GPI anchor biosynthesis III — ethanolamine-phosphate additions; PIGN/PIGG/PIGF/PIGO

As the trimannosyl core of the glycosylphosphatidylinositol (GPI) anchor is built, three ethanolamine-phosphate (EtNP) groups are transferred from phosphatidylethanolamine onto the mannoses by three ER-membrane EtNP transferases. PIGN (GPI-ET-I) adds EtNP to the first mannose; PIGG (GPI-ET-II), together with its accessory subunit PIGF, adds EtNP to the second mannose (a side-branch EtNP removed after the anchor is attached to protein); and PIGO (GPI-ET-III), also partnered by PIGF, adds the bridging EtNP to the third mannose — the ethanolamine-phosphate whose amino group forms the amide bond to the protein C-terminus at the transamidation step. PIGF is a non-catalytic accessory subunit shared by PIGO and PIGG, required to stabilise both. Defects cause GPI-deficiency disease: PIGN (multiple congenital anomalies-hypotonia-seizures syndrome 1, MCAHS1), PIGO (hyperphosphatasia with mental retardation syndrome 2, HPMRS2), PIGG (an intellectual-disability/seizure GPIBD) and PIGF (inherited GPI deficiency).

MODULE:gpi_anchor_ethanolamine_phosphateDRAFTMetabolic Pathwaymodules/gpi_anchor_ethanolamine_phosphate.yaml
GPI anchor biosynthetic processGO:0006506
GO:0006506
GPI anchor biosynthetic process
The module is grounded in GPI anchor biