SC5AC_HUMAN
ID SC5AC_HUMAN Reviewed; 618 AA.
AC Q1EHB4; Q86UC7;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 2.
DT 03-AUG-2022, entry version 125.
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 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, INHIBITION, SUBCELLULAR
RP 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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Mount D.B.;
RT "Sequence of a novel human sodium-solute cotransporter similar to the
RT sodium-iodide transporter.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
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).
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 (By similarity). Mediates electroneutral uptake
CC of lactate, with a stoichiometry of 2 Na(+) for each lactate (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:17692818}.
CC -!- ACTIVITY REGULATION: Cotransport of monocarboxylates and nicotinate
CC strongly inhibited by ibuprofen, fenoprofen and ketoprofen.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:17692818}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:17692818}. Note=Detected at the brush border
CC membrane of the kidney. Colocalizes with viementin in Mueller cells (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q1EHB4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q1EHB4-2; Sequence=VSP_033994, VSP_033995;
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000305}.
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DR EMBL; AY299482; AAQ73572.1; -; mRNA.
DR EMBL; AC083755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC049207; AAH49207.1; -; mRNA.
DR CCDS; CCDS7860.2; -. [Q1EHB4-1]
DR RefSeq; NP_848593.2; NM_178498.3. [Q1EHB4-1]
DR AlphaFoldDB; Q1EHB4; -.
DR SMR; Q1EHB4; -.
DR BioGRID; 127745; 4.
DR IntAct; Q1EHB4; 2.
DR MINT; Q1EHB4; -.
DR STRING; 9606.ENSP00000379326; -.
DR TCDB; 2.A.21.5.6; the solute:sodium symporter (sss) family.
DR GlyGen; Q1EHB4; 1 site.
DR iPTMnet; Q1EHB4; -.
DR PhosphoSitePlus; Q1EHB4; -.
DR BioMuta; SLC5A12; -.
DR DMDM; 189046187; -.
DR jPOST; Q1EHB4; -.
DR MassIVE; Q1EHB4; -.
DR PaxDb; Q1EHB4; -.
DR PeptideAtlas; Q1EHB4; -.
DR PRIDE; Q1EHB4; -.
DR ProteomicsDB; 61209; -. [Q1EHB4-1]
DR ProteomicsDB; 61210; -. [Q1EHB4-2]
DR Antibodypedia; 48784; 22 antibodies from 15 providers.
DR DNASU; 159963; -.
DR Ensembl; ENST00000280467.10; ENSP00000280467.6; ENSG00000148942.15. [Q1EHB4-2]
DR Ensembl; ENST00000396005.8; ENSP00000379326.3; ENSG00000148942.15. [Q1EHB4-1]
DR GeneID; 159963; -.
DR KEGG; hsa:159963; -.
DR MANE-Select; ENST00000396005.8; ENSP00000379326.3; NM_178498.4; NP_848593.2.
DR UCSC; uc001mra.3; human. [Q1EHB4-1]
DR CTD; 159963; -.
DR DisGeNET; 159963; -.
DR GeneCards; SLC5A12; -.
DR HGNC; HGNC:28750; SLC5A12.
DR HPA; ENSG00000148942; Tissue enhanced (epididymis, intestine, kidney).
DR MIM; 612455; gene.
DR neXtProt; NX_Q1EHB4; -.
DR OpenTargets; ENSG00000148942; -.
DR PharmGKB; PA134873929; -.
DR VEuPathDB; HostDB:ENSG00000148942; -.
DR eggNOG; KOG2349; Eukaryota.
DR GeneTree; ENSGT00940000159545; -.
DR HOGENOM; CLU_018808_11_1_1; -.
DR InParanoid; Q1EHB4; -.
DR OMA; GFFSHTM; -.
DR OrthoDB; 1180002at2759; -.
DR PhylomeDB; Q1EHB4; -.
DR TreeFam; TF316728; -.
DR PathwayCommons; Q1EHB4; -.
DR Reactome; R-HSA-427601; Multifunctional anion exchangers.
DR SignaLink; Q1EHB4; -.
DR BioGRID-ORCS; 159963; 7 hits in 1063 CRISPR screens.
DR GenomeRNAi; 159963; -.
DR Pharos; Q1EHB4; Tdark.
DR PRO; PR:Q1EHB4; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q1EHB4; protein.
DR Bgee; ENSG00000148942; Expressed in adult mammalian kidney and 75 other tissues.
DR ExpressionAtlas; Q1EHB4; baseline and differential.
DR Genevisible; Q1EHB4; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0015129; F:lactate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005343; F:organic acid:sodium symporter activity; TAS:Reactome.
DR GO; GO:0015293; F:symporter activity; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
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 2: Evidence at transcript 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..618
FT /note="Sodium-coupled monocarboxylate transporter 2"
FT /id="PRO_0000337680"
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..82
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 83..103
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 104..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..618
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 386..396
FT /note="LLFGVMCTSMA -> RYSWWTFYSIS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033994"
FT VAR_SEQ 397..618
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033995"
FT VARIANT 510
FT /note="V -> L (in dbSNP:rs12278761)"
FT /id="VAR_043703"
FT CONFLICT 285
FT /note="I -> V (in Ref. 2; AAQ73572)"
FT /evidence="ECO:0000305"
FT CONFLICT 396
FT /note="A -> S (in Ref. 2; AAQ73572)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 618 AA; 67647 MW; 01D5F954BD28EF6F CRC64;
MEVKNFAVWD YVVFAALFFI SSGIGVFFAI KERKKATSRE FLVGGRQMSF GPVGLSLTAS
FMSAVTVLGT PSEVYRFGAS FLVFFIAYLF VILLTSELFL PVFYRSGITS TYEYLQLRFN
KPVRYAATVI YIVQTILYTG VVVYAPALAL NQVTGFDLWG SVFATGIVCT FYCTLGGLKA
VVWTDAFQMV VMIVGFLTVL IQGSTHAGGF HNVLEQSTNG SRLHIFDFDV DPLRRHTFWT
ITVGGTFTWL GIYGVNQSTI QRCISCKTEK HAKLALYFNL LGLWIILVCA VFSGLIMYSH
FKDCDPWTSG IISAPDQLMP YFVMEIFATM PGLPGLFVAC AFSGTLSTVA SSINALATVT
FEDFVKSCFP HLSDKLSTWI SKGLCLLFGV MCTSMAVAAS VMGGVVQASL SIHGMCGGPM
LGLFSLGIVF PFVNWKGALG GLLTGITLSF WVAIGAFIYP APASKTWPLP LSTDQCIKSN
VTATGPPVLS SRPGIADTWY SISYLYYSAV GCLGCIVAGV IISLITGRQR GEDIQPLLIR
PVCNLFCFWS KKYKTLCWCG VQHDSGTEQE NLENGSARKQ GAESVLQNGL RRESLVHVPG
YDPKDKSYNN MAFETTHF
