Structure, function, and tissue expression pattern of human SN2, a subtype of the amino acid transport system N

Takeo Nakanishi, Mitsuru Sugawara, Wei Huang, Robert G. Martindale, Frederick H. Leibach, Malliga E. Ganapathy, Puttur D Prasad, Vadivel Ganapathy

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

We have cloned a new subtype of the amino acid transport system N from a human liver cell line. This transporter, designated SN2, consists of 472 amino acids and exhibits 62% identity with human SN1 at the level of amino acid sequence. SN2-specific transcripts are expressed predominantly in the stomach, brain, liver, lung, and intestinal tract. The sizes of the transcripts vary in different tissues, indicating tissue-specific alternative splicing of the SN2 mRNA. In contrast, SN1 is expressed primarily in the brain and liver and there is no evidence for the presence of multiple transcripts of varying size for SN1. When expressed in mammalian cells, the cloned human SN2 mediates Na+-coupled transport of system N-specific amino acid substrates (glutamine, asparagine, and histidine). In addition, SN2 also transports serine, alanine, and glycine. Anionic amino acids, cationic amino acids, imino acids, and N-alkylated amino acids are not recognized as substrates by human SN2. The SN2-mediated transport process is Li+-tolerant and highly pH-dependent. The Michaelis-Menten constant for histidine uptake via human SN2 is 0.6 ± 0.1 mM. The gene coding for SN2 is located on human chromosome Xp11.23. Successful cloning of SN2 provides the first molecular evidence for the existence of subtypes within the amino acid transport system N in mammalian tissues.

Original languageEnglish (US)
Pages (from-to)1343-1348
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume281
Issue number5
DOIs
StatePublished - Jan 1 2001

Keywords

  • Amino acid transport
  • Functional expression
  • Primary structure
  • System N
  • Tissue expression pattern

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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