Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter

J Clin Invest. 1994 Mar;93(3):1326-31. doi: 10.1172/JCI117091.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology
  • Chromosome Mapping*
  • Cloning, Molecular
  • Humans
  • Liver / metabolism*
  • Molecular Sequence Data
  • Organic Anion Transporters, Sodium-Dependent*
  • Symporters*
  • Xenopus laevis

Substances

  • Carrier Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • Symporters
  • sodium-bile acid cotransporter

Associated data

  • GENBANK/L21893