ALG3

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	ACCEPT	Summary: The inherited ER location matches the compartment of ALG3 precursor synthesis. Reason: PAINT places ER localization at PTN000291297. Human ALG3 membrane-associated reaction evidence and the protected UniProt location support this ancestral assertion. Retain the organelle resolution of the source; the more specific membrane and lumenal-face assertions describe the same core site and do not make the broad location non-core. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000291297 SUPPORTS TRANSFER The cached PTHR12646 PAINT table places ER localization at this IBD node. Human ALG3 membrane biology supports the inherited organelle assertion. Supporting Evidence: file:human/ALG3/ALG3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-446188 This reaction occurs in the ER lumen and uses a different mannose donor (dolichyl-phosphate-mannose) than the previous steps.
GO:0009101 glycoprotein biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: ALG3 performs a glycan-precursor synthesis step used in glycoprotein biosynthesis. Reason: The PTN000291297 glycoprotein-biosynthesis assertion is supported by the human enzyme reaction and abnormal glycoprotein glycans in ALG3 deficiency. The gene product performs mannose transfer during precursor assembly, so its participation is more than a phenotype of necessity. The broad process remains valid core biology at the PAINT resolution. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000291297 SUPPORTS TRANSFER The cached PTHR12646 IBD assigns glycoprotein biosynthesis to this node. Human ALG3 catalyzes precursor assembly, supporting the inherited role at this broad process resolution. Supporting Evidence: PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol PMID:10581255 N-glycosylation is abnormal because of the transfer of truncated oligosaccharides in addition to that of full-length oligosaccharides and because of the incomplete utilization of N-glycosylation sites.
GO:0052925 dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT activity identifies the specific inherited ALG3 mannose-transfer reaction. Reason: PTN000291297 carries the donor/acceptor-specific activity. Human fibroblast membrane assays and human cDNA complementation of yeast alg3 support the conserved enzyme identity. The human target contributing experimental evidence to the ancestral inference is legitimate, not circular. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000291297 SUPPORTS TRANSFER The cached PTHR12646 IBD assigns the specific reaction to this node. Human target evidence supports inheritance; its presence among descendant experimental evidence is legitimate. Supporting Evidence: PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol PMID:10581255 The mannosyltransferase is the structural and functional orthologue of the Saccharomyces cerevisiae ALG3 gene.
GO:0000030 mannosyltransferase activity	IEA GO_REF:0000002	MODIFY	Summary: The InterPro mannosyltransferase assertion can be resolved to the specific human reaction. Reason: InterPro:IPR007873 supports the ALG3-family mannosyltransferase assignment. Human functional evidence additionally identifies the Dol-P-Man donor, Man5GlcNAc2-PP-Dol acceptor and alpha-1,3 linkage. Refine the broad MF to GO:0052925 for this target without claiming that the family mapping itself proves every descendant substrate. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR007873 SUPPORTS TRANSFER The family mapping supplies true broad mannosyltransferase activity. Independent human reaction evidence supports a target-specific MF refinement without making the source a wrong-family assignment. Proposed replacements: dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity Supporting Evidence: file:human/ALG3/ALG3-uniprot.txt Belongs to the glycosyltransferase ALG3 family. PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: The UniProt mapping places ALG3 in the ER membrane. Reason: UniProtKB-SubCell:SL-0097 maps the curated ER-membrane location. The membrane-associated lipid-linked reaction and human ALG3 topology agree with this source, with no demonstrated location-mapping defect. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0097 SUPPORTS TRANSFER The mapped ER-membrane location agrees with the protected human record and membrane reaction. Supporting Evidence: file:human/ALG3/ALG3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-446188 This reaction occurs in the ER lumen and uses a different mannose donor (dolichyl-phosphate-mannose) than the previous steps.
