id: O60762
gene_symbol: DPM1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DPM1 is the catalytic subunit of the dolichol-phosphate mannose (Dol-P-Man)
  synthase complex (DPM1/DPM2/DPM3). It transfers mannose from GDP-mannose onto dolichyl
  phosphate to form dolichyl-phosphate-mannose (Dol-P-Man) at the endoplasmic reticulum
  membrane (EC 2.4.1.83). Dol-P-Man is the lipid-linked mannosyl donor used for the
  lumenal mannose additions to the N-glycan precursor, for glycosylphosphatidylinositol
  (GPI) anchor synthesis, and for protein O-mannosylation and C-mannosylation. Unlike
  the yeast enzyme, human DPM1 lacks its own membrane-spanning domain and is tethered
  to the ER membrane by DPM3 (via a DPM3 C-terminal coiled-coil) and stabilized by
  DPM2, which also enhances catalytic activity. DPM1 is a glycosyltransferase family
  2 enzyme that binds GDP-mannose and a divalent metal cation. Loss-of-function variants
  cause DPM1-congenital disorder of glycosylation (CDG type Ie), which can present
  with dystroglycanopathy-type congenital muscular dystrophy.
existing_annotations:
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) annotation placing DPM1 activity at the ER membrane,
      consistent with the experimentally established ER-membrane localization of the
      DPM synthase complex.
    action: ACCEPT
    reason: DPM1 catalytic activity occurs at the cytosolic face of the ER membrane;
      DPM1 is tethered there by DPM3. This is the correct site of action.
    supported_by:
    - reference_id: PMID:16280320
      supporting_text: the catalytic subunit of the enzyme, to
    - reference_id: PMID:9724629
      supporting_text: essential for the ER localization and stable expression of
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic annotation linking DPM1 to synthesis of the dolichol-linked
      oligosaccharide (LLO) N-glycan precursor. Dol-P-Man produced by DPM1 donates
      the lumenal mannose additions (ALG3/ALG9/ALG12) that extend the LLO precursor,
      so DPM1 acts upstream of and within this process.
    action: ACCEPT
    reason: The Dol-P-Man made by DPM1 supplies the mannosyl residues added to the
      dolichol-linked oligosaccharide precursor in the ER lumen; a well-supported
      biological role.
    supported_by:
    - reference_id: PMID:9535917
      supporting_text: It donates four mannosyl residues in the
- term:
    id: GO:0004582
    label: dolichyl-phosphate beta-D-mannosyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic annotation of the core catalytic molecular function of DPM1
      transferring mannose from GDP-mannose to dolichyl phosphate. This is the exact
      current GOA molecular-function term and the defining activity of the protein.
    action: ACCEPT
    reason: DPM1 is the catalytic subunit of DPM synthase; the dolichyl-phosphate
      beta-D-mannosyltransferase activity (EC 2.4.1.83, RHEA:21184) is directly demonstrated
      and conserved across orthologs.
    supported_by:
    - reference_id: PMID:9724629
      supporting_text: Mammalian DPM1 is catalytic
    - reference_id: PMID:10835346
      supporting_text: catalytic DPM1 and regulatory
- term:
    id: GO:0004582
    label: dolichyl-phosphate beta-D-mannosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation of the core catalytic activity from InterPro/EC/RHEA
      mappings (IPR039528 DPM1-like; EC 2.4.1.83; RHEA:21184), agreeing with the experimental
      and phylogenetic evidence.
    action: ACCEPT
    reason: The IEA mapping is to the correct, specific molecular function and matches
      the experimentally verified catalytic activity.
    supported_by:
    - reference_id: file:human/DPM1/DPM1-uniprot.txt
      supporting_text: EC=2.4.1.83
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation to the endoplasmic reticulum from the UniProt subcellular
      location keyword mapping. Correct but less specific than the ER membrane term.
    action: ACCEPT
    reason: DPM1 localizes to the ER; this parent-level location is accurate, though
      ER membrane (GO:0005789) is the more precise term.
    supported_by:
    - reference_id: file:human/DPM1/DPM1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum'
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA electronic annotation linking DPM1 to GPI anchor biosynthesis. Dol-P-Man
      produced by DPM1 donates the three mannose residues of the GPI anchor core,
      so DPM1 acts upstream of this pathway.
    action: KEEP_AS_NON_CORE
    reason: This is a downstream pathway that depends on the Dol-P-Man mannosyl donor
      supplied by DPM1, not the enzyme's direct molecular function. Real but not the
      core function; DPM1 provides the substrate rather than acting in the GPI-mannosylation
      steps itself.
    supported_by:
    - reference_id: PMID:9535917
      supporting_text: all three mannosyl residues in the
- term:
    id: GO:0043048
    label: dolichyl monophosphate biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA electronic annotation to dolichyl monophosphate biosynthetic process.
