ALG10 (ALG10A) is an endoplasmic reticulum membrane, multi-pass alpha-1,2-glucosyltransferase (EC 2.4.1.256) that catalyzes the final, glucose-capping step of dolichol-linked oligosaccharide (LLO) assembly. Acting on the lumenal face of the ER, it transfers glucose from dolichyl-phosphate-glucose (Dol-P-Glc, not UDP-Glc) onto the Glc2Man9GlcNAc2-PP-dolichol intermediate, adding the third and terminal alpha-1,2-linked glucose to produce the mature, fully assembled Glc3Man9GlcNAc2-PP-dolichol precursor. This mature glycan is the substrate transferred en bloc by the oligosaccharyltransferase (OST) complex onto asparagine residues of nascent polypeptides during protein N-linked glycosylation; the terminal glucose added by ALG10 is the key recognition signal for efficient OST transfer, and its subsequent glucosidase trimming feeds the calnexin/calreticulin glycoprotein quality-control cycle. ALG10 belongs to the ALG10 glucosyltransferase family (CAZy GT59).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically-inferred ER localization. ALG10 is a multi-pass ER membrane enzyme whose catalytic (LLO glucosylation) activity occurs at the ER; this is consistent with UniProt. Correct but less specific than the ER membrane term. Reason: UniProt records ALG10 as an endoplasmic reticulum membrane protein, and LLO assembly is an ER-localized process. IBA localization to the ER is well supported by the family and by the multi-pass membrane topology. Supporting Evidence: file:human/ALG10/ALG10-uniprot.txt operates in the biosynthetic pathway of |
| GO:0006487 protein N-linked glycosylation | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process. ALG10 completes assembly of the LLO precursor that OST transfers to asparagine residues of nascent proteins, so it is directly required for protein N-linked glycosylation. Reason: The IBA inference (drawn from broadly conserved ALG10 orthologs) matches UniProt's description of ALG10's role in producing the glycan precursor used in protein asparagine (N)-glycosylation. This is a core function of the gene. Supporting Evidence: file:human/ALG10/ALG10-uniprot.txt adds the third and last glucose residue from dolichyl phosphate glucose |
| GO:0106073 dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. This is the Dol-P-Glc-dependent alpha-1,2-glucosyltransferase activity (EC 2.4.1.256, RHEA:29543) that adds the third/terminal glucose to Glc2Man9GlcNAc2-PP-dolichol, yielding Glc3Man9GlcNAc2-PP-dolichol. Reason: This is the defining catalytic activity of ALG10, supported by UniProt (EC 2.4.1.256, RHEA:29543) and the phylogenetic inference across ALG10 orthologs. It is the correct, specific molecular function term. Supporting Evidence: file:human/ALG10/ALG10-uniprot.txt Glc(2)Man(9)GlcNAc(2)-PP-Dol to produce Glc(3)Man(9)GlcNAc(2)-PP-Dol. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: ER membrane localization from UniProt subcellular-location mapping. ALG10 is a multi-pass ER membrane protein (10 predicted transmembrane helices). Reason: UniProt SUBCELLULAR LOCATION records ALG10 as an endoplasmic reticulum membrane, multi-pass membrane protein, consistent with its role as an integral ER membrane glucosyltransferase. This is the appropriate, specific cellular component. Supporting Evidence: file:human/ALG10/ALG10-uniprot.txt Endoplasmic reticulum membrane |
| GO:0006488 dolichol-linked oligosaccharide biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: Core biological process. ALG10 performs the terminal glucosylation step of dolichol-linked oligosaccharide biosynthesis, producing the mature Glc3Man9GlcNAc2-PP-dolichol. Reason: InterPro2GO mapping (IPR016900, Alg10) to LLO biosynthesis is accurate and, in fact, is the most specific pathway term for ALG10's role; supported by UniProt's description of the dolichol-linked oligosaccharide assembly pathway. Supporting Evidence: file:human/ALG10/ALG10-uniprot.txt operates in the biosynthetic pathway of |
| GO:0106073 dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Same core molecular function as the IBA annotation, here derived electronically from EC 2.4.1.256 / RHEA:29543 / InterPro IPR016900. Reason: Correct and consistent with the IBA and ISS annotations of the same term; the EC/RHEA/InterPro basis matches UniProt's catalytic-activity record. Supporting Evidence: file:human/ALG10/ALG10-uniprot.txt Glc(2)Man(9)GlcNAc(2)-PP-Dol to produce Glc(3)Man(9)GlcNAc(2)-PP-Dol. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from the HuRI high-throughput binary (yeast two-hybrid) interactome screen (interaction with CD79A, UniProtKB:P11912). This is an uninformative molecular function term that does not describe ALG10's actual activity. Reason: "protein binding" (GO:0005515) conveys no specific functional information and this interaction comes from a systematic proteome-wide screen rather than a targeted study of ALG10 function. Per curation policy the experimental annotation is not removed, but it is flagged as an over-annotation relative to ALG10's core glucosyltransferase function. Supporting Evidence: PMID:32296183 a reference map of the human protein interactome, generated systematically and comprehensively |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from the HuRI binary interactome screen (interaction with FBLN1, UniProtKB:P23142-4). Uninformative MF term from a systematic screen. Reason: As above: high-throughput binary interaction, not a specific function; retained as experimental but flagged over-annotated. Does not inform ALG10's core molecular function. Supporting Evidence: PMID:32296183 a reference map of the human protein interactome, generated systematically and comprehensively |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from the HuRI binary interactome screen (interaction with SHISAL1, UniProtKB:Q3SXP7). Uninformative MF term from a systematic screen. Reason: High-throughput binary interaction; uninformative "protein binding" not describing ALG10's actual activity. Retained as experimental but flagged over-annotated. Supporting Evidence: PMID:32296183 a reference map of the human protein interactome, generated systematically and comprehensively |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from the HuRI binary interactome screen (interaction with SERP2, UniProtKB:Q8N6R1). Uninformative MF term from a systematic screen. Reason: High-throughput binary interaction; uninformative "protein binding". Retained as experimental but flagged over-annotated relative to the core glucosyltransferase function. Supporting Evidence: PMID:32296183 a reference map of the human protein interactome, generated systematically and comprehensively |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from the HuRI binary interactome screen (interaction with HERPUD2, UniProtKB:Q9BSE4). Uninformative MF term from a systematic screen. Reason: High-throughput binary interaction; uninformative "protein binding". Retained as experimental but flagged over-annotated. Supporting Evidence: PMID:32296183 a reference map of the human protein interactome, generated systematically and comprehensively |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from the HuRI binary interactome screen (interaction with ERGIC3, UniProtKB:Q9Y282). Uninformative MF term from a systematic screen. Reason: High-throughput binary interaction; uninformative "protein binding". Retained as experimental but flagged over-annotated relative to ALG10's core function. Supporting Evidence: PMID:32296183 a reference map of the human protein interactome, generated systematically and comprehensively |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: ER membrane localization transferred by sequence similarity from the ortholog (UniProtKB:Q5I7T1). Consistent with UniProt and with the multi-pass membrane topology. Reason: Agrees with the IEA SubCell ER membrane annotation and UniProt subcellular location; the appropriate, specific cellular component for this integral ER membrane enzyme. Supporting Evidence: file:human/ALG10/ALG10-uniprot.txt Endoplasmic reticulum membrane |
| GO:0106073 dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Core molecular function transferred by sequence similarity from the ortholog (UniProtKB:Q5I7T1); same activity as the IBA/IEA annotations. Reason: Consistent with the IBA and IEA annotations of GO:0106073 and with UniProt's catalytic-activity record (EC 2.4.1.256, RHEA:29543). Correct and specific. Supporting Evidence: file:human/ALG10/ALG10-uniprot.txt Glc(2)Man(9)GlcNAc(2)-PP-Dol to produce Glc(3)Man(9)GlcNAc(2)-PP-Dol. |
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Download this section (compressed HTML)Q: Does human ALG10A functionally differ from its paralog ALG10B in the terminal glucosylation step, and are they redundant in vivo?
Q: Is the reported modulation of the Kv1.1 (KCNA1) potassium channel a moonlighting function of ALG10, or an indirect consequence of altered N-glycosylation?
Experiment: In vitro glucosyltransferase assay using purified ALG10, Dol-P-Glc donor and Glc2Man9GlcNAc2-PP-dolichol acceptor to confirm formation of Glc3Man9GlcNAc2-PP-dolichol and measure kinetics.
Experiment: CRISPR knockout of ALG10 in human cells followed by LLO profiling (fluorophore-assisted carbohydrate electrophoresis / mass spectrometry) to confirm accumulation of the Glc2Man9GlcNAc2 intermediate and hypoglycosylation of reporter glycoproteins.
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