SC5AC_MOUSE
ID SC5AC_MOUSE Reviewed; 619 AA.
AC Q49B93; Q0D2G1; Q6A4K8;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Sodium-coupled monocarboxylate transporter 2;
DE AltName: Full=Electroneutral sodium monocarboxylate cotransporter;
DE AltName: Full=Low-affinity sodium-lactate cotransporter;
DE AltName: Full=Solute carrier family 5 member 12;
GN Name=Slc5a12; Synonyms=Smct2;
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] (ISOFORM 1), FUNCTION, STOICHIOMETRY, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16104846; DOI=10.1042/bj20050927;
RA Srinivas S.R., Gopal E., Zhuang L., Itagaki S., Martin P.M., Fei Y.-J.,
RA Ganapathy V., Prasad P.D.;
RT "Cloning and functional identification of slc5a12 as a sodium-coupled low-
RT affinity transporter for monocarboxylates (SMCT2).";
RL Biochem. J. 392:655-664(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J;
RA Mount D.B.;
RT "Sequence of a novel sodium solute cotransporter similar to the Na-iodide
RT transporter.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Kidney;
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-619 (ISOFORM 1).
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, SUBCELLULAR LOCATION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=16873376; DOI=10.1074/jbc.c600189200;
RA Thangaraju M., Ananth S., Martin P.M., Roon P., Smith S.B., Sterneck E.,
RA Prasad P.D., Ganapathy V.;
RT "c/ebpdelta null mouse as a model for the double knock-out of slc5a8 and
RT slc5a12 in kidney.";
RL J. Biol. Chem. 281:26769-26773(2006).
RN [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17692818; DOI=10.1016/j.bbamem.2007.06.031;
RA Gopal E., Umapathy N.S., Martin P.M., Ananth S., Gnana-Prakasam J.P.,
RA Becker H., Wagner C.A., Ganapathy V., Prasad P.D.;
RT "Cloning and functional characterization of human SMCT2 (SLC5A12) and
RT expression pattern of the transporter in kidney.";
RL Biochim. Biophys. Acta 1768:2690-2697(2007).
RN [8]
RP POSSIBLE FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17591909; DOI=10.1167/iovs.06-0888;
RA Martin P.M., Dun Y., Mysona B., Ananth S., Roon P., Smith S.B.,
RA Ganapathy V.;
RT "Expression of the sodium-coupled monocarboxylate transporters SMCT1
RT (SLC5A8) and SMCT2 (SLC5A12) in retina.";
RL Invest. Ophthalmol. Vis. Sci. 48:3356-3363(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Acts as an electroneutral and low-affinity sodium (Na(+))-
CC dependent sodium-coupled solute transporter. Catalyzes the transport
CC across the plasma membrane of many monocarboxylates such as lactate,
CC pyruvate, nicotinate, propionate, butyrate and beta-D-hydroxybutyrate.
CC May be responsible for the first step of reabsorption of
CC monocarboxylates from the lumen of the proximal tubule of the kidney
CC and the small intestine. May play also a role in monocarboxylates
CC transport in the retina. Mediates electroneutral uptake of lactate,
CC with a stoichiometry of 2 Na(+) for each lactate.
CC {ECO:0000269|PubMed:16104846, ECO:0000269|PubMed:16873376}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:16873376, ECO:0000269|PubMed:17692818}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:16873376,
CC ECO:0000269|PubMed:17692818}. Note=Detected at the brush border
CC membrane of the kidney. Colocalizes with vimentin in Mueller cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q49B93-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q49B93-2; Sequence=VSP_033996;
CC -!- TISSUE SPECIFICITY: Expressed in the cortical region of the kidney
CC corresponding to the proximal tubule. Expressed in Mueller cells of the
CC inner retina (at protein level). Isoform 1 is expressed in the retina,
CC kidney, small intestine and skeletal muscle. Isoform 2 is not detected
CC in the kidney, small intestine and skeletal muscle. In the kidney,
CC expressed predominantly in tubular epithelial cells of the cortical
CC region and in the convoluted portions of the proximal tubule (pars
CC convoluta). In the small intestine, its expression is highest in the
CC proximal part and gradually decreased towards the distal end. Expressed
CC in the neural retina. Not detected in the caecum and colon.
CC {ECO:0000269|PubMed:16104846, ECO:0000269|PubMed:16873376,
CC ECO:0000269|PubMed:17591909, ECO:0000269|PubMed:17692818}.
CC -!- INDUCTION: Up-regulated by CEBPD. {ECO:0000269|PubMed:16873376}.
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000305}.
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DR EMBL; AY964639; AAY32930.1; -; mRNA.
DR EMBL; AF529222; AAQ09530.1; -; mRNA.
DR EMBL; AK144004; BAE25658.1; -; mRNA.
DR EMBL; AK165419; BAE38174.1; -; mRNA.
DR EMBL; AL732495; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX005257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC121791; AAI21792.1; -; mRNA.
DR CCDS; CCDS16512.1; -. [Q49B93-2]
DR CCDS; CCDS50656.1; -. [Q49B93-1]
DR RefSeq; NP_001003915.1; NM_001003915.2. [Q49B93-2]
DR RefSeq; NP_001171095.1; NM_001177624.1. [Q49B93-1]
DR AlphaFoldDB; Q49B93; -.
