N-glycan LLO assembly II — ER-lumenal face + glucosylation (to Glc3Man9GlcNAc2-PP-dolichol); RFT1/ALG3/ALG9/ALG12/ALG6/ALG8/ALG10

After the Man5GlcNAc2-PP-dolichol intermediate is flipped from the cytoplasmic to the lumenal face of the endoplasmic-reticulum membrane (by the RFT1 flippase), the dolichol-linked oligosaccharide (LLO) is completed inside the ER lumen to the mature Glc3Man9GlcNAc2-PP-dolichol donor for protein N-linked glycosylation. Unlike the cytoplasmic-face steps, the lumenal glycosyltransferases use lipid-linked donors: dolichyl-phosphate-mannose (Dol-P-Man) for the mannose additions and dolichyl-phosphate-glucose (Dol-P-Glc) for the glucose additions. Four mannoses are added: ALG3 (alpha-1,3) adds the sixth mannose, ALG9 (alpha-1,2) adds the seventh and, later, the ninth mannose, and ALG12 (alpha-1,6) adds the eighth, giving Man9GlcNAc2-PP-dolichol. Three glucoses then cap the glycan: ALG6 (alpha-1,3) adds the first glucose, ALG8 (alpha-1,3) the second, and ALG10 (alpha-1,2) the third and terminal glucose, producing the mature Glc3Man9GlcNAc2-PP-dolichol. The terminal glucose is the recognition signal for efficient transfer of the glycan to nascent proteins by the oligosaccharyltransferase (and, after transfer, for glucosidase trimming and calnexin/calreticulin quality control). Inherited defects in each step cause a congenital disorder of glycosylation (CDG type I): ALG3-CDG (CDG-Id), ALG9-CDG (CDG-Il / Gillessen-Kaesbach-Nishimura syndrome), ALG12-CDG (CDG-Ig), ALG6-CDG (CDG-Ic, one of the commonest CDG-I subtypes) and ALG8-CDG (CDG-Ih).

