ALG9

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000026 alpha-1,2-mannosyltransferase activity	IBA GO_REF:0000033	MODIFY	Summary: Refine the inherited alpha-1,2-mannosyltransferase activity to both measured lipid-linked acceptor reactions. Reason: The PAINT parent activity is biologically correct. Human patient glycan profiles and complementation support both ALG9 steps, and purified human ALG9 isoform 1 independently transfers mannose to synthetic Man6 and Man8 lipid-linked acceptors in PMID:41807832. The two existing substrate-specific descendants describe this chemistry more precisely. This is a specificity refinement for human ALG9, not evidence of an erroneous ancestral placement or functional loss. The unreconstructed ancestral node is not being assigned both precise acceptor reactions on the basis of this human assay. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000509239 UNRESOLVED This is the actual ancestral node in the seeded WITH/FROM chain. The full IBD experiment/tree placement was not independently recovered; the annotation judgment is corroborated by human genetic, biochemical and structural evidence. Target membership among extant supporting records is legitimate, not circular. Proposed replacements: dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity Supporting Evidence: PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f). PMID:15148656 The functional homology between the human ALG9 and Saccharomyces cerevisiae ALG9, as well as the deleterious effect of the E523K mutation detected in the patient with CDG, were confirmed by a yeast complementation assay lacking the ALG9 gene.
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Retain the ancestral ER-membrane location and activity context. Reason: ALG9 catalyzes ER-luminal lipid-linked oligosaccharide assembly as a membrane protein. Human ALG9 structural and biochemical work supports a membrane-embedded enzyme with 11 transmembrane helices, independently corroborating the UniProt ER assignment and the inherited is_active_in qualifier. The complete PAINT IBD placement was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000509188 UNRESOLVED This is the actual ancestral node in the seeded WITH/FROM chain. The full IBD experiment/tree placement was not independently recovered; the annotation judgment is corroborated by human genetic, biochemical and structural evidence. Target membership among extant supporting records is legitimate, not circular. Supporting Evidence: file:human/ALG9/ALG9-uniprot.txt Endoplasmic reticulum membrane PMID:41807832 ALG9 and ALG12 are classified as GT-22 enzymes. They contain 11 TM helices and a cytosolic N terminus. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0006487 protein N-linked glycosylation	IBA GO_REF:0000033	ACCEPT	Summary: Retain participation in protein N-linked glycosylation. Reason: ALG9 performs two catalytic steps in biosynthesis of the lipid-linked glycan precursor. Patient cells accumulate the substrates of these steps and transfer incomplete oligosaccharides to proteins. This is direct precursor-assembly work within N-linked glycosylation, with the narrower LLO process also retained. The PAINT ancestral placement is not being rejected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000509239 UNRESOLVED This is the actual ancestral node in the seeded WITH/FROM chain. The full IBD experiment/tree placement was not independently recovered; the annotation judgment is corroborated by human genetic, biochemical and structural evidence. Target membership among extant supporting records is legitimate, not circular. Supporting Evidence: PMID:15148656 Using this approach, we have found, in a patient with CDG, a deficiency of the ALG9 alpha 1,2 mannosyltransferase enzyme, which causes an accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures, which was paralleled by the transfer of incomplete oligosaccharides precursors to protein. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Retain the mapped UniProt ER-membrane location. Reason: The actual electronic source is UniProt subcellular-location term SL-0097. The cached human entry explicitly assigns the ER membrane; human ALG9 structure and its luminal lipid-linked substrate chemistry independently corroborate this membrane compartment. The mapping is not a separate localization assay. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0097 SUPPORTS TRANSFER Cached human UniProt subcellular-location statement explicitly identifies endoplasmic reticulum membrane; the mapping retains that scope. Supporting Evidence: file:human/ALG9/ALG9-uniprot.txt Endoplasmic reticulum membrane PMID:41807832 ALG9 and ALG12 are classified as GT-22 enzymes. They contain 11 TM helices and a cytosolic N terminus.
