DPM1

Summary: The ancestral ER-membrane activity placement is consistent with the human DPM synthase complex.

Reason: The exact human O60762 leaf descends from PAINT node PTN000092441, whose literal IBD specifies ER membrane. The target sequence matches the ungapped family alignment. Human DPM1 fractionation and the DPM1–DPM3 anchoring studies independently support this location. Target experimental evidence within the IBD is expected and is not circular support.

Summary: DPM1 supplies the mannosyl donor for dolichol-linked oligosaccharide biosynthesis.

Reason: The human leaf lies below the actual IBD node PTN000092440, with yeast and Candida experimental pathway annotations in the donor records. There is no target-specific loss of this donor-supply role. Retain the established pathway context, while distinguishing DPM1-catalyzed Dol-P-Man synthesis from the subsequent glycosyltransferase steps that extend the oligosaccharide. The compact catalytic core uses GO:0180047; this disposition is not a claim that PAINT ancestry is wrong.

Summary: Dolichyl-phosphate beta-D-mannosyltransferase is DPM1’s conserved catalytic activity.

Reason: The exact target path includes PTN002459128 and its literal GO:0004582 IBD. Experimental descendant support includes human DPM1 itself, which is legitimate evidence for ancestral placement. Human complementation, the membrane-anchored DPM1 fusion and human DPM1-containing reconstituted complexes establish the reaction. Retain the imported source assertion; the synthesized core makes the demonstrated complex context explicit without reclassifying DPM1 as noncatalytic.

Summary: The combined electronic mappings identify the correct DPM1 mannosyltransferase reaction.

Reason: The source mapping combines ARBA, InterPro, orthology and EC/Rhea evidence. Official O60762 assigns EC 2.4.1.83 and GDP-mannose transfer to dolichyl phosphate, matching the exact GO:0004582 definition and human experiments. ARBA00088233 explicitly outputs this activity from its family conditions; no independent rerun of the rule’s full classifier is claimed.

Summary: Refine the broad ER location to the demonstrated ER membrane association.

Reason: The UniProt subcellular-location mapping correctly places DPM1 in the ER. Human DPM1 fractionation with membrane markers and DPM3-dependent membrane tethering support ER membrane more specifically. This does not describe DPM1 as an integral transmembrane protein or negate the broader ER location.

Proposed replacements: endoplasmic reticulum membrane

Summary: Dol-P-Man synthesis supplies mannose for GPI-anchor biosynthesis.

Reason: ARBA00026293 includes the metazoan DPM-family pathway assignment, and human DPM1 complementation restores Dol-P-Man and GPI-anchored protein production in a mouse mutant host. Retain this established downstream pathway context. DPM1 produces the lipid-linked donor; it is not the GPI-N-acetylglucosaminyltransferase or a GPI mannosyltransferase. The separate regulatory association of DPM2 with GPI-GnT in PMID:10944123 is not transferred to DPM1.

Summary: Replace Dol-P formation with the actual product, dolichol phosphate mannose.

Reason: ARBA00095221 outputs GO:0043048, whose current definition concerns formation of dolichyl monophosphate. DPM1 instead consumes dolichyl phosphate and GDP-mannose to form Dol-P-Man. GO:0180047 captures the experimentally demonstrated biosynthetic step. This is a reaction-product correction, not a claim that GO:0043048 is obsolete or that it is an ancestor of GO:0180047.

Proposed replacements: dolichol phosphate mannose biosynthetic process

Summary: DPM1 associates with the anchoring subunit DPM3 in the active synthase complex.

Reason: The original human-cell study supports DPM1–DPM3 association, including DPM2-null-cell experiments. The reciprocal antibody result is limited by epitope accessibility and does not erase the positive recovery. DPM3 is an anchoring and stabilizing partner, not an independently catalytic enzyme. Retain positive generic binding under the project policy while the catalytic core and complex term express its biological role; no additional binding mechanism or quantitative stoichiometry is inferred. The DPM3-specific abstract finding under PMID:10835346 supplies the association context; the DPM2-stability sentence is not evidence for this pair.

Summary: Controlled tagged co-immunoprecipitation supports DPM1–DPM3 association.

Reason: The recovered original includes GST-DPM1 and FLAG-DPM3 co-immunoprecipitation with control proteins in human cells. This is positive association evidence within the synthase, distinct from the paper’s DPM2-specific association with GPI-GnT. Retain generic binding as non-core because the DPM3 anchoring relation is already represented by the synthase complex; do not infer that DPM1 shares DPM2’s GPI-GnT regulatory interaction. In the recovered original, Figure 5A and its Results report FLAG-DPM3 co-precipitation with GST-DPM1 in human JY5 cells, with GST-ALDH and FLAG-ALDH controls; the GPI-donor statement is a separate pathway finding.

Summary: Human DPM1–DPM3 association is reduced by the disease-associated G152V substitution.

Reason: The original compares tagged wild-type and G152V DPM1 with DPM3 in human 293T cells and controls their expression in whole extracts. Positive wild-type recovery supports the interaction; mutant loss informs complex stability. Keep this generic binding record as non-core without assigning an independent catalytic activity to DPM3 or calling cellular co-immunoprecipitation a purified direct-interface assay.

Summary: The validated binary interaction with TDO2 supports enzyme binding.

Reason: The literal IntAct records join human DPM1 to P48775/TDO2 and include a validated two-hybrid retest, separate from the screening records. TDO2 is an experimentally characterized tryptophan dioxygenase, so GO:0019899 describes the partner class. The paper’s quadruplicate retesting and identity checks support qualitative binary capacity; dataset-wide orthogonal validation is not asserted for this pair. No native complex, metabolic regulation or DPM1 tryptophan-catabolic function is inferred.

Proposed replacements: enzyme binding

Summary: The TDO2 interaction in the allele-perturbation map supports enzyme binding.

Reason: The source-specific records contain validated DPM1–TDO2 two-hybrid binding as well as array and pooled screening entries. Recorded DPM1 positions 92 and 248 are labeled mutations with no effect on this interaction; they do not establish a new activity or clinical rescue. TDO2’s catalytic identity warrants GO:0019899. The published ORF sequencing and pairwise retesting procedures are independently verified, while no pair-specific orthogonal validation or native physiological role is claimed.

Proposed replacements: enzyme binding

Summary: The HuRI MEOX2-clone interaction supports DNA-binding transcription factor binding.

Reason: The literal partner is Q6FHY5, with a sequence ROGID matching the assayed record. It differs from reviewed MEOX2/P50222 by one glutamine deletion in an N-terminal glutamine run, outside the retained homeobox. Official MEOX2 evidence establishes sequence-specific transcription-factor function. HuRI includes a validated two-hybrid retest for the pair, supporting the binding class without demonstrating that DPM1 regulates transcription or that all natural MEOX2 products behave identically.

Proposed replacements: DNA-binding transcription factor binding

Summary: Reactome places DPM1’s donor-synthesis reaction within the dolichol-linked glycan pathway.

Reason: R-HSA-162699 explicitly carries GO:0006488 and contains the DPM1:DPM2:DPM3-catalyzed synthesis reaction R-HSA-162721. This supports the existing pathway context. The reaction makes Dol-P-Man; other enzymes extend the oligosaccharide, and the separate reorientation event in the pathway is not evidence that DPM1 is a flippase. Retain the pathway annotation without creating a second core mechanism.

Summary: Human DPM1-containing complexes synthesize Dol-P-Man in reconstituted membranes.

Reason: The original isolates GST/FLAG-DPM1-containing human complexes and detects radiolabeled lipid product after liposome reconstitution. Separate subunit experiments establish DPM1 as catalytic, DPM3 as its stabilizing anchor and DPM2 as an activity enhancer. This supports the imported catalytic annotation without claiming that isolated, unanchored DPM1 was assayed.

Summary: Human DPM1 is associated with the ER membrane in the subunit-expression experiments.

Reason: The original follows tagged human DPM1 in membrane fractions with ER, Golgi and plasma-membrane markers in hamster cells. DPM2 promotes its ER distribution and stability. The immunofluorescence panel in this study concerns tagged rat DPM2, so it is not cited as human DPM1 imaging. Later DPM3 work establishes the anchoring mechanism.

Summary: DPM1 is the catalytic member of the mammalian DPM synthase complex.

Reason: Human DPM1-containing complex purification and subunit interaction experiments identify DPM1, DPM2 and DPM3. This fits GO:0033185. Activity without DPM2 under DPM3 overexpression shows that complex membership does not entail an absolute three-subunit requirement in every engineered condition.

Summary: The original measures Dol-P-Man synthesis, not formation of Dol-P.

Reason: GDP-mannose is transferred to dolichyl phosphate in the reconstituted assay. The measured lipid product therefore matches GO:0180047. GO:0043048 instead defines synthesis of the dolichyl-monophosphate substrate. Preserve the experimental source and refine its process assignment to the demonstrated product.

Proposed replacements: dolichol phosphate mannose biosynthetic process

Summary: Human DPM1 complementation restores Dol-P-Man biosynthesis.

Reason: Human cDNA expressed in mouse class-E cells restores the radiolabeled Dol-P-Man product and GPI-related phenotypes. The microsomal assay uses dolichyl phosphate as an input, so the corrected process is formation of Dol-P-Man rather than formation of Dol-P itself. This is a human-gene complementation result in a mouse host, not purified human-protein catalysis.

Proposed replacements: dolichol phosphate mannose biosynthetic process

Summary: The membrane-anchored DPM1 construct produces Dol-P-Man from supplied Dol-P.

Reason: Human GST-DPM1 fused to the rat microsomal-ALDH membrane anchor restores microsomal DPM synthase activity in DPM2-null hamster Lec15 cells. The product is Dol-P-Man, supporting GO:0180047 rather than Dol-P biosynthesis. This experiment does not test absence of DPM3 and does not establish isolated soluble DPM1 activity.

Proposed replacements: dolichol phosphate mannose biosynthetic process

Summary: DPM3-dependent stabilization supports DPM1’s established catalytic activity.

Reason: The source abstract reports a DPM3-defective CHO line with undetectable microsomal DPM synthase activity and identifies DPM1 as the catalytic subunit. The exact human DPM1–hamster DPM3 source context is retained. The original body remains inaccessible, so specific constructs and assay panels are not reconstructed from the abstract; independent human complementation and reconstitution establish the same catalytic function.

Summary: Dol-P-Man production is the directly demonstrated biosynthetic step.

Reason: The human DPM1-containing complex converts GDP-mannose and dolichyl phosphate into Dol-P-Man in liposomes. GO:0180047 precisely names this reaction’s product and is the biosynthetic process in the single catalytic core.

Summary: DPM3 loss disrupts the DPM1-dependent mannose supply required for GPI-anchor synthesis.

Reason: The source abstract reports loss of GPI-anchored proteins and microsomal DPM synthase activity in DPM3-defective CHO cells. Retain the existing genetic pathway context, corroborated by human DPM1 complementation in PMID:9535917. This does not imply that DPM1 catalyzes glycosyl transfer onto the GPI precursor itself, and no unobserved full-text assay details are claimed.

Summary: The archaeal donor and independent human experiments support Dol-P-Man biosynthesis.

Reason: The literal donor Q8U4M3 is Pyrococcus furiosus DPM synthase. PMID:28743912 directly assays its GDP-mannose-dependent Dol-P-Man formation and resolves product-containing structures. This conserved reaction is independently established for human DPM1-containing complexes. The donor’s four-transmembrane topology and high-temperature assay conditions are not transferred to human DPM1.

Summary: Divalent-metal binding is a cofactor property of the mannosyltransferase active site.

Reason: The Q8U4M3 donor structures and enzyme assays in PMID:28743912 directly support a divalent-metal-dependent catalytic site. Human DPM1 is annotated to this conserved cofactor property and its microsomal assays use divalent ions. Retain broad metal binding as non-core rather than inventing a separate activity or claiming that the donor’s exact ion occupancy and stoichiometry were measured on human DPM1. The donor paper directly resolves GDP–Mg2+ and GDP-mannose–Mn2+ coordination and measures divalent-ion-dependent transfer by recombinant archaeal Q8U4M3; it does not measure human DPM1 metal occupancy.

Summary: The DPM1 disease-reaction model retains the enzyme at the ER membrane.

Reason: R-HSA-4717406 links through catalyst 9631868 to complex 9631831 and the DPM1-variant set 4717364, whose members reference O60762. Their modeled compartment is ER membrane. Retain this location with the source’s variant context; a failed reaction does not imply that wild-type DPM1 is inactive or that every variant retains normal activity.

Summary: Refine broad membrane association using independent DPM1 ER-membrane evidence.

Reason: The YTS membrane-proteome abstract describes fraction preparation and mass spectrometry, but the DPM1-specific peptide table and ER assignment in that experiment were not independently recovered. The positive curated membrane annotation is retained in essence. Human DPM1 fractionation and DPM3 tethering independently establish ER membrane, supporting this gene-level refinement without asserting that the YTS experiment resolved that compartment or exhaustively localizing every detected molecule.

Proposed replacements: endoplasmic reticulum membrane

Summary: DPM1 was positively identified in an isolated human sperm nuclear fraction.

Reason: The linked author thesis explicitly identifies DPM1/O60762 in the isolated human sperm-nuclear preparation (Table 8.1, physical PDF page 194, printed page 193): 13.1% sequence coverage and two peptides. Its Methods describe CTAB/digitonin isolation, repeated washes and microscopy assessment, followed by LC-MS/MS with FDR 0.05 and a minimum of two peptides including at least one unique peptide. Annex 8.2 identifies the 2011 Proteomics article and its supplementary information. These positive, target-resolved data support contextual nuclear-fraction localization. They do not establish a nuclear catalytic role, stable residency or a route of entry; DPM1-specific spectra or orthogonal imaging were not independently inspected. The preparation must not be described as crude or contaminated solely because DPM1 also acts at the ER. This differs from PMID:19946888, whose DPM1-specific target table was not recovered and whose ER-membrane refinement instead uses independent localization evidence.

Summary: The normal Reactome synthase reaction includes ER-membrane DPM1.

Reason: Reaction R-HSA-162721 links to catalyst 162705, complex R-HSA-162692 and DPM1 entity R-HSA-162865, whose reference is O60762 and compartment is ER membrane. The entity’s residues 2–260 reflect initiator-methionine processing, not an additional splice product.

Summary: DPM1 remains an ER-membrane component in the DPM3-L85S disease model.

Reason: R-HSA-4719354 links through catalyst 9631797 to DPM1:DPM2:DPM3 L85S complex 9631746. Its DPM1 member is the normal O60762 entity R-HSA-162865. Retain the location while distinguishing the defective DPM3 partner and reduced complex function from an asserted DPM1 mutation.

Summary: DPM1 is an ER-membrane member of the DPM2-Y23C disease-reaction complex.

Reason: R-HSA-4719375 links to catalyst 9631985 and complex 9631812, containing normal DPM1 entity R-HSA-162865 alongside variant DPM2. The compartment annotation agrees with direct human DPM1 localization and does not transfer the partner’s mutation or functional deficit to the DPM1 sequence.

Summary: Membrane association is supported and can be refined to ER membrane.

Reason: The original partitions GST-human DPM1 into membrane fractions in CHO and Lec15 cells, rather than demonstrating a transmembrane segment. The later marker-resolved fractionation and DPM3-anchoring experiments specify ER membrane for the functional complex. Refine using that combined evidence while retaining the older assay’s broader membrane scope.

Proposed replacements: endoplasmic reticulum membrane

Summary: Reconstituted human DPM1-containing complex has dolichyl-phosphate mannosyltransferase activity.

Reason: Radiolabeled GDP-mannose is incorporated into the lipid product after reconstitution of isolated human DPM1-containing complexes in liposomes. DPM1 is the catalytic subunit; this source-specific IDA remains valid independently of the separate EXP assertion and of the core’s conservative complex-contribution representation.

Summary: Biochemical isolation identifies DPM1 in the three-subunit synthase complex.

Reason: The human-cell isolation and reconstitution study establishes DPM1, DPM2 and DPM3 as components of DPM synthase. Its IDA complex annotation is retained alongside the distinct IPI source assertion. DPM2-independent activity under engineered DPM3 overexpression does not negate normal complex membership.

Summary: Human DPM1 complementation restores the specific Dol-P-Man-producing activity.

Reason: Expression of human DPM1 in mouse class-E mutant cells restores the radiolabeled Dol-P-Man product in microsomal assays. The assay is not purified human DPM1, and its mammalian-host dependence is explicit, but it supports the specific catalytic identity together with the later fusion and reconstitution studies. The two raw curator/date contexts that normalize to this assertion remain preserved in the source reconciliation.

Summary: Refine ER localization to its measured membrane association.

Reason: The original marker-resolved fractionation follows tagged human DPM1 in hamster cells and identifies its DPM2-supported ER-membrane pool. This supports the more informative GO:0005789. The experiment does not turn DPM1 into an integral membrane protein, and the source’s separate rat-DPM2 immunofluorescence is not a DPM1 imaging assay.

Proposed replacements: endoplasmic reticulum membrane

Summary: Human DPM1 restores the mannose-donor supply needed for GPI-anchor production.

Reason: The original measures restoration of Dol-P-Man and GPI-related products in mouse class-E cells expressing human DPM1. Retain the established pathway context and its source metadata. The performed DPM1 step is donor synthesis, while other glycosyltransferases assemble the GPI glycan; no direct GPI-mannosyltransferase activity is assigned to DPM1.

Summary: ER anchoring of human DPM1 supports GPI-anchor synthesis through Dol-P-Man production.

Reason: The human DPM1–rat microsomal-ALDH fusion restores CD59 surface expression and microsomal DPM synthase activity in DPM2-null hamster cells. This supports the pathway connection while distinguishing the engineered rescue from direct catalysis of GPI assembly. DPM3 was not removed in this experiment.

Summary: Human DPM1 associates with the mammalian DPM synthase machinery.

Reason: The original co-immunoprecipitates tagged human DPM1 with rat DPM2 in hamster cells and measures associated synthase function. The later identification of DPM3 revises the interpretation of the DPM1 C-terminal contact: DPM3 is the direct anchoring partner. This refines the interaction architecture without invalidating DPM1 complex membership or requiring all three subunits to have been identified in the earlier paper.

Summary: The original fractionation supports DPM1 association with ER membranes.

Reason: Tagged human DPM1 follows the ER membrane fraction when DPM2 supports its localization and stability. The later DPM3 studies identify the membrane-tethering partner. These are compatible gene-level location observations with explicit human-construct/hamster-host scope, not evidence for a DPM1 transmembrane helix.

Summary: DPM1-dependent donor synthesis supports the established GPI-anchor pathway annotation.

Reason: Human DPM1 rescue in mouse class-E cells restores Dol-P-Man and GPI-related biosynthesis. Keep this original assertion, distinct from the separately imported source context, while describing the molecular role accurately as provision of lipid-linked mannose rather than direct construction of the GPI glycan.

Summary: DPM1 supplies the mannose donor used in protein O-mannosylation.

Reason: The original PMID:9535917 human experiments establish Dol-P-Man synthesis; its explicit introductory O-mannosylation example concerns yeast, so it is not presented as a measured human protein-O-mannosylation assay. Independent human DPM1 disease evidence in PMID:23856421 links impaired DPM synthase to reduced alpha-dystroglycan glycoepitope staining. Retain the established donor-supply pathway context, without assigning DPM1 the transfer of mannose onto serine or threonine residues.

Summary: The reported association with CHIP/STUB1 supports ubiquitin protein ligase binding.

Reason: The source abstract explicitly reports strong association of free DPM1 with CHIP, the chaperone-dependent E3 ubiquitin ligase STUB1, in the context of DPM1 degradation without DPM3. This positive association and STUB1’s independently established E3 identity justify GO:0031625. The original body was not recovered, so the precise construct, contact interface and ubiquitination mechanism are not independently resolved; the refinement does not assign E3 activity to DPM1.

Proposed replacements: ubiquitin protein ligase binding