PIG-M transfers the first mannose to glycosylphosphatidylinositol on the lumenal side of the ER

EMBO J. 2001 Jan 15;20(1-2):250-61. doi: 10.1093/emboj/20.1.250.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Membrane / enzymology
  • Cloning, Molecular
  • Endoplasmic Reticulum / metabolism*
  • Glycosylphosphatidylinositols / metabolism*
  • Humans
  • Mannosyltransferases / chemistry
  • Mannosyltransferases / genetics
  • Mannosyltransferases / metabolism*
  • Molecular Sequence Data
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Transfection


  • Glycosylphosphatidylinositols
  • Recombinant Proteins
  • Mannosyltransferases
  • PIGM protein, human
  • glycosylphosphatidylinositol mannosyltransferase I