title: Isolation of cDNA coding for an ubiquitous membrane protein deficient in high Na+, low K+ stomatocytic erythrocytes.
abstract: Human red blood cells (RBCs) that are deficient in an integral membrane-associated protein ("stomatin") of apparent molecular mass 31 Kd show a catastrophic increase in passive membrane permeability to the univalent cations Na+ and K+ and are stomatocytic in shape. We have purified this protein from normal RBC membranes and isolated a cDNA clone coding for it. The deduced protein sequence is unrelated to that of any known ion-transport-related protein. Selective solubilization studies using detergents show that while the protein is strongly associated with the phospholipid bilayer, it also binds to the cytoskeleton. The predicted polypeptide has a single trans-membranous hydrophobic segment near the N-terminus, which would locate it in the membrane; the large C-terminal domain is hydrophilic and cytoplasmic in orientation and is presumed to be responsible for the attachment to the cytoskeleton. By inference, the protein has the function of closing a latent ion channel. The messenger RNA encoding this protein is ubiquitously distributed in different human cell types and tissues and is thus presumably a widely distributed regulator of transmembrane cation fluxes. As a membrane-bound inhibitor protein of Na+ and K+ transport, it is unique among the known components of membrane-transport proteins.
authors.affiliation: Department of Medicine, University College and Middlesex Medical School, Rayne Institute, London, UK.
authors.forename: G W
authors.initials: GW
authors.lastname: Stewart
authors.forename: B E
authors.initials: BE
authors.lastname: Hepworth-Jones
authors.forename: J N
authors.initials: JN
authors.lastname: Keen
authors.forename: B C
authors.initials: BC
authors.lastname: Dash
authors.forename: A C
authors.initials: AC
authors.lastname: Argent
authors.forename: C M
authors.initials: CM
authors.lastname: Casimir
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D001798:Blood Proteins / Q000235:genetics*; D004247:DNA / Q000302:isolation & purification*; D004910:Erythrocyte Membrane / Q000737:chemistry* / Q000378:metabolism; D004913:Erythrocytes, Abnormal / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009154:Mutation; D011188:Potassium / Q000097:blood*; D012333:RNA, Messenger / Q000032:analysis; D012964:Sodium / Q000097:blood*
chemical_list: D001798:Blood Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C036860:STOM protein, human; D004247:DNA; D012964:Sodium; D011188:Potassium