      DPM1 consumes dolichyl phosphate (Dol-P) as a substrate and produces Dol-P-Man;
      it is part of the broader dolichyl-phosphate/mannose metabolic pathway.
    action: ACCEPT
    reason: DPM1 acts on dolichyl phosphate metabolism as the mannosyltransferase
      that converts Dol-P to Dol-P-Man; a broader process term that is compatible
      with the enzyme's role, retained but less specific than dolichol phosphate mannose
      biosynthetic process (GO:0180047).
    supported_by:
    - reference_id: PMID:10835346
      supporting_text: catalytic DPM1 and regulatory
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10835346
  qualifier: enables
  review:
    summary: IPI to DPM3 (Q9P2X0). The DPM1-DPM3 interaction is real and functionally
      central (DPM3 tethers and stabilizes DPM1), but the bare protein binding term
      is uninformative about molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: 'The underlying interaction is genuine and biologically important, but
      per curation guidelines the generic protein binding (GO:0005515) MF term conveys
      no functional information; the meaningful content (DPM synthase complex, DPM3
      tethering) is captured by GO:0033185 and the catalytic MF. Not removed per policy
      on experimental interaction annotations.'
    supported_by:
    - reference_id: PMID:10835346
      supporting_text: DPM1 requires DPM2 for its stable expression
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10944123
  qualifier: enables
  review:
    summary: IPI to DPM3 (Q9P2X0) sourced from IntAct via the PIG-P/DPM2 GPI-GnT regulation
      paper. Bare protein binding term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative molecular-function term; the biologically relevant relationships
      (DPM synthase complex membership, DPM2/DPM3 regulation of the mannosyl-donor
      pathway) are better captured by the complex and process annotations. Retained,
      not removed.
    supported_by:
    - reference_id: PMID:10944123
      supporting_text: generates a mannosyl donor for GPI
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23856421
  qualifier: enables
  review:
    summary: IPI to DPM3 (Q9P2X0) from the DPM1-CDG paper, in which the disease variant
      p.Gly152Val reduces DPM1 binding to DPM3. Real and disease-relevant interaction,
      but the generic term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: The DPM1-DPM3 interaction is genuine and clinically important, but protein
      binding (GO:0005515) is uninformative as a molecular function; complex membership
      (GO:0033185) captures the substance. Not removed.
    supported_by:
    - reference_id: PMID:23856421
      supporting_text: reduced binding to DPM3, an essential,
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: IPI to TDO2 (P48775) from a proteome-scale binary interactome map. No
      evidence this reflects a specific DPM1 function; bare protein binding term.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput binary interactome hit to an unrelated protein; uninformative
      generic MF term with no demonstrated functional relevance to DPM1. Retained
      per policy rather than removed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: IPI to TDO2 (P48775) from a large-scale interactome-perturbation study.
      Bare protein binding term, no functional information.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput interactome-derived interaction; uninformative MF term
      with no established DPM1-specific function. Retained, not removed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: IPI to MEOX2 (Q6FHY5) from the HuRI reference binary interactome map.
      Bare protein binding term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Systematic Y2H interactome hit to an unrelated transcription factor; uninformative
      generic MF term without demonstrated biological relevance to DPM1. Retained
      per policy.
