N-glycan trimming and processing in Drosophila melanogaster

After oligosaccharyltransferase transfers Glc3Man9GlcNAc2 to asparagine residues of nascent proteins, the N-glycan is trimmed in the endoplasmic reticulum and then remodelled in the Golgi apparatus. In the ER, glucosidase I (Gcs1) removes the outer glucose and the glucosidase II heterodimer (Gcs2alpha catalytic and Gcs2beta regulatory subunits) removes the two inner glucoses; these steps also control entry into and exit from the calnexin-calreticulin folding cycle. Class I alpha-1,2-mannosidases trim mannoses in the ER and cis-Golgi. In the Golgi, GlcNAc transferase I (Mgat1) adds GlcNAc to the alpha-1,3 arm, which allows alpha-mannosidase II to remove two further mannoses. In insects most N-glycans are then converted to paucimannose glycans by the Golgi beta-N-acetylglucosaminidase Fused lobes (fdl), while a smaller fraction is extended to hybrid and complex glycans by GlcNAc transferase II, core fucosyltransferases, galactosyl-, GalNAc-, glucuronyl- and sialyltransferases.

MODULE:dmel_n_glycan_processingDRAFTCONCRETEMetabolic Pathwaymodules/dmel_n_glycan_processing.yaml
N-glycan processingGO:0006491
FB:FBgg0002122
FlyBase gene group PGERT: Endoplasmic reticulum n-glycan trimming
FlyBase release FB2026_03 groups 4 D. melanogaster genes as endoplasmic reticulum n-glycan trimming (PGERT); this module models that group.
FB:FBgg0002123
FlyBase gene group PGGOT: Golgi n-glycan trimming
FlyBase release FB2026_03 groups 4 D. melanogaster genes as golgi n-glycan trimming (PGGOT); this module models that group.
FB:FBgg0002124
FlyBase gene group PGGOD: Golgi n-glycan diversification
FlyBase release FB2026_03 groups 9 D. melanogaster genes as golgi n-glycan diversification (PGGOD); this module models that group.
FB:FBgg0002131
FlyBase gene group GLU2ABII: Glucosidase ii complex
FlyBase release FB2026_03 groups 2 D. melanogaster genes as glucosidase ii complex (GLU2ABII); this module models that group.
GO:0006491
N-glycan processing
GO term grounding the module as N-glycan processing.

Boundary. The module starts after transfer of the lipid-linked oligosaccharide to protein (oligosaccharyltransferase is outside the module) and covers ER trimming, Golgi trimming and Golgi diversification, the three FlyBase N-glycan processing groups plus the glucosidase II complex group. Core fucosylation by FutA and Fut6 needs the GlcNAc added by Mgat1 and can occur before or after mannosidase II trimming, so the order within the diversification part is shown only where it is clear. GlcAT-P and GlcAT-S are glucuronyltransferases that act on N-glycans and glycolipids (GlcAT-P is also in the O-GalNAc branch of dmel_protein_o_glycosylation); GalT1 is a beta-1,3-galactosyltransferase. No molecular function is assigned to the regulatory Gcs2beta subunit or to alpha-Man-IIb, whose in vitro activity differs from that of classical mannosidase II. Molecular functions of Gcs1, alpha-Man-Ib and Mgat1 follow orthology; the others are supported by assays of the fly enzymes in GO. FlyBase groups realized by this module: PGERT (FBgg0002122), PGGOT (FBgg0002123), PGGOD (FBgg0002124), GLU2ABII (FBgg0002131). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_n_glycan_processing.yaml. Member genes with a gene review in this repository: alpha-Man-Ia.

14Nodes
13Parts
0Variant Sets
0Variants
16Annotons
9Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:dmel_n_glycan_processing deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • glucosidase_i → glucosidase_ii [NOT_CHECKED]
  • glucosidase_ii → er_mannosidase [NOT_CHECKED]
  • er_mannosidase → golgi_mannosidase_i [NOT_CHECKED]
  • golgi_mannosidase_i → gnt1 [NOT_CHECKED]
  • gnt1 → golgi_mannosidase_ii [NOT_CHECKED]
  • golgi_mannosidase_ii → paucimannose_formation [NOT_CHECKED]
  • golgi_mannosidase_ii → golgi_diversification [NOT_CHECKED]

Function consistency and core coverage

1 gene-function check(s) reflected in core functions · 0 conflict(s) · 11 evidence or coverage gap(s) (12 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
glucosidase_i_gcs1 Gcs1
UniProtKB:Q9VZ04
Gene
Glc3Man9GlcNAc2 oligosaccharide glucosidase activity
GO:0004573
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
glucosidase_ii_complex/gcs2alpha Gcs2alpha
UniProtKB:A4V4V1
Complex Unit
Glc2Man9GlcNAc2 oligosaccharide glucosidase activity
GO:0106407
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
er_mannosidase_alpha_man_ib alpha-Man-Ib
UniProtKB:Q9VAP8
Gene
mannosyl-oligosaccharide 1,2-alpha-mannosidase activity
GO:0004571
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
golgi_mannosidase_i_alpha_man_ia alpha-Man-Ia
UniProtKB:P53624
Gene
mannosyl-oligosaccharide 1,2-alpha-mannosidase activity
GO:0004571
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gnt1_mgat1 Mgat1
UniProtKB:A1ZBV7
Gene
alpha-1,3-mannosylglycoprotein 2-beta-N-acetylglucosaminyltransferase activity
GO:0003827
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
golgi_mannosidase_ii_alpha_man_iia alpha-Man-IIa
UniProtKB:Q24451
Gene
mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase activity
GO:0004572
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
paucimannose_formation_fdl fdl
UniProtKB:Q8WSF3
Gene
beta-N-acetylglucosaminidase activity
GO:0016231
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
gnt2_mgat2 Mgat2
UniProtKB:A0A0B4KHE4
Gene
alpha-1,6-mannosylglycoprotein 2-beta-N-acetylglucosaminyltransferase activity
GO:0008455
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
core_fucosylation_fut6 Fut6
UniProtKB:Q9VYV5
Gene
glycoprotein 6-alpha-L-fucosyltransferase activity
GO:0008424
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
core_fucosylation_futa FutA
UniProtKB:Q9VUL9
Gene
glycoprotein 3-alpha-L-fucosyltransferase activity
GO:0018392
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
antenna_elongation_beta4galnacta beta4GalNAcTA
UniProtKB:Q7KN92
Gene
N-acetyl-beta-glucosaminyl-derivative 4-beta-N-acetylgalactosaminyltransferase activity
GO:0033842
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
sialylation_siat Siat
UniProtKB:Q9W121
Gene
beta-galactoside alpha-2,6-sialyltransferase activity
GO:0003835
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.

Gene-review completeness (1/17 grounded genes reviewed)

0 complete review(s) · 1 with deep research · 16 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
Mgat2 A0A0B4KHE4 ✗ — —
GalT1 A1Z8R6 ✗ — —
Mgat1 A1ZBV7 ✗ — —
Gcs2alpha A4V4V1 ✗ — —
alpha-Man-Ia P53624 ✓ 14/15 ✓
alpha-Man-IIa Q24451 ✗ — —
beta4GalNAcTA Q7KN92 ✗ — —
fdl Q8WSF3 ✗ — —
alpha-Man-Ib Q9VAP8 ✗ — —
alpha-Man-IIb Q9VF33 ✗ — —
Gcs2beta Q9VJD1 ✗ — —
GlcAT-S Q9VLA1 ✗ — —
GlcAT-P Q9VTG7 ✗ — —
FutA Q9VUL9 ✗ — —
Fut6 Q9VYV5 ✗ — —
Gcs1 Q9VZ04 ✗ — —
Siat Q9W121 ✗ — —

Details

Context
Drosophila melanogasterNCBITaxon:7227
N-glycan processingMetabolic Pathwaydmel_n_glycan_processing

ER and Golgi trimming of protein-linked Glc3Man9GlcNAc2 and its conversion to paucimannose, hybrid and complex N-glycans.

N-glycan processingGO:0006491
Context
Drosophila melanogasterNCBITaxon:7227

Connections

Glc2Man9GlcNAc2 is the substrate of glucosidase II.
Deglucosylated Man9GlcNAc2 is trimmed by ER mannosidase.
Man8GlcNAc2 is trimmed further to Man5GlcNAc2 in the Golgi.
Man5GlcNAc2 is the acceptor for GlcNAc transferase I.
Alpha-mannosidase II requires the GlcNAc added by GlcNAc transferase I.
GlcNAcMan3GlcNAc2 is trimmed by Fused lobes to paucimannose.
GlcNAcMan3GlcNAc2 is alternatively extended to complex glycans.
Part 1: step 1, removal of the terminal alpha-1,2-glucose
Glucosidase I trimmingReactionglucosidase_i

Annotons

Gcs1 Glucosidase I trimming
glucosidase_i_gcs1
Participant: Gene Product: Gcs1
Gene Product:

Function

Glc3Man9GlcNAc2 oligosaccharide glucosidase activityGO:0004573

Processes

endoplasmic reticulum N-glycan trimmingGO:0140277
Part 2: step 2, removal of the two inner alpha-1,3-glucoses
Glucosidase II complexProtein Complexglucosidase_ii

Annotons

Glucosidase II complex
glucosidase_ii_complex
Participant: Protein Complex: Glucosidase II complex
Protein Complex:
Glucosidase II complexGO:0017177
Active units:
Gcs2alpha
Participant: Gene Product: Gcs2alpha
Gene Product:
Role: catalytic alpha subunit
Function:
Glc2Man9GlcNAc2 oligosaccharide glucosidase activityGO:0106407
Gcs2beta
Participant: Gene Product: Gcs2beta
Gene Product:
Role: regulatory beta subunit that retains the complex in the ER
Part 3: step 3, ER mannose trimming
ER alpha-1,2-mannosidase trimmingReactioner_mannosidase

