DPM2 regulates biosynthesis of dolichol phosphate-mannose in mammalian cells: correct subcellular localization and stabilization of DPM1, and binding of dolichol phosphate

EMBO J. 1998 Sep 1;17(17):4920-9. doi: 10.1093/emboj/17.17.4920.


Biosynthesis of glycosylphosphatidylinositol and N-glycan precursor is dependent upon a mannosyl donor, dolichol phosphate-mannose (DPM). The Thy-1negative class E mutant of mouse lymphoma and Lec15 mutant Chinese hamster ovary (CHO) cells are incapable of DPM synthesis. The class E mutant is defective in the DPM1 gene which encodes a mammalian homologue of Saccharomyces cerevisiae Dpm1p that is a DPM synthase, whereas Lec15 is a different mutant, indicating that mammalian DPM1 is not sufficient for DPM synthesis. Here we report expression cloning of a new gene, DPM2, which is defective in Lec15 cells. DPM2, an 84 amino acid membrane protein expressed in the endoplasmic reticulum (ER), makes a complex with DPM1 that is essential for the ER localization and stable expression of DPM1. Moreover, DPM2 enhances binding of dolichol phosphate, a substrate of DPM synthase. Mammalian DPM1 is catalytic because a fusion protein of DPM1 that was stably expressed in the ER synthesized DPM without DPM2. Therefore, biosynthesis of DPM in mammalian cells is regulated by DPM2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Compartmentation
  • Cloning, Molecular
  • Dolichol Monophosphate Mannose / metabolism*
  • Dolichol Phosphates / metabolism*
  • Endoplasmic Reticulum / enzymology
  • Gene Expression
  • Genetic Complementation Test
  • Humans
  • Mannosyltransferases / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Rats
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid


  • Carrier Proteins
  • Dolichol Phosphates
  • Membrane Proteins
  • Dolichol Monophosphate Mannose
  • DPM2 protein, human
  • Mannosyltransferases
  • dolichyl-phosphate beta-D-mannosyltransferase

Associated data

  • GENBANK/AB013359
  • GENBANK/AB013360
  • GENBANK/AB013361