DPM1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation placing DPM1 activity at the ER membrane, consistent with the experimentally established ER-membrane localization of the DPM synthase complex. 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. Supporting Evidence: PMID:16280320 the catalytic subunit of the enzyme, to PMID:9724629 essential for the ER localization and stable expression of
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: PMID:9535917 It donates four mannosyl residues in the
GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: PMID:9724629 Mammalian DPM1 is catalytic PMID:10835346 catalytic DPM1 and regulatory
GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity	IEA GO_REF:0000120	ACCEPT	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. Reason: The IEA mapping is to the correct, specific molecular function and matches the experimentally verified catalytic activity. Supporting Evidence: file:human/DPM1/DPM1-uniprot.txt EC=2.4.1.83
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation to the endoplasmic reticulum from the UniProt subcellular location keyword mapping. Correct but less specific than the ER membrane term. Reason: DPM1 localizes to the ER; this parent-level location is accurate, though ER membrane (GO:0005789) is the more precise term. Supporting Evidence: file:human/DPM1/DPM1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum
GO:0006506 GPI anchor biosynthetic process	IEA GO_REF:0000117	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:9535917 all three mannosyl residues in the
GO:0043048 dolichyl monophosphate biosynthetic process	IEA GO_REF:0000117	ACCEPT	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. 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). Supporting Evidence: PMID:10835346 catalytic DPM1 and regulatory
GO:0005515 protein binding	IPI PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	MARK AS OVER ANNOTATED	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. 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. Supporting Evidence: PMID:10835346 DPM1 requires DPM2 for its stable expression
GO:0005515 protein binding	IPI PMID:10944123 Initial enzyme for glycosylphosphatidylinositol biosynthesis...	MARK AS OVER ANNOTATED	Summary: IPI to DPM3 (Q9P2X0) sourced from IntAct via the PIG-P/DPM2 GPI-GnT regulation paper. Bare protein binding term is uninformative. 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. Supporting Evidence: PMID:10944123 generates a mannosyl donor for GPI
GO:0005515 protein binding	IPI PMID:23856421 Congenital disorder of glycosylation due to DPM1 mutations p...	MARK AS OVER ANNOTATED	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. 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. Supporting Evidence: PMID:23856421 reduced binding to DPM3, an essential,
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: IPI to TDO2 (P48775) from a proteome-scale binary interactome map. No evidence this reflects a specific DPM1 function; bare protein binding term. 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.
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: IPI to TDO2 (P48775) from a large-scale interactome-perturbation study. Bare protein binding term, no functional information. Reason: High-throughput interactome-derived interaction; uninformative MF term with no established DPM1-specific function. Retained, not removed.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: IPI to MEOX2 (Q6FHY5) from the HuRI reference binary interactome map. Bare protein binding term. Reason: Systematic Y2H interactome hit to an unrelated transcription factor; uninformative generic MF term without demonstrated biological relevance to DPM1. Retained per policy.
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	TAS Reactome:R-HSA-162699	ACCEPT	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. Reason: Correctly places DPM1 within dolichol-linked oligosaccharide biosynthesis as the source of the mannosyl donor; consistent with the phylogenetic annotation. Supporting Evidence: Reactome:R-HSA-162699 the donor of mannose groups in the synthesis of the dolichyl pyrophosphate-linked precursor oligosaccharide in asparagine-linked glycosylation
GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity	EXP PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	ACCEPT	Summary: Experimental annotation of the core catalytic activity of DPM1 in the DPM synthase complex. This is the defining, verified molecular function. Reason: Direct experimental evidence that DPM1 is the catalytic subunit generating Dol-P-Man; the exact current GOA MF term. Supporting Evidence: PMID:10835346 catalytic DPM1 and regulatory
GO:0005789 endoplasmic reticulum membrane	NAS PMID:9724629 DPM2 regulates biosynthesis of dolichol phosphate-mannose in...	ACCEPT	Summary: Non-traceable/author-statement annotation (ComplexPortal) locating DPM1 at the ER membrane, where the DPM synthase complex resides. 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. Supporting Evidence: PMID:9724629 essential for the ER localization and stable expression of
GO:0033185 dolichol-phosphate-mannose synthase complex	IPI PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	ACCEPT	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. Reason: Directly demonstrated three-subunit complex; DPM1 is the catalytic member. Correct and specific cellular-component annotation. Supporting Evidence: PMID:10835346 human DPM synthase consists of three
GO:0043048 dolichyl monophosphate biosynthetic process	IDA PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	ACCEPT	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. 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. Supporting Evidence: PMID:10835346 catalytic DPM1 and regulatory
GO:0043048 dolichyl monophosphate biosynthetic process	IDA PMID:9535917 A homologue of Saccharomyces cerevisiae Dpm1p is not suffici...	ACCEPT	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. Reason: Functional complementation demonstrates DPM1's role in synthesis of the dolichyl-phosphate mannosyl donor; supports the process annotation. Supporting Evidence: PMID:9535917 Human and mouse DPM1 cDNA restored
GO:0043048 dolichyl monophosphate biosynthetic process	IDA PMID:9724629 DPM2 regulates biosynthesis of dolichol phosphate-mannose in...	ACCEPT	Summary: Experimental annotation from the DPM2 study showing DPM1 is the catalytic component of the Dol-P-Man synthesis reaction at the ER. Reason: Supports DPM1's role in dolichyl-phosphate mannose synthesis; a broader process term compatible with GO:0180047. Supporting Evidence: PMID:9724629 Mammalian DPM1 is catalytic
GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity	IGI PMID:16280320 DPM1, the catalytic subunit of dolichol-phosphate mannose sy...	ACCEPT	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). Reason: Consistent with DPM1 being the catalyst; the exact current GOA MF term. Supporting Evidence: PMID:16280320 the catalytic subunit of the enzyme, to
GO:0180047 dolichol phosphate mannose biosynthetic process	IDA PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	ACCEPT	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. 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. Supporting Evidence: PMID:10835346 catalytic DPM1 and regulatory
GO:0006506 GPI anchor biosynthetic process	IGI PMID:16280320 DPM1, the catalytic subunit of dolichol-phosphate mannose sy...	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:16280320 required for synthesis of the
GO:0180047 dolichol phosphate mannose biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity annotation to dolichol phosphate mannose biosynthetic process, transferred from an ortholog. Matches the experimentally established core process. Reason: Correct and specific process annotation, concordant with the IDA evidence for the same term. Supporting Evidence: PMID:10835346 catalytic DPM1 and regulatory
GO:0046872 metal ion binding	ISS GO_REF:0000024	KEEP AS NON CORE	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. 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. Supporting Evidence: file:human/DPM1/DPM1-uniprot.txt Binds 1 divalent metal cation
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4717406	ACCEPT	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). Reason: Correct primary location of the DPM synthase complex; consistent with experimental evidence. Supporting Evidence: Reactome:R-HSA-4717406 a heterotrimeric protein embedded in the endoplasmic reticulum membrane
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: High-throughput mass-spectrometry membrane-proteome annotation to the generic membrane term. Uninformative parent of the specific ER membrane location. 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. Supporting Evidence: PMID:19946888 identified 1843 proteins with high confidence scores
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	REMOVE	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. 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. Supporting Evidence: PMID:21630459 403 different proteins have been identified from the isolated sperm nuclei PMID:9724629 essential for the ER localization and stable expression of
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-162721	ACCEPT	Summary: Reactome TAS annotation locating the DPM synthase reaction at the ER membrane. Reason: Correct location; the mannosyltransferase reaction occurs at the ER membrane. Supporting Evidence: Reactome:R-HSA-162721 a heterotrimeric protein embedded in the endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4719354	ACCEPT	Summary: Reactome TAS annotation (defective DPM3 reaction) placing the DPM synthase at the ER membrane. Reason: Correct ER-membrane location for the DPM synthase complex that includes DPM1. Supporting Evidence: Reactome:R-HSA-4719354 Defective DPM3 does not transfer mannose to DOLP to form DOLPman
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4719375	ACCEPT	Summary: Reactome TAS annotation (defective DPM2 reaction) placing the DPM synthase at the ER membrane. Reason: Correct ER-membrane location for the DPM synthase complex that includes DPM1. Supporting Evidence: Reactome:R-HSA-4719375 Defective DPM2 does not transfer mannose to DOLP to form DOLPman
GO:0016020 membrane	IDA PMID:9535917 A homologue of Saccharomyces cerevisiae Dpm1p is not suffici...	MARK AS OVER ANNOTATED	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. 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. Supporting Evidence: PMID:9535917 lacking a hydrophobic transmembrane
GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity	IDA PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	ACCEPT	Summary: Direct experimental annotation of the core catalytic activity; DPM1 is the catalyst of the three-subunit DPM synthase complex. Reason: Well-supported, exact current GOA MF term for the defining function of DPM1. Supporting Evidence: PMID:10835346 catalytic DPM1 and regulatory
GO:0033185 dolichol-phosphate-mannose synthase complex	IDA PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	ACCEPT	Summary: Experimental annotation of DPM1 as part of the dolichol-phosphate-mannose synthase complex (DPM1/DPM2/DPM3). Specific and informative. Reason: Directly demonstrated complex membership; DPM1 is the catalytic subunit. Supporting Evidence: PMID:10835346 human DPM synthase consists of three
GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity	IDA PMID:9535917 A homologue of Saccharomyces cerevisiae Dpm1p is not suffici...	ACCEPT	Summary: Experimental (complementation) annotation of the catalytic mannosyltransferase activity; human/mouse DPM1 restored Dol-P-Man synthesis in deficient mammalian cells. Reason: Supports DPM1 as the mannosyltransferase; exact current GOA MF term. Supporting Evidence: PMID:9535917 Human and mouse DPM1 cDNA restored
GO:0005783 endoplasmic reticulum	IDA PMID:9724629 DPM2 regulates biosynthesis of dolichol phosphate-mannose in...	ACCEPT	Summary: Experimental annotation locating DPM1 in the endoplasmic reticulum. Correct but at the parent (organelle) level relative to ER membrane. Reason: DPM1 is an ER protein; this experimental location is accurate. Supporting Evidence: PMID:9724629 essential for the ER localization and stable expression of
GO:0006506 GPI anchor biosynthetic process	IDA PMID:9535917 A homologue of Saccharomyces cerevisiae Dpm1p is not suffici...	KEEP AS NON CORE	Summary: Experimental annotation placing DPM1 upstream of GPI anchor biosynthesis, supplying the Dol-P-Man that donates the GPI core mannoses. Reason: Downstream pathway that depends on the DPM1-produced mannosyl donor; real but non-core relative to the direct catalytic function. Supporting Evidence: PMID:9535917 all three mannosyl residues in the
GO:0006506 GPI anchor biosynthetic process	IDA PMID:9724629 DPM2 regulates biosynthesis of dolichol phosphate-mannose in...	KEEP AS NON CORE	Summary: Experimental annotation linking DPM1/DPM synthase to GPI anchor biosynthesis via provision of the Dol-P-Man mannosyl donor. Reason: Downstream GPI pathway dependent on DPM1's product; real but non-core. Supporting Evidence: PMID:9724629 Biosynthesis of glycosylphosphatidylinositol and N-glycan precursor is dependent
GO:0033185 dolichol-phosphate-mannose synthase complex	IDA PMID:9724629 DPM2 regulates biosynthesis of dolichol phosphate-mannose in...	ACCEPT	Summary: Experimental annotation of DPM1 as part of the DPM synthase complex, from the study identifying DPM2 as an essential complex partner. Reason: Directly supports DPM1 complex membership; specific and informative CC term. Supporting Evidence: PMID:9724629 makes a complex
GO:0005789 endoplasmic reticulum membrane	IDA PMID:9724629 DPM2 regulates biosynthesis of dolichol phosphate-mannose in...	ACCEPT	Summary: Experimental annotation locating DPM1 at the ER membrane, the site of the DPM synthase complex. Reason: Correct and specific primary location; consistent with DPM2/DPM3-mediated ER-membrane tethering. Supporting Evidence: PMID:9724629 essential for the ER localization and stable expression of
GO:0006506 GPI anchor biosynthetic process	IDA PMID:9535917 A homologue of Saccharomyces cerevisiae Dpm1p is not suffici...	KEEP AS NON CORE	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. Reason: Downstream pathway dependent on the DPM1-produced mannosyl donor rather than DPM1's direct molecular function; real but non-core. Supporting Evidence: PMID:9535917 all three mannosyl residues in the
GO:0035269 protein O-linked glycosylation via mannose	IDA PMID:9535917 A homologue of Saccharomyces cerevisiae Dpm1p is not suffici...	KEEP AS NON CORE	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). 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. Supporting Evidence: PMID:9535917 it also donates one PMID:23856421 reduced α-dystroglycan immunostaining
GO:0005515 protein binding	IPI PMID:16280320 DPM1, the catalytic subunit of dolichol-phosphate mannose sy...	MARK AS OVER ANNOTATED	Summary: IPI whose WITH/FROM is UniProtKB:Q9UNE7, i.e. STUB1/CHIP (not DPM3, which is Q9P2X0). The same study reports that free, unassembled DPM1 is strongly associated with the chaperone-dependent E3 ubiquitin ligase CHIP and is rapidly degraded by the proteasome when DPM3 is absent. Real interaction, but the bare protein binding term is uninformative. Reason: The DPM1-CHIP association is genuine but reflects chaperone-dependent quality control of unassembled DPM1 (ubiquitin-dependent degradation of the free subunit) rather than a functional partnership in Dol-P-Man synthesis. Protein binding (GO:0005515) conveys no functional detail, and the underlying biology would be better captured by a degradation/quality-control term than by a bare binding term. Retained per policy rather than removed. Note that the DPM1-DPM3 interaction also reported in this paper is annotated separately on the GO:0005515 rows carrying UniProtKB:Q9P2X0. Supporting Evidence: PMID:16280320 Free DPM1 was strongly associated with the C terminus of Hsc70-interacting protein (CHIP), a chaperone-dependent E3 ubiquitin ligase

Gene Description

Existing Annotations Review

Core Functions

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.

References

Suggested Questions for Experts

Suggested Experiments

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Notes

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