Alpha-Man-Ia (mas-1, CG32684) is a Golgi class I alpha-1,2-mannosidase of glycoside hydrolase family 47 (GH47) that trims alpha-1,2-linked mannose residues from high-mannose (Man9/Man8GlcNAc2) N-glycans on glycoproteins, a step that precedes the action of Golgi mannosidase II and GlcNAc-transferase I in N-glycan maturation. Two promoters produce isoforms that are single-pass type II membrane proteins with different cytoplasmic N-termini and a shared luminal Ca2+-dependent catalytic domain. Recombinant enzyme trims oligomannosidic glycans, and null flies are viable but accumulate Man8GlcNAc2 and show low-penetrance defects in the embryonic peripheral nervous system, wing and eye, reflecting partial redundancy with other mannose-trimming routes. The gene is expressed maternally and zygotically, with prominent expression in lobula plate giant neurons.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi residence fits the type-II glycan-processing enzyme. Reason: The mas-1 mutant glycan study identifies the product as Golgi mannosidase I, and the original mas-1 molecular analysis reports type-II transmembrane protein isoforms. PTN000201534 is therefore a safe Golgi alpha-mannosidase node for the Drosophila IA-related branch. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000201534 Β· PANTHER:PTN000201534 SUPPORTS TRANSFER PTN000201534 places Golgi membrane on the PTHR11742 Golgi class-I branch using plant MNS1/MNS2 and mouse Man1a1/Man1a2 descendant evidence; this matches the directly supported Golgi processing role of Drosophila alpha-Man-Ia. Supporting Evidence: PMID:9654102 The mas-1 gene of Drosophila melanogaster encodes Golgi mannosidase I (MAS-1) PMID:7729592 Both transcripts code for type II transmembrane proteins which differ in their N-terminal parts. |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Golgi residence fits the type-II glycan-processing enzyme. Reason: The mas-1 mutant glycan study identifies the product as Golgi mannosidase I, and the original mas-1 molecular analysis reports type-II transmembrane protein isoforms; together they support Golgi membrane association for this glycan-processing enzyme. Supporting Evidence: PMID:9654102 The mas-1 gene of Drosophila melanogaster encodes Golgi mannosidase I (MAS-1) PMID:7729592 Both transcripts code for type II transmembrane proteins which differ in their N-terminal parts. |
| GO:0000139 Golgi membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Golgi residence fits the type-II glycan-processing enzyme. Reason: The mas-1 mutant glycan study identifies the product as Golgi mannosidase I, and the original mas-1 molecular analysis reports type-II transmembrane protein isoforms; together they support Golgi membrane association for this glycan-processing enzyme. Supporting Evidence: PMID:9654102 The mas-1 gene of Drosophila melanogaster encodes Golgi mannosidase I (MAS-1) PMID:7729592 Both transcripts code for type II transmembrane proteins which differ in their N-terminal parts. |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The enzyme removes alpha-1,2-linked mannose from oligomannosidic N-glycans. Reason: Recombinant mas-1 is active toward oligomannosidic glycans, and mas-1 deletion causes Man8GlcNAc2 accumulation. Together these support the catalytic annotation on alpha-Man-Ia rather than transfer solely from a GH47 family label. PTN000201533 transfers the shared mannosyl-oligosaccharide 1,2-alpha-mannosidase chemistry, which is retained across ER and Golgi GH47 branches even though the branches differ in compartment and process. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000201533 Β· PANTHER:PTN000201533 SUPPORTS TRANSFER PTN000201533 asserts the common GH47 alpha-1,2-mannosidase activity across ER and Golgi class-I enzymes. The target also appears as FB:FBgn0259170 among the descendant seeds because FlyBase has direct mas-1 experimental evidence; that self seed corroborates the node placement rather than making it circular. Supporting Evidence: PMID:23979800 Some of the recombinant mannosidases were demonstrably active towards oligomannosidic glycans, specifically, the Co(II)-requiring ManIIb, two 'acidic' mannosidases and the class I mas-1 mannosidase. PMID:9654102 There is an accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1 enzyme. |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | IDA PMID:23979800 Characterisation of class I and II Ξ±-mannosidases from Droso... | ACCEPT | Summary: The enzyme removes alpha-1,2-linked mannose from oligomannosidic N-glycans. Reason: Recombinant mas-1 is active toward oligomannosidic glycans, and mas-1 deletion causes Man8GlcNAc2 accumulation. Together these support the catalytic annotation on alpha-Man-Ia rather than transfer solely from a GH47 family label. Supporting Evidence: PMID:23979800 Some of the recombinant mannosidases were demonstrably active towards oligomannosidic glycans, specifically, the Co(II)-requiring ManIIb, two 'acidic' mannosidases and the class I mas-1 mannosidase. PMID:9654102 There is an accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1 enzyme. |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The enzyme removes alpha-1,2-linked mannose from oligomannosidic N-glycans. Reason: Recombinant mas-1 is active toward oligomannosidic glycans, and mas-1 deletion causes Man8GlcNAc2 accumulation. Together these support the catalytic annotation on alpha-Man-Ia rather than transfer solely from a GH47 family label. Supporting Evidence: PMID:23979800 Some of the recombinant mannosidases were demonstrably active towards oligomannosidic glycans, specifically, the Co(II)-requiring ManIIb, two 'acidic' mannosidases and the class I mas-1 mannosidase. PMID:9654102 There is an accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1 enzyme. |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | IMP PMID:9654102 Mutant analysis reveals an alternative pathway for N-linked ... | ACCEPT | Summary: The enzyme removes alpha-1,2-linked mannose from oligomannosidic N-glycans. Reason: Recombinant mas-1 is active toward oligomannosidic glycans, and mas-1 deletion causes Man8GlcNAc2 accumulation. Together these support the catalytic annotation on alpha-Man-Ia rather than transfer solely from a GH47 family label. Supporting Evidence: PMID:23979800 Some of the recombinant mannosidases were demonstrably active towards oligomannosidic glycans, specifically, the Co(II)-requiring ManIIb, two 'acidic' mannosidases and the class I mas-1 mannosidase. PMID:9654102 There is an accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1 enzyme. |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | ISS GO_REF:0000024 | ACCEPT | Summary: The enzyme removes alpha-1,2-linked mannose from oligomannosidic N-glycans. Reason: Recombinant mas-1 is active toward oligomannosidic glycans, and mas-1 deletion causes Man8GlcNAc2 accumulation. Together these support the catalytic annotation on alpha-Man-Ia rather than transfer solely from a GH47 family label. Supporting Evidence: PMID:23979800 Some of the recombinant mannosidases were demonstrably active towards oligomannosidic glycans, specifically, the Co(II)-requiring ManIIb, two 'acidic' mannosidases and the class I mas-1 mannosidase. PMID:9654102 There is an accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1 enzyme. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Calcium binding is a cofactor feature of the GH47 catalytic apparatus. Reason: The calcium-dependent GH47 mechanism makes this inferred binding annotation reasonable; it is ancillary to glycan hydrolysis rather than a distinct calcium-signaling function. Supporting Evidence: file:DROME/alpha-Man-Ia/alpha-Man-Ia-uniprot.txt Name=Ca(2+); Xref=ChEBI:CHEBI:29108; file:DROME/alpha-Man-Ia/alpha-Man-Ia-deep-research-falcon.md Conserved GH47 enzymes employ an active-site CaΒ²βΊ and conserved acidic and substrate-binding residues. |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: ER residence is over-propagated from the ER mannosidase branch onto a Golgi-branch enzyme. Reason: The ER IBD sits on the GH47 root node PTN000201533, and all of its seeds come from the ER mannosidase I (SF55 MAN1B1, yeast and Candida MNS1) and MNL2 (SF103) lineages. Drosophila alpha-Man-Ia is in PTHR11742:SF6, together with its paralog