ID   S13A4_HUMAN             Reviewed;         626 AA.
AC   Q9UKG4; A4D1Q4; Q8N631;
DT   19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT   20-JAN-2009, sequence version 2.
DT   02-OCT-2024, entry version 166.
DE   RecName: Full=Solute carrier family 13 member 4;
DE   AltName: Full=Na(+)/sulfate cotransporter SUT-1;
DE   AltName: Full=NaS2;
GN   Name=SLC13A4; Synonyms=SUT1;
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, TISSUE SPECIFICITY, TRANSPORTER
RP   ACTIVITY, AND ACTIVITY REGULATION.
RC   TISSUE=Endothelial cell;
RX   PubMed=10535998; DOI=10.1073/pnas.96.22.12772;
RA   Girard J.-P., Baekkevold E.S., Feliu J., Brandtzaeg P., Amalric F.;
RT   "Molecular cloning and functional analysis of SUT-1, a sulfate transporter
RT   from human high endothelial venules.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:12772-12777(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA   Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA   Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA   Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA   Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA   Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA   Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA   Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA   Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA   Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA   Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA   Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA   Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [6]
RP   FUNCTION, TISSUE SPECIFICITY, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=15607730; DOI=10.1016/j.bbrc.2004.11.102;
RA   Markovich D., Regeer R.R., Kunzelmann K., Dawson P.A.;
RT   "Functional characterization and genomic organization of the human Na(+)-
RT   sulfate cotransporter hNaS2 gene (SLC13A4).";
RL   Biochem. Biophys. Res. Commun. 326:729-734(2005).
CC   -!- FUNCTION: Sodium:sulfate symporter that mediates sulfate reabsorption
CC       in the high endothelial venules (HEV). {ECO:0000269|PubMed:10535998,
CC       ECO:0000269|PubMed:15607730}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3 Na(+)(out) + sulfate(out) = 3 Na(+)(in) + sulfate(in);
CC         Xref=Rhea:RHEA:71951, ChEBI:CHEBI:16189, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:10535998, ECO:0000269|PubMed:15607730};
CC   -!- ACTIVITY REGULATION: Transport is inhibited by thiosulfate, phosphate,
CC       molybdate, selenate and tungstate. Not inhibited by oxalate, citrate,
CC       succinate, phenol red or 4,4'-diisothiocyanostilbene-2,2'-disulfonic
CC       acid (DIDS). {ECO:0000269|PubMed:10535998}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.38 mM for sulfate {ECO:0000269|PubMed:15607730};
CC         KM=22.77 mM for sodium {ECO:0000269|PubMed:15607730};
CC   -!- INTERACTION:
CC       Q9UKG4; O00590: ACKR2; NbExp=3; IntAct=EBI-12808018, EBI-13379418;
CC       Q9UKG4; P27352: CBLIF; NbExp=3; IntAct=EBI-12808018, EBI-3953638;
CC       Q9UKG4; P11912: CD79A; NbExp=6; IntAct=EBI-12808018, EBI-7797864;
CC       Q9UKG4; Q92903: CDS1; NbExp=3; IntAct=EBI-12808018, EBI-13295305;
CC       Q9UKG4; Q9HA82: CERS4; NbExp=3; IntAct=EBI-12808018, EBI-2622997;
CC       Q9UKG4; Q8NET1: DEFB108B; NbExp=3; IntAct=EBI-12808018, EBI-13346443;