MODULE:n_glycan_llo_assembly_lumenalDRAFTMetabolic Pathwaymodules/n_glycan_llo_assembly_lumenal.yaml
dolichol-linked oligosaccharide biosynthetic processGO:0006488 protein N-linked glycosylationGO:0006487
GO:0006488
dolichol-linked oligosaccharide biosynthetic process
The module is grounded in dolichol-linked oligosaccharide biosynthetic process (GO:0006488); it covers the lumenal-face completion of the LLO to Glc3Man9GlcNAc2-PP-dolichol.
GO:0006487
protein N-linked glycosylation
The mature glucosylated LLO is the donor for protein N-linked glycosylation (GO:0006487); each enzyme's loss reduces N-glycan occupancy (CDG type I).
Reactome:R-HSA-446193
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
Step order, intermediates and reaction stoichiometries follow the human Reactome LLO biosynthesis sub-pathway (R-HSA-446188/446215/446198/446216/446202/446189 for the lumenal steps).
file:human/RFT1/RFT1-ai-review.yaml
RFT1 gene review (human)
The Man5GlcNAc2-PP-dolichol translocation step (UniProtKB:Q96AA3, GO:0140303) matches the completed human RFT1 review.
file:human/ALG3/ALG3-ai-review.yaml
ALG3 gene review (human)
The first lumenal mannose (6th, alpha-1,3) step (UniProtKB:Q92685, GO:0052925) matches the completed human ALG3 review.
file:human/ALG9/ALG9-ai-review.yaml
ALG9 gene review (human)
The 7th- and 9th-mannose (alpha-1,2) steps (UniProtKB:Q9H6U8, GO:0052926/GO:0052918) match the completed human ALG9 review.
file:human/ALG12/ALG12-ai-review.yaml
ALG12 gene review (human)
The 8th-mannose (alpha-1,6) step (UniProtKB:Q9BV10, GO:0052917) matches the completed human ALG12 review.
file:human/ALG6/ALG6-ai-review.yaml
ALG6 gene review (human)
The first-glucose (alpha-1,3) step (UniProtKB:Q9Y672, GO:0042281) matches the completed human ALG6 review.
file:human/ALG8/ALG8-ai-review.yaml
ALG8 gene review (human)
The second-glucose (alpha-1,3) step (UniProtKB:Q9BVK2, GO:0042283) matches the completed human ALG8 review.
file:human/ALG10/ALG10-ai-review.yaml
ALG10 gene review (human)
The third/terminal-glucose (alpha-1,2) step (UniProtKB:Q5BKT4, GO:0106073) matches the completed human ALG10 review.
YeastPathways:GLUCOSE-MANNOSYL-CHITO-DOLICHOL
lipid-linked oligosaccharide biosynthesis (S. cerevisiae, SGD YeastPathways)
The YeastCyc frame spans both LLO modules. Lumenal reactions: RXN3O-291 (ALG3), RXN3O-3 and RXN3O-259 (ALG9), RXN3O-11 (ALG12), RXN3O-411 (ALG6), RXN3O-412 (ALG8) and RXN3O-413 (DIE2/ALG10). All gene assignments were retained.
PMID:11308030
Biosynthesis of lipid-linked oligosaccharides in yeast: the ALG3 gene encodes the Dol-P-Man:Man5GlcNAc2-PP-Dol mannosyltransferase.
ALG3 adds the first Dol-P-Man-derived mannose on the lumenal side.
PMID:15987956
ALG9 mannosyltransferase is involved in two different steps of lipid-linked oligosaccharide biosynthesis.
Yeast ALG9 adds both the seventh and the ninth mannose.
PMID:10336995
Ordered assembly of the asymmetrically branched lipid-linked oligosaccharide in the endoplasmic reticulum is ensured by the substrate specificity of the individual glycosyltransferases.
ALG12 adds the alpha-1,6 mannose to Man7GlcNAc2-PP-Dol; substrate specificity enforces ordered assembly.
PMID:8877369
Isolation of the ALG6 locus of Saccharomyces cerevisiae required for glucosylation in the N-linked glycosylation pathway.
ALG6 is required for the first glucosylation of the LLO.
PMID:9597543
The ALG10 locus of Saccharomyces cerevisiae encodes the alpha-1,2 glucosyltransferase of the endoplasmic reticulum: the terminal glucose of the lipid-linked oligosaccharide is required for efficient N-linked glycosylation.
ALG10 (DIE2) adds the terminal alpha-1,2 glucose.
PMID:23751184
N-linked protein glycosylation in the endoplasmic reticulum.
Review of LLO assembly on both faces of the ER membrane, centred on S. cerevisiae.
9Nodes
8Parts
0Variant Sets
0Variants
8Annotons
7Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:n_glycan_llo_assembly_lumenal 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.

  • rft1_flip → alg3_step [NOT_CHECKED]
    A dolichol-linked glycan intermediate links the steps; no CoA carrier is involved.
  • alg3_step → alg9_step7 [NOT_CHECKED]
    A dolichol-linked glycan intermediate links the steps; no CoA carrier is involved.
  • alg9_step7 → alg12_step [NOT_CHECKED]
    A dolichol-linked glycan intermediate links the steps; no CoA carrier is involved.
  • alg12_step → alg9_step9 [NOT_CHECKED]
    A dolichol-linked glycan intermediate links the steps; no CoA carrier is involved.
  • alg9_step9 → alg6_step [NOT_CHECKED]
    A dolichol-linked glycan intermediate links the steps; no CoA carrier is involved.
  • alg6_step → alg8_step [NOT_CHECKED]
    A dolichol-linked glycan intermediate links the steps; no CoA carrier is involved.
  • alg8_step → alg10_step [NOT_CHECKED]
    A dolichol-linked glycan intermediate links the steps; no CoA carrier is involved.

