.
DR EMBL; CH471055; EAW64748.1; -; Genomic_DNA.
DR EMBL; BC126197; AAI26198.1; -; mRNA.
DR EMBL; BC136431; AAI36432.1; -; mRNA.
DR EMBL; AF075260; AAC27755.1; -; mRNA.
DR EMBL; AL389979; CAB97535.1; -; mRNA.
DR CCDS; CCDS2730.1; -. [Q9NP91-2]
DR CCDS; CCDS43077.1; -. [Q9NP91-1]
DR RefSeq; NP_064593.1; NM_020208.3. [Q9NP91-1]
DR RefSeq; NP_071800.1; NM_022405.3. [Q9NP91-2]
DR AlphaFoldDB; Q9NP91; -.
DR SMR; Q9NP91; -.
DR BioGRID; 120108; 38.
DR IntAct; Q9NP91; 9.
DR STRING; 9606.ENSP00000346298; -.
DR TCDB; 2.A.22.6.8; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; Q9NP91; 2 sites.
DR iPTMnet; Q9NP91; -.
DR PhosphoSitePlus; Q9NP91; -.
DR BioMuta; SLC6A20; -.
DR DMDM; 46397768; -.
DR MassIVE; Q9NP91; -.
DR PaxDb; Q9NP91; -.
DR PeptideAtlas; Q9NP91; -.
DR PRIDE; Q9NP91; -.
DR ProteomicsDB; 81934; -. [Q9NP91-1]
DR ProteomicsDB; 81935; -. [Q9NP91-2]
DR Antibodypedia; 29592; 29 antibodies from 15 providers.
DR DNASU; 54716; -.
DR Ensembl; ENST00000353278.8; ENSP00000296133.5; ENSG00000163817.16. [Q9NP91-2]
DR Ensembl; ENST00000358525.9; ENSP00000346298.4; ENSG00000163817.16. [Q9NP91-1]
DR GeneID; 54716; -.
DR KEGG; hsa:54716; -.
DR MANE-Select; ENST00000358525.9; ENSP00000346298.4; NM_020208.4; NP_064593.1.
DR UCSC; uc011bai.3; human. [Q9NP91-1]
DR CTD; 54716; -.
DR DisGeNET; 54716; -.
DR GeneCards; SLC6A20; -.
DR HGNC; HGNC:30927; SLC6A20.
DR HPA; ENSG00000163817; Group enriched (choroid plexus, intestine).
DR MalaCards; SLC6A20; -.
DR MIM; 138500; phenotype.
DR MIM; 242600; phenotype.
DR MIM; 605616; gene.
DR neXtProt; NX_Q9NP91; -.
DR OpenTargets; ENSG00000163817; -.
DR Orphanet; 42062; Iminoglycinuria.
DR PharmGKB; PA134865308; -.
DR VEuPathDB; HostDB:ENSG00000163817; -.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000155873; -.
DR InParanoid; Q9NP91; -.
DR OMA; FNNINHR; -.
DR OrthoDB; 547281at2759; -.
DR PhylomeDB; Q9NP91; -.
DR TreeFam; TF343812; -.
DR PathwayCommons; Q9NP91; -.
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-5619101; Variant SLC6A20 contributes towards hyperglycinuria (HG) and iminoglycinuria (IG).
DR Reactome; R-HSA-5660686; Variant SLC6A20 contributes towards hyperglycinuria (HG) and iminoglycinuria (IG).
DR SignaLink; Q9NP91; -.
DR BioGRID-ORCS; 54716; 13 hits in 1070 CRISPR screens.
DR ChiTaRS; SLC6A20; human.
DR GeneWiki; SLC6A20; -.
DR GenomeRNAi; 54716; -.
DR Pharos; Q9NP91; Tbio.
DR PRO; PR:Q9NP91; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NP91; protein.
DR Bgee; ENSG00000163817; Expressed in pigmented layer of retina and 123 other tissues.
DR ExpressionAtlas; Q9NP91; baseline and differential.
DR Genevisible; Q9NP91; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
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; IDA:UniProtKB.
DR GO; GO:0015199; F:amino-acid betaine transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0015188; F:L-isoleucine transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0015193; F:L-proline transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015175; F:neutral amino acid transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0005298; F:proline:sodium symporter activity; ISS:ARUK-UCL.
DR GO; GO:0089718; P:amino acid import across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0006865; P:amino acid transport; IDA:UniProtKB.
DR GO; GO:0015838; P:amino-acid betaine transport; ISS:ARUK-UCL.
DR GO; GO:0015816; P:glycine transport; IMP:UniProtKB.
DR GO; GO:1903806; P:L-isoleucine import across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:1904271; P:L-proline import across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:1905647; P:proline import across plasma membrane; IMP:ARUK-UCL.
DR GO; GO:0015824; P:proline transport; IMP:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
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 1: Evidence at protein level;
KW Alternative splicing; Amino-acid transport; Cell membrane; Glycoprotein;
KW Membrane; Reference proteome; Symport; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..592
FT /note="Sodium- and chloride-dependent transporter XTRP3"
FT /id="PRO_0000214812"
FT TOPO_DOM 1..5
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 6..26
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..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 CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 195..231
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11352561,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_050002"
FT VARIANT 9
FT /note="A -> G (in dbSNP:rs2271615)"
FT /id="VAR_021862"
FT VARIANT 199
FT /note="T -> M (common variant that contributes to
FT hyperglycinuria and iminoglycinuria in patients carrying
FT variants in SLC36A2, SLC6A19 or SLC6A18; results in SLC6A20
FT inactivation due to a 8-fold decrease of Vmax;
FT dbSNP:rs17279437)"
FT /evidence="ECO:0000269|PubMed:19033659"
FT /id="VAR_052068"
FT CONFLICT 31
FT /note="F -> N (in Ref. 2; AAC27755)"
FT /evidence="ECO:0000305"
FT CONFLICT 217
FT /note="L -> V (in Ref. 2; AAC27755)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 592 AA; 65914 MW; AF6E94E19895377F CRC64;
MEKARPLWAN SLQFVFACIS YAVGLGNVWR FPYLCQMYGG GSFLVPYIIM LIVEGMPLLY
LELAVGQRMR QGSIGAWRTI SPYLSGVGVA SVVVSFFLSM YYNVINAWAF WYLFHSFQDP
LPWSVCPLNG NHTGYDEECE KASSTQYFWY RKTLNISPSL QENGGVQWEP ALCLLLAWLV
VYLCILRGTE STGKVVYFTA SLPYCVLIIY LIRGLTLHGA TNGLMYMFTP KIEQLANPKA
WINAATQIFF SLGLGFGSLI AFASYNEPSN NCQKHAIIVS LINSFTSIFA SIVTFSIYGF
KATFNYENCL KKVSLLLTNT FDLEDGFLTA SNLEQVKGYL ASAYPSKYSE MFPQIKNCSL
ESELDTAVQG TGLAFIVYTE AIKNMEVSQL WSVLYFFMLL MLGIGSMLGN TAAILTPLTD
SKIISSHLPK EAISGLVCLV NCAIGMVFTM EAGNYWFDIF NDYAATLSLL LIVLVETIAV
CYVYGLRRFE SDLKAMTGRA VSWYWKVMWA GVSPLLIVSL FVFYLSDYIL TGTLKYQAWD
ASQGQLVTKD YPAYALAVIG LLVASSTMCI PLAALGTFVQ RRLKRGDADP VA