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162699
  qualifier: involved_in
  review:
    summary: Reactome traceable-author-statement annotation for synthesis of dolichyl-phosphate
      mannose within LLO biosynthesis. Dol-P-Man produced by DPM1 donates the lumenal
      mannoses of the dolichol-linked oligosaccharide precursor.
    action: ACCEPT
    reason: Correctly places DPM1 within dolichol-linked oligosaccharide biosynthesis
      as the source of the mannosyl donor; consistent with the phylogenetic annotation.
    supported_by:
    - reference_id: Reactome:R-HSA-162699
      supporting_text: the donor of mannose groups in the synthesis of the dolichyl
        pyrophosphate-linked precursor oligosaccharide in asparagine-linked glycosylation
- term:
    id: GO:0004582
    label: dolichyl-phosphate beta-D-mannosyltransferase activity
  evidence_type: EXP
  original_reference_id: PMID:10835346
  qualifier: enables
  review:
    summary: Experimental annotation of the core catalytic activity of DPM1 in the
      DPM synthase complex. This is the defining, verified molecular function.
    action: ACCEPT
    reason: Direct experimental evidence that DPM1 is the catalytic subunit generating
      Dol-P-Man; the exact current GOA MF term.
    supported_by:
    - reference_id: PMID:10835346
      supporting_text: catalytic DPM1 and regulatory
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: NAS
  original_reference_id: PMID:9724629
  qualifier: located_in
  review:
    summary: Non-traceable/author-statement annotation (ComplexPortal) locating DPM1
      at the ER membrane, where the DPM synthase complex resides.
    action: ACCEPT
    reason: The ER membrane is the established location of the DPM synthase complex;
      consistent with experimental evidence that DPM2/DPM3 tether and stabilize DPM1
      in the ER.
    supported_by:
    - reference_id: PMID:9724629
      supporting_text: essential for the ER localization and stable expression of
- term:
    id: GO:0033185
    label: dolichol-phosphate-mannose synthase complex
  evidence_type: IPI
  original_reference_id: PMID:10835346
  qualifier: part_of
  review:
    summary: DPM1 is a component of the dolichol-phosphate-mannose synthase complex
      composed of DPM1 (catalytic), DPM2 and DPM3. This is the specific, informative
      complex annotation.
    action: ACCEPT
    reason: Directly demonstrated three-subunit complex; DPM1 is the catalytic member.
      Correct and specific cellular-component annotation.
    supported_by:
    - reference_id: PMID:10835346
      supporting_text: human DPM synthase consists of three
- term:
    id: GO:0043048
    label: dolichyl monophosphate biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:10835346
  qualifier: involved_in
  review:
    summary: Experimental annotation to dolichyl monophosphate biosynthetic process.
      DPM1 acts in the dolichyl-phosphate/Dol-P-Man branch of dolichol metabolism,
      converting Dol-P plus GDP-mannose to Dol-P-Man.
    action: ACCEPT
    reason: Consistent with the enzyme's demonstrated role in the dolichyl-phosphate
      mannose synthesis reaction; a broader process term compatible with the specific
      GO:0180047 annotation.
    supported_by:
    - reference_id: PMID:10835346
      supporting_text: catalytic DPM1 and regulatory
- term:
    id: GO:0043048
    label: dolichyl monophosphate biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:9535917
  qualifier: acts_upstream_of_or_within
  review:
    summary: Experimental (complementation) annotation. DPM1 cDNA restored Dol-P-Man
      synthesis in Dol-P-Man-deficient mammalian mutant cells, demonstrating its role
      in the dolichyl-phosphate mannose pathway.
    action: ACCEPT
    reason: Functional complementation demonstrates DPM1's role in synthesis of the
      dolichyl-phosphate mannosyl donor; supports the process annotation.
    supported_by:
    - reference_id: PMID:9535917
      supporting_text: Human and mouse DPM1 cDNA restored
- term:
    id: GO:0043048
    label: dolichyl monophosphate biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:9724629
  qualifier: acts_upstream_of_or_within
  review:
    summary: Experimental annotation from the DPM2 study showing DPM1 is the catalytic
      component of the Dol-P-Man synthesis reaction at the ER.
    action: ACCEPT
    reason: Supports DPM1's role in dolichyl-phosphate mannose synthesis; a broader
      process term compatible with GO:0180047.
    supported_by:
    - reference_id: PMID:9724629
      supporting_text: Mammalian DPM1 is catalytic
- term:
    id: GO:0004582
    label: dolichyl-phosphate beta-D-mannosyltransferase activity
  evidence_type: IGI
  original_reference_id: PMID:16280320
  qualifier: enables
  review:
    summary: Genetic-interaction-based annotation of the catalytic activity, from
      the study establishing that DPM3 tethers the catalytic DPM1 subunit to the ER
      membrane (loss of DPM3 abolishes DPM synthase activity).