Function consistency and core coverage

21 gene-function check(s) reflected in core functions · 0 conflict(s) · 2 evidence or coverage gap(s) (30 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
rft1_activity RFT1 (human)
UniProtKB:Q96AA3
Family Representative 		ATP-independent Man5GlcNAc2-PP-dolichol translocase (scramblase) activity
GO:0140303 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg3_activity ALG3 (human)
UniProtKB:Q92685
Family Representative 		dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity
GO:0052925 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg3_activity ALG3 (Saccharomyces cerevisiae)
UniProtKB:P38179
Family Representative 		dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity
GO:0052925 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg3_activity alg3 (Schizosaccharomyces pombe)
UniProtKB:Q9Y7I4
Family Representative 		dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity
GO:0052925 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg9_activity_m7 ALG9 (human)
UniProtKB:Q9H6U8
Family Representative 		dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
GO:0052926 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg9_activity_m7 ALG9 (Saccharomyces cerevisiae)
UniProtKB:P53868
Family Representative 		dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
GO:0052926 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg9_activity_m7 alg9 (Schizosaccharomyces pombe)
UniProtKB:Q9P7Q9
Family Representative 		dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
GO:0052926 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg12_activity ALG12 (human)
UniProtKB:Q9BV10
Family Representative 		dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activity
GO:0052917 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg12_activity ALG12 (Saccharomyces cerevisiae)
UniProtKB:P53730
Family Representative 		dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activity
GO:0052917 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg12_activity alg12 (Schizosaccharomyces pombe)
UniProtKB:Q9USD4
Family Representative 		dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activity
GO:0052917 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg9_activity_m9 ALG9 (human)
UniProtKB:Q9H6U8
Family Representative 		dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
GO:0052918 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg9_activity_m9 ALG9 (Saccharomyces cerevisiae)
UniProtKB:P53868
Family Representative 		dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
GO:0052918 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg9_activity_m9 alg9 (Schizosaccharomyces pombe)
UniProtKB:Q9P7Q9
Family Representative 		dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
GO:0052918 		Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
alg6_activity ALG6 (human)
UniProtKB:Q9Y672
Family Representative 		dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
GO:0042281 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg6_activity ALG6 (Saccharomyces cerevisiae)
UniProtKB:Q12001
Family Representative 		dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
GO:0042281 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg6_activity alg6 (Schizosaccharomyces pombe)
UniProtKB:O43053
Family Representative 		dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
GO:0042281 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg8_activity ALG8 (human)
UniProtKB:Q9BVK2
Family Representative 		dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
GO:0042283 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg8_activity ALG8 (Saccharomyces cerevisiae)
UniProtKB:P40351
Family Representative 		dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
GO:0042283 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg8_activity alg8 (Schizosaccharomyces pombe)
UniProtKB:Q10479
Family Representative 		dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
GO:0042283 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg10_activity ALG10 (human)
UniProtKB:Q5BKT4
Family Representative 		dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity
GO:0106073 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg10_activity DIE2/ALG10 (Saccharomyces cerevisiae)
UniProtKB:P50076
Family Representative 		dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity
GO:0106073 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
alg10_activity alg10 (Schizosaccharomyces pombe)
UniProtKB:Q10254
Family Representative 		dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity
GO:0106073 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rft1_activity RFT1 family
PANTHER:PTHR13117:SF5
Family 		ATP-independent Man5GlcNAc2-PP-dolichol translocase (scramblase) activity
GO:0140303 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR13117:SF5.
alg3_activity ALG3 mannosyltransferase family
PANTHER:PTHR12646
Family 		dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity
GO:0052925 		Family Supported
Family review supports GO:0052925 FAMILY_WIDE. Asserted by n_glycan_llo_assembly_lumenal; accepted by ALG3, alg3 and human ALG3.
alg9_activity_m7 ALG9 Dol-P-Man alpha-1,2-mannosyltransferase subfamily
PANTHER:PTHR22760:SF2
Family 		dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
GO:0052926 		Family Supported
Family review supports GO:0052926 for PANTHER:PTHR22760:SF2. ALG9 (SF2); n_glycan_llo_assembly_lumenal asserts it on the base family.
alg12_activity ALG12 Dol-P-Man alpha-1,6-mannosyltransferase subfamily
PANTHER:PTHR22760:SF1
Family 		dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activity
GO:0052917 		Family Supported
Family review supports GO:0052917 for PANTHER:PTHR22760:SF1. ALG12 (SF1).
alg9_activity_m9 ALG9 Dol-P-Man alpha-1,2-mannosyltransferase subfamily
PANTHER:PTHR22760:SF2
Family 		dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity
GO:0052918 		Family Supported
Family review supports GO:0052918 for PANTHER:PTHR22760:SF2. ALG9 (SF2), its second reaction.
alg6_activity ALG6 Dol-P-Glc alpha-1,3-glucosyltransferase subfamily
PANTHER:PTHR12413:SF1
Family 		dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
GO:0042281 		Family Supported
Family review supports GO:0042281 for PANTHER:PTHR12413:SF1. ALG6 (SF1); n_glycan_llo_assembly_lumenal asserts it on the base family.
alg8_activity ALG8 Dol-P-Glc alpha-1,3-glucosyltransferase subfamily
PANTHER:PTHR12413:SF2
Family 		dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
GO:0042283 		Family Supported
Family review supports GO:0042283 for PANTHER:PTHR12413:SF2. ALG8 (SF2); n_glycan_llo_assembly_lumenal asserts it on the base family.
alg10_activity ALG10 Dol-P-Glc alpha-1,2-glucosyltransferase family
PANTHER:PTHR12989
Family 		dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity
GO:0106073 		Family Supported
Family review supports GO:0106073 FAMILY_WIDE. Asserted by n_glycan_llo_assembly_lumenal; accepted by DIE2, alg10 and ALG10.

