ID   S13A5_HUMAN             Reviewed;         568 AA.
AC   Q86YT5; B3KXR0; B7Z4P2; B7ZLB4; F8W7N2; Q6ZMG1;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   27-MAR-2024, entry version 151.
DE   RecName: Full=Na(+)/citrate cotransporter;
DE            Short=NaCT {ECO:0000303|PubMed:12445824};
DE   AltName: Full=Sodium-coupled citrate transporter {ECO:0000303|PubMed:12445824};
DE   AltName: Full=Sodium-dependent citrate transporter;
DE   AltName: Full=Solute carrier family 13 member 5;
GN   Name=SLC13A5; Synonyms=NACT;
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] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP   TRANSPORT ACTIVITY.
RX   PubMed=12445824; DOI=10.1016/s0006-291x(02)02669-4;
RA   Inoue K., Zhuang L., Ganapathy V.;
RT   "Human Na+ -coupled citrate transporter: primary structure, genomic
RT   organization, and transport function.";
RL   Biochem. Biophys. Res. Commun. 299:465-471(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC   TISSUE=Brain;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton 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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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, TRANSPORT ACTIVITY, AND ACTIVITY REGULATION.
RX   PubMed=12826022; DOI=10.1042/bj20030827;
RA   Inoue K., Zhuang L., Maddox D.M., Smith S.B., Ganapathy V.;
RT   "Human sodium-coupled citrate transporter, the orthologue of Drosophila
RT   Indy, as a novel target for lithium action.";
RL   Biochem. J. 374:21-26(2003).
RN   [7]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-562.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [8]
RP   FUNCTION, AND TRANSPORT ACTIVITY.
RX   PubMed=26324167; DOI=10.1124/jpet.115.226902;
RA   Zwart R., Peeva P.M., Rong J.X., Sher E.;
RT   "Electrophysiological characterization of human and mouse sodium-dependent
RT   citrate transporters (NaCT/SLC13A5) reveal species differences with respect
RT   to substrate sensitivity and cation dependence.";
RL   J. Pharmacol. Exp. Ther. 355:247-254(2015).
RN   [9]
RP   INVOLVEMENT IN DEE25, AND VARIANTS DEE25 ARG-219; MET-227 AND PRO-488.
RX   PubMed=24995870; DOI=10.1016/j.ajhg.2014.06.006;
RA   Thevenon J., Milh M., Feillet F., St-Onge J., Duffourd Y., Juge C.,
RA   Roubertie A., Heron D., Mignot C., Raffo E., Isidor B., Wahlen S.,
RA   Sanlaville D., Villeneuve N., Darmency-Stamboul V., Toutain A.,
RA   Lefebvre M., Chouchane M., Huet F., Lafon A., de Saint Martin A., Lesca G.,
RA   El Chehadeh S., Thauvin-Robinet C., Masurel-Paulet A., Odent S.,
RA   Villard L., Philippe C., Faivre L., Riviere J.B.;
RT   "Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy
RT   with seizure onset in the first days of life.";
RL   Am. J. Hum. Genet. 95:113-120(2014).
RN   [10]
RP   INVOLVEMENT IN DEE25, FUNCTION, TRANSPORT ACTIVITY, SUBCELLULAR LOCATION,
RP   VARIANTS DEE25 MET-142; ARG-219; MET-227; 341-TRP--THR-568 DEL; LEU-427 AND
RP   HIS-524, AND CHARACTERIZATION OF VARIANTS DEE25 MET-142; ARG-219; MET-227;
RP   341-TRP--THR-568 DEL; LEU-427 AND HIS-524.
RX   PubMed=26384929; DOI=10.1093/brain/awv263;
RG   Autosomal recessive working group of the EuroEPINOMICS RES Consortium;
RA   Hardies K., de Kovel C.G., Weckhuysen S., Asselbergh B., Geuens T.,
RA   Deconinck T., Azmi A., May P., Brilstra E., Becker F., Barisic N.,
RA   Craiu D., Braun K.P., Lal D., Thiele H., Schubert J., Weber Y.,
RA   van 't Slot R., Nuernberg P., Balling R., Timmerman V., Lerche H.,
RA   Maudsley S., Helbig I., Suls A., Koeleman B.P., De Jonghe P.;
RT   "Recessive mutations in SLC13A5 result in a loss of citrate transport and
RT   cause neonatal epilepsy, developmental delay and teeth hypoplasia.";
RL   Brain 138:3238-3250(2015).
RN   [11]
RP   CHARACTERIZATION OF VARIANTS DEE25 ARG-219; MET-227 AND PRO-488,
RP   CHARACTERIZATION OF VARIANTS GLU-219; ASN-243; PRO-420 AND ARG-485,
RP   FUNCTION, TRANSPORT ACTIVITY, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=30054523; DOI=10.1038/s41598-018-29547-8;
RA   Selch S., Chafai A., Sticht H., Birkenfeld A.L., Fromm M.F., Koenig J.;
RT   "Analysis of naturally occurring mutations in the human uptake transporter
RT   NaCT important for bone and brain development and energy metabolism.";
RL   Sci. Rep. 8:11330-11330(2018).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (3.04 ANGSTROMS) OF 1-568 IN COMPLEX WITH INHIBITOR,
RP   FUNCTION, TRANSPORTER ACTIVITY, SUBUNIT, ACTIVITY REGULATION, AND
RP   MUTAGENESIS OF GLY-409 AND ILE-410.
RX   PubMed=33597751; DOI=10.1038/s41586-021-03230-x;
RA   Sauer D.B., Song J., Wang B., Hilton J.K., Karpowich N.K., Mindell J.A.,
RA   Rice W.J., Wang D.N.;
RT   "Structure and inhibition mechanism of the human citrate transporter
RT   NaCT.";
RL   Nature 591:157-161(2021).
CC   -!- FUNCTION: High-affinity sodium/citrate cotransporter that mediates the
CC       entry of citrate into cells, which is a critical participant of
CC       biochemical pathways (PubMed:12445824, PubMed:26324167,
CC       PubMed:26384929, PubMed:30054523, PubMed:33597751, PubMed:12826022).
CC       May function in various metabolic processes in which citrate has a
CC       critical role such as energy production (Krebs cycle), fatty acid
CC       synthesis, cholesterol synthesis, glycolysis, and gluconeogenesis
CC       (PubMed:12826022). Transports citrate into the cell in a Na(+)-
CC       dependent manner, recognizing the trivalent form of citrate
CC       (physiological pH) rather than the divalent form (PubMed:12445824,
CC       PubMed:26324167, PubMed:26384929, PubMed:30054523, PubMed:33597751,
CC       PubMed:12826022). Can recognize succinate as a substrate, but its
CC       affinity for succinate is several fold lower than for citrate
CC       (PubMed:26324167). The stoichiometry is probably 4 Na(+) for each
CC       carboxylate, irrespective of whether the translocated substrate is
CC       divalent or trivalent, rendering the process electrogenic
CC       (PubMed:12445824, PubMed:12826022). Involved in the regulation of
CC       citrate levels in the brain (By similarity).
CC       {ECO:0000250|UniProtKB:Q67BT3, ECO:0000269|PubMed:12445824,
CC       ECO:0000269|PubMed:12826022, ECO:0000269|PubMed:26324167,
CC       ECO:0000269|PubMed:26384929, ECO:0000269|PubMed:30054523,
CC       ECO:0000269|PubMed:33597751}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=citrate(out) + 4 Na(+)(out) = citrate(in) + 4 Na(+)(in);
CC         Xref=Rhea:RHEA:65664, ChEBI:CHEBI:16947, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:12445824, ECO:0000269|PubMed:12826022,
CC         ECO:0000269|PubMed:26324167, ECO:0000269|PubMed:26384929,
CC         ECO:0000269|PubMed:30054523, ECO:0000269|PubMed:33597751};
CC   -!- ACTIVITY REGULATION: Inhibited by (R)-2-(4-(tert-butyl)phenethyl)-2-
CC       hydroxysuccinic acid (also known as PF-06649298) (PubMed:33597751).
CC       Stimulated by Li(+) in the presence of Na(+), moreover changes
CC       stoichiometry from 4:1 to 2:1 Na(+):citrate (PubMed:12826022).
CC       {ECO:0000269|PubMed:12826022, ECO:0000269|PubMed:33597751}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1439 uM for citrate {ECO:0000269|PubMed:30054523};
CC         Vmax=13910 pmol/min/mg enzyme toward citrate
CC         {ECO:0000269|PubMed:30054523};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:33597751}.
CC   -!- INTERACTION:
CC       Q86YT5; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-12002412, EBI-10173507;
CC       Q86YT5; P11912: CD79A; NbExp=3; IntAct=EBI-12002412, EBI-7797864;
CC       Q86YT5; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12002412, EBI-3867333;
CC       Q86YT5; P48165: GJA8; NbExp=3; IntAct=EBI-12002412, EBI-17458373;
CC       Q86YT5; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-12002412, EBI-712073;
CC       Q86YT5; Q9BS75: KLHL20; NbExp=3; IntAct=EBI-12002412, EBI-10693436;
CC       Q86YT5; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-12002412, EBI-11749135;
CC       Q86YT5; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-12002412, EBI-10171774;
CC       Q86YT5; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-12002412, EBI-1052037;
CC       Q86YT5; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-12002412, EBI-10176379;
CC       Q86YT5; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-12002412, EBI-11953334;
CC       Q86YT5; Q9BYR7: KRTAP3-2; NbExp=3; IntAct=EBI-12002412, EBI-751260;
CC       Q86YT5; Q701N4: KRTAP5-2; NbExp=3; IntAct=EBI-12002412, EBI-11958178;
CC       Q86YT5; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-12002412, EBI-3958099;
CC       Q86YT5; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-12002412, EBI-1044640;
CC       Q86YT5; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-12002412, EBI-1043191;
CC       Q86YT5; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-12002412, EBI-11958364;
CC       Q86YT5; Q99750: MDFI; NbExp=3; IntAct=EBI-12002412, EBI-724076;
CC       Q86YT5-1; Q86YT5-1: SLC13A5; NbExp=2; IntAct=EBI-26979686, EBI-26979686;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26384929,
CC       ECO:0000269|PubMed:30054523}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=Q86YT5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q86YT5-2; Sequence=VSP_043098;
CC       Name=3;
CC         IsoId=Q86YT5-3; Sequence=VSP_054910;
CC       Name=4;
CC         IsoId=Q86YT5-4; Sequence=VSP_055652;
CC   -!- TISSUE SPECIFICITY: Expressed most predominantly in the liver, with
CC       moderate expression detectable in the brain and testis.
CC       {ECO:0000269|PubMed:12445824}.
CC   -!- DISEASE: Developmental and epileptic encephalopathy 25, with
CC       amelogenesis imperfecta (DEE25) [MIM:615905]: An autosomal recessive
CC       disease characterized by subclinical seizures appearing in the first
CC       days of life, evolving to severe epileptic disease. Affected
CC       individuals have profound or severe delayed development with lack of
CC       speech, and most patients do not acquire the ability to sit. Additional
CC       variable features include axial hypotonia, peripheral hypertonia, and
CC       abnormal involuntary movements such as dystonia and choreoathetosis.
CC       Dental abnormalities, including delayed eruption, hypodontia, tooth
CC       hypoplasia, yellow discoloration, thin enamel, and enamel chipping are
CC       observed in most patients. {ECO:0000269|PubMed:24995870,
CC       ECO:0000269|PubMed:26384929, ECO:0000269|PubMed:30054523}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the SLC13A/DASS transporter (TC 2.A.47) family.
CC       NADC subfamily. {ECO:0000305}.
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DR   EMBL; AY151833; AAN86530.1; -; mRNA.
DR   EMBL; AK172785; BAD18766.1; -; mRNA.
DR   EMBL; AK127797; BAG54572.1; -; mRNA.
DR   EMBL; AK297612; BAH12628.1; -; mRNA.
DR   EMBL; AC004706; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471108; EAW90292.1; -; Genomic_DNA.
DR   EMBL; BC104795; AAI04796.1; -; mRNA.
DR   EMBL; BC112151; AAI12152.1; -; mRNA.
DR   EMBL; BC143689; AAI43690.1; -; mRNA.
DR   CCDS; CCDS11079.1; -. [Q86YT5-1]
DR   CCDS; CCDS45593.1; -. [Q86YT5-2]
DR   CCDS; CCDS67136.1; -. [Q86YT5-4]
DR   CCDS; CCDS67137.1; -. [Q86YT5-3]
DR   RefSeq; NP_001137310.1; NM_001143838.2. [Q86YT5-2]
DR   RefSeq; NP_001271438.1; NM_001284509.1. [Q86YT5-3]
DR   RefSeq; NP_001271439.1; NM_001284510.1. [Q86YT5-4]
DR   RefSeq; NP_808218.1; NM_177550.4. [Q86YT5-1]
DR   PDB; 7JSJ; EM; 3.12 A; A/B=1-568.
DR   PDB; 7JSK; EM; 3.04 A; A/B=1-568.
DR   PDBsum; 7JSJ; -.
DR   PDBsum; 7JSK; -.
DR   AlphaFoldDB; Q86YT5; -.
DR   EMDB; EMD-22456; -.
DR   EMDB; EMD-22457; -.
DR   SMR; Q86YT5; -.
DR   BioGRID; 129763; 22.
DR   IntAct; Q86YT5; 19.
DR   STRING; 9606.ENSP00000406220; -.
DR   BindingDB; Q86YT5; -.
DR   ChEMBL; CHEMBL3769293; -.
DR   DrugBank; DB09154; Sodium citrate.
DR   GuidetoPHARMACOLOGY; 981; -.
DR   TCDB; 2.A.47.1.9; the divalent anion:na(+) symporter (dass) family.
DR   GlyCosmos; Q86YT5; 1 site, No reported glycans.
DR   GlyGen; Q86YT5; 1 site.
DR   iPTMnet; Q86YT5; -.
DR   PhosphoSitePlus; Q86YT5; -.
DR   BioMuta; SLC13A5; -.
DR   DMDM; 74714197; -.
DR   MassIVE; Q86YT5; -.
DR   MaxQB; Q86YT5; -.
DR   PaxDb; 9606-ENSP00000406220; -.
DR   PeptideAtlas; Q86YT5; -.
DR   ProteomicsDB; 29975; -.
DR   ProteomicsDB; 70466; -. [Q86YT5-1]
DR   ProteomicsDB; 70467; -. [Q86YT5-2]
DR   Antibodypedia; 23824; 137 antibodies from 23 providers.
DR   DNASU; 284111; -.
DR   Ensembl; ENST00000293800.10; ENSP00000293800.6; ENSG00000141485.17. [Q86YT5-3]
DR   Ensembl; ENST00000381074.8; ENSP00000370464.4; ENSG00000141485.17. [Q86YT5-4]
DR   Ensembl; ENST00000433363.7; ENSP00000406220.2; ENSG00000141485.17. [Q86YT5-1]
DR   Ensembl; ENST00000573648.5; ENSP00000459372.1; ENSG00000141485.17. [Q86YT5-2]
DR   GeneID; 284111; -.
DR   KEGG; hsa:284111; -.
DR   MANE-Select; ENST00000433363.7; ENSP00000406220.2; NM_177550.5; NP_808218.1.
DR   UCSC; uc002gdj.5; human. [Q86YT5-1]
DR   AGR; HGNC:23089; -.
DR   CTD; 284111; -.
DR   DisGeNET; 284111; -.
DR   GeneCards; SLC13A5; -.
DR   HGNC; HGNC:23089; SLC13A5.
DR   HPA; ENSG00000141485; Tissue enriched (liver).
DR   MalaCards; SLC13A5; -.
DR   MIM; 608305; gene.
DR   MIM; 615905; phenotype.
DR   neXtProt; NX_Q86YT5; -.
DR   OpenTargets; ENSG00000141485; -.
DR   Orphanet; 1946; Amelocerebrohypohidrotic syndrome.
DR   Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR   PharmGKB; PA134950956; -.
DR   VEuPathDB; HostDB:ENSG00000141485; -.
DR   eggNOG; KOG1281; Eukaryota.
DR   GeneTree; ENSGT01030000234550; -.
DR   HOGENOM; CLU_005170_9_1_1; -.
DR   InParanoid; Q86YT5; -.
DR   OMA; IWWMTEA; -.
DR   OrthoDB; 1359392at2759; -.
DR   PhylomeDB; Q86YT5; -.
DR   TreeFam; TF312913; -.
DR   PathwayCommons; Q86YT5; -.
DR   Reactome; R-HSA-433137; Sodium-coupled sulphate, di- and tri-carboxylate transporters.
DR   SABIO-RK; Q86YT5; -.
DR   SignaLink; Q86YT5; -.
DR   BioGRID-ORCS; 284111; 12 hits in 1147 CRISPR screens.
DR   ChiTaRS; SLC13A5; human.
DR   GenomeRNAi; 284111; -.
DR   Pharos; Q86YT5; Tchem.
DR   PRO; PR:Q86YT5; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q86YT5; Protein.
DR   Bgee; ENSG00000141485; Expressed in right lobe of liver and 104 other cell types or tissues.
DR   ExpressionAtlas; Q86YT5; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0015137; F:citrate transmembrane transporter activity; IDA:ARUK-UCL.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0005343; F:organic acid:sodium symporter activity; IDA:UniProtKB.
DR   GO; GO:0017153; F:sodium:dicarboxylate symporter activity; IBA:GO_Central.
DR   GO; GO:0015141; F:succinate transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0015742; P:alpha-ketoglutarate transport; IDA:UniProtKB.
DR   GO; GO:0071285; P:cellular response to lithium ion; IDA:UniProtKB.
DR   GO; GO:0015746; P:citrate transport; IDA:UniProtKB.
DR   GO; GO:0015741; P:fumarate transport; IDA:UniProtKB.
DR   GO; GO:0015729; P:oxaloacetate transport; IDA:UniProtKB.
DR   GO; GO:0015744; P:succinate transport; IDA:UniProtKB.
DR   CDD; cd01115; SLC13_permease; 1.
DR   InterPro; IPR031312; Na/sul_symport_CS.
DR   InterPro; IPR001898; SLC13A/DASS.
DR   PANTHER; PTHR10283; SOLUTE CARRIER FAMILY 13 MEMBER; 1.
DR   PANTHER; PTHR10283:SF109; SOLUTE CARRIER FAMILY 13 MEMBER 5; 1.
DR   Pfam; PF00939; Na_sulph_symp; 1.
DR   PROSITE; PS01271; NA_SULFATE; 1.
DR   Genevisible; Q86YT5; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Amelogenesis imperfecta; Cell membrane;
KW   Disease variant; Epilepsy; Glycoprotein; Ion transport; Membrane;
KW   Reference proteome; Sodium; Sodium transport; Symport; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..568
FT                   /note="Na(+)/citrate cotransporter"
FT                   /id="PRO_0000260101"
FT   TRANSMEM        13..33
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        53..73
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        80..100
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        124..144
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        215..235
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        252..272
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        311..331
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        353..373
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        406..426
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        439..459
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        487..507
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        528..548
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        562
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   VAR_SEQ         35..77
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_055652"
FT   VAR_SEQ         124..140
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_054910"
FT   VAR_SEQ         479..524
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_043098"
FT   VARIANT         142
FT                   /note="T -> M (in DEE25; no loss of localization to plasma
FT                   membrane; loss of function in citrate transport;
FT                   dbSNP:rs761917087)"
FT                   /evidence="ECO:0000269|PubMed:26384929"
FT                   /id="VAR_078912"
FT   VARIANT         219
FT                   /note="G -> E (loss of localization to plasma membrane;
FT                   loss of function in citrate transport; dbSNP:rs150024888)"
FT                   /evidence="ECO:0000269|PubMed:30054523"
FT                   /id="VAR_084747"
FT   VARIANT         219
FT                   /note="G -> R (in DEE25; loss of function in citrate
FT                   transport; loss of localization to plasma membrane;
FT                   dbSNP:rs144332569)"
FT                   /evidence="ECO:0000269|PubMed:24995870,
FT                   ECO:0000269|PubMed:26384929, ECO:0000269|PubMed:30054523"
FT                   /id="VAR_078913"
FT   VARIANT         227
FT                   /note="T -> M (in DEE25; loss of function in citrate
FT                   transport; no effect on localization to plasma membrane;
FT                   dbSNP:rs587777577)"
FT                   /evidence="ECO:0000269|PubMed:24995870,
FT                   ECO:0000269|PubMed:26384929, ECO:0000269|PubMed:30054523"
FT                   /id="VAR_078914"
FT   VARIANT         243
FT                   /note="D -> N (no effect on localization to plasma
FT                   membrane; no effect on its function in citrate transport;
FT                   dbSNP:rs142262032)"
FT                   /evidence="ECO:0000269|PubMed:30054523"
FT                   /id="VAR_084748"
FT   VARIANT         341..568
FT                   /note="Missing (in DEE25; loss of localization to plasma
FT                   membrane; loss of function in citrate transport)"
FT                   /evidence="ECO:0000269|PubMed:26384929"
FT                   /id="VAR_078915"
FT   VARIANT         420
FT                   /note="L -> P (loss of localization to plasma membrane;
FT                   loss of function in citrate transport; dbSNP:rs150738356)"
FT                   /evidence="ECO:0000269|PubMed:30054523"
FT                   /id="VAR_084749"
FT   VARIANT         427
FT                   /note="S -> L (in DEE25; loss of localization to plasma
FT                   membrane; loss of function in citrate transport;
FT                   dbSNP:rs548065551)"
FT                   /evidence="ECO:0000269|PubMed:26384929"
FT                   /id="VAR_078916"
FT   VARIANT         485
FT                   /note="L -> R (no effect on localization to plasma
FT                   membrane; reduced function in citrate transport; increased
FT                   Km and Vmax values compared with that of wild type with
FT                   citrate as substrate; dbSNP:rs148049520)"
FT                   /evidence="ECO:0000269|PubMed:30054523"
FT                   /id="VAR_084750"
FT   VARIANT         488
FT                   /note="L -> P (in DEE25; loss of function in citrate
FT                   transport; loss of localization to plasma membrane;
FT                   dbSNP:rs587777578)"
FT                   /evidence="ECO:0000269|PubMed:24995870,
FT                   ECO:0000269|PubMed:30054523"
FT                   /id="VAR_078917"
FT   VARIANT         524
FT                   /note="D -> H (in DEE25; loss of function in citrate
FT                   transport; no effect on localization to plasma membrane;
FT                   dbSNP:rs863225448)"
FT                   /evidence="ECO:0000269|PubMed:26384929"
FT                   /id="VAR_078918"
FT   MUTAGEN         409
FT                   /note="G->Q: No effect on its function in citrate
FT                   transport."
FT                   /evidence="ECO:0000269|PubMed:33597751"
FT   MUTAGEN         410
FT                   /note="I->A,F: Significant loss of function in citrate
FT                   transport."
FT                   /evidence="ECO:0000269|PubMed:33597751"
FT   MUTAGEN         410
FT                   /note="I->V: No effect on its function in citrate
FT                   transport."
FT                   /evidence="ECO:0000269|PubMed:33597751"
FT   CONFLICT        269
FT                   /note="W -> R (in Ref. 2; BAD18766)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        330
FT                   /note="W -> R (in Ref. 2; BAH12628)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        376
FT                   /note="K -> R (in Ref. 2; BAD18766)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        475
FT                   /note="I -> V (in Ref. 2; BAH12628)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        548
FT                   /note="G -> E (in Ref. 2; BAH12628)"
FT                   /evidence="ECO:0000305"
FT   HELIX           16..19
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           20..23
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           25..28
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           34..50
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           56..59
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           62..66
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   TURN            67..71
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           75..79
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           80..82
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           85..102
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           106..117
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           121..136
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           142..157
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           202..219
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           220..222
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   STRAND          223..227
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           228..240
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   STRAND          246..248
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           250..275
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           293..296
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           299..309
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           314..332
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           356..366
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   TURN            367..369
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           399..404
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           408..427
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           429..436
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           439..442
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           445..459
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   TURN            460..462
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           465..482
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           488..498
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           505..507
FT                   /evidence="ECO:0007829|PDB:7JSJ"
FT   HELIX           509..515
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           522..546
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   HELIX           548..552
FT                   /evidence="ECO:0007829|PDB:7JSK"
FT   TURN            553..555
FT                   /evidence="ECO:0007829|PDB:7JSK"
SQ   SEQUENCE   568 AA;  63062 MW;  B8995E56618DECCB CRC64;
     MASALSYVSK FKSFVILFVT PLLLLPLVIL MPAKFVRCAY VIILMAIYWC TEVIPLAVTS
     LMPVLLFPLF QILDSRQVCV QYMKDTNMLF LGGLIVAVAV ERWNLHKRIA LRTLLWVGAK
     PARLMLGFMG VTALLSMWIS NTATTAMMVP IVEAILQQME ATSAATEAGL ELVDKGKAKE
     LPGSQVIFEG PTLGQQEDQE RKRLCKAMTL CICYAASIGG TATLTGTGPN VVLLGQMNEL
     FPDSKDLVNF ASWFAFAFPN MLVMLLFAWL WLQFVYMRFN FKKSWGCGLE SKKNEKAALK
     VLQEEYRKLG PLSFAEINVL ICFFLLVILW FSRDPGFMPG WLTVAWVEGE TKYVSDATVA
     IFVATLLFIV PSQKPKFNFR SQTEEERKTP FYPPPLLDWK VTQEKVPWGI VLLLGGGFAL
     AKGSEASGLS VWMGKQMEPL HAVPPAAITL ILSLLVAVFT ECTSNVATTT LFLPIFASMS
     RSIGLNPLYI MLPCTLSASF AFMLPVATPP NAIVFTYGHL KVADMVKTGV IMNIIGVFCV
     FLAVNTWGRA IFDLDHFPDW ANVTHIET
//