alg-2 encodes an endoplasmic-reticulum membrane GT4-family GDP-mannose-dependent mannosyltransferase. By orthology to characterized fungal and human ALG2 proteins, it is expected to act during the cytoplasmic phase of dolichol-linked oligosaccharide assembly for N-linked glycosylation, adding the alpha-1,3-linked second mannose to Man1GlcNAc2-PP-dolichol and the alpha-1,6-linked third mannose to Man2GlcNAc2-PP-dolichol.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000033 alpha-1,3-mannosyltransferase activity | IBA GO_REF:0000033 | MODIFY | Summary: The PTHR45918 PAINT node correctly places Neurospora alg-2 in the conserved ALG2 bifunctional mannosyltransferase clade, but this parent-level alpha-1,3-mannosyltransferase term should be refined to the dolichol-linked, Man1GlcNAc2-PP-Dol-specific reaction. Reason: GO:0000033 is true but generic. The same protein is also annotated to GO:0004378, which names the acceptor used in ALG2's alpha-1,3 mannosyltransferase reaction. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000282458 · PANTHER:PTN000282458 SUPPORTS TRANSFER The PAINT node is correctly scoped to the ALG2 clade; only the GO term granularity is too broad for the Man1GlcNAc2-PP-Dol reaction. Proposed replacements: GDP-Man:Man(1)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity Supporting Evidence: file:interpro/panther/PTHR45918/PTHR45918-paint.tsv PTHR45918 PTN000282458 GO:0000033 F IBD false file:genes/NEUCR/alg-2/alg-2-uniprot.txt Mannosylates Man(2)GlcNAc(2)-dolichol diphosphate and Man(1)GlcNAc(2)-dolichol diphosphate to form Man(3)GlcNAc(2)-dolichol diphosphate. |
| GO:0004378 GDP-Man:Man(1)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated transfer of the EC 2.4.1.132/RHEA:29515 ALG2 reaction. This is the first of alg-2's two core mannosyltransferase activities and matches the UniProt catalytic annotation inferred from S. cerevisiae Alg2. Supporting Evidence: file:genes/NEUCR/alg-2/alg-2-uniprot.txt Xref=Rhea:RHEA:29515 PMID:16878994 this enzyme actually carries out an alpha1,3-mannosylation, followed by an alpha1,6-mannosylation, to form the first branched pentasaccharide intermediate of the pathway |
| GO:0004378 GDP-Man:Man(1)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Manual similarity transfer from S. cerevisiae Alg2 of the Man1GlcNAc2-PP-Dol alpha-1,3-mannosyltransferase activity. Neurospora alg-2 falls in the same PANTHER ALG2 subfamily and UniProt assigns the same conserved reaction from the yeast protein. Supporting Evidence: file:genes/NEUCR/alg-2/alg-2-uniprot.txt Xref=Rhea:RHEA:29515 |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to endoplasmic reticulum membrane. This is the expected site of the cytoplasmically oriented ALG2 reactions during lipid-linked oligosaccharide assembly. Supporting Evidence: file:genes/NEUCR/alg-2/alg-2-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Manual similarity transfer from S. cerevisiae Alg2 of ER membrane localization. This is consistent with the conserved ER membrane localization of ALG2 enzymes. Supporting Evidence: file:genes/NEUCR/alg-2/alg-2-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0006488 dolichol-linked oligosaccharide biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference that alg-2 participates in dolichol-linked oligosaccharide biosynthesis. The PTN000282458 node is shared by characterized ALG2 orthologs, and Neurospora alg-2 is in the single ALG2 subfamily. Supporting Evidence: file:interpro/panther/PTHR45918/PTHR45918-paint.tsv PTHR45918 PTN000282458 GO:0006488 P IBD false file:interpro/panther/PTHR45918/PTHR45918-entries.csv Q8X0H8,"Alpha-1,3/1,6-mannosyltransferase alg-2" |
| GO:0009101 glycoprotein biosynthetic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: Broad InterPro2GO glycoprotein-biosynthetic-process transfer from the ALG2 domain. True as an ancestor process, but less informative than the accepted dolichol-linked oligosaccharide biosynthetic process row. Supporting Evidence: file:genes/NEUCR/alg-2/alg-2-uniprot.txt DR InterPro; IPR027054; ALG2. |
| GO:0012505 endomembrane system | IBA GO_REF:0000033 | MODIFY | Summary: PAINT inference to the endomembrane system. alg-2 does act in the endomembrane system, but the propagated location is too general for an ER membrane mannosyltransferase. Reason: The IBA location should be refined to GO:0005789, matching the ER membrane localization transferred from S. cerevisiae and the UniProt subcellular-location mapping. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000282458 · PANTHER:PTN000282458 SUPPORTS TRANSFER The PAINT node is correct for the ALG2 clade, but the endomembrane term is a broad ancestor of the ER membrane localization. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:interpro/panther/PTHR45918/PTHR45918-paint.tsv PTHR45918 PTN000282458 GO:0012505 C IBD false file:genes/NEUCR/alg-2/alg-2-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0016757 glycosyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO transfer of the generic glycosyltransferase activity from the glycosyltransferase-family domain. alg-2's two specific GDP-mannose:dolichol-linked oligosaccharide transferase activities are known. Reason: Replace the generic enzymatic parent with the two specific reactions that add the second and third mannoses in the LLO pathway. Proposed replacements: GDP-Man:Man(1)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity GDP-Man:Man(2)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activity Supporting Evidence: file:genes/NEUCR/alg-2/alg-2-uniprot.txt DR InterPro; IPR001296; Glyco_trans_1. |
| GO:0102704 GDP-Man:Man(2)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated transfer of the EC 2.4.1.257/RHEA:29519 ALG2 reaction. This is the second core mannosyltransferase activity that forms the branched Man3GlcNAc2-PP-dolichol intermediate. Supporting Evidence: file:genes/NEUCR/alg-2/alg-2-uniprot.txt Xref=Rhea:RHEA:29519 PMID:16878994 this enzyme actually carries out an alpha1,3-mannosylation, followed by an alpha1,6-mannosylation, to form the first branched pentasaccharide intermediate of the pathway |
| GO:0102704 GDP-Man:Man(2)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Manual similarity transfer from S. cerevisiae Alg2 of the Man2GlcNAc2-PP-Dol alpha-1,6-mannosyltransferase activity. The same reaction is assigned to Neurospora alg-2 by Rhea/EC mapping and is consistent with the conserved ALG2 family placement. Supporting Evidence: file:genes/NEUCR/alg-2/alg-2-uniprot.txt Xref=Rhea:RHEA:29519 |
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