GO:0016757 glycosyltransferase activity	IEA GO_REF:0000002	MODIFY	Summary: Refine the generic glycosyltransferase assignment to the two ALG9 reactions. Reason: The inspected InterPro-to-GO entry maps IPR005599 to the broad glycosyltransferase activity, a correct family-level assignment. The domain name alone does not establish a GPI-specific reaction. Independent human enzyme assays identify Dol-P-Man-dependent Man6-to-Man7 and Man8-to-Man9 activities, so these two existing descendants provide the appropriate functional specificity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR005599 SUPPORTS TRANSFER The static interpro2go mapping explicitly assigns GO:0016757. It establishes a broad glycosyltransferase family association; the substrate-specific refinement rests on human ALG9 experiments. Proposed replacements: dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity Supporting Evidence: PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0052918 dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Retain the Dol-P-Man-dependent Man8-to-Man9 reaction. Reason: The cached UniProt catalytic record links RHEA:29539 and EC:2.4.1.261 to this exact lipid-linked glycan reaction. The current GO definition matches those substrates and products. Genetic complementation and patient glycan profiles support the step, and purified human isoform 1 directly catalyzes it with synthetic Dol25-linked substrates in PMID:41807832. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:29539 SUPPORTS TRANSFER Exact reaction cross-reference read in the cached human UniProt catalytic-activity entry; independently matched to the live GO reaction definition. EC:2.4.1.261 SUPPORTS TRANSFER Exact enzyme class in the same human catalytic record, with genetic and subsequent purified-human-enzyme support. Supporting Evidence: PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f). PMID:15148656 The functional homology between the human ALG9 and Saccharomyces cerevisiae ALG9, as well as the deleterious effect of the E523K mutation detected in the patient with CDG, were confirmed by a yeast complementation assay lacking the ALG9 gene. file:human/ALG9/ALG9-uniprot.txt Xref=Rhea:RHEA:29539, file:human/ALG9/ALG9-uniprot.txt EC=2.4.1.261;
GO:0052926 dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Retain the Dol-P-Man-dependent Man6-to-Man7 reaction. Reason: The cached UniProt catalytic record links RHEA:29531 and EC:2.4.1.259 to this exact lipid-linked glycan reaction. The current GO definition matches those substrates and products. Genetic complementation and patient glycan profiles support the step, and purified human isoform 1 directly catalyzes it with synthetic Dol25-linked substrates in PMID:41807832. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:29531 SUPPORTS TRANSFER Exact reaction cross-reference read in the cached human UniProt catalytic-activity entry; independently matched to the live GO reaction definition. EC:2.4.1.259 SUPPORTS TRANSFER Exact enzyme class in the same human catalytic record, with genetic and subsequent purified-human-enzyme support. Supporting Evidence: PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f). PMID:15148656 The functional homology between the human ALG9 and Saccharomyces cerevisiae ALG9, as well as the deleterious effect of the E523K mutation detected in the patient with CDG, were confirmed by a yeast complementation assay lacking the ALG9 gene. file:human/ALG9/ALG9-uniprot.txt Xref=Rhea:RHEA:29531, file:human/ALG9/ALG9-uniprot.txt EC=2.4.1.259;
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	TAS Reactome:R-HSA-446193	ACCEPT	Summary: Retain ALG9 participation in dolichol-linked oligosaccharide biosynthesis. Reason: The Reactome pathway contains precursor assembly before transfer to nascent proteins. ALG9 itself performs the seventh- and ninth-mannose additions, so this process describes catalytic participation rather than only a downstream consequence of glycosylation deficiency. The pathway summary is contextual; direct ALG9 evidence comes from the human genetic and enzyme studies. Supporting Evidence: PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f). PMID:15148656 Using this approach, we have found, in a patient with CDG, a deficiency of the ALG9 alpha 1,2 mannosyltransferase enzyme, which causes an accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures, which was paralleled by the transfer of incomplete oligosaccharides precursors to protein.
