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2.A.21.5.3
Na+-dependent short chain fatty acid transporter SLC5A8 (tumor suppressor gene product, down-regulated in colon cancer) (substrates: lactate, pyruvate, acetate, propionate, butyrate (Km ≈1 mM)) [propionate:Na+ = 1:3] (Miyauchi et al., 2004). Pyroglutamate (5-oxoproline) is also transported in a Na+- coupled mechanism (Miyauchi et al., 2010). SMCT1 and SMCT2 may transport monocarboxylate drugs (e.g. nicotinate and its derivatives) across the intestinal brush boarder membrane (Gopal et al., 2007; Frank et al. 2008). Wilson et al., 2009 have proposed mechanistic details. SMCT1 can transport urate in a testosterone regulated process (Hosoyamada et al., 2010).  It's phsiological functions have been reviewed (Halestrap 2013). Transports anti-tumor agents, 3-bromopyruvate anddichloroacetate (Su et al. 2016).

Accession Number:Q8N695
Protein Name:Sodium-coupled monocarboxylate transporter 1
Length:610
Molecular Weight:66578.00
Species: [9606]
Number of TMSs:13
Location1 / Topology2 / Orientation3: Apical cell membrane1 / Multi-pass membrane protein2
Substrate Na+, Lactate, pyruvate, Acetate, Propionate, Butyrate

Cross database links:

Genevestigator: Q8N695 Q8N695
eggNOG: prNOG17651 COG0591
HEGENOM: HBG446891 HOG000261662
RefSeq: NP_666018.3   
Entrez Gene ID: 160728   
Pfam: PF00474   
OMIM: 608044  gene
KEGG: hsa:160728    hsa:160728   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0016021 C:integral to membrane
GO:0022803 F:passive transmembrane transporter activity
GO:0015293 F:symporter activity
GO:0006915 P:apoptosis
GO:0006814 P:sodium ion transport
GO:0055085 P:transmembrane transport
GO:0005886 C:plasma membrane
GO:0006915 P:apoptotic process
GO:0006811 P:ion transport

References (28)

[1] “Identification and characterization of a putative human iodide transporter located at the apical membrane of thyrocytes.”  Rodriguez A.-M.et.al.   12107270
[2] “SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers.”  Li H.et.al.   12829793
[3] “Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids.”  Miyauchi S.et.al.   14966140
[4] “The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter.”  Coady M.J.et.al.   15090606
[5] “The finished DNA sequence of human chromosome 12.”  Scherer S.E.et.al.   16541075
[6] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[7] “Expression of the apical iodide transporter in human thyroid tissues: a comparison study with other iodide transporters.”  Lacroix L.et.al.   15001644
[8] “Aberrant methylation and histone deacetylation associated with silencing of SLC5A8 in gastric cancer.”  Ueno M.et.al.   15361710
[9] “Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8.”  Hong C.et.al.   15867356
[10] “SLC5A8 triggers tumor cell apoptosis through pyruvate-dependent inhibition of histone deacetylases.”  Thangaraju M.et.al.   17178845
[11] “Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain.”  Martin P.M.et.al.   16805814
[12] “Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8).”  Itagaki S.et.al.   16729224
[13] “Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by promoter hypermethylation in prostate tumor.”  Park J.Y.et.al.   18037591
[14] “Transport of nicotinate and structurally related compounds by human SMCT1 (SLC5A8) and its relevance to drug transport in the mammalian intestinal tract.”  Gopal E.et.al.   17245649
[15] “Identification and characterization of a putative human iodide transporter located at the apical membrane of thyrocytes.”  Rodriguez A.-M.et.al.   12107270
[16] “SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers.”  Li H.et.al.   12829793
[17] “Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids.”  Miyauchi S.et.al.   14966140
[18] “The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter.”  Coady M.J.et.al.   15090606
[19] “The finished DNA sequence of human chromosome 12.”  Scherer S.E.et.al.   16541075
[20] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[21] “Expression of the apical iodide transporter in human thyroid tissues: a comparison study with other iodide transporters.”  Lacroix L.et.al.   15001644
[22] “Aberrant methylation and histone deacetylation associated with silencing of SLC5A8 in gastric cancer.”  Ueno M.et.al.   15361710
[23] “Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8.”  Hong C.et.al.   15867356
[24] “SLC5A8 triggers tumor cell apoptosis through pyruvate-dependent inhibition of histone deacetylases.”  Thangaraju M.et.al.   17178845
[25] “Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain.”  Martin P.M.et.al.   16805814
[26] “Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8).”  Itagaki S.et.al.   16729224
[27] “Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by promoter hypermethylation in prostate tumor.”  Park J.Y.et.al.   18037591
[28] “Transport of nicotinate and structurally related compounds by human SMCT1 (SLC5A8) and its relevance to drug transport in the mammalian intestinal tract.”  Gopal E.et.al.   17245649

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FASTA formatted sequence
1:	MDTPRGIGTF VVWDYVVFAG MLVISAAIGI YYAFAGGGQQ TSKDFLMGGR RMTAVPVALS 
61:	LTASFMSAVT VLGTPSEVYR FGAIFSIFAF TYFFVVVISA EVFLPVFYKL GITSTYEYLE 
121:	LRFNKCVRLC GTVLFIVQTI LYTGIVIYAP ALALNQVTGF DLWGAVVATG VVCTFYCTLG 
181:	GLKAVIWTDV FQVGIMVAGF ASVIIQAVVM QGGISTILND AYDGGRLNFW NFNPNPLQRH 
241:	TFWTIIIGGT FTWTSIYGVN QSQVQRYISC KSRFQAKLSL YINLVGLWAI LTCSVFCGLA 
301:	LYSRYHDCDP WTAKKVSAPD QLMPYLVLDI LQDYPGLPGL FVACAYSGTL STVSSSINAL 
361:	AAVTVEDLIK PYFRSLSERS LSWISQGMSV VYGALCIGMA ALASLMGALL QAALSVFGMV 
421:	GGPLMGLFAL GILVPFANSI GALVGLMAGF AISLWVGIGA QIYPPLPERT LPLHLDIQGC 
481:	NSTYNETNLM TTTEMPFTTS VFQIYNVQRT PLMDNWYSLS YLYFSTVGTL VTLLVGILVS 
541:	LSTGGRKQNL DPRYILTKED FLSNFDIFKK KKHVLSYKSH PVEDGGTDNP AFNHIELNSD 
601:	QSGKSNGTRL