GO:0006487 protein N-linked glycosylation	IEA GO_REF:0000117	ACCEPT	Summary: ALG3 catalyzes precursor assembly within protein N-linked glycosylation. Reason: ARBA:ARBA00085866 supplies the seeded electronic process assertion. The cached rule catalog identifies this output, although the precise historical condition that matched ALG3 was not recovered. Independent human donor/acceptor assays and glycan profiles support the target process: ALG3 makes the lipid-linked precursor used for N-glycosylation. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00085866 UNRESOLVED The seeded rule ID and GO:0006487 output occur in the local catalog. The exact historical ALG3-matching condition was not recovered; independently verified human chemistry supports the target process, so no rule failure is inferred. Supporting Evidence: PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol PMID:10581255 N-glycosylation is abnormal because of the transfer of truncated oligosaccharides in addition to that of full-length oligosaccharides and because of the incomplete utilization of N-glycosylation sites.
GO:0052925 dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: The combined Rhea/EC mapping identifies the exact ALG3 catalytic reaction. Reason: RHEA:29527 and EC:2.4.1.258 specify Dol-P-Man-dependent addition to Man5GlcNAc2-PP-Dol. The protected human catalytic record and original functional experiments agree with GO:0052925. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:29527 SUPPORTS TRANSFER This source identifies the Dol-P-Man-dependent transfer to Man5GlcNAc2-PP-Dol in the protected human catalytic record. EC:2.4.1.258 SUPPORTS TRANSFER This source identifies the Dol-P-Man-dependent transfer to Man5GlcNAc2-PP-Dol in the protected human catalytic record. Supporting Evidence: PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol file:human/ALG3/ALG3-uniprot.txt EC=2.4.1.258
GO:0005515 protein binding	IPI PMID:21516116 Next-generation sequencing to generate interactome datasets.	REMOVE	Summary: Stitch-seq provides experimentally retested binary interaction evidence. Reason: The study combines pooled sequencing with pairwise yeast two-hybrid retesting. Preserve the curated interaction evidence, but remove the uninformative protein-binding term under the review policy. The inspected evidence does not resolve an additional specific ALG3 molecular function; this decision does not declare the reported pair false or discard it because of study size. Supporting Evidence: PMID:21516116 We experimentally retested by pairwise Y2H all sISTs starting from fresh yeast transformants stored in our collection
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	REMOVE	Summary: The disease-variant study profiles human molecular interactions. Reason: The paper functionally profiles missense variants using interaction assays. Its locally extracted full text is partial, and the exact ALG3 pair-level experiment was not independently recovered. Remove the generic protein-binding term for its lack of functional specificity while retaining the IPI provenance and uncertainty about the uninspected assay details; this is not a finding that the interaction is incorrect. Supporting Evidence: PMID:25910212 Here we functionally profile several thousand missense mutations across a spectrum of Mendelian disorders using various interaction assays.
GO:0005515 protein binding	IPI PMID:29547901 Molecular partners of hNOT/ALG3, the human counterpart of th...	REMOVE	Summary: The dedicated ALG3 study reports homodimers and interactions with several cellular partners. Reason: The cached abstract reports Y2H interactions, ALG3 homodimers, and in vivo interactions with OSBP, OSBPL9, LRP1, SYPL1 and CREB3. It distinguishes binding to the CREB3 precursor from binding to its proteolytic products. These interactions do not resolve an ALG3 protease or adaptor molecular function. Remove the generic protein-binding term for lack of functional specificity while preserving the positive interaction results. A separate CREB3-activation process assertion would require resolving the work performed by ALG3. Supporting Evidence: PMID:29547901 We disclose the building of hNOT/ALG3 homodimers PMID:29547901 its in vivo interaction with the functionally linked proteins OSBP, OSBPL9 and LRP1, the SYPL1 protein and the transcription factor CREB3
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	REMOVE	Summary: The variant-interaction map includes yeast two-hybrid assays and orthogonal validation of a subset. Reason: PMID:31515488 experimentally tests the effects of missense variants on protein interactions. Its PCA retesting supports study quality, without demonstrating that the specific ALG3 pair was among that subset. Remove the uninformative generic MF while preserving the curated interaction and source; study scale is not a reason to call a binding result false. Supporting Evidence: PMID:31515488 our PCA retest demonstrated the reproducibility and validated the quality of our Y2H-generated SNV-interaction network
