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Na+-coupled monocarboxylate transporter 1 (electrogenic Na+ monocarboxylate cotransporter, Na+ iodide-related cotransporter, apical iodide transporter, solute carrier family 5 member 8, SLC5A8, AIT, SMCT, SMCT1)
Function:
- electrogenic Na+ & Cl- dependent Na+ coupled solute transporter
- transport of monocarboxylates
a) short-chain fatty acids L-lactate, D-lactate, pyruvate, acetate, propionate, valerate, butyrate
b) drugs nicotinate, benzoate, salicylate & 5-aminosalicylate
c) ketone bodies beta-D-hydroxybutyrate, acetoacetate & alpha-ketoisocaproate
- Na+:substrate stoichiometry of between 4:1 & 2:1
- catalyzes passive carrier mediated diffusion of iodide
- mediates iodide transport from the thyrocyte into the colloid lumen through the apical membrane
- may be responsible for the absorption of D- lactate & monocarboxylate drugs from the intestinal tract
- acts as a tumor suppressor, suppressing colony formation in colon cancer, prostate cancer & glioma cell lines
- may play a critical role in the entry of L-lactate & ketone bodies into neurons by a process driven by an electrochemical Na+ gradient & hence contribute to the maintenance of the energy status & function of neurons
Inhibition:
- increase of iodide influx inhibited by addition of perchlorate (NaClO4), a competitive inhibitor of iodide uptake catalyzed by Na+ iodide symporter
- cotransport of monocarboxylates & nicotinate strongly inhibited by probenecid, nonsteroid anti-inflammatory drugs (ibuprofen, fenoprofen, ketprofen, naproxen) (Na+-dependent) or by prolonged exposure to external concentrations of monocarboxylates
Kinetic parameters:
- KM=1442 uM for beta-D-hydroxybutyate
- KM=2327 uM for beta-L-hydroxybutyate
- KM=1088 uM for D-lactate
- KM=184 uM for L-lactate
- KM=387 uM for pyruvate
- KM=213 uM for acetoacetate
- KM=209 uM for alpha-ketoisocaproate
Structure:
- belongs to the Na+:solute symporter (SSF) (TC 2.A.21) family
Compartment:
- membrane
- expressed at the apical membrane of normal tall thyrocytes & of colonic epithelial cells
Expression:
- expressed in normal thyroid, localized at the apical pole of thyroid cells facing the colloid lumen
- expressed in normal colon
- present in normal kidney cortex, brain, prostate, gastric mucosa & breast tissue
- expression reactivated on treatment with a demethylating drug, 5-azacytidine
Pathology:
- down-regulated in some primary cancers due to aberrant methylation
- significantly down-regulated in primary gliomas, gastric cancer, prostate cancer & breast cancer
- expression profoundly decreased in thyroid carcinomas
- absent in colon aberrant crypt foci & colon cancers
General
glycoprotein
solute carrier family 5 (SLC5, SLC5A)
transmembrane 13 protein
Properties
SIZE: entity length = 610 aa
MW = 67 kD
COMPARTMENT: cellular membrane
MOTIF: exoplasmic domain {1-9}
transmembrane domain {10-30}
cytoplasmic loop {31-51}
transmembrane domain {52-72}
exoplasmic loop {73-83}
transmembrane domain {84-104}
cytoplasmic loop {105-132}
transmembrane domain {133-153}
exoplasmic loop {154-161}
transmembrane domain {162-182}
cytoplasmic loop {183-189}
transmembrane domain {190-210}
exoplasmic loop {211-239}
transmembrane domain {240-260}
cytoplasmic loop {261-279}
transmembrane domain {280-300}
exoplasmic loop {301-336}
transmembrane domain {337-359}
cytoplasmic loop {360-389}
transmembrane domain {390-410}
exoplasmic loop {411-415}
transmembrane domain {416-436}
cytoplasmic loop {437-439}
transmembrane domain {440-460}
exoplasmic loop {461-518}
MOTIF: N-glycosylation site {N485}
transmembrane domain {519-539}
cytoplasmic domain {540-610}
MOTIF: lysine-rich region {569-572}
MOTIF: lysine residue (SEVERAL)
Database Correlations
OMIM 608044
UniProt Q8N695
Pfam PF00474
References
UniProt :accession Q8N695