2.A.28.1.2
Liver/ileal bile acid:Na⁺ symporter, ASBT, ISBT or NTCP2 (SLC10A2) of 348 aas and 7 TMSs (Mareninova et al. 2005) (essential for liver or intestinal bile acid transport and homeostasis (Rao et al., 2008). This BART superfamily protein has been modeled in 3-dimensions using the 3-D structure of bacteriorhodopsin (a TOG superfamily member) (Zhang et al. 2004). TMS4 forms part of the substrate translocation pathway (Khantwal and Swaan, 2008); TMS7 plays a role in substrate binding and translocation (González et al., 2012); TMS1 contributes to substrate translocation and protein stability (da Silva et al., 2011), and TMS2 coordinates Na⁺ translocation (Sabit et al. 2013).  NTCP serves as the Hepatitis B Virus (HBV) receptor, and drugs developed to target NTCP induce autophagy and may provide therapy for HBV (Zhang et al. 2015). Decreased activity leads to luminal bile salt concentrations and either increased eletrolyte secretion or decreased reabsolption (van der Mark et al., 2014). Function and stability depend on N-glycosylation (Muthusamy et al. 2015).  Specific inhibitors are known (Slijepcevic and van de Graaf 2017). It has a 7 TMS topology (Banerjee and Swaan 2006). Chronic hepatitis B, C and D viruses (HBV, HCV and HDV) infect the liver and cause cancer. The three viruses are exclusively hepatotropic, and NTCP mediates the transport of bile acids and plays a key role in HBV HCV and HDV entry into hepatocytes. It modulates HCV infection by regulating innate antiviral immune responses in the liver (Eller et al. 2018). The S-acylation status of hASBT regulates its function, metabolic stability, membrane expression, and phosphorylation state (Ayewoh et al. 2020). The GXXXG/A motifs in TMS2 and TMS7 are important for proper folding and sorting of NTCP, and they indirectly affect glycosylation, homodimerization, and bile acid transport, as well as its HBV/HDV receptor function (Palatini et al. 2021). Structural plasticity is a feature of rheostat positions in the human Na⁺/taurocholate cotransporting polypeptide (NTCP) (Ruggiero et al. 2022). A monoclonal antibody against human NTCP blocks Hepatitis B virus infection (Takemori et al. 2022). NTCP interacts directly with the first 48 residues of the N-myristoylated N-terminal preS1 domain of the hepatitis viral large protein. 3-d structural analyses suggest that members of the SLC10 family share a common mechanism of bile acid transport, but the NTCP structure displays an additional pocket formed by residues that are known to interact with preS1 (Park et al. 2022). Genetic variants of NTCP gene influence hepatitis B vaccine failure (Chen et al. 2022).  Enhanced oral absorption and liver distribution of polymeric nanoparticles can be achieved through traveling the enterohepatic circulation pathways of bile acids using ASBT (Wang et al. 2022).  Novel inhibitors of NTCP have been identified (Song et al. 2024).