GO:0098553 lumenal side of endoplasmic reticulum membrane	IC PMID:15148656 Identification and functional analysis of a defect in the hu...	ACCEPT	Summary: Retain the inferred luminal face of the ER membrane. Reason: The 2004 human glycan/complementation study places ALG9 at the luminal assembly steps; this IC annotation does not claim that paper performed direct topology microscopy. Independent human ALG9 structures in PMID:41807832 locate the lipid-linked acceptor head group and catalytic cleft at the luminal membrane interface, consistent with the ER-luminal reaction context. Supporting Evidence: file:human/ALG9/ALG9-uniprot.txt Endoplasmic reticulum membrane PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f). Reactome:R-HSA-446215 This reaction occurs in the ER lumen and uses dolichyl phosphate D-mannose as the mannose donor with ALG9 mediating the reaction.
GO:0006487 protein N-linked glycosylation	IMP PMID:15148656 Identification and functional analysis of a defect in the hu...	ACCEPT	Summary: Retain the human mutation-supported N-linked glycosylation role. Reason: Patient fibroblasts in PMID:15148656 accumulate Man6 and Man8 lipid-linked intermediates and transfer incompletely assembled oligosaccharides to proteins. The recovered full article also tests patient-derived human ALG9 constructs by yeast complementation. These results establish the enzyme contribution to precursor assembly and glycosylation; clinical developmental phenotypes are not separate catalytic roles. Supporting Evidence: PMID:15148656 Using this approach, we have found, in a patient with CDG, a deficiency of the ALG9 alpha 1,2 mannosyltransferase enzyme, which causes an accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures, which was paralleled by the transfer of incomplete oligosaccharides precursors to protein. PMID:15148656 The functional homology between the human ALG9 and Saccharomyces cerevisiae ALG9, as well as the deleterious effect of the E523K mutation detected in the patient with CDG, were confirmed by a yeast complementation assay lacking the ALG9 gene.
GO:0006487 protein N-linked glycosylation	IMP PMID:15945070 CDG-IL: an infant with a novel mutation in the ALG9 gene and...	ACCEPT	Summary: Retain the independently observed human glycosylation defect. Reason: PMID:15945070 reports hypoglycosylated transferrin, Man6/Man8 lipid-linked glycan accumulation in patient fibroblasts and causal complementation evidence for p.Y286C. These positive results support participation in N-linked glycosylation. The local cache is abstract-only, so detailed experimental controls beyond that account are not inferred. Supporting Evidence: PMID:15945070 Hypoglycosylation was confirmed by the typical CDG type 1 pattern of serum transferrin analyzed by isoelectric focusing. PMID:15945070 A defect in the ALG9 enzyme was suggested by the accumulation of the DolPP-GlcNAc2Man6 and DolPP-GlcNAc2Man8 in the patient's fibroblasts and confirmed by mutation analysis: the patient is homozygous for the ALG9 mutation p.Y286C. PMID:15945070 The causal effect of the mutation was shown by complementation assays in alg9 deficient yeast cells.
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	IGI PMID:15148656 Identification and functional analysis of a defect in the hu...	ACCEPT	Summary: Retain the complementation-supported LLO biosynthesis role. Reason: Human ALG9 constructs complement an ALG9-deficient yeast background in the cited study. The WITH/FROM protein P53868 is yeast Alg9, identifying the genetic assay context rather than a direct human localization experiment. The cached abstract reports functional homology and the deleterious E523K effect in yeast complementation; the externally read full assay context is documented in ALG9-notes.md. ALG9 directly performs mannose additions in LLO assembly, independently confirmed by purified human enzyme. Supporting Evidence: PMID:15148656 The functional homology between the human ALG9 and Saccharomyces cerevisiae ALG9, as well as the deleterious effect of the E523K mutation detected in the patient with CDG, were confirmed by a yeast complementation assay lacking the ALG9 gene. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0006488 dolichol-linked oligosaccharide biosynthetic process	IGI PMID:15945070 CDG-IL: an infant with a novel mutation in the ALG9 gene and...	