Dolichol-phosphate mannosyltransferase subunit 1 (DPM1)

The protein contains 260 amino acids for an estimated molecular weight of 29634 Da.

 

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; catalytic subunit of the dolichol-phosphate mannose (DPM) synthase complex. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 86%
Model score: 17

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VariantDescription
CDG1E
CDG1E
CDG1E

The reference OMIM entry for this protein is 603503

Dolichyl-phosphate mannosyltransferase 1, catalytic subunit; dpm1
Dolichol-phosphate mannosyltransferase 1
Dolichol-phosphate-mannose synthase 1
Mpd synthase; mpds

DESCRIPTION

The DPM1 gene encodes the cytoplasmic catalytic subunit of dolichol-phosphate-mannose synthase (EC 2.4.1.83), an enzyme complex that synthesizes dolichol-phosphate-mannose (Dol-P-Man) from GDP-mannose and dolichol-phosphate. DPM2 (603564) and DPM3 (605951) are integral endoplasmic reticulum membrane proteins that stabilize the complex. Dol-P-Man serves as a donor of mannosyl residues in various eukaryotic glycosylation processes, including N-glycosylation of asparagine residues and O-mannosylation of alpha-dystroglycan (DAG1; 128239) (summary by Garcia-Silva et al., 2004 and Yang et al., 2013).

CLONING

The S. cerevisiae dpm1 gene encodes a Dol-P-Man synthase that is a transmembrane protein expressed in the endoplasmic reticulum. By searching an EST database for homologs of yeast dpm1, Tomita et al. (1998) identified human and mouse DPM1 cDNAs. The predicted 260-amino acid human protein shares approximately 30% identity with yeast dpm1. However, DPM1 lacks the C-terminal transmembrane domain found in dpm1 and does not contain a signal sequence. Independently, Colussi et al. (1997) cloned human, rat, nematode, and S. pombe DPM1 cDNAs. They reported that the predicted human and rat proteins are 93% identical. Sequence analysis indicated that the human, S. pombe, and nematode DPM1 proteins lack the hydrophobic C-terminal domain found in S. cerevisiae dpm1. However, both human and S. cerevisiae DPM1 complemented the lethal S. pombe dpm1+ mutation.

GENE FUNCTION

Mouse Thy1 (188230)-negative thymoma mutant cells of complementation class E do not synthesize Dol-P-Man and consequently do not synthesize the glycosylphosphatidylinositol (GPI) core, resulting in the defective surface expression of GPI-anchored proteins, such as Thy1. Tomita et al. (1998) found that expression of DPM1 in class E mutant mouse cells completely restored surface expression of Thy1, and sequence analysis revealed that the mutant cells have an inactivating mutation in the murine Dpm1 gene. However, the mammalian DPM1 cDNAs did not complement another Dol-P-Man synthesis mutant, hamster Lec15 cells, whereas yeast dpm1 restored both class E and Lec15 cells. Tomita et al. (1998) concluded that mammalian cells require DPM1 and an additional protein for synthesis of Dol-P-Man. See DPM2 (603564). Maeda et al. (2000) purified human Dol-P-Man synthase and demonstrated that the enzyme is a protein complex with 3 subunits, DPM1, DPM2, and DPM3 (605951). They concluded that DPM1 is stabilized by an association with the C-terminal domain of DPM3, which is stabilized by an association with DPM2.

MOLECULAR GENETICS

In 2 unrelated patients with congenital disorder of glycosylation Ie (608799), Kim et al. (2000) identified mutations in the DPM1 gene (603503.0001; 603503.0002). In 2 sibs with CDG Ie, Imbach et al. (2000) identified compound heterozygosity for 2 mutations in the DPM1 gene (603503.0001; 603503.0003). Garcia-Silva et al. (2004) identified a homozygous missense mutation in the DPM1 gene (603503.0004) in a girl with a relatively mild form of CDG Ie. In 2 sibs, born of consanguineous Algerian parents, with CDG Ie, Dancourt et al. (2006) identified a homozygous splice site mutation in the DPM1 gene (603503.0005). Each unaffected parent was heterozygous for the mutation. Patient cells showed only 8% residual enzyme activity and a more than 90% reduction in DPM1 transcript levels. In a boy with CDG type Ie, Yang et al. (2013) ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603503 was added.