Annotons

alpha-Man-Ib ER alpha-1,2-mannosidase trimming
er_mannosidase_alpha_man_ib
Participant: Gene Product: alpha-Man-Ib
Gene Product:
alpha-Man-IbUniProtKB:Q9VAP8

Function

mannosyl-oligosaccharide 1,2-alpha-mannosidase activityGO:0004571

Processes

endoplasmic reticulum N-glycan trimmingGO:0140277
Part 4: step 4, trimming to Man5GlcNAc2
Golgi alpha-1,2-mannosidase I trimmingReactiongolgi_mannosidase_i

Annotons

alpha-Man-Ia Golgi alpha-1,2-mannosidase I trimming
golgi_mannosidase_i_alpha_man_ia
Participant: Gene Product: alpha-Man-Ia
Gene Product:
alpha-Man-IaUniProtKB:P53624

Function

mannosyl-oligosaccharide 1,2-alpha-mannosidase activityGO:0004571

Processes

Golgi apparatus N-glycan mannose trimmingGO:1904381
Part 5: step 5, GlcNAc addition to the alpha-1,3 mannose arm
GlcNAc transferase IReactiongnt1

Annotons

Mgat1 GlcNAc transferase I
gnt1_mgat1
Participant: Gene Product: Mgat1
Gene Product:

Function

alpha-1,3-mannosylglycoprotein 2-beta-N-acetylglucosaminyltransferase activityGO:0003827
Part 6: step 6, removal of the alpha-1,3 and alpha-1,6 mannoses of the 6-arm
Golgi alpha-mannosidase II trimmingReactiongolgi_mannosidase_ii

Annotons

alpha-Man-IIa Golgi alpha-mannosidase II trimming
golgi_mannosidase_ii_alpha_man_iia
Participant: Gene Product: alpha-Man-IIa
Gene Product:
alpha-Man-IIaUniProtKB:Q24451

Function

mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase activityGO:0004572

Processes

Golgi apparatus N-glycan mannose trimmingGO:1904381
Part 7: step 7a, removal of the GlcNAc added by GlcNAc transferase I
Paucimannose formation by Fused lobesReactionpaucimannose_formation

Annotons

fdl Paucimannose formation by Fused lobes
paucimannose_formation_fdl
Participant: Gene Product: fdl
Gene Product:

Function

beta-N-acetylglucosaminidase activityGO:0016231
Part 8: step 7b, extension to hybrid and complex N-glycans
Golgi N-glycan diversificationMetabolic Pathwaygolgi_diversification
Golgi apparatus N-glycan diversificationGO:0016258

Connections

GlcNAc residues on both arms are substrates for antenna extension.
Sialic acid is added to terminal galactose.
Part 1: GlcNAc addition to the alpha-1,6 mannose arm
GlcNAc transferase IIReactiongnt2

Annotons

Mgat2 GlcNAc transferase II
gnt2_mgat2
Participant: Gene Product: Mgat2
Gene Product:

Function

alpha-1,6-mannosylglycoprotein 2-beta-N-acetylglucosaminyltransferase activityGO:0008455
Part 2: alternative Golgi mannose trimming
Alternative alpha-mannosidase IIReactionalternative_mannosidase_ii

Annotons

alpha-Man-IIb Alternative alpha-mannosidase II
alternative_mannosidase_ii_alpha_man_iib
Participant: Gene Product: alpha-Man-IIb
Gene Product:
alpha-Man-IIbUniProtKB:Q9VF33
Part 3: alpha-1,6 and alpha-1,3 fucosylation of the core GlcNAc
Core fucosylationReactioncore_fucosylation

Annotons

Fut6 Core fucosylation
core_fucosylation_fut6
Participant: Gene Product: Fut6
Gene Product:

Function

glycoprotein 6-alpha-L-fucosyltransferase activityGO:0008424
FutA Core fucosylation
core_fucosylation_futa
Participant: Gene Product: FutA
Gene Product:

Function

glycoprotein 3-alpha-L-fucosyltransferase activityGO:0018392
Part 4: galactose, GalNAc and glucuronic acid addition to antennae
Antenna elongationReactionantenna_elongation

Annotons

GalT1 Antenna elongation
antenna_elongation_galt1
Participant: Gene Product: GalT1
Gene Product:
beta4GalNAcTA Antenna elongation
antenna_elongation_beta4galnacta
Participant: Gene Product: beta4GalNAcTA
Gene Product:
beta4GalNAcTAUniProtKB:Q7KN92

Function

N-acetyl-beta-glucosaminyl-derivative 4-beta-N-acetylgalactosaminyltransferase activityGO:0033842
GlcAT-P Antenna elongation
antenna_elongation_glcat_p
Participant: Gene Product: GlcAT-P
Gene Product:
GlcAT-S Antenna elongation
antenna_elongation_glcat_s
Participant: Gene Product: GlcAT-S
Gene Product:
Part 5: terminal alpha-2,6 sialylation
SialylationReactionsialylation

Annotons

Siat Sialylation
sialylation_siat
Participant: Gene Product: Siat
Gene Product:

Function

beta-galactoside alpha-2,6-sialyltransferase activityGO:0003835