    action: ACCEPT
    reason: Consistent with DPM1 being the catalyst; the exact current GOA MF term.
    supported_by:
    - reference_id: PMID:16280320
      supporting_text: the catalytic subunit of the enzyme, to
- term:
    id: GO:0180047
    label: dolichol phosphate mannose biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:10835346
  qualifier: involved_in
  review:
    summary: Experimental annotation to the specific process of dolichol phosphate
      mannose biosynthesis. This is the most precise biological-process term for DPM1
      the reaction it directly catalyzes and is a core function.
    action: ACCEPT
    reason: Directly matches the enzyme's demonstrated catalytic role (GDP-mannose
      plus Dol-P to Dol-P-Man). Most specific and appropriate BP term; core function.
    supported_by:
    - reference_id: PMID:10835346
      supporting_text: catalytic DPM1 and regulatory
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IGI
  original_reference_id: PMID:16280320
  qualifier: involved_in
  review:
    summary: Genetic-interaction annotation linking DPM1/DPM3 to GPI anchor biosynthesis
      (DPM3-defective cells lack GPI-anchored proteins). Dol-P-Man from DPM1 supplies
      the three mannoses of the GPI anchor.
    action: KEEP_AS_NON_CORE
    reason: Downstream pathway dependent on the Dol-P-Man donor produced by DPM1 rather
      than DPM1's own molecular function. Real and important (GPI defects underlie
      the disease phenotype) but non-core.
    supported_by:
    - reference_id: PMID:16280320
      supporting_text: required for synthesis of the
- term:
    id: GO:0180047
    label: dolichol phosphate mannose biosynthetic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity annotation to dolichol phosphate mannose biosynthetic
      process, transferred from an ortholog. Matches the experimentally established
      core process.
    action: ACCEPT
    reason: Correct and specific process annotation, concordant with the IDA evidence
      for the same term.
    supported_by:
    - reference_id: PMID:10835346
      supporting_text: catalytic DPM1 and regulatory
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: Sequence-similarity annotation for divalent metal-cation binding, transferred
      from the archaeal ortholog Q8U4M3. UniProt records a divalent metal cation (Mg2+/Mn2+/Ca2+)
      binding site (residue 120) required for the glycosyltransferase reaction.
    action: KEEP_AS_NON_CORE
    reason: DPM1 is a GT2-family glycosyltransferase that binds a divalent metal cation
      to coordinate the GDP-mannose donor; this is a genuine ancillary molecular function
      supporting catalysis but is not the informative core function on its own.
    supported_by:
    - reference_id: file:human/DPM1/DPM1-uniprot.txt
      supporting_text: Binds 1 divalent metal cation
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4717406
  qualifier: located_in
  review:
    summary: Reactome TAS annotation locating DPM1 at the ER membrane (in the reaction
      representing defective DPM1 that fails to form Dol-P-Man in DPM1-CDG).
    action: ACCEPT
    reason: Correct primary location of the DPM synthase complex; consistent with
      experimental evidence.
    supported_by:
    - reference_id: Reactome:R-HSA-4717406
      supporting_text: a heterotrimeric protein embedded in the endoplasmic reticulum
        membrane
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: High-throughput mass-spectrometry membrane-proteome annotation to the
      generic membrane term. Uninformative parent of the specific ER membrane location.
    action: MARK_AS_OVER_ANNOTATED
    reason: The generic membrane (GO:0016020) term adds no information beyond the specific
      and well-supported ER membrane (GO:0005789) annotation; derived from a bulk
      NK-cell membrane proteome rather than a DPM1-focused study.
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: identified 1843 proteins with high confidence scores
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  qualifier: located_in
  review:
    summary: High-throughput proteomics annotation placing DPM1 in the nucleus, derived
      from a sperm-nucleus proteome catalogue. This contradicts the well-established
      ER-membrane localization of this integral ER glycosyltransferase.
    action: REMOVE
    reason: Spurious localization from a bulk sperm-nucleus proteomics dataset (co-purifying
      contaminant); DPM1 is an ER-membrane enzyme with no evidence of a nuclear function.
