Molecular cloning, primary structure, and expression of the human growth factor-activatable Na+/H+ antiporter

Cell. 1989 Jan 27;56(2):271-80. doi: 10.1016/0092-8674(89)90901-x.


We present the complete sequence of a cDNA encoding the human amiloride-sensitive Na+/H+ antiporter. After functional complementation of a mouse fibroblast mutant by gene transfer, we isolated a 0.8 kb genomic probe from a third-cycle mouse transformant. The probe detects gene amplification in Na+/H+ antiporter "overexpressers" and a single class of mRNA of ca. 5.6 kb in human, mouse, and hamster cells. With this probe we isolated a 4 kb cDNA from a library constructed from a mouse transformant in which the transfected human gene was amplified. This cDNA includes a noncoding leader of 407 bp, a 2682 bp open reading frame, and a 3' noncoding sequence containing a mouse B1 repeated element. The amino acid sequence predicts a protein of Mr = 99,354 with an N-terminal amphipathic domain that contains 10 putative transmembrane-spanning segments and two potential glycosylation sites, followed by a hydrophilic stretch of 395 residues, presumably cytoplasmic. Stable expression of the transfected cDNA in Na+/H+ antiporter-deficient cells restored the key functional features of this transporter: H+i-activated Na+ influx, amiloride sensitivity, and pHi regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiloride / pharmacology
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics*
  • Cell Line
  • Cloning, Molecular / methods*
  • Genes*
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Protein Conformation
  • RNA, Messenger / genetics
  • Restriction Mapping
  • Sodium-Hydrogen Exchangers
  • Species Specificity
  • Transfection


  • Carrier Proteins
  • RNA, Messenger
  • Sodium-Hydrogen Exchangers
  • Amiloride

Associated data

  • GENBANK/J03163