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Gene Review

DPM1  -  dolichyl-phosphate mannosyltransferase...

Homo sapiens

Synonyms: CDGIE, DPM synthase subunit 1, Dolichol-phosphate mannose synthase subunit 1, Dolichol-phosphate mannosyltransferase subunit 1, Dolichyl-phosphate beta-D-mannosyltransferase subunit 1, ...


DPM1 forms a complex with DPM2 and DPM3 [1] [2] (DPM synthase) which produces the Dol-P-Man which is the mannose donor in the N-glycan pathway.

In the N-glycan biosynthesis pathway, a sugar composed of 9 mannoses and other 5 sugars is assembled in 14 consecutive reactions, each one catalyzed by a different enzyme, and divided in two parts.

In the first part, the N-glycan precursor is synthetized on the ER membrane but in the cytosol; while in the second part, the sugar is flipped in the ER lumen and assembled there.

The function of the DPM1 complex is to provide the Dol-P-Man necessary for the Man addition reactions in the second part of the biosynthesis ; without Dol-P-Man, glycosilation can't occur, because it is impossible to add the mannoses necessary to complete the N-glycan precursor.



Functions (from Uniprot)

Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of proteins.


Disease relevance of DPM1


High impact information on DPM1

  • Furthermore, mannose supplementation failed to improve the glycosylation status of DPM1-deficient fibroblast cells, thus precluding a possible therapeutic application of mannose in the patients [4].
  • DPM1, the gene coding for the catalytic subunit of Dol-P-Man synthase, was altered in both patients [5].
  • Here, we report that GPI-GnT requires another component, termed PIG-P, and that DPM2, which regulates dolichol-phosphate-mannose synthase, also regulates GPI-GnT [6].
  • We provide evidence that L.mexicana dolichol-phosphate-mannose synthase (DPMS), a key enzyme in GPI biosynthesis, is localized to a distinct tubular subdomain of the endoplasmic reticulum (ER), based on the localization of a green fluorescent protein (GFP)-DPMS chimera and subcellular fractionation experiments [7].
  • DPMS catalyzes the formation of dolichol-phosphate mannose, the sugar donor for all mannose additions in the biosynthesis of both the anchor and free GPIs, except for a alpha1-3-linked mannose residue that is added exclusively to the free GPIs and lipophosphoglycan anchor precursors [8].

Biological context of DPM1


Anatomical context of DPM1

  • CHO2.38 cells were negative for GPI-anchored proteins, and microsomes from these cells showed no detectable DPM synthase activity, indicating that DPM3 is an essential component of this enzyme [9].
  • Perturbation of microtubules and DPMS tubule structure in vivo results in the selective accumulation of GPI anchor precursors, but not free GPIs [7].
  • This tubular membrane (termed the DPMS tubule) is also enriched in other enzymes involved in GPI biosynthesis, can be specifically stained with the fluorescent lipid, BODIPY-C5-ceramide, and appears to be connected to specific subpellicular microtubules that underlie the plasma membrane [7].
  • Finally, the increased degradation of the DPMS chimeras in stationary phase promastigotes coincides with an increase in the lytic capacity of the MVT lysosome and changes in the morphology of this organelle [12].
  • These factors, then, appear to be more useful than clinical and physical data as indicators of the potential response of facial pain patients with either MPDS or organic TMJ deficits to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)[13]

Associations of DPM1 with chemical compounds

  • Lipid-linked oligosaccharides in the endoplasmic reticulum of patient fibroblasts showed an accumulation of the dolichyl pyrophosphate Man(5)GlcNAc(2) structure, compatible with the reduced dolichol-phosphate-mannose synthase (DolP-Man synthase) activity detected in these patients [4].
  • The DPMS tubule is closely associated morphologically with the single Golgi apparatus in non-dividing and dividing cells, appears to exclude luminal ER resident proteins and is labeled, together with the Golgi apparatus, with another GFP chimera containing the heterologous human Golgi marker beta1,2-N-acetylglucosaminyltransferase-I [7].
  • In conclusion, it appears that therapeutic ultrasound can be used effectively to alleviate discomfort of MPDS that does not respond to occlusal splint therapy [14].

Other interactions of DPM1


Analytical, diagnostic and therapeutic context of DPM1

  • Free DPM1 was strongly associated with the C terminus of Hsc70-interacting protein (CHIP), a chaperone-dependent E3 ubiquitin ligase, suggesting that DPM1 is ubiquitinated, at least in part, by CHIP [9].
  • Electron microscopy and subcellular fractionation studies suggest that the DPMS chimeras are transported from the ER to the lumen of the MVT via the Golgi apparatus and a population of 200-nm multivesicular bodies [12].
  • METHODS: All 9-1-1 calls were processed using MPDS protocols to determine whether the patient required ALS or basic life support (BLS) services [16].
  • Thirty-one patients with spinal tumors underwent reconstructive surgery with our spinal instrumentation system (MPDS and MADS), with or without our new vertebral tumor prosthesis [17].
  • Objective: This retrospective study evaluated the appropriateness of requests assigned the alpha determinant at the time of dispatch by Emergency Medical Dispatchers using the Medical Priority Dispatch System (MPDS) [18].


