Human Nongastric H,K-ATPase: Current View On Structure And Functional Properties

  • Gail Adams
  • Manoranjani Tillekeratne
  • Nikolay B. Pestov
  • Nikolai N. Modyanov


The P-type ATPases comprise a large number of highly diverse transport ATPases that are predominantly involved in the active transport of cations across biological membranes. All of these ion pumps share a common feature: formation of a phosphorylated intermediate during the reaction cycle (26,39). Different K+-dependent animal ATPases (X,K-ATPases) are the most closely related among various P-type ATPases. All of the known X,K-ATPases function as cation exchangers that pump K+ into the cell and Na+ or H+ out of the cell. X,K-ATPases exhibit a much higher level of sequence homology between their catalytic α-subunits than with other P-ATPases, and contain a second component, a ß-subunit which is absent in other P-ATPases (26,39,53). The catalytic α-subunits are large polytopic proteins (~110 kDa) with 10 transmembrane segments and contain most of the ATPase functional domains such as the ATP-hydrolyzing center and the binding sites for cations and specific inhibitors (8,26,53). The glycosylated ß-subunits (core protein ~ 30–35 kDa) have a relatively short cytoplasmic N-terminal domain, a single transmembrane segment, and a large ectodomain containing three conserved disulfide bridges and several carbohydrate chains (11,19). The X,K-ATPase family combines three distinct groups of ion pumps. Two groups, one consisting of the Na,K-ATPase isozymes formed by four α three ß isoforms and the second which includes the gastric H,K-ATPase, have long been known and studied extensively (26,53). The recently discovered catalytic a-subunits of nongastric H,K-ATPases encoded by the human ATP1 AL1 (alternative name ATP12A) gene and its animal homologues represent the third distinct group (23,27,36).


ATPase Activity Xenopus Oocyte Cardiac Glycoside Proton Transport Animal Homologue 
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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Gail Adams
    • 1
  • Manoranjani Tillekeratne
    • 1
  • Nikolay B. Pestov
    • 1
  • Nikolai N. Modyanov
    • 1
  1. 1.Department of PharmacologyMedical College of OhioToledoUSA

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