DPM3

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) localization of DPM3 to the ER membrane, where the DPM synthase complex acts. This is consistent with the experimentally determined localization and with DPM3 being a multi-pass ER membrane protein. Reason: The ER membrane is the established site of the DPM synthase complex and of DPM3, corroborated by IDA localization and the UniProt subcellular location. Supporting Evidence: file:human/DPM3/DPM3-uniprot.txt Endoplasmic reticulum membrane; Multi-pass
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) involvement in dolichol-linked oligosaccharide biosynthesis. DPM synthase produces Dol-P-Man, the mannosyl donor consumed during assembly of the dolichol-linked oligosaccharide (N-glycan precursor), so DPM3 contributes to this process as part of the complex. Reason: DPM3 is required for DPM synthase activity, which supplies the Dol-P-Man mannosyl donor used in dolichol-linked oligosaccharide (LLO) assembly and downstream glycosylation. Supporting Evidence: PMID:10835346 N-glycan and protein O- and C-mannosylation.
GO:0033185 dolichol-phosphate-mannose synthase complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of DPM3 as part of the dolichol-phosphate-mannose synthase complex. This is the defining complex membership of DPM3 and is strongly supported experimentally. Reason: DPM3 is one of the three subunits (DPM1/DPM2/DPM3) of the human DPM synthase complex; complex membership is directly established experimentally. Supporting Evidence: PMID:10835346 The third subunit, DPM3, comprises 92 amino acids associated with DPM1
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation of ER membrane localization from the UniProt subcellular-location vocabulary mapping. Matches the curated UniProt location and the experimental IDA evidence. Reason: The IEA ER-membrane localization agrees with the UniProt subcellular location and with experimental evidence; correctly mapped. Supporting Evidence: file:human/DPM3/DPM3-uniprot.txt Endoplasmic reticulum membrane; Multi-pass
GO:0009101 glycoprotein biosynthetic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO (IEA) mapping to glycoprotein biosynthesis. This is a broad downstream process term - DPM synthase supplies the Dol-P-Man donor for protein glycosylation, so DPM3 contributes indirectly, but glycoprotein biosynthesis is a general consequence rather than DPM3's direct/core role. Reason: Correct in direction (DPM synthase output feeds glycoprotein biosynthesis) but broad and downstream; retained as a non-core process. The core BP is the biosynthesis of the Dol-P-Man donor itself. Supporting Evidence: file:human/DPM3/DPM3-uniprot.txt Protein modification; protein glycosylation.
GO:0005515 protein binding	IPI PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation capturing physical interaction of DPM3 with DPM1 (O60762), DPM2 (O94777), and Xenopus Dpm2 (Q9Z325). These are the functionally central interactions of DPM3, but the bare "protein binding" term is uninformative about the anchoring/adaptor role. Reason: The DPM1/DPM2 interactions are real and central, but "protein binding" is an uninformative molecular-function term. The specific biology is better represented by the protein-membrane adaptor activity MF (GO:0043495) and the DPM synthase complex CC (GO:0033185), both already annotated. Supporting Evidence: PMID:10835346 via its C-terminal domain and with DPM2 via its N-terminal portion.
GO:0005515 protein binding	IPI PMID:10944123 Initial enzyme for glycosylphosphatidylinositol biosynthesis...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation from the DPM2/GPI-GnT regulation study, recording physical interaction of DPM3 with DPM1 (O60762) and DPM2 (O94777) in the shared DPM-synthase/GPI-anchor context. Reason: The interactions are genuine, but the bare "protein binding" term is uninformative; the anchoring role is captured by the protein-membrane adaptor MF and the DPM synthase complex CC terms. Supporting Evidence: PMID:10944123 DPM2, but not two other components of
GO:0005515 protein binding	IPI PMID:23856421 Congenital disorder of glycosylation due to DPM1 mutations p...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation supported by the DPM1-CDG study, which showed the pathogenic DPM1 variant has reduced binding to DPM3, an essential non-catalytic subunit - i.e. it documents the DPM1-DPM3 physical interaction. Reason: The DPM1-DPM3 interaction is real and disease-relevant, but "protein binding" is uninformative; the adaptor MF and complex CC terms convey the actual biology. Supporting Evidence: PMID:23856421 reduced binding to DPM3, an essential,
