title: PIG-B, a membrane protein of the endoplasmic reticulum with a large lumenal domain, is involved in transferring the third mannose of the GPI anchor.
abstract: Many eukaryotic cell surface proteins are bound to the membrane via the glycosylphosphatidylinositol (GPI) anchor that is covalently linked to their carboxy-terminus. The GPI anchor precursor is synthesized in the endoplasmic reticulum (ER) and post-translationally linked to protein. We cloned a human gene termed PIG-B (phosphatidylinositol glycan of complementation class B) that is involved in transferring the third mannose. PIG-B encodes a 554 amino acid, ER transmembrane protein with an amino-terminal portion of approximately 60 amino acids on the cytoplasmic side and a large carboxy-terminal portion of 470 amino acids within the ER lumen. A mutant PIG-B lacking the cytoplasmic portion remains active, indicating that the functional site of PIG-B resides on the lumenal side of the ER membrane. The PIG-B gene was localized to chromosome 15 at q21-q22. This autosomal location would explain why PIG-B is not involved in the defective GPI anchor synthesis in paroxysmal nocturnal hemoglobinuria, which is always caused by a somatic mutation of the X-linked PIG-A gene.
authors.affiliation: Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Inoue
authors.forename: K
authors.initials: K
authors.lastname: Ohishi
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: N
authors.initials: N
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: J
authors.initials: J
authors.lastname: Takeda
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004287:Dolichol Monophosphate Mannose / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005796:Genes; D017261:Glycosylphosphatidylinositols / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D008358:Mannose / Q000378:metabolism*; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017384:Sequence Deletion; D013945:Thymoma / Q000235:genetics / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics / Q000473:pathology
chemical_list: D018076:DNA, Complementary; D017261:Glycosylphosphatidylinositols; D011993:Recombinant Fusion Proteins; D004287:Dolichol Monophosphate Mannose; D008364:Mannosyltransferases; C102168:PIGB protein, human; C022755:dolichyl-phosphate beta-D-mannosyltransferase; D008358:Mannose