Gene-review completeness (19/19 grounded genes reviewed)

18 complete review(s) · 7 with deep research · 0 missing review · 12 reviewed but lacking deep research

Gene Review Complete Deep research
alg10 Q10254 ✓ ✓ ✗
ALG10 Q5BKT4 ✓ ✓ ✗
ALG12 P53730 ✓ ✓ ✓
ALG12 Q9BV10 ✓ 22/23 ✗
alg12 Q9USD4 ✓ ✓ ✗
ALG3 P38179 ✓ ✓ ✓
ALG3 Q92685 ✓ ✓ ✗
alg3 Q9Y7I4 ✓ ✓ ✗
alg6 O43053 ✓ ✓ ✗
ALG6 Q12001 ✓ ✓ ✓
ALG6 Q9Y672 ✓ ✓ ✗
ALG8 P40351 ✓ ✓ ✓
alg8 Q10479 ✓ ✓ ✗
ALG8 Q9BVK2 ✓ ✓ ✗
ALG9 P53868 ✓ ✓ ✓
ALG9 Q9H6U8 ✓ ✓ ✗
alg9 Q9P7Q9 ✓ ✓ ✗
DIE2 P50076 ✓ ✓ ✓
RFT1 Q96AA3 ✓ ✓ ✓

Details

Context
eukaryotesNCBITaxon:2759
lumenal side of endoplasmic reticulum membraneGO:0098553 endoplasmic reticulum membraneGO:0005789
N-glycan LLO assembly, lumenal face + glucosylation (to Glc3Man9GlcNAc2-PP-dolichol)Metabolic Pathwayn_glycan_llo_assembly_lumenal
dolichol-linked oligosaccharide biosynthetic processGO:0006488 protein N-linked glycosylationGO:0006487
Context
eukaryotesNCBITaxon:2759
lumenal side of endoplasmic reticulum membraneGO:0098553 endoplasmic reticulum membraneGO:0005789

