ALG11 is an endoplasmic reticulum membrane alpha-1,2-mannosyltransferase (EC 2.4.1.131) of the dolichol-linked oligosaccharide (LLO) assembly pathway. Using GDP-mannose as donor, it adds the fourth and fifth mannose residues onto Man3GlcNAc2-PP-dolichol to produce Man5GlcNAc2-PP-dolichol, the final cytoplasmic-face LLO intermediate; this glycan is then flipped into the ER lumen (by RFT1) for continued assembly and eventual transfer to nascent proteins during protein N-linked glycosylation. It is a single-pass ER membrane protein whose catalytic domain faces the cytosol and belongs to the glycosyltransferase group 1 family (GT4 subfamily). Loss of function causes ALG11-CDG (congenital disorder of glycosylation type Ip), a multisystem disorder with under-glycosylated serum glycoproteins.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004377 GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred core molecular function. This is the exact biochemical activity ALG11 catalyzes and is directly supported by experimental characterization in human cells. Reason: Core molecular function of ALG11. The IBA is concordant with the human IDA (PMID:20080937) and with the UniProt-curated catalytic activity (EC 2.4.1.131). Supporting Evidence: PMID:20080937 caused by the deficiency of GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase, encoded by the file:human/ALG11/ALG11-uniprot.txt Catalyzes, on CC the cytoplasmic face of the endoplasmic reticulum, the addition of the CC fourth and fifth mannose residues |
| GO:0006488 dolichol-linked oligosaccharide biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred participation in dolichol-linked oligosaccharide (LLO) biosynthesis, the pathway in which ALG11 adds the fourth and fifth mannoses to Man3GlcNAc2-PP-dolichol. Reason: Core biological process. Concordant with the human IMP (PMID:20080937), where patient fibroblasts accumulate the LLO intermediates upstream of the ALG11 step. Supporting Evidence: PMID:20080937 accumulation of Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred site of action at the ER membrane, where LLO assembly occurs on the cytoplasmic face. Reason: Core cellular component. Concordant with UniProt subcellular location and the human IDA localization study (PMID:20080937). Supporting Evidence: file:human/ALG11/ALG11-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0004377 GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated electronic inference of the same core catalytic activity from InterPro, RHEA:29523 and EC:2.4.1.131 mappings. Reason: Correct and specific. The RHEA/EC mapping matches the experimentally verified reaction, and this is the core molecular function. Supporting Evidence: file:human/ALG11/ALG11-uniprot.txt EC=2.4.1.131 {ECO:0000269|PubMed:20080937} |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Automated electronic inference of ER membrane localization from the UniProt Subcellular Location keyword mapping. Reason: Correct core localization, consistent with curated UniProt location and experimental IDA. Supporting Evidence: file:human/ALG11/ALG11-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0016757 glycosyltransferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (IPR001296, Glyco_trans_1) domain-based inference of a general glycosyltransferase activity. Reason: Correct but a broad parent of the specific mannosyltransferase activity (GO:0004377). Acceptable as a domain-level IEA that is legitimately more general than the experimentally supported term; not misleading. Supporting Evidence: file:human/ALG11/ALG11-uniprot.txt Belongs to the glycosyltransferase group 1 family |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Single high-throughput affinity-purification mass spectrometry (BioPlex) interaction with GLA (alpha-galactosidase A, P06280). Bare "protein binding" is uninformative about ALG11's molecular function. Reason: The IPI derives from a proteome-scale AP-MS screen and captures a physical co-purification rather than a characterized functional interaction; the term "protein binding" adds no information about ALG11's actual mannosyltransferase function. Retained (not removed) per curation policy for experimental IPIs, but flagged as over-annotation. Supporting Evidence: PMID:33961781 affinity purification of 10,128 human proteins-half the proteome-in 293T cells |
| GO:0006488 dolichol-linked oligosaccharide biosynthetic process | IMP PMID:20080937 A severe human metabolic disease caused by deficiency of the... | ACCEPT | Summary: Human mutant-phenotype evidence (patient with p.L86S) for a role in LLO biosynthesis; patient fibroblasts accumulate Man3GlcNAc2-PP-dolichol/Man4GlcNAc2-PP-dolichol and are deficient in elongating Man3GlcNAc2-PP-dolichol. Reason: Directly supported core biological process; the phenotype pinpoints the ALG11 step in LLO assembly, and complementation with WT hALG11 rescued it. Supporting Evidence: PMID:20080937 deficient in elongating Man3GlcNAc2-PP-dolichol |
| GO:0004377 GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity | IDA PMID:20080937 A severe human metabolic disease caused by deficiency of the... | ACCEPT | Summary: Direct assay of ALG11 mannosyltransferase activity in human fibroblasts; the CDG1P p.L86S variant decreases this activity, establishing the catalytic function experimentally. Reason: Core molecular function with direct experimental support. This is the exact GOA molecular-function term used in core_functions. Supporting Evidence: PMID:20080937 caused by the deficiency of GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase, encoded by the file:human/ALG11/ALG11-uniprot.txt EC=2.4.1.131 {ECO:0000269|PubMed:20080937} |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:20080937 A severe human metabolic disease caused by deficiency of the... | ACCEPT | Summary: Immunofluorescence localization of ALG11 to the ER in control and patient fibroblasts; the p.L86S variant does not mislocalize the protein. Reason: Directly supported core cellular component. The localization study confirms ER membrane residence and shows the disease variant retains normal localization. Supporting Evidence: PMID:20080937 indicating no mislocalization or file:human/ALG11/ALG11-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0006487 protein N-linked glycosylation | IMP PMID:20080937 A severe human metabolic disease caused by deficiency of the... | ACCEPT | Summary: Human mutant-phenotype evidence for a role in protein N-linked glycosylation; the patient shows partial loss of complete N-glycan side chains (serum transferrin hypoglycosylation, a CDG-I signature). Reason: Core biological process. ALG11 builds the LLO precursor that is ultimately transferred to asparagine residues; its deficiency causes the underglycosylation phenotype diagnostic of CDG-I. Supporting Evidence: PMID:20080937 the partial loss of complete N-glycan |
| GO:0000026 alpha-1,2-mannosyltransferase activity | TAS Reactome:R-HSA-4551297 | ACCEPT | Summary: Reactome author-statement annotation to the general alpha-1,2-mannosyltransferase activity, the parent of the specific ALG11 activity term. Reason: Correct but a less-specific parent of GO:0004377. Retained as an accurate (if more general) molecular-function annotation from a reliable TAS source. Supporting Evidence: Reactome:R-HSA-4551297 transfers the fourth and fifth mannoses (Man) to the N-glycan precursor in an alpha-1,2 orientation |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-4551297 | ACCEPT | Summary: Reactome author-statement localization of ALG11 to the ER membrane, where it acts on the cytosolic face during LLO assembly. Reason: Correct core cellular component, concordant with the IDA and IBA evidence. Supporting Evidence: Reactome:R-HSA-4551297 These additions are the last two on the cytosolic side of the ER membrane |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: High-throughput mass-spectrometry detection of ALG11 in a membrane-proteome survey of the YTS NK-like cell line. Generic "membrane" localization. Reason: A proteome-scale membrane-fraction survey (ALG11 was not the study subject) supporting only the very general term "membrane", which is subsumed by the specific and well-supported "endoplasmic reticulum membrane". Retained but flagged as over-annotation. Supporting Evidence: PMID:19946888 identified 1843 proteins with high confidence |
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