GO:0005789 endoplasmic reticulum membrane	NAS PMID:9724629 DPM2 regulates biosynthesis of dolichol phosphate-mannose in...	ACCEPT	Summary: ComplexPortal NAS annotation of ER membrane localization. The cited study established that the DPM complex resides and functions in the ER membrane (where DPM2 makes a complex with DPM1 essential for ER localization of DPM1). Reason: Consistent with all other localization evidence placing DPM3 and the DPM synthase complex in the ER membrane. Supporting Evidence: PMID:9724629 with DPM1 that is 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: ComplexPortal IPI annotation of DPM3 as part of the DPM synthase complex, based on the physical demonstration that DPM3 is the third subunit associating with DPM1 and DPM2. Reason: Directly supported experimental complex membership; this is a defining, core annotation for DPM3. Supporting Evidence: PMID:10835346 The third subunit, DPM3, comprises 92 amino acids associated with DPM1
GO:0043048 dolichyl monophosphate biosynthetic process	IDA PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	MODIFY	Summary: IDA annotation to dolichyl monophosphate (Dol-P) biosynthesis. This term denotes formation of dolichyl monophosphate, which is the SUBSTRATE of DPM synthase, not its product. DPM synthase (and thus DPM3) makes Dol-P-Man from Dol-P + GDP-mannose; it does not synthesize Dol-P itself. The evidence in PMID:10835346 concerns restoration of Dol-P-Man (DPM) biosynthesis. Reason: The term is a misfit - DPM3 contributes to biosynthesis of dolichol phosphate mannose (Dol-P-Man), not dolichyl monophosphate. The IDA evidence supports the Dol-P-Man process term instead. Proposed replacements: dolichol phosphate mannose biosynthetic process Supporting Evidence: PMID:10835346 restored the biosynthesis of DPM with an
GO:0043495 protein-membrane adaptor activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation (from ortholog Q4LDX8) to protein-membrane adaptor activity. This is the most informative molecular-function term for DPM3, whose role is to tether the catalytic DPM1 subunit (which lacks a transmembrane domain) to the ER membrane, bridging it to DPM2. This captures DPM3's true non-catalytic anchoring/scaffolding function. Reason: Best represents DPM3's core molecular function - anchoring the soluble catalytic DPM1 to the ER membrane. Directly consistent with the UniProt FUNCTION statement and experimental data. Supporting Evidence: file:human/DPM3/DPM3-uniprot.txt synthase complex; tethers catalytic subunit DPM1 to the endoplasmic
GO:0180047 dolichol phosphate mannose biosynthetic process	IDA PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	ACCEPT	Summary: IDA annotation to dolichol phosphate mannose (Dol-P-Man) biosynthesis. This is the core biological process of DPM3, which is required for assembly and activity of the DPM synthase that produces Dol-P-Man. Overexpression of DPM3 in DPM2-null Lec15 cells restored DPM biosynthesis. Reason: Correct core process, directly supported by experimental evidence that DPM3 is required for Dol-P-Man biosynthesis. Supporting Evidence: PMID:10835346 restored the biosynthesis of DPM with an
GO:0035269 protein O-linked glycosylation via mannose	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation to protein O-mannosylation. DPM synthase supplies the Dol-P-Man donor used for O-mannosylation of alpha-dystroglycan; loss of DPM3 causes an alpha-dystroglycanopathy with reduced O-mannosylation. However, this is a downstream process that consumes DPM synthase output rather than DPM3's own direct enzymatic step. Reason: Biologically connected (and the basis of the DPM3-CDG dystroglycanopathy), but DPM3 acts upstream by producing the mannosyl donor; O-mannosylation itself is performed by other enzymes. Retained as non-core. Supporting Evidence: file:human/DPM3/DPM3-uniprot.txt reduced O-mannosylation of alpha-dystroglycan.