Lumenal-face + glucosylation segment of dolichol-linked oligosaccharide (LLO) assembly, grounded to the human enzymes ALG3 (UniProtKB:Q92685, GO:0052925, EC 2.4.1.258), ALG9 (Q9H6U8, GO:0052926 + GO:0052918, EC 2.4.1.259/261), ALG12 (Q9BV10, GO:0052917, EC 2.4.1.260), ALG6 (Q9Y672, GO:0042281, EC 2.4.1.267), ALG8 (Q9BVK2, GO:0042283, EC 2.4.1.265) and ALG10 (Q5BKT4, GO:0106073, EC 2.4.1.256). GO molecular-function/location terms were taken from the completed human gene reviews and verified against the local go.db; Reactome reaction ids/titles were verified against the local reactome cache (ALG10 has no cached WT Reactome reaction, so its node is grounded on EC 2.4.1.256 and the umbrella pathway R-HSA-446193). Each step uses a PANTHER family selector with the human enzyme as representative so the module generalises across orthologs/paralogs; ALG9/ALG12 share PTHR22760 and ALG6/ALG8 share PTHR12413. ALG9 appears twice (steps 3 and 5) because it is bifunctional (adds both the 7th and 9th mannoses). All lumenal steps use lipid-linked donors — Dol-P-Man for mannoses, Dol-P-Glc for glucoses — supplied by the dolichol/sugar-donor module (DOLK, SRD5A3, DPM1/2/3, MPDU1, ALG5; to follow). Upstream is the cytoplasmic-face module (DPAGT1/ALG13/ALG14/ALG1/ALG2/ALG11 -> Man5GlcNAc2-PP-Dol), whose product RFT1 (step 1 here) flips to the lumenal face; downstream the mature Glc3Man9GlcNAc2-PP-Dol is transferred to protein by the oligosaccharyltransferase. Disorders: each step's loss is a CDG type I (ALG3-, ALG9-, ALG12-, ALG6-, ALG8-CDG; ALG6-CDG/CDG-Ic is one of the commonest). ALIGN (YeastPathways project, 2026-10): S. cerevisiae (ALG3 P38179, ALG9 P53868, ALG12 P53730, ALG6 Q12001, ALG8 P40351, DIE2/ALG10 P50076) and S. pombe (alg3 Q9Y7I4, alg9 Q9P7Q9, alg12 Q9USD4, alg6 O43053, alg8 Q10479, alg10 Q10254) exemplars were added; all fall in the same PANTHER families as the human representatives. YeastCyc gene assignments are correct (ALG9 twice, DIE2 = ALG10). Connections were converted to PRECEDES. GO-CAM disagreements: the SGD model places every lumenal enzyme in cytosol and gives ALG12 only GO:0000009; the PomBase model places them at the ER membrane and agrees with the step order. The lipid-linked donors come from dolichol_phosphate_sugar_donor_supply.

Connections

rft1_flip -> alg3_step Precedes
Lumenally exposed Man5GlcNAc2-PP-dolichol receives the 6th mannose from ALG3.
alg3_step -> alg9_step7 Precedes
Man6GlcNAc2-PP-dolichol from ALG3 receives the 7th mannose from ALG9.
alg9_step7 -> alg12_step Precedes
Man7GlcNAc2-PP-dolichol receives the 8th mannose from ALG12.
alg12_step -> alg9_step9 Precedes
Man8GlcNAc2-PP-dolichol receives the 9th mannose from ALG9, completing Man9.
alg9_step9 -> alg6_step Precedes
Man9GlcNAc2-PP-dolichol receives the first glucose from ALG6.
alg6_step -> alg8_step Precedes
Glc1Man9GlcNAc2-PP-dolichol receives the second glucose from ALG8.
alg8_step -> alg10_step Precedes
Glc2Man9GlcNAc2-PP-dolichol receives the terminal glucose from ALG10, giving the mature LLO.
Part 1: Transbilayer translocation of Man5GlcNAc2-PP-dolichol, entry step to the lumenal segment
Man5GlcNAc2-PP-dolichol (cytoplasmic leaflet) to Man5GlcNAc2-PP-dolichol (lumenal leaflet)Transport Steprft1_flip

Annotons

RFT1: Man5GlcNAc2-PP-dolichol scramblase (flippase)
rft1_activity
Participant: Family: RFT1 family
Family:
RFT1 familyPANTHER:PTHR13117:SF5
Representative Members: RFT1 (human)UniProtKB:Q96AA3

Function

ATP-independent Man5GlcNAc2-PP-dolichol translocase (scramblase) activityGO:0140303
Substrates: Man5GlcNAc2-PP-dolichol (cytoplasmic leaflet)
Products: Man5GlcNAc2-PP-dolichol (lumenal leaflet)

Locations

endoplasmic reticulum membraneGO:0005789

Delivers the cytoplasmically built Man5 intermediate to the lumenal leaflet for ALG3; deficiency = RFT1-CDG (CDG-In), with accumulation of Man5GlcNAc2-PP-dolichol.

