S13A5_MOUSE
ID S13A5_MOUSE Reviewed; 572 AA.
AC Q67BT3;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 129.
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 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]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Inoue K., Fei Y.-J., Zhuang L., Gopal E., Miyauchi S., Ganapathy V.;
RT "Functional features and genomic organization of mouse NaCT, a sodium-
RT coupled transporter for citric acid cycle intermediates.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
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 [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32682952; DOI=10.1016/j.nbd.2020.105018;
RA Henke C., Toellner K., van Dijk R.M., Miljanovic N., Cordes T., Twele F.,
RA Broeer S., Ziesak V., Rohde M., Hauck S.M., Vogel C., Welzel L.,
RA Schumann T., Willmes D.M., Kurzbach A., El-Agroudy N.N., Bornstein S.R.,
RA Schneider S.A., Jordan J., Potschka H., Metallo C.M., Koehling R.,
RA Birkenfeld A.L., Loescher W.;
RT "Disruption of the sodium-dependent citrate transporter SLC13A5 in mice
RT causes alterations in brain citrate levels and neuronal network
RT excitability in the hippocampus.";
RL Neurobiol. Dis. 143:105018-105018(2020).
CC -!- FUNCTION: High-affinity sodium/citrate cotransporter that mediates
CC citrate entry into cells (PubMed:26324167). Transports citrate in a
CC Na(+)-dependent manner, transport process is electrogenic and
CC recognizes the trivalent form of citrate rather than the divalent form
CC (PubMed:26324167). 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 > succinate ~
CC fumarate ~ oxaloacetate ~ malate > alpha-ketoglutarate ~ isocitrate
CC (PubMed:26324167). Citrate transporter activity is lost when sodium
CC 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 this potentiating
CC effect disappears in the presence of high concentrations of citrate
CC (PubMed:26324167). Involved in the regulation of citrate levels in the
CC brain (PubMed:32682952). {ECO:0000269|PubMed:26324167,
CC ECO:0000269|PubMed:32682952}.
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:26324167};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q86YT5}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q86YT5};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Mice show increased propensity for epileptic
CC seizures, proepileptogenic neuronal excitability changes in the
CC hippocampus, and significant citrate level alterations in the CSF and
CC brain tissue. {ECO:0000269|PubMed:32682952}.
CC -!- SIMILARITY: Belongs to the SLC13A/DASS transporter (TC 2.A.47) family.
CC NADC subfamily. {ECO:0000305}.
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DR EMBL; AY368893; AAR14317.1; -; mRNA.
DR EMBL; AK048662; BAE20664.1; -; mRNA.
DR EMBL; AL929071; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS24983.1; -.
DR RefSeq; NP_001004148.1; NM_001004148.4.
DR AlphaFoldDB; Q67BT3; -.
DR SMR; Q67BT3; -.
DR STRING; 10090.ENSMUSP00000021161; -.
DR BindingDB; Q67BT3; -.
DR ChEMBL; CHEMBL3769294; -.
DR GlyGen; Q67BT3; 2 sites.
DR iPTMnet; Q67BT3; -.
DR PhosphoSitePlus; Q67BT3; -.
DR PaxDb; Q67BT3; -.
DR PRIDE; Q67BT3; -.
DR ProteomicsDB; 255442; -.
DR Antibodypedia; 23824; 122 antibodies from 22 providers.
DR DNASU; 237831; -.
DR Ensembl; ENSMUST00000021161; ENSMUSP00000021161; ENSMUSG00000020805.
DR GeneID; 237831; -.
DR KEGG; mmu:237831; -.
DR UCSC; uc007jym.2; mouse.
DR CTD; 284111; -.
DR MGI; MGI:3037150; Slc13a5.
DR VEuPathDB; HostDB:ENSMUSG00000020805; -.
DR eggNOG; KOG1281; Eukaryota.
DR GeneTree; ENSGT01030000234550; -.
DR HOGENOM; CLU_005170_9_1_1; -.
DR InParanoid; Q67BT3; -.
DR OMA; LHGMNTY; -.
DR OrthoDB; 389981at2759; -.
DR PhylomeDB; Q67BT3; -.
DR TreeFam; TF312913; -.
DR Reactome; R-MMU-433137; Sodium-coupled sulphate, di- and tri-carboxylate transporters.
DR BioGRID-ORCS; 237831; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q67BT3; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q67BT3; protein.
DR Bgee; ENSMUSG00000020805; Expressed in vault of skull and 63 other tissues.
DR ExpressionAtlas; Q67BT3; baseline and differential.
DR Genevisible; Q67BT3; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0015137; F:citrate transmembrane transporter activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005343; F:organic acid:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0017153; F:sodium:dicarboxylate symporter activity; ISO:MGI.
DR GO; GO:0015141; F:succinate transmembrane transporter activity; IDA:MGI.
DR GO; GO:0015142; F:tricarboxylic acid transmembrane transporter activity; IDA:MGI.
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 GO; GO:0006842; P:tricarboxylic acid transport; IDA:MGI.
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 2: Evidence at transcript level;
KW Cell membrane; Glycoprotein; Ion transport; Membrane; Reference proteome;
KW Sodium; Sodium transport; Symport; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..572
FT /note="Solute carrier family 13 member 5"
FT /id="PRO_0000260102"
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 218..238
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..275
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 315..335
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 357..377
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 443..463
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 491..511
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 532..552
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 566
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 572 AA; 63823 MW; 329C8C48C6624739 CRC64;
MDSAKTCVTK FKSFAILLFT PILMLPLVIL IPDKFARCAY VIVIMAVYWC TDVIPVAVTS
LLPVLLFPLL KVLDSKQVCI QYMKDTNMLF LGSLIVAVAV ERWKLHKRVA LRMLLFVGTK
PSRLMLGFMF VTAFLSMWIS NTAATAMMIP IVEAMLQQMI AANTAVEASL GTLELLDKNK
TSELPGSQVV FEDPNVQEQE DEETKNMYKA MHLCVCYSAS IGGTATLTGT GPNVVLLGQM
QELFPDSKDV LNYASWFGFA FPNMVMMLVL AWLWLQCLYM RHNLKKTCIC CGEKKRDTEK
IAYKVLNEEY QKLGSLSYPE CNVLFCFTLL VILWFSRDPG FMPGWLSFAW VEGNTVHITD
ATVAIFVAIL LFIIPSQKPK FNFSSQTEEE RKTPFYPPAL LDWKVAQEKV PWDIVLLLGG
GFAMAKGCET SGLSKWMAAQ MEPLRLVKPA VITLILSCLV AMTTECTSNV ATTTLFLPIF
ASMARSIGIH PLYVMIPCTM SASLAFMLPV ATPPNAIVFA YGHLRVVDMM KTGLIMNFVG
ILSVFLSVNT WGRAMFNLDN FPDWANSTSV NT