GO:0008047 enzyme activator activity	IDA PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	KEEP AS NON CORE	Summary: IDA annotation to enzyme activator activity. DPM3 increases DPM synthase output - overexpression restored DPM biosynthesis with an increase in DPM1, and DPM3 directly stabilizes DPM1. The activation, however, is achieved through stabilization/membrane anchoring of the catalytic subunit rather than classic allosteric enzyme activation. Reason: Defensible - DPM3 raises catalytic activity of the complex - but the mechanism is structural stabilization/anchoring, which is more precisely captured by protein-membrane adaptor activity (GO:0043495). Retained as non-core rather than removed. Supporting Evidence: PMID:10835346 indicating that DPM3 directly stabilized DPM1.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4719354	ACCEPT	Summary: Reactome TAS localization of DPM3 to the ER membrane, from the pathway describing defective DPM3 failing to form Dol-P-Man. Consistent with all other ER-membrane evidence. Reason: Reactome curated localization agrees with experimental and phylogenetic ER-membrane annotations. Supporting Evidence: Reactome:R-HSA-4719354 Normally, the DPM3 subunit tethers the catalytic DPM1 subunit to the ER membrane.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: High-throughput MS detection of DPM3 in an NK-cell (YTS) membrane proteome, yielding a generic "membrane" localization. DPM3 is indeed a membrane protein, but this generic term is subsumed by the specific ER-membrane annotations. Reason: Generic "membrane" is uninformative given the well-supported ER-membrane (GO:0005789) localization; derived from a large-scale membrane-proteome screen not specific to DPM3. Supporting Evidence: PMID:19946888 Isolated membranes were
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-162721	ACCEPT	Summary: Reactome TAS localization of DPM3 to the ER membrane, from the pathway for the Dol-P-Man synthesis reaction (dolichyl phosphate + GDP-mannose -> dolichyl phosphate D-mannose) catalysed by the ER-membrane DPM synthase. Reason: Consistent with all other ER-membrane localization evidence. Supporting Evidence: Reactome:R-HSA-162721 a heterotrimeric protein embedded in the endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4717406	ACCEPT	Summary: Reactome TAS localization of DPM3 to the ER membrane, from the pathway describing defective DPM1 failing to form Dol-P-Man; the DPM complex (including DPM3) is annotated at the ER membrane. Reason: Consistent with the other ER-membrane localization annotations. Supporting Evidence: file:human/DPM3/DPM3-uniprot.txt Endoplasmic reticulum membrane; Multi-pass
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4719375	ACCEPT	Summary: Reactome TAS localization of DPM3 to the ER membrane, from the pathway describing defective DPM2 failing to form Dol-P-Man; the DPM complex (including DPM3) is annotated at the ER membrane. Reason: Consistent with the other ER-membrane localization annotations. Supporting Evidence: file:human/DPM3/DPM3-uniprot.txt Endoplasmic reticulum membrane; Multi-pass
GO:0005783 endoplasmic reticulum	IDA PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	ACCEPT	Summary: IDA localization of DPM3 to the endoplasmic reticulum. This is the parent organelle term; the more specific and equally well-supported ER membrane term is the informative localization. Reason: Correct localization, directly determined; retained (as the parent of the more specific ER-membrane term) but non-core relative to ER membrane. Supporting Evidence: file:human/DPM3/DPM3-uniprot.txt Endoplasmic reticulum membrane; Multi-pass
GO:0033185 dolichol-phosphate-mannose synthase complex	IDA PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	ACCEPT	Summary: IDA annotation (UniProt) of DPM3 as part of the DPM synthase complex, based on the direct experimental demonstration that human DPM synthase consists of DPM1, DPM2 and DPM3. Reason: Directly supported experimental complex membership; a defining core annotation. Supporting Evidence: PMID:10835346 The third subunit, DPM3, comprises 92 amino acids associated with DPM1
GO:0005789 endoplasmic reticulum membrane	IDA PMID:10835346 Human dolichol-phosphate-mannose synthase consists of three ...	ACCEPT	Summary: IDA localization of DPM3 to the ER membrane, directly determined in the study that characterized the human DPM synthase complex. Reason: Directly determined ER-membrane localization; the core, informative cellular-component annotation for DPM3. Supporting Evidence: file:human/DPM3/DPM3-uniprot.txt Endoplasmic reticulum membrane; Multi-pass

Gene Description

Existing Annotations Review

Core Functions

DPM3 is the membrane-anchoring/adaptor subunit that tethers the catalytic DPM1 subunit (which has no transmembrane domain) to the endoplasmic reticulum membrane and bridges it to DPM2, as part of the dolichol-phosphate mannose (DPM) synthase complex.

References

📚 Additional Documentation

Notes

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