Part 2: 6th mannose (alpha-1,3), first lumenal step
Man5GlcNAc2-PP-dolichol to Man6GlcNAc2-PP-dolicholReactionalg3_step

Annotons

ALG3: Dol-P-Man alpha-1,3-mannosyltransferase
alg3_activity
Participant: Family: ALG3 mannosyltransferase family
Family:
ALG3 mannosyltransferase familyPANTHER:PTHR12646
Representative Members: ALG3 (human)UniProtKB:Q92685 ALG3 (Saccharomyces cerevisiae)UniProtKB:P38179 alg3 (Schizosaccharomyces pombe)UniProtKB:Q9Y7I4

Function

dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activityGO:0052925
Substrates: dolichyl-phosphate-mannose (Dol-P-Man) Man5GlcNAc2-PP-dolichol
Products: Man6GlcNAc2-PP-dolichol dolichyl phosphate

Locations

endoplasmic reticulum membraneGO:0005789

First lumenal mannose; deficiency = ALG3-CDG (CDG-Id).

Part 3: 7th mannose (alpha-1,2)
Man6GlcNAc2-PP-dolichol to Man7GlcNAc2-PP-dolicholReactionalg9_step7

Annotons

ALG9: Dol-P-Man alpha-1,2-mannosyltransferase (7th Man)
alg9_activity_m7
Participant: Family: ALG9 Dol-P-Man alpha-1,2-mannosyltransferase subfamily
Family:
ALG9 Dol-P-Man alpha-1,2-mannosyltransferase subfamily
Representative Members: ALG9 (human)UniProtKB:Q9H6U8 ALG9 (Saccharomyces cerevisiae)UniProtKB:P53868 alg9 (Schizosaccharomyces pombe)UniProtKB:Q9P7Q9

Function

dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activityGO:0052926
Substrates: dolichyl-phosphate-mannose (Dol-P-Man) Man6GlcNAc2-PP-dolichol
Products: Man7GlcNAc2-PP-dolichol dolichyl phosphate

Locations

endoplasmic reticulum membraneGO:0005789

7th mannose; ALG9 is bifunctional and later adds the 9th mannose. Deficiency = ALG9-CDG (CDG-Il) / Gillessen-Kaesbach-Nishimura syndrome.

Part 4: 8th mannose (alpha-1,6)
Man7GlcNAc2-PP-dolichol to Man8GlcNAc2-PP-dolicholReactionalg12_step

Annotons

ALG12: Dol-P-Man alpha-1,6-mannosyltransferase
alg12_activity
Participant: Family: ALG12 Dol-P-Man alpha-1,6-mannosyltransferase subfamily
Family:
ALG12 Dol-P-Man alpha-1,6-mannosyltransferase subfamily
Representative Members: ALG12 (human)UniProtKB:Q9BV10 ALG12 (Saccharomyces cerevisiae)UniProtKB:P53730 alg12 (Schizosaccharomyces pombe)UniProtKB:Q9USD4

Function

dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase activityGO:0052917
Substrates: dolichyl-phosphate-mannose (Dol-P-Man) Man7GlcNAc2-PP-dolichol
Products: Man8GlcNAc2-PP-dolichol dolichyl phosphate

Locations

endoplasmic reticulum membraneGO:0005789

8th mannose; deficiency = ALG12-CDG (CDG-Ig).

Part 5: 9th mannose (alpha-1,2) — completes Man9
Man8GlcNAc2-PP-dolichol to Man9GlcNAc2-PP-dolicholReactionalg9_step9

Annotons

ALG9: Dol-P-Man alpha-1,2-mannosyltransferase (9th Man)
alg9_activity_m9
Participant: Family: ALG9 Dol-P-Man alpha-1,2-mannosyltransferase subfamily
Family:
ALG9 Dol-P-Man alpha-1,2-mannosyltransferase subfamily
Representative Members: ALG9 (human)UniProtKB:Q9H6U8 ALG9 (Saccharomyces cerevisiae)UniProtKB:P53868 alg9 (Schizosaccharomyces pombe)UniProtKB:Q9P7Q9

Function

dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activityGO:0052918
Substrates: dolichyl-phosphate-mannose (Dol-P-Man) Man8GlcNAc2-PP-dolichol
Products: Man9GlcNAc2-PP-dolichol dolichyl phosphate

Locations

endoplasmic reticulum membraneGO:0005789

9th mannose (same enzyme as step 2), completing the Man9 core.