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI records binary interactions through repeated yeast two-hybrid screens. Reason: The source uses three Y2H assay versions, repeated screens, pairwise retesting and sequence confirmation. These support experimentally assessed interaction data; the generic protein-binding term still does not identify a specific ALG3 molecular function. Remove that term without denying the partners or assuming every ALG3 interaction was individually validated in an orthogonal assay. Supporting Evidence: PMID:32296183 We screened this search space a total of nine times with a panel of three Y2H assay versions
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	TAS Reactome:R-HSA-446193	ACCEPT	Summary: ALG3 adds the sixth mannose during dolichol-linked oligosaccharide assembly. Reason: The Reactome parent pathway contains the ALG3 transfer event R-HSA-446188. Human microsomal donor/acceptor experiments identify the blocked reaction, and human cDNA complementation restores precursor extension in yeast. ALG3 directly performs this biosynthetic step. Supporting Evidence: Reactome:R-HSA-446188 The sixth mannose is added to the N-glycan precursor. PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol PMID:10581255 The defect results in the accumulation of the LLO intermediate and, due to its leaky nature, a residual formation of full-length LLOs.
GO:0098553 lumenal side of endoplasmic reticulum membrane	IC PMID:10581255 Carbohydrate deficient glycoprotein syndrome type IV: defici...	ACCEPT	Summary: ALG3 performs its donor-dependent reaction at the lumenal face of the ER membrane. Reason: This IC assertion is a curator inference from the lipid-linked pathway topology and the Dol-P-Man-dependent extension step, not a direct imaging result claimed from the abstract. The same evidence is explicitly represented in GO-CAM 65c57c3400000687, activity 65d7e4ac00000326, with GO:0052925, GO:0098553 and GO:0006488. Reactome independently records the reaction compartment. Supporting Evidence: Reactome:R-HSA-446188 This reaction occurs in the ER lumen and uses a different mannose donor (dolichyl-phosphate-mannose) than the previous steps. PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol
GO:0005789 endoplasmic reticulum membrane	IDA PMID:10581255 Carbohydrate deficient glycoprotein syndrome type IV: defici...	ACCEPT	Summary: The human ALG3 reaction is associated with the ER membrane. Reason: The original full paper measures transferase activity in fibroblast microsomal extracts and discusses the multipass sequence and C-terminal ER retrieval motif. Together with the curated human membrane location this supports the seeded IDA compartment. The recovered assay is not purified human protein or an independently identified microscopy experiment, and those methods are not attributed to the source. Supporting Evidence: file:human/ALG3/ALG3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol
GO:0006487 protein N-linked glycosylation	IDA PMID:10581255 Carbohydrate deficient glycoprotein syndrome type IV: defici...	ACCEPT	Summary: Human ALG3 deficiency changes the glycans transferred onto proteins. Reason: The original study measures both lipid-linked precursors and protein-linked glycans, finding truncated chains and incomplete site occupancy. Its donor/acceptor assays and cDNA complementation identify ALG3 as the enzyme supplying a precursor-assembly step of protein N-linked glycosylation, rather than merely a protein whose phenotype correlates with glycosylation. Supporting Evidence: PMID:10581255 N-glycosylation is abnormal because of the transfer of truncated oligosaccharides in addition to that of full-length oligosaccharides and because of the incomplete utilization of N-glycosylation sites. PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	IDA PMID:10581255 Carbohydrate deficient glycoprotein syndrome type IV: defici...	ACCEPT	Summary: Human biochemical experiments place ALG3 in lipid-linked oligosaccharide biosynthesis. Reason: Patient cells accumulate Man5 precursor and show defective Dol-P-Man-dependent transfer in microsomal assays; normal human ALG3 cDNA complements yeast alg3. Residual complete precursors remain detectable, so the disease allele is leaky rather than a universal complete block. Supporting Evidence: PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol PMID:10581255 The defect results in the accumulation of the LLO intermediate and, due to its leaky nature, a residual formation of full-length LLOs. PMID:10581255 The mannosyltransferase is the structural and functional orthologue of the Saccharomyces cerevisiae ALG3 gene.