DR SMR; Q49B93; -.
DR STRING; 10090.ENSMUSP00000047340; -.
DR GlyGen; Q49B93; 2 sites.
DR iPTMnet; Q49B93; -.
DR PhosphoSitePlus; Q49B93; -.
DR jPOST; Q49B93; -.
DR MaxQB; Q49B93; -.
DR PaxDb; Q49B93; -.
DR PRIDE; Q49B93; -.
DR ProteomicsDB; 256607; -. [Q49B93-1]
DR ProteomicsDB; 256608; -. [Q49B93-2]
DR Antibodypedia; 48784; 22 antibodies from 15 providers.
DR DNASU; 241612; -.
DR Ensembl; ENSMUST00000045972; ENSMUSP00000047340; ENSMUSG00000041644. [Q49B93-2]
DR Ensembl; ENSMUST00000111026; ENSMUSP00000106655; ENSMUSG00000041644. [Q49B93-1]
DR GeneID; 241612; -.
DR KEGG; mmu:241612; -.
DR UCSC; uc008lmw.2; mouse. [Q49B93-2]
DR UCSC; uc008lmx.2; mouse. [Q49B93-1]
DR CTD; 159963; -.
DR MGI; MGI:2138890; Slc5a12.
DR VEuPathDB; HostDB:ENSMUSG00000041644; -.
DR eggNOG; KOG2349; Eukaryota.
DR GeneTree; ENSGT00940000159545; -.
DR HOGENOM; CLU_018808_11_1_1; -.
DR InParanoid; Q49B93; -.
DR OMA; GFFSHTM; -.
DR OrthoDB; 1180002at2759; -.
DR PhylomeDB; Q49B93; -.
DR TreeFam; TF316728; -.
DR Reactome; R-MMU-427601; Multifunctional anion exchangers.
DR BioGRID-ORCS; 241612; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Slc5a12; mouse.
DR PRO; PR:Q49B93; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q49B93; protein.
DR Bgee; ENSMUSG00000041644; Expressed in adult mammalian kidney and 27 other tissues.
DR ExpressionAtlas; Q49B93; baseline and differential.
DR Genevisible; Q49B93; MM.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0015129; F:lactate transmembrane transporter activity; IDA:CACAO.
DR GO; GO:0015293; F:symporter activity; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; IBA:GO_Central.
DR CDD; cd11520; SLC5sbd_SMCT2; 1.
DR Gene3D; 1.20.1730.10; -; 1.
DR InterPro; IPR038377; Na/Glc_symporter_sf.
DR InterPro; IPR001734; Na/solute_symporter.
DR InterPro; IPR042700; SMCT2_SLC5sbd.
DR Pfam; PF00474; SSF; 1.
DR TIGRFAMs; TIGR00813; sss; 1.
DR PROSITE; PS50283; NA_SOLUT_SYMP_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Ion transport; Membrane;
KW Reference proteome; Sodium; Sodium transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..619
FT /note="Sodium-coupled monocarboxylate transporter 2"
FT /id="PRO_0000337681"
FT TOPO_DOM 1..9
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..47
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 48..68
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 69..80
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..101
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 102..128
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 129..149
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 150..157
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..180
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..235
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 276..296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 297..321
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 322..342
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 343..385
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 386..406
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 407..411
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 412..432
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 433..437
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..458
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 459..504
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 505..525
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 526..619
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 219
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 409..436
FT /note="ALSIHGMCGGPMLGLFTLGLVFPFVNWK -> PGIVSQERAITGSFQRNLAS
FT VCYGVSIWKLIM (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_033996"
SQ SEQUENCE 619 AA; 67951 MW; B1C36211590A511A CRC64;
MRVKNFEAWD YVVFAGLFVI SSGIGVFFAI KERKKTTSRE FLVGGRQMSF GPVALSLTAS
FMSAVTVLGT PAEVYRFGAS FFLFLISYVF VVFFTSELFL PVFYRSGITS TYEYLQLRFN
KPVRYAATII YIVQTILYTG VVVYAPALAL NQVTGFNLWA SVFATGIVCT FYCSLGGLKA
VVWTDAFQMV VMIVGFLTVL IQGSNHVGGF NNVLEKAGNG SRLHIVDFDV DPLRRHTFWT
ITIGGTFTWL GVYGVNQSTI QRCISCKTEK HAKLALYFNL LGLWIIVACA VFSGLIMYSH
FKDCDPWTSG VISAPDQLMP YFVMEIFATM PGLPGLFVAC AFSGTLSTVA ASINALATVT
FEDFVKSCFP HLSDKLSTWI SKGLCILFGI MCTSMAVVAS LMGSVVQAAL SIHGMCGGPM
LGLFTLGLVF PFVNWKGALG GLLTGITLSF WVAIGSFIYP APESKTLPLP LSTEHCVELN
ITTTVAPQIS SRPVLADTWY SLSYLYFSAV GCLGCIAAGI IISFLTGKQR GKDIDPLLIR
PVCNLFCFWS KKYKTLCWCG VQHDRETEQD YLDSGSAWKQ GVESGLQNGL KQDTLAQIPG
YNPKEKSYSN SVPEKTTYF