ACCEPT	Summary: Retain the complementation-supported LLO biosynthesis role. Reason: Human ALG9 constructs complement an ALG9-deficient yeast background in the cited study. The WITH/FROM protein P53868 is yeast Alg9, identifying the genetic assay context rather than a direct human localization experiment. The accessible 2005 abstract reports p.Y286C causality by complementation and patient glycan accumulation; its full assay details remain inaccessible. ALG9 directly performs mannose additions in LLO assembly, independently confirmed by purified human enzyme. Supporting Evidence: PMID:15945070 The causal effect of the mutation was shown by complementation assays in alg9 deficient yeast cells. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0052918 dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity	IGI PMID:15148656 Identification and functional analysis of a defect in the hu...	ACCEPT	Summary: Retain the genetically supported Man8-to-Man9 mannosyltransferase activity. Reason: The original evidence combines human ALG9 mutation and glycan-precursor accumulation with complementation in ALG9-deficient yeast (P53868 in WITH/FROM). It supports the Man8 acceptor step, without being a purified-human kinetic assay. The 2004 full article directly distinguishes wild-type human and E523K constructs; that full-text access was external to the abstract-only cache, as documented in ALG9-notes.md. Purified human ALG9 isoform 1 subsequently catalyzes the corresponding Dol25-linked reaction in PMID:41807832, independently supporting this precise activity. Supporting Evidence: PMID:15148656 Using this approach, we have found, in a patient with CDG, a deficiency of the ALG9 alpha 1,2 mannosyltransferase enzyme, which causes an accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures, which was paralleled by the transfer of incomplete oligosaccharides precursors to protein. PMID:15148656 The functional homology between the human ALG9 and Saccharomyces cerevisiae ALG9, as well as the deleterious effect of the E523K mutation detected in the patient with CDG, were confirmed by a yeast complementation assay lacking the ALG9 gene. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0052918 dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity	IGI PMID:15945070 CDG-IL: an infant with a novel mutation in the ALG9 gene and...	ACCEPT	Summary: Retain the genetically supported Man8-to-Man9 mannosyltransferase activity. Reason: The original evidence combines human ALG9 mutation and glycan-precursor accumulation with complementation in ALG9-deficient yeast (P53868 in WITH/FROM). It supports the Man8 acceptor step, without being a purified-human kinetic assay. The 2005 abstract describes the causal p.Y286C complementation result; uninspected full-text details are not asserted. Purified human ALG9 isoform 1 subsequently catalyzes the corresponding Dol25-linked reaction in PMID:41807832, independently supporting this precise activity. Supporting Evidence: PMID:15945070 A defect in the ALG9 enzyme was suggested by the accumulation of the DolPP-GlcNAc2Man6 and DolPP-GlcNAc2Man8 in the patient's fibroblasts and confirmed by mutation analysis: the patient is homozygous for the ALG9 mutation p.Y286C. PMID:15945070 The causal effect of the mutation was shown by complementation assays in alg9 deficient yeast cells. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0052926 dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity	IGI PMID:15148656 Identification and functional analysis of a defect in the hu...	ACCEPT	Summary: Retain the genetically supported Man6-to-Man7 mannosyltransferase activity. Reason: The original evidence combines human ALG9 mutation and glycan-precursor accumulation with complementation in ALG9-deficient yeast (P53868 in WITH/FROM). It supports the Man6 acceptor step, without being a purified-human kinetic assay. The 2004 full article directly distinguishes wild-type human and E523K constructs; that full-text access was external to the abstract-only cache, as documented in ALG9-notes.md. Purified human ALG9 isoform 1 subsequently catalyzes the corresponding Dol25-linked reaction in PMID:41807832, independently supporting this precise activity. Supporting Evidence: PMID:15148656 Using this approach, we have found, in a patient with CDG, a deficiency of the ALG9 alpha 1,2 mannosyltransferase enzyme, which causes an accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures, which was paralleled by the transfer of incomplete oligosaccharides precursors to protein. PMID:15148656 The functional homology between the human ALG9 and Saccharomyces cerevisiae ALG9, as well as the deleterious effect of the E523K mutation detected in the patient with CDG, were confirmed by a yeast complementation assay lacking the ALG9 gene. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0052926 dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity	IGI PMID:15945070 CDG-IL: an infant with a novel mutation in the ALG9 gene and...	