  1. Dolichol-phosphate mannose synthase: structure, function and regulation. Maeda, Y., Kinoshita, T. Biochim. Biophys. Acta. (2008) [Pubmed]
  2. Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1, DPM2 and DPM3. Maeda, Y., Tanaka, S., Hino, J., Kangawa, K., Kinoshita, T. EMBO. J. (2000) [Pubmed]
  3. A gene encoding a homologue of dolichol phosphate-beta-D-mannose synthase is required for infection of Streptomyces coelicolor A3(2) by phage (phi)C31. Cowlishaw, D.A., Smith, M.C. J. Bacteriol. (2002) [Pubmed]
  4. Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital disorder of glycosylation type Ie. Imbach, T., Schenk, B., Schollen, E., Burda, P., Stutz, A., Grunewald, S., Bailie, N.M., King, M.D., Jaeken, J., Matthijs, G., Berger, E.G., Aebi, M., Hennet, T. J. Clin. Invest. (2000) [Pubmed]
  5. Dolichol phosphate mannose synthase (DPM1) mutations define congenital disorder of glycosylation Ie (CDG-Ie). Kim, S., Westphal, V., Srikrishna, G., Mehta, D.P., Peterson, S., Filiano, J., Karnes, P.S., Patterson, M.C., Freeze, H.H. J. Clin. Invest. (2000) [Pubmed]
  6. Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and is regulated by DPM2. Watanabe, R., Murakami, Y., Marmor, M.D., Inoue, N., Maeda, Y., Hino, J., Kangawa, K., Julius, M., Kinoshita, T. EMBO J. (2000) [Pubmed]
  7. Glycosylphosphatidylinositol biosynthetic enzymes are localized to a stable tubular subcompartment of the endoplasmic reticulum in Leishmania mexicana. Ilgoutz, S.C., Mullin, K.A., Southwell, B.R., McConville, M.J. EMBO J. (1999) [Pubmed]
  8. Evidence that free GPI glycolipids are essential for growth of Leishmania mexicana. Ilgoutz, S.C., Zawadzki, J.L., Ralton, J.E., McConville, M.J. EMBO J. (1999) [Pubmed]
  9. DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered to and stabilized on the endoplasmic reticulum membrane by DPM3. Ashida, H., Maeda, Y., Kinoshita, T. J. Biol. Chem. (2006) [Pubmed]
  10. A new intronic mutation in the DPM1 gene is associated with a milder form of CDG Ie in two French siblings. Dancourt, J., Vuillaumier-Barrot, S., de Baulny, H.O., Sfaello, I., Barnier, A., le Bizec, C., Dupre, T., Durand, G., Seta, N., Moore, S.E. Pediatr. Res. (2006) [Pubmed]
  11. A single point mutation resulting in an adversely reduced expression of DPM2 in the Lec15.1 cells. Pu, L., Scocca, J.R., Walker, B.K., Krag, S.S. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  12. Regulated degradation of an endoplasmic reticulum membrane protein in a tubular lysosome in Leishmania mexicana. Mullin, K.A., Foth, B.J., Ilgoutz, S.C., Callaghan, J.M., Zawadzki, J.L., McFadden, G.I., McConville, M.J. Mol. Biol. Cell (2001) [Pubmed]
  13. Predictors of treatment outcome in patients with myofascial pain-dysfunction syndrome and organic temporomandibular joint disorders. Lipton, J.A., Marbach, J.J. The Journal of prosthetic dentistry. (1984) [Pubmed]
  14. Alleviation of myofascial pain with ultrasonic therapy. Esposito, C.J., Veal, S.J., Farman, A.G. The Journal of prosthetic dentistry. (1984) [Pubmed]
  15. Coupling of the dolichol-P-P-oligosaccharide pathway to translation by perturbation-sensitive regulation of the initiating enzyme, GlcNAc-1-P transferase. Gao, N., Lehrman, M.A. J. Biol. Chem. (2002) [Pubmed]
  16. Effectiveness of a medical priority dispatch protocol for abdominal pain. Kennedy, J.D., Sweeney, T.A., Roberts, D., O'Connor, R.E. Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors. (2003) [Pubmed]
  17. Treatment of tumors of the spine. Ozaki, T., Halm, H., Liljenqvist, U., Winkelmann, W. Hiroshima J. Med. Sci. (1997) [Pubmed]
  18. Low Acuity EMS Dispatch Criteria Can Reliably Identify Patients without High-Acuity Illness or Injury. Hinchey, P., Myers, B., Zalkin, J., Lewis, R., Garner, D. Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors (2007) [Pubmed]
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