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Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter.
Open accessAbstract
We have used a cDNA probe from a cloned rat liver Na+/taurocholate cotransporting polypeptide (Ntcp) to screen a human liver cDNA library. A 1,599-bp cDNA clone that encodes a human Na+/taurocholate cotransporting polypeptide (NTCP) was isolated. The human NTCP consists of 349 amino acids (calculated molecular mass of 38 kD) and exhibits 77% amino acid homology with the rat Ntcp. In vitro translation experiments indicate that the protein is glycosylated and has a molecular weight similar to the rat Ntcp. Injection of in vitro transcribed cRNA into Xenopus laevis oocytes resulted in the expression of Na(+)-dependent taurocholate uptake. Saturation kinetics indicated that the human NTCP has a higher affinity for taurocholate (apparent Km = 6 microM) than the previously cloned rat protein (apparent Km = 25 microM). NTCP-mediated taurocholate uptake into oocytes was inhibited by all major bile acid derivatives (100 microM), bumetanide (500 microM), and bromosulphophthalein (100 microM). Southern blot analysis of genomic DNA from a panel of human/hamster somatic cell hybrids mapped the human NTCP gene to chromosome 14.
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Cited by
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280
Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma
Gao, Q., Zhu, H., Dong, L., Shi, W., Chen, R., Song, Z., Huang, C., Li, J., Dong, X., Zhou, Y., et al. (2019) · Cell · doi:10.1016/j.cell.2019.08.052 · Cited by 1,096
Bile salt transporters: molecular characterization, function, and regulation
Trauner, M., & Boyer, J. L. (2003) · Physiological Reviews · doi:10.1152/physrev.00027.2002 · Cited by 999
Bile Acid Transporters: Structure, Function, Regulation and Pathophysiological Implications
Alrefai, W. A., & Gill, R. K. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9289-1 · Cited by 500
Hennemann, G., Docter, R., Friesema, E. C. H., de Jong, M., Krenning, E. P., & Visser, T. J. (2001) · Endocrine Reviews · doi:10.1210/edrv.22.4.0435 · Cited by 394
Metadata
- Authors
- Hagenbuch, B., & Meier, P. J.
- Venue
- Journal of Clinical Investigation
- Published
- 1994-03-01
- Volume
- 93
- Issue
- 3
- Pages
- 1326-1331
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2105517464
- Cited by
- 464
- References
- 0
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. https://app.cochat.ai/papers/10.1172/jci117091
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- Hagenbuch, B., & Meier, P. J. (1994). Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. Journal of Clinical Investigation. https://doi.org/10.1172/jci117091
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