alpha-Man-Ic, C. elegans mans-1 and Arabidopsis MNS1. It also descends from PTN000201534, where PAINT separately placed Golgi membrane using the Golgi class I enzymes (Arabidopsis MNS1/MNS2, mouse Man1a1/Man1a2). The fly product is described as Golgi mannosidase I, a type II membrane protein. A type II Golgi enzyme passes through the ER on the way to the Golgi, so transient ER presence is expected, but "is active in ER" is a property of the ER-mannosidase branch. No fly-specific localization study places alpha-Man-Ia activity in the ER. I treat this as compartmental over-propagation from a GH47 ancestor placed too deep for cellular component. The ER assertion is correct for the ER-branch seeds, so I mark it as over-annotated rather than removing it. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000201533 Β· PANTHER:PTN000201533 SUPPORTS SOURCE BUT NOT TARGET PTN000201533 correctly covers ER-resident MAN1B/MNS1 descendants but is too high for cellular component; it also reaches the Golgi IA-related SF6 branch containing Drosophila alpha-Man-Ia. Supporting Evidence: PMID:9654102 The mas-1 gene of Drosophila melanogaster encodes Golgi mannosidase I (MAS-1) file:interpro/panther/PTHR11742/PTHR11742-entries.csv P53624,"Mannosyl-oligosaccharide alpha-1,2-mannosidase IA",protein,7227,Drosophila melanogaster,Drosophila melanogaster (Fruit fly),alpha-Man-Ia,667,PTHR11742:SF6,"MANNOSYL-OLIGOSACCHARIDE ALPHA-1,2-MANNOSIDASE IA-RELATED",True file:interpro/panther/PTHR11742/PTHR11742-entries.csv Q9UKM7,"Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase",protein,9606,Homo sapiens,Homo sapiens (Human),MAN1B1,699,PTHR11742:SF55,"ENDOPLASMIC RETICULUM MANNOSYL-OLIGOSACCHARIDE 1,2-ALPHA-MANNOSIDASE",True |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: N-glycan mannose trimming specifies the broad carbohydrate process. Reason: Man8GlcNAc2 accumulation in the mutant identifies a direct glycoprotein-processing role rather than undifferentiated carbohydrate metabolism. Proposed replacements: Golgi apparatus N-glycan mannose trimming Supporting Evidence: PMID:9654102 There is an accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1 enzyme. |
| GO:0012505 endomembrane system | HDA PMID:19317464 Mapping organelle proteins and protein complexes in Drosophi... | MODIFY | Summary: The LOPIT endomembrane-system assignment is correct but less specific than the combined evidence. Reason: The embryo LOPIT organelle-proteomics study places the protein in the endomembrane system. That fits the Golgi glycan-processing role, but the assay cannot tell the ER, Golgi and post-Golgi compartments apart. Taken with the gene-specific type II membrane topology and the Golgi mannosidase I identity, the evidence supports the more specific Golgi membrane term, which the gene already carries through IBA, ISS and IEA rows. Proposed replacements: Golgi membrane Supporting Evidence: PMID:9654102 The mas-1 gene of Drosophila melanogaster encodes Golgi mannosidase I (MAS-1) PMID:7729592 Both transcripts code for type II transmembrane proteins which differ in their N-terminal parts. PMID:19317464 we apply LOPIT, a mass-spectrometry based technique that simultaneously maps proteins to specific subcellular compartments, to Drosophila embryos |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Membrane membership is correct but should be refined to Golgi membrane. Reason: The original mas-1 molecular analysis reports type II transmembrane products, and UniProt places a transmembrane segment at residues 19-39, so membrane association is correct. The term is less specific than the evidence supports, because the protein is a Golgi mannosidase I. The appropriate refinement is Golgi membrane, which the gene already carries through other rows. Proposed replacements: Golgi membrane Supporting Evidence: PMID:7729592 Both transcripts code for type II transmembrane proteins which differ in their N-terminal parts. PMID:9654102 The mas-1 gene of Drosophila melanogaster encodes Golgi mannosidase I (MAS-1) |
| GO:0036503 ERAD quality control pathway | IBA GO_REF:0000033 | UNDECIDED | Summary: A dedicated ERAD role is not established for the Golgi-trimming enzyme. Reason: The ERAD IBD sits on the GH47 root node PTN000201533. Its seeds include ER-branch enzymes (MAN1B1, yeast MNS1 and MNL2, fission yeast SPAC2E1P5.01c) and one Golgi class IA enzyme, human MAN1A1 (SF31). Including MAN1A1 shows that the PAINT curator deliberately extended ERAD participation to Golgi-type class I mannosidases, so the call cannot be dismissed as a simple ER-branch leak. The Drosophila evidence neither supports nor refutes it. The mas-1 studies measured steady-state N-glycan profiles and developmental phenotypes, and none tested degradation of a misfolded glycoprotein. The fly enzyme is also in a different subfamily (SF6) from the MAN1A1 seed. Recombinant activity on oligomannosidic glycans fits the mannose trimming that marks ERAD substrates, but it does not show that the fly enzyme takes part in ERAD. The cached literature does not let me check the MAN1A1 ERAD evidence behind the seed, so I leave this undecided rather than accept or remove it. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000201533 Β· PANTHER:PTN000201533 UNRESOLVED PTN000201533's ERAD seed set mixes ER-associated GH47 descendants with human MAN1A1, a Golgi class-IA enzyme; the node therefore needs source-level adjudication before transfer to Drosophila alpha-Man-Ia can be accepted or rejected. Supporting Evidence: PMID:23979800 Some of the recombinant mannosidases were demonstrably active towards oligomannosidic glycans, specifically, the Co(II)-requiring ManIIb, two 'acidic' mannosidases and the class I mas-1 mannosidase. PMID:9654102 There is an accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1 enzyme. file:interpro/panther/PTHR11742/PTHR11742-entries.csv P53624,"Mannosyl-oligosaccharide alpha-1,2-mannosidase IA",protein,7227,Drosophila melanogaster,Drosophila melanogaster (Fruit fly),alpha-Man-Ia,667,PTHR11742:SF6,"MANNOSYL-OLIGOSACCHARIDE ALPHA-1,2-MANNOSIDASE IA-RELATED",True |
| GO:1904381 Golgi apparatus N-glycan mannose trimming | IMP PMID:9654102 Mutant analysis reveals an alternative pathway for N-linked ... | ACCEPT | Summary: Golgi N-glycan mannose trimming is the direct biological process. Reason: The mutant glycan profile accumulates an enzyme substrate while retaining compensatory processing routes, establishing a normal contribution to mannose trimming without requiring lethality. Supporting Evidence: PMID:9654102 There is an accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1 enzyme. |
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Download this section (compressed HTML)Q: Does alpha-Man-Ia contribute to trimming of misfolded glycoproteins for ERAD in Drosophila, as has been proposed for mammalian Golgi mannosidase IA, or is its role limited to maturation of secreted and membrane glycoproteins?
Q: Which of the other Drosophila GH47 paralogs (including alpha-Man-Ib and alpha-Man-Ic) supply the alternative mannose-trimming route that lets mas-1 null flies keep near-normal N-glycan profiles?
Experiment: Profile N-glycans in alpha-Man-Ia; alpha-Man-Ic double mutants (same PANTHER subfamily SF6) and test whether the Man8GlcNAc2 accumulation of the single mutant becomes a block at Man9/Man8.
Hypothesis: The SF6 paralog alpha-Man-Ic provides the redundant Golgi alpha-1,2-mannosidase activity in mas-1 nulls.
Type: genetic interaction and glycomics
Experiment: Measure degradation kinetics of a model misfolded glycoprotein (for example a fly-expressed alpha1-antitrypsin NHK variant) in alpha-Man-Ia null versus wild-type cells, to test the ERAD IBA.
Hypothesis: alpha-Man-Ia contributes to mannose trimming that targets misfolded glycoproteins to ERAD.
Type: ERAD substrate turnover assay
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Download this section (compressed HTML)&agr;-Mannosidase class I a (&agr;-Man-Ia) encodes a transmembrane enzyme that catalyzes the sequential removal of &agr;-1,2-linked mannose residues from protein N-linked glycan Man(9)GlcNAc(2) to produce Man(5)GlcNAc(2). It is involved in the processing of protein N-glycans in the Golgi apparatus.
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