S13A5_HUMAN
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 03-AUG-2022, entry version 142.
DE RecName: Full=Solute carrier family 13 member 5;
DE AltName: Full=Na(+)/citrate cotransporter;
DE Short=NaCT;
DE AltName: Full=Sodium-coupled citrate transporter;
DE AltName: Full=Sodium-dependent citrate transporter;
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 TRANSPORTER 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 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 [7]
RP FUNCTION, AND TRANSPORTER 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 [8]
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 [9]
RP INVOLVEMENT IN DEE25, FUNCTION, TRANSPORTER 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 [10]
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, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND
RP BIOPHYSICOCHEMICAL 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 [11]
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
CC citrate entry into cells (PubMed:12445824, PubMed:26324167,
CC PubMed:26384929, PubMed:30054523, PubMed:33597751). Transports citrate
CC in a Na(+)-dependent manner, transport process is electrogenic and
CC recognizes the trivalent form of citrate rather than the divalent form
CC (PubMed:12445824, PubMed:26324167, PubMed:26384929, PubMed:30054523,
CC PubMed:33597751). Although citrate is its main substrate, other
CC intermediates of the citric acid cycle, such as succinate, fumarate,
CC malate, oxaloacetate and alpha-ketoglutarate can serve as substrates
CC but with a much lower affinity compared to citrate (PubMed:26324167).
CC Shows a substrate sensitivity in the order of citrate > malate ~ alpha-
CC ketoglutarate > succinate ~ fumarate > oxaloacetate ~ isocitrate
CC (PubMed:26324167). Shows substantial citrate transporter activity when
CC sodium ions are replaced by either potassium or choline ions
CC (PubMed:26324167). Transport activity is potentiated by lithium ions in
CC the presence of low concentrations of citrate but is inhibited by
CC lithium ions in the presence of high concentrations of citrate
CC (PubMed:26324167). Involved in the regulation of citrate levels in the
CC brain (By similarity). {ECO:0000250|UniProtKB:Q67BT3,
CC ECO:0000269|PubMed:12445824, 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:26324167,
CC ECO:0000269|PubMed:26384929, ECO:0000269|PubMed:30054523,
CC ECO:0000269|PubMed:33597751};
CC -!- ACTIVITY REGULATION: Inhibited by (R)-2-(4-(tert-butyl)phenethyl)-2-
CC hydroxysuccinic acid (also known as PF-06649298).
CC {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 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 GlyGen; Q86YT5; 1 site.
DR iPTMnet; Q86YT5; -.
DR PhosphoSitePlus; Q86YT5; -.
DR BioMuta; SLC13A5; -.
DR DMDM; 74714197; -.
DR MassIVE; Q86YT5; -.
DR MaxQB; Q86YT5; -.
DR PaxDb; Q86YT5; -.
DR PeptideAtlas; Q86YT5; -.
DR PRIDE; Q86YT5; -.
DR ProteomicsDB; 29975; -.
DR ProteomicsDB; 70466; -. [Q86YT5-1]
DR ProteomicsDB; 70467; -. [Q86YT5-2]
DR Antibodypedia; 23824; 122 antibodies from 22 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 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 Orphanet; 3006; Pyridoxine-dependent epilepsy.
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; LHGMNTY; -.
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; 11 hits in 1069 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 103 other tissues.
DR ExpressionAtlas; Q86YT5; baseline and differential.
DR Genevisible; Q86YT5; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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:0098656; P:anion transmembrane transport; IBA:GO_Central.
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 InterPro; IPR031312; Na/sul_symport_CS.
DR InterPro; IPR001898; SLC13A/DASS.
DR Pfam; PF00939; Na_sulph_symp; 1.
DR PROSITE; PS01271; NA_SULFATE; 1.
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="Solute carrier family 13 member 5"
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