GO:0052925 dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity	IDA PMID:10581255 Carbohydrate deficient glycoprotein syndrome type IV: defici...	ACCEPT	Summary: Human biochemical and complementation evidence identifies the specific ALG3 transferase. Reason: The cached human study identifies the enzyme transferring mannose from Dol-P-Man to Man5GlcNAc2-PP-dolichol and establishes structural and functional orthology to yeast ALG3. The protected human UniProt reaction specifies the alpha-1,3 linkage. These findings support the precise catalytic assignment. The reported leaky defect leaves residual full-length precursors; it does not establish complete loss of activity or purified-human-enzyme kinetics. Supporting Evidence: PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol PMID:10581255 The defect results in the accumulation of the LLO intermediate and, due to its leaky nature, a residual formation of full-length LLOs.
GO:0000033 alpha-1,3-mannosyltransferase activity	TAS Reactome:R-HSA-446188	MODIFY	Summary: The normal Reactome event resolves the donor and acceptor beyond the broad linkage-specific MF. Reason: R-HSA-446188 describes sixth-mannose addition using Dol-P-Man. Refine the true alpha-1,3-mannosyltransferase assertion to the established substrate-specific GO:0052925; this preserves the activity category and expresses the known human chemistry. Proposed replacements: dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity Supporting Evidence: Reactome:R-HSA-446188 The sixth mannose is added to the N-glycan precursor. Reactome:R-HSA-446188 This reaction occurs in the ER lumen and uses a different mannose donor (dolichyl-phosphate-mannose) than the previous steps. PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol
GO:0000033 alpha-1,3-mannosyltransferase activity	TAS Reactome:R-HSA-4720473	MODIFY	Summary: The disease event identifies the normal ALG3 reaction that pathogenic variants impair. Reason: R-HSA-4720473 first describes normal sixth-mannose transfer before the defective-variant context. Refine the broad MF to the resolved normal reaction GO:0052925. This gene-level assignment does not claim that every disease variant retains normal activity; the original disease-event source and the leaky G118D evidence are preserved. Proposed replacements: dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity Supporting Evidence: Reactome:R-HSA-4720473 adds the sixth mannose (although the first to be derived from dolichyl-phosphate-mannose, DOLPman) PMID:10581255 the mannosyltransferase that transfers mannose from dolichyl-phosphate mannose on to the lipid-linked oligosaccharide (LLO) intermediate Man(5)GlcNAc(2)-PP-dolichol PMID:10581255 The defect results in the accumulation of the LLO intermediate and, due to its leaky nature, a residual formation of full-length LLOs.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4720473	ACCEPT	Summary: The disease reaction retains the ER-membrane compartment of ALG3. Reason: The event describes defective ALG3 in the normal membrane reaction context, consistent with the human location and lipid-linked donor/acceptor chemistry. It is not treated as a direct localization assay for each listed pathogenic variant. Supporting Evidence: file:human/ALG3/ALG3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-446188 This reaction occurs in the ER lumen and uses a different mannose donor (dolichyl-phosphate-mannose) than the previous steps.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-446188	ACCEPT	Summary: The normal Reactome mannose-transfer reaction acts at the ER membrane. Reason: R-HSA-446188 specifies a lumenal reaction using a lipid-linked donor, and the protected human record specifies ER membrane. Retain the source membrane resolution alongside the separate lumenal-side annotation. Supporting Evidence: file:human/ALG3/ALG3-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Reactome:R-HSA-446188 This reaction occurs in the ER lumen and uses a different mannose donor (dolichyl-phosphate-mannose) than the previous steps.

Gene Description

Existing Annotations Review

Core Functions

Transfers mannose from Dol-P-Man to Man5GlcNAc2-PP-dolichol in an alpha-1,3 linkage at the lumenal face of the ER membrane, producing the Man6 intermediate during assembly of the lipid-linked precursor used for protein N-linked glycosylation.

References

Suggested Questions for Experts

📚 Additional Documentation

Notes

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