ACCEPT	Summary: Retain the genetically supported Man6-to-Man7 mannosyltransferase activity. Reason: The original evidence combines human ALG9 mutation and glycan-precursor accumulation with complementation in ALG9-deficient yeast (P53868 in WITH/FROM). It supports the Man6 acceptor step, without being a purified-human kinetic assay. The 2005 abstract describes the causal p.Y286C complementation result; uninspected full-text details are not asserted. Purified human ALG9 isoform 1 subsequently catalyzes the corresponding Dol25-linked reaction in PMID:41807832, independently supporting this precise activity. Supporting Evidence: PMID:15945070 A defect in the ALG9 enzyme was suggested by the accumulation of the DolPP-GlcNAc2Man6 and DolPP-GlcNAc2Man8 in the patient's fibroblasts and confirmed by mutation analysis: the patient is homozygous for the ALG9 mutation p.Y286C. PMID:15945070 The causal effect of the mutation was shown by complementation assays in alg9 deficient yeast cells. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0000026 alpha-1,2-mannosyltransferase activity	TAS Reactome:R-HSA-446215	MODIFY	Summary: Refine this event to the specific seventh-mannose transfer. Reason: Reactome R-HSA-446215 identifies the seventh-mannose step, which has the more precise existing GO reaction term GO:0052926. The source explicitly identifies the lipid-linked acceptor, Dol-P-Man donor and luminal reaction. Refining the generic alpha-1,2-mannosyltransferase term preserves that event-specific substrate scope. Proposed replacements: dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity Supporting Evidence: Reactome:R-HSA-446215 The seventh mannose is added to the N-glycan precursor. This reaction occurs in the ER lumen and uses dolichyl phosphate D-mannose as the mannose donor with ALG9 mediating the reaction. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0000026 alpha-1,2-mannosyltransferase activity	TAS Reactome:R-HSA-446216	MODIFY	Summary: Refine this event to the specific ninth-mannose transfer. Reason: Reactome R-HSA-446216 identifies the ninth-mannose step, which has the more precise existing GO reaction term GO:0052918. The source explicitly identifies the lipid-linked acceptor, Dol-P-Man donor and luminal reaction. Refining the generic alpha-1,2-mannosyltransferase term preserves that event-specific substrate scope. Proposed replacements: dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity Supporting Evidence: Reactome:R-HSA-446216 The last mannose is added to the N-glycan precursor. This reaction occurs in the ER lumen, uses Dolichyl phosphate D-mannose as the mannose donor, and is catalyzed by ALG9. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0000026 alpha-1,2-mannosyltransferase activity	TAS Reactome:R-HSA-4720478	MODIFY	Summary: Refine this event to the specific seventh-mannose transfer. Reason: Reactome R-HSA-4720478 identifies the seventh-mannose step, which has the more precise existing GO reaction term GO:0052926. This is a defective-ALG9 loss-of-function event, not an experiment showing that the defective protein enables normal transfer. The gene-level wild-type activity is independently established by patient complementation and purified human ALG9 assays. Refining the generic alpha-1,2-mannosyltransferase term preserves that event-specific substrate scope. Proposed replacements: dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity Supporting Evidence: Reactome:R-HSA-4720478 Alpha-1,2-mannosyltransferase ALG9 (ALG9) normally catalyses the transfer of mannose to the lipid-linked oligosaccharide (LLO) precursor. It adds the 7th and 9th mannose moieties to LLO. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0000026 alpha-1,2-mannosyltransferase activity	TAS Reactome:R-HSA-9035514	MODIFY	Summary: Refine this event to the specific ninth-mannose transfer. Reason: Reactome R-HSA-9035514 identifies the ninth-mannose step, which has the more precise existing GO reaction term GO:0052918. This is a defective-ALG9 loss-of-function event, not an experiment showing that the defective protein enables normal transfer. The gene-level wild-type activity is independently established by patient complementation and purified human ALG9 assays. Refining the generic alpha-1,2-mannosyltransferase term preserves that event-specific substrate scope. Proposed replacements: dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity Supporting Evidence: Reactome:R-HSA-9035514 Alpha-1,2-mannosyltransferase ALG9 (ALG9) normally catalyses the transfer of mannose to the lipid-linked oligosaccharide (LLO) precursor. It adds the 7th and 9th mannose moieties to LLO. PMID:41807832 Assays with Dol25-PP-GlcNAc2Man6 or Dol25-PP-GlcNAc2Man8 acceptor substrates confirmed the dual activity of ALG9 in vitro (Fig. 1d,f).
