title: The CD39 lymphoid cell activation antigen. Molecular cloning and structural characterization.
abstract: CD39, a 70- to 100-kDa molecule expressed primarily on activated lymphoid cells, was previously shown to mediate B cell homotypic adhesion when ligated with a subset of anti-CD39 mAbs. In the present study, we describe the cloning and molecular characterization of human and murine CD39. The nucleotide sequence of human CD39 includes an open reading frame encoding a putative 510 amino acid protein with six potential N-linked glycosylation sites, 11 Cys residues, and two potential transmembrane regions. Murine CD39 shares 75% amino acid sequence identity with human CD39 but fails to cross-react with anti-human CD39 mAbs. Although there were no significant similarities with other mammalian genes, considerable homology was found between CD39 and a guanosine diphosphatase from yeast. A series of mouse-human hybrid molecules was constructed to determine the general topology of CD39 and the location of a biologically functional epitope. These findings and supporting evidence from an anti-CD39 mAb-selected phage peptide display library indicate a likely model wherein a short intracellular N-terminus is followed by a large extracellular loop containing the epitope recognized by stimulatory anti-CD39 mAbs, and a short intracellular C terminus. The results demonstrate that CD39 is a novel cell surface glycoprotein with unusual structural characteristics.
authors.affiliation: Immunex Research and Development Corporation, Seattle, WA 98101.
authors.forename: C R
authors.initials: CR
authors.lastname: Maliszewski
authors.forename: G J
authors.initials: GJ
authors.lastname: Delespesse
authors.forename: M A
authors.initials: MA
authors.lastname: Schoenborn
authors.forename: R J
authors.initials: RJ
authors.lastname: Armitage
authors.forename: W C
authors.initials: WC
authors.lastname: Fanslow
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: E
authors.initials: E
authors.lastname: Baker
authors.forename: G R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: K
authors.initials: K
authors.lastname: Poindexter
authors.forename: C
authors.initials: C
authors.lastname: Birks
mesh_terms: D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001081:Apyrase; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D002879:Chromosomes, Human, Pair 10; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D018604:Epitope Mapping; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011755:Pyrophosphatases / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D015703:Antigens, CD; D018076:DNA, Complementary; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D000251:Adenosine Triphosphatases; D011755:Pyrophosphatases; C010357:guanosine-diphosphatase; D001081:Apyrase; C067869:CD39 antigen