Part 6: 1st glucose (alpha-1,3)
Man9GlcNAc2-PP-dolichol to Glc1Man9GlcNAc2-PP-dolicholReactionalg6_step

Annotons

ALG6: Dol-P-Glc alpha-1,3-glucosyltransferase
alg6_activity
Participant: Family: ALG6 Dol-P-Glc alpha-1,3-glucosyltransferase subfamily
Family:
ALG6 Dol-P-Glc alpha-1,3-glucosyltransferase subfamily
Representative Members: ALG6 (human)UniProtKB:Q9Y672 ALG6 (Saccharomyces cerevisiae)UniProtKB:Q12001 alg6 (Schizosaccharomyces pombe)UniProtKB:O43053

Function

dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase activityGO:0042281
Substrates: dolichyl-phosphate-glucose (Dol-P-Glc) Man9GlcNAc2-PP-dolichol
Products: Glc1Man9GlcNAc2-PP-dolichol dolichyl phosphate

Locations

endoplasmic reticulum membraneGO:0005789

First glucose; deficiency = ALG6-CDG (CDG-Ic, a common CDG-I subtype).

Part 7: 2nd glucose (alpha-1,3)
Glc1Man9GlcNAc2-PP-dolichol to Glc2Man9GlcNAc2-PP-dolicholReactionalg8_step

Annotons

ALG8: Dol-P-Glc alpha-1,3-glucosyltransferase
alg8_activity
Participant: Family: ALG8 Dol-P-Glc alpha-1,3-glucosyltransferase subfamily
Family:
ALG8 Dol-P-Glc alpha-1,3-glucosyltransferase subfamily
Representative Members: ALG8 (human)UniProtKB:Q9BVK2 ALG8 (Saccharomyces cerevisiae)UniProtKB:P40351 alg8 (Schizosaccharomyces pombe)UniProtKB:Q10479

Function

dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activityGO:0042283
Substrates: dolichyl-phosphate-glucose (Dol-P-Glc) Glc1Man9GlcNAc2-PP-dolichol
Products: Glc2Man9GlcNAc2-PP-dolichol dolichyl phosphate

Locations

lumenal side of endoplasmic reticulum membraneGO:0098553

Second glucose; deficiency = ALG8-CDG (CDG-Ih).

Part 8: 3rd/terminal glucose (alpha-1,2) — mature LLO
Glc2Man9GlcNAc2-PP-dolichol to Glc3Man9GlcNAc2-PP-dolichol (mature LLO)Reactionalg10_step

Annotons

ALG10: Dol-P-Glc alpha-1,2-glucosyltransferase
alg10_activity
Participant: Family: ALG10 Dol-P-Glc alpha-1,2-glucosyltransferase family
Family:
ALG10 Dol-P-Glc alpha-1,2-glucosyltransferase familyPANTHER:PTHR12989
Representative Members: ALG10 (human)UniProtKB:Q5BKT4 DIE2/ALG10 (Saccharomyces cerevisiae)UniProtKB:P50076 alg10 (Schizosaccharomyces pombe)UniProtKB:Q10254

Function

dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activityGO:0106073
Substrates: dolichyl-phosphate-glucose (Dol-P-Glc) Glc2Man9GlcNAc2-PP-dolichol
Products: Glc3Man9GlcNAc2-PP-dolichol (mature LLO) dolichyl phosphate

Locations

endoplasmic reticulum membraneGO:0005789

Terminal glucose completing Glc3Man9GlcNAc2-PP-dolichol, the mature LLO transferred to protein by the oligosaccharyltransferase.