Sodium/bile acid cotransporter

Sodium/bile acid cotransporter also known as the Na⁺-taurocholate cotransporting polypeptide (NTCP) or liver bile acid transporter (LBAT) is a protein that in humans is encoded by the SLC10A1 (solute carrier family 10 member 1) gene.^[5][6]

SLC10A1
Identifiers
Aliases	SLC10A1, NTCP, solute carrier family 10 member 1, FHCA2
External IDs	OMIM: 182396; MGI: 97379; HomoloGene: 31126; GeneCards: SLC10A1; OMA:SLC10A1 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q24.1 Start 69,775,416 bp[1] End 69,797,241 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12 D1|12 37.21 cM Start 80,999,957 bp[2] End 81,015,479 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver testicle sural nerve Achilles tendon granulocyte internal globus pallidus gallbladder muscle of thigh kidney blood Top expressed in left lobe of liver gallbladder sexually immature organism embryo granulocyte zygote blastocyst morula morula thoracic diaphragm More reference expression data BioGPS More reference expression data
Gene ontology Molecular function bile acid transmembrane transporter activity symporter activity virus receptor activity bile acid:sodium symporter activity Cellular component integral component of membrane plasma membrane basolateral plasma membrane integral component of plasma membrane membrane Biological process sodium ion transport viral entry into host cell viral process ion transport transmembrane transport bile acid and bile salt transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6554 20493 Ensembl ENSG00000100652 ENSMUSG00000021135 UniProt Q14973 O08705 RefSeq (mRNA) NM_003049 NM_001177561 NM_011387 NM_001361972 RefSeq (protein) NP_003040 NP_001171032 NP_035517 NP_001348901 Location (UCSC) Chr 14: 69.78 – 69.8 Mb Chr 12: 81 – 81.02 Mb PubMed search [3] [4]
Wikidata
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Structure

Sodium/bile acid cotransporters are integral membrane glycoproteins. Human NTCP contains 349 amino acids and has a mass of 56 kDa.^[7]

Function

Bile acid:sodium symporters participate in the enterohepatic circulation of bile acids. Two homologous transporters are involved in the reabsorption of bile acids. One of these absorbs bile acids from the intestinal lumen, the bile duct, and the kidney with an apical localization (ileal sodium/bile acid cotransporter). The other is this protein and is expressed in the basolateral membranes of hepatocytes (NTCP).^[7]

As a cotransporter, NTCP binds two sodium ions and one (conjugated) bile salt molecule, thereby providing a hepatic influx of bile salts. Other transported molecules include steroid hormones, thyroid hormones and various xenobiotics:^[7]

Hepatitis virus entry

NTCP is a cell surface receptor necessary for the entry of hepatitis B and hepatitis D virus.^[8] This entry mechanism is inhibited by myrcludex B,^[9] cyclosporin A, progesterone, propranolol, bosentan, ezetimibe, bexarotene^[10] as well as NTCP substrates like taurocholate, tauroursodeoxycholate and bromosulfophthalein.^[7]

SLC10A1-deficiency

Individuals that lack functional NTCP have been identified.^[11] These individuals display highly elevated bile salt levels in plasma, but without a clear phenotype. In areas of the world with a high prevalence of HBV, there are multiple individuals who carry the NTCP p.S267F polymorphism on both alleles; this makes NTCP inactive as a bile acid transporter, but provides protection against HBV infection.^[12]

NTCP-deficient mice have also been created. These mice have reduced hepatic bile salt uptake but plasma bile salt levels are less clearly elevated, as the rodent-specific OATP1a/1b transporters provide can partially replace the function of NTCP.^[13] Nevertheless, this NTCP-knockout animal model pointed to possible additional (non-HBV) aspects of NTCP-deficiency. NTCP-deficient mice are partially protected against the problems associated with a high-calorie diet, including excessive weight gain^[14] and to liver damage in cholestasis.^[15] These effects of NTCP deficiency have not yet been replicated in humans.

See also

• Solute carrier family