      This is a demonstrably wrong location from an untargeted HDA screen, not an experimental
      functional annotation.
    supported_by:
    - reference_id: PMID:21630459
      supporting_text: 403 different proteins have been identified from the isolated
        sperm nuclei
    - reference_id: PMID:9724629
      supporting_text: essential for the ER localization and stable expression of
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-162721
  qualifier: located_in
  review:
    summary: Reactome TAS annotation locating the DPM synthase reaction at the ER
      membrane.
    action: ACCEPT
    reason: Correct location; the mannosyltransferase reaction occurs at the ER membrane.
    supported_by:
    - reference_id: Reactome:R-HSA-162721
      supporting_text: a heterotrimeric protein embedded in
        the endoplasmic reticulum
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4719354
  qualifier: located_in
  review:
    summary: Reactome TAS annotation (defective DPM3 reaction) placing the DPM synthase
      at the ER membrane.
    action: ACCEPT
    reason: Correct ER-membrane location for the DPM synthase complex that includes
      DPM1.
    supported_by:
    - reference_id: Reactome:R-HSA-4719354
      supporting_text: Defective DPM3 does not transfer mannose to DOLP to form DOLPman
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4719375
  qualifier: located_in
  review:
    summary: Reactome TAS annotation (defective DPM2 reaction) placing the DPM synthase
      at the ER membrane.
    action: ACCEPT
    reason: Correct ER-membrane location for the DPM synthase complex that includes
      DPM1.
    supported_by:
    - reference_id: Reactome:R-HSA-4719375
      supporting_text: Defective DPM2 does not transfer mannose to DOLP to form DOLPman
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:9535917
  qualifier: located_in
  review:
    summary: Experimental annotation to the generic membrane term. DPM1 associates
      with the ER membrane (via DPM2/DPM3), but the generic membrane term is uninformative
      relative to the specific ER membrane annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: 'The specific location (ER membrane, GO:0005789) is better supported and
      more informative; the bare membrane term adds nothing. Note DPM1 itself lacks
      a transmembrane domain and is membrane-associated through DPM3. Retained rather
      than removed as it derives from an experimental study.'
    supported_by:
    - reference_id: PMID:9535917
      supporting_text: lacking a hydrophobic transmembrane
- term:
    id: GO:0004582
    label: dolichyl-phosphate beta-D-mannosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:10835346
  qualifier: enables
  review:
    summary: Direct experimental annotation of the core catalytic activity; DPM1 is
      the catalyst of the three-subunit DPM synthase complex.
    action: ACCEPT
    reason: Well-supported, exact current GOA MF term for the defining function of
      DPM1.
    supported_by:
    - reference_id: PMID:10835346
      supporting_text: catalytic DPM1 and regulatory
- term:
    id: GO:0033185
    label: dolichol-phosphate-mannose synthase complex
  evidence_type: IDA
  original_reference_id: PMID:10835346
  qualifier: part_of
  review:
    summary: Experimental annotation of DPM1 as part of the dolichol-phosphate-mannose
      synthase complex (DPM1/DPM2/DPM3). Specific and informative.
    action: ACCEPT
    reason: Directly demonstrated complex membership; DPM1 is the catalytic subunit.
    supported_by:
    - reference_id: PMID:10835346
      supporting_text: human DPM synthase consists of three
- term:
    id: GO:0004582
    label: dolichyl-phosphate beta-D-mannosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:9535917
  qualifier: enables
  review:
    summary: Experimental (complementation) annotation of the catalytic mannosyltransferase
      activity; human/mouse DPM1 restored Dol-P-Man synthesis in deficient mammalian
      cells.
    action: ACCEPT
    reason: Supports DPM1 as the mannosyltransferase; exact current GOA MF term.
    supported_by:
    - reference_id: PMID:9535917
      supporting_text: Human and mouse DPM1 cDNA restored
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:9724629
  qualifier: located_in
  review:
    summary: Experimental annotation locating DPM1 in the endoplasmic reticulum. Correct
      but at the parent (organelle) level relative to ER membrane.
    action: ACCEPT
    reason: DPM1 is an ER protein; this experimental location is accurate.
    supported_by:
    - reference_id: PMID:9724629
      supporting_text: essential for the ER localization and stable expression of
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:9535917
  qualifier: acts_upstream_of_or_within
  review:
    summary: Experimental annotation placing DPM1 upstream of GPI anchor biosynthesis,
      supplying the Dol-P-Man that donates the GPI core mannoses.
    action: KEEP_AS_NON_CORE
    reason: Downstream pathway that depends on the DPM1-produced mannosyl donor; real
      but non-core relative to the direct catalytic function.
    supported_by:
    - reference_id: PMID:9535917
      supporting_text: all three mannosyl residues in the
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:9724629
  qualifier: acts_upstream_of_or_within
  review:
    summary: Experimental annotation linking DPM1/DPM synthase to GPI anchor biosynthesis
      via provision of the Dol-P-Man mannosyl donor.
    action: KEEP_AS_NON_CORE
    reason: Downstream GPI pathway dependent on DPM1's product; real but non-core.
    supported_by:
    - reference_id: PMID:9724629
      supporting_text: Biosynthesis of glycosylphosphatidylinositol and N-glycan precursor
        is dependent
- term:
    id: GO:0033185
    label: dolichol-phosphate-mannose synthase complex
  evidence_type: IDA
  original_reference_id: PMID:9724629
  qualifier: part_of
  review:
    summary: Experimental annotation of DPM1 as part of the DPM synthase complex,
      from the study identifying DPM2 as an essential complex partner.
    action: ACCEPT
    reason: Directly supports DPM1 complex membership; specific and informative CC
      term.
    supported_by:
    - reference_id: PMID:9724629
      supporting_text: makes a complex
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:9724629
  qualifier: located_in
  review:
    summary: Experimental annotation locating DPM1 at the ER membrane, the site of
      the DPM synthase complex.
    action: ACCEPT
    reason: Correct and specific primary location; consistent with DPM2/DPM3-mediated
      ER-membrane tethering.
    supported_by:
    - reference_id: PMID:9724629
      supporting_text: essential for the ER localization and stable expression of
- term:
    id: GO:0006506
    label: GPI anchor biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:9535917
  qualifier: involved_in
  review:
    summary: Experimental annotation linking DPM1 to GPI anchor biosynthesis (duplicate
      of the acts_upstream_of_or_within annotation with involved_in qualifier). DPM1
      supplies the Dol-P-Man donor for the GPI core mannoses.
    action: KEEP_AS_NON_CORE
    reason: Downstream pathway dependent on the DPM1-produced mannosyl donor rather
      than DPM1's direct molecular function; real but non-core.
    supported_by:
    - reference_id: PMID:9535917
      supporting_text: all three mannosyl residues in the
- term:
    id: GO:0035269
    label: protein O-linked glycosylation via mannose
  evidence_type: IDA
  original_reference_id: PMID:9535917
  qualifier: involved_in
  review:
    summary: Experimental annotation linking DPM1 to protein O-mannosylation. Dol-P-Man
      produced by DPM1 is the donor for O-mannosylation (relevant to the dystroglycanopathy
      phenotype in DPM1-CDG).
    action: KEEP_AS_NON_CORE
    reason: Downstream O-mannosylation pathway that depends on the DPM1-produced Dol-P-Man
      donor rather than DPM1's direct catalytic activity; real and clinically relevant
      (alpha-dystroglycan O-mannosylation) but non-core.
    supported_by:
    - reference_id: PMID:9535917
      supporting_text: it also donates one
    - reference_id: PMID:23856421
      supporting_text: reduced α-dystroglycan immunostaining
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16280320
  qualifier: enables
  review:
    summary: IPI to DPM3 (Q9UNE7) from the study showing DPM3 tethers and stabilizes
      the catalytic DPM1 subunit at the ER membrane. Real, functionally central interaction
      but the bare protein binding term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: The DPM1-DPM3 interaction is genuine and biologically important (ER tethering,
      stabilization), but protein binding (GO:0005515) conveys no functional detail;
      the substance is captured by the complex (GO:0033185) and catalytic-MF annotations.
      Retained per policy rather than removed.
    supported_by:
    - reference_id: PMID:16280320
      supporting_text: the catalytic subunit of the enzyme, to
core_functions:
- description: Catalytic subunit of the dolichol-phosphate mannose synthase complex;
    transfers mannose from GDP-mannose to dolichyl phosphate to form dolichyl-phosphate-mannose
    (Dol-P-Man) at the ER membrane.
  molecular_function:
    id: GO:0004582
    label: dolichyl-phosphate beta-D-mannosyltransferase activity
  directly_involved_in:
  - id: GO:0180047
    label: dolichol phosphate mannose biosynthetic process
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  in_complex:
    id: GO:0033185
    label: dolichol-phosphate-mannose synthase complex
  supported_by:
  - reference_id: PMID:10835346
    supporting_text: catalytic DPM1 and regulatory
  - reference_id: PMID:9724629
    supporting_text: Mammalian DPM1 is catalytic
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10835346
  title: Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1,
    DPM2 and DPM3.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defining paper establishing the three-subunit DPM synthase complex
      (DPM1 catalytic, DPM2/DPM3 regulatory/stabilizing). Abstract-only in cache but
      title/authors match PubMed.
- id: PMID:10944123
  title: Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P
    and is regulated by DPM2.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Supports co-regulation of GPI-GnT and DPM synthase via DPM2; cited
      as an IntAct protein-binding source but is peripheral to direct DPM1 function.
- id: PMID:16280320
  title: DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered
    to and stabilized on the endoplasmic reticulum membrane by DPM3.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes DPM3-mediated ER-membrane tethering/stabilization of
      the catalytic DPM1 subunit; DPM3 loss abolishes DPM synthase activity.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Bulk NK-cell membrane proteome; supports only a generic membrane
      localization, not a DPM1-specific function.
- id: PMID:21630459
  title: Proteomic characterization of the human sperm nucleus.
  findings: []
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: Sperm-nucleus proteome catalogue used to annotate DPM1 to nucleus;
      the nuclear localization is a likely co-purifying contaminant and contradicts
      established ER localization (basis for REMOVE).
- id: PMID:23856421
  title: Congenital disorder of glycosylation due to DPM1 mutations presenting with
    dystroglycanopathy-type congenital muscular dystrophy.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: DPM1-CDG case; p.Gly152Val reduces DPM3 binding and DPM1 activity,
      with dystroglycanopathy (O-mannosylation) features.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput binary interactome map; source of a generic protein-binding
      IPI (TDO2) without demonstrated DPM1-specific relevance.
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Large-scale interactome-perturbation study; source of a generic
      protein-binding IPI without demonstrated DPM1-specific relevance.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HuRI reference binary interactome; source of a generic protein-binding
      IPI (MEOX2) without demonstrated DPM1-specific relevance.
- id: PMID:9535917
  title: A homologue of Saccharomyces cerevisiae Dpm1p is not sufficient for synthesis
    of dolichol-phosphate-mannose in mammalian cells.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cloned human/mouse DPM1; showed mammalian DPM1 lacks a transmembrane
      domain and needs an additional gene (DPM2) for Dol-P-Man synthesis.
- id: PMID:9724629
  title: 'DPM2 regulates biosynthesis of dolichol phosphate-mannose in mammalian cells:
    correct subcellular localization and stabilization of DPM1, and binding of dolichol
    phosphate.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Identified DPM2; showed DPM2 is required for ER localization/stability
      of DPM1 and that DPM1 is the catalytic subunit.
- id: Reactome:R-HSA-162699
  title: Synthesis of dolichyl-phosphate mannose
  findings: []
- id: Reactome:R-HSA-162721
  title: dolichyl phosphate + GDP-alpha-D-mannose -> dolichyl phosphate D-mannose
  findings: []
- id: Reactome:R-HSA-4717406
  title: Defective DPM1 does not transfer mannose to DOLP to form DOLPman
  findings: []
- id: Reactome:R-HSA-4719354
  title: Defective DPM3 does not transfer mannose to DOLP to form DOLPman
  findings: []
- id: Reactome:R-HSA-4719375
  title: Defective DPM2 does not transfer mannose to DOLP to form DOLPman
  findings: []
- id: file:human/DPM1/DPM1-uniprot.txt
  title: UniProtKB entry O60762 (DPM1_HUMAN)
  findings: []