PIG-M transfers the first mannose to glycosylphosphatidylinositol on the lumenal side of the ER.
Glycosylphosphatidylinositol (GPI) acts as a membrane anchor of many cell surface proteins. Its structure and biosynthetic pathway are generally conserved among eukaryotic organisms, with a number of differences. In particular, mammalian and protozoan mannosyltransferases needed for addition of the first mannose (GPI-MT-I) have different substrate specificities and are targets of species- specific inhibitors of GPI biosynthesis. GPI-MT-I, however, has not been molecularly characterized. Characterization of GPI-MT-I would also help to clarify the topology of GPI biosynthesis. Here, we report a human cell line defective in GPI-MT-I and the gene responsible, PIG-M. PIG-M encodes a new type of mannosyltransferase of 423 amino acids, bearing multiple transmembrane domains. PIG-M has a functionally important DXD motif, a characteristic of many glycosyltransferases, within a domain facing the lumen of the endoplasmic reticulum (ER), indicating that transfer of the first mannose to GPI occurs on the lumenal side of the ER membrane.
Maeda
Y
Y
Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Watanabe
R
R
Harris
C L
CL
Hong
Y
Y
Ohishi
K
K
Kinoshita
K
K
Kinoshita
T
T
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D008364:Mannosyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014162:Transfection
D017261:Glycosylphosphatidylinositols; D011994:Recombinant Proteins; D008364:Mannosyltransferases; C486036:PIGM protein, human; C423034:glycosylphosphatidylinositol mannosyltransferase I