CC       Q9UKG4; Q96Q80: DERL3; NbExp=3; IntAct=EBI-12808018, EBI-12831318;
CC       Q9UKG4; P52803: EFNA5; NbExp=3; IntAct=EBI-12808018, EBI-1753674;
CC       Q9UKG4; Q5NDL2-3: EOGT; NbExp=3; IntAct=EBI-12808018, EBI-13052900;
CC       Q9UKG4; Q7Z2K6: ERMP1; NbExp=3; IntAct=EBI-12808018, EBI-10976398;
CC       Q9UKG4; P36382: GJA5; NbExp=3; IntAct=EBI-12808018, EBI-750433;
CC       Q9UKG4; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-12808018, EBI-13345167;
CC       Q9UKG4; Q9BZJ8: GPR61; NbExp=3; IntAct=EBI-12808018, EBI-12808020;
CC       Q9UKG4; P46695: IER3; NbExp=3; IntAct=EBI-12808018, EBI-1748945;
CC       Q9UKG4; P24593: IGFBP5; NbExp=3; IntAct=EBI-12808018, EBI-720480;
CC       Q9UKG4; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-12808018, EBI-12070086;
CC       Q9UKG4; P41143: OPRD1; NbExp=3; IntAct=EBI-12808018, EBI-2624456;
CC       Q9UKG4; Q7RTS5: OTOP3; NbExp=3; IntAct=EBI-12808018, EBI-12853910;
CC       Q9UKG4; Q96G79: SLC35A4; NbExp=3; IntAct=EBI-12808018, EBI-12363689;
CC       Q9UKG4; Q6ICL7: SLC35E4; NbExp=3; IntAct=EBI-12808018, EBI-12867720;
CC       Q9UKG4; Q9H2H9: SLC38A1; NbExp=3; IntAct=EBI-12808018, EBI-9978441;
CC       Q9UKG4; Q8IVJ1: SLC41A1; NbExp=3; IntAct=EBI-12808018, EBI-12266234;
CC       Q9UKG4; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-12808018, EBI-348587;
CC       Q9UKG4; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-12808018, EBI-2852148;
CC       Q9UKG4; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-12808018, EBI-11988865;
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in placenta and testis with
CC       intermediate levels in brain and lower levels in heart, thymus and
CC       liver. {ECO:0000269|PubMed:10535998, ECO:0000269|PubMed:15607730}.
CC   -!- SIMILARITY: Belongs to the SLC13A/DASS transporter (TC 2.A.47) family.
CC       NADC subfamily. {ECO:0000305}.
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DR   EMBL; AF169301; AAF05907.1; -; mRNA.
DR   EMBL; AC091736; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH236950; EAL24058.1; -; Genomic_DNA.
DR   EMBL; CH471070; EAW83858.1; -; Genomic_DNA.
DR   EMBL; BC030689; AAH30689.1; -; mRNA.
DR   CCDS; CCDS5840.1; -.
DR   RefSeq; NP_001305121.1; NM_001318192.1.
DR   RefSeq; NP_036582.2; NM_012450.3.
DR   AlphaFoldDB; Q9UKG4; -.
DR   SMR; Q9UKG4; -.
DR   BioGRID; 117650; 29.
DR   IntAct; Q9UKG4; 25.
DR   STRING; 9606.ENSP00000297282; -.
DR   DrugBank; DB09499; Thiosulfuric acid.
DR   TCDB; 2.A.47.1.14; the divalent anion:na(+) symporter (dass) family.
DR   iPTMnet; Q9UKG4; -.
DR   PhosphoSitePlus; Q9UKG4; -.
DR   BioMuta; SLC13A4; -.
DR   DMDM; 221222500; -.
DR   MassIVE; Q9UKG4; -.
DR   PaxDb; 9606-ENSP00000297282; -.
DR   PeptideAtlas; Q9UKG4; -.
DR   ProteomicsDB; 84786; -.
DR   Antibodypedia; 46129; 99 antibodies from 18 providers.
DR   DNASU; 26266; -.
DR   Ensembl; ENST00000354042.8; ENSP00000297282.5; ENSG00000164707.17.
DR   GeneID; 26266; -.
DR   KEGG; hsa:26266; -.
DR   UCSC; uc003vta.4; human.
DR   AGR; HGNC:15827; -.
DR   CTD; 26266; -.
DR   DisGeNET; 26266; -.
DR   GeneCards; SLC13A4; -.
DR   HGNC; HGNC:15827; SLC13A4.
DR   HPA; ENSG00000164707; Tissue enriched (choroid).
DR   MIM; 604309; gene.
DR   neXtProt; NX_Q9UKG4; -.
DR   OpenTargets; ENSG00000164707; -.
DR   PharmGKB; PA38045; -.
DR   VEuPathDB; HostDB:ENSG00000164707; -.
DR   eggNOG; KOG1281; Eukaryota.
DR   GeneTree; ENSGT01030000234550; -.
DR   HOGENOM; CLU_005170_9_1_1; -.
DR   InParanoid; Q9UKG4; -.
DR   OMA; GGICIAK; -.
DR   OrthoDB; 1359392at2759; -.
DR   PhylomeDB; Q9UKG4; -.
DR   TreeFam; TF312913; -.
DR   PathwayCommons; Q9UKG4; -.
DR   Reactome; R-HSA-433137; Sodium-coupled sulphate, di- and tri-carboxylate transporters.
DR   SignaLink; Q9UKG4; -.
DR   BioGRID-ORCS; 26266; 16 hits in 1141 CRISPR screens.
DR   ChiTaRS; SLC13A4; human.
DR   GenomeRNAi; 26266; -.
DR   Pharos; Q9UKG4; Tbio.
DR   PRO; PR:Q9UKG4; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q9UKG4; protein.
DR   Bgee; ENSG00000164707; Expressed in choroid plexus epithelium and 121 other cell types or tissues.
DR   ExpressionAtlas; Q9UKG4; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0015382; F:sodium:sulfate symporter activity; IDA:UniProtKB.
DR   GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0008272; P:sulfate transport; TAS:ProtInc.
DR   GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR   CDD; cd01115; SLC13_permease; 1.
DR   InterPro; IPR001898; SLC13A/DASS.
DR   PANTHER; PTHR10283; SOLUTE CARRIER FAMILY 13 MEMBER; 1.
DR   PANTHER; PTHR10283:SF63; SOLUTE CARRIER FAMILY 13 MEMBER 4; 1.
DR   Pfam; PF00939; Na_sulph_symp; 1.
PE   1: Evidence at protein level;
KW   Ion transport; Membrane; Proteomics identification; Reference proteome;
KW   Sodium; Sodium transport; Symport; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..626
FT                   /note="Solute carrier family 13 member 4"
FT                   /id="PRO_0000172495"
FT   TRANSMEM        13..33
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        52..72
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        77..97
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        113..133
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        274..294
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        309..329
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        372..392
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        414..434
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        466..486
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        499..519
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        543..563
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        590..610
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          217..252
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        217..248
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         451
FT                   /note="P -> S (in dbSNP:rs36004833)"
FT                   /id="VAR_057193"
FT   CONFLICT        198
FT                   /note="E -> DR (in Ref. 1; AAF05907)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        245
FT                   /note="P -> R (in Ref. 5; AAH30689)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        539
FT                   /note="L -> M (in Ref. 1; AAF05907)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   626 AA;  69358 MW;  D84A18376DFAFA2B CRC64;
     MGLLQGLLRV RKLLLVVCVP LLLLPLPVLH PSSEASCAYV LIVTAVYWVS EAVPLGAAAL
     VPAFLYPFFG VLRSNEVAAE YFKNTTLLLV GVICVAAAVE KWNLHKRIAL RMVLMAGAKP
     GMLLLCFMCC TTLLSMWLSN TSTTAMVMPI VEAVLQELVS AEDEQLVAGN SNTEEAEPIS
     LDVKNSQPSL ELIFVNEESN ADLTTLMHNE NLNGVPSITN PIKTANQHQG KKQHPSQEKP
     QVLTPSPRKQ KLNRKYRSHH DQMICKCLSL SISYSATIGG LTTIIGTSTS LIFLEHFNNQ
     YPAAEVVNFG TWFLFSFPIS LIMLVVSWFW MHWLFLGCNF KETCSLSKKK KTKREQLSEK
     RIQEEYEKLG DISYPEMVTG FFFILMTVLW FTREPGFVPG WDSFFEKKGY RTDATVSVFL
     GFLLFLIPAK KPCFGKKNDG ENQEHSLGTE PIITWKDFQK TMPWEIVILV GGGYALASGS
     KSSGLSTWIG NQMLSLSSLP PWAVTLLACI LVSIVTEFVS NPATITIFLP ILCSLSETLH
     INPLYTLIPV TMCISFAVML PVGNPPNAIV FSYGHCQIKD MVKAGLGVNV IGLVIVMVAI
     NTWGVSLFHL DTYPAWARVS NITDQA
//