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4720478	ACCEPT	Summary: Retain the ER-membrane placement of ALG9. Reason: Reactome R-HSA-4720478 places ALG9 in the ER-membrane machinery for luminal LLO assembly. The defective event supplies pathway context, not a separate assay proving the localization of every mutant. The cached human UniProt location and independent human ALG9 structure corroborate this compartment. No finer localization than the source supports is substituted. Supporting Evidence: file:human/ALG9/ALG9-uniprot.txt Endoplasmic reticulum membrane PMID:41807832 ALG9 and ALG12 are classified as GT-22 enzymes. They contain 11 TM helices and a cytosolic N terminus.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-9035514	ACCEPT	Summary: Retain the ER-membrane placement of ALG9. Reason: Reactome R-HSA-9035514 places ALG9 in the ER-membrane machinery for luminal LLO assembly. The defective event supplies pathway context, not a separate assay proving the localization of every mutant. The cached human UniProt location and independent human ALG9 structure corroborate this compartment. No finer localization than the source supports is substituted. Supporting Evidence: file:human/ALG9/ALG9-uniprot.txt Endoplasmic reticulum membrane PMID:41807832 ALG9 and ALG12 are classified as GT-22 enzymes. They contain 11 TM helices and a cytosolic N terminus.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	ACCEPT	Summary: Retain the broad membrane assignment without adding screen-specific compartment claims. Reason: The cited study profiles isolated YTS-cell membranes, but the ALG9-specific supplementary identification was not independently recovered from the abstract-only cache or primary search. The curator's HDA target assertion is therefore not independently re-demonstrated here. The broad location is nevertheless clearly correct for ALG9: independent purified human ALG9 structural work resolves 11 transmembrane helices. Accept that corroborated membrane association while preserving the original broad term; the screen does not establish an ER-specific pool or plasma-membrane activity. Supporting Evidence: PMID:19946888 The present study was initiated to define the composition of the membrane proteome of the Natural Killer (NK) like cell line YTS. PMID:41807832 ALG9 and ALG12 are classified as GT-22 enzymes. They contain 11 TM helices and a cytosolic N terminus.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-446215	ACCEPT	Summary: Retain the ER-membrane placement of ALG9. Reason: Reactome R-HSA-446215 places ALG9 in the ER-membrane machinery for luminal LLO assembly. Its luminal mannose-transfer reaction is consistent with a membrane-embedded enzyme acting on lipid-linked substrates. The cached human UniProt location and independent human ALG9 structure corroborate this compartment. No finer localization than the source supports is substituted. Supporting Evidence: file:human/ALG9/ALG9-uniprot.txt Endoplasmic reticulum membrane PMID:41807832 ALG9 and ALG12 are classified as GT-22 enzymes. They contain 11 TM helices and a cytosolic N terminus.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-446216	ACCEPT	Summary: Retain the ER-membrane placement of ALG9. Reason: Reactome R-HSA-446216 places ALG9 in the ER-membrane machinery for luminal LLO assembly. Its luminal mannose-transfer reaction is consistent with a membrane-embedded enzyme acting on lipid-linked substrates. The cached human UniProt location and independent human ALG9 structure corroborate this compartment. No finer localization than the source supports is substituted. Supporting Evidence: file:human/ALG9/ALG9-uniprot.txt Endoplasmic reticulum membrane PMID:41807832 ALG9 and ALG12 are classified as GT-22 enzymes. They contain 11 TM helices and a cytosolic N terminus.

Gene Description

Existing Annotations Review

Core Functions

ALG9 transfers the seventh mannose from dolichyl-phosphate-mannose to the Man6 lipid-linked N-glycan precursor at the luminal face of the ER membrane. This completes the B branch before the intervening ALG12 addition.

ALG9 transfers the ninth mannose from dolichyl-phosphate-mannose to the Man8 lipid-linked N-glycan precursor at the luminal face of the ER membrane. This completes the C branch after ALG12 adds the eighth mannose.

References

Suggested Questions for Experts

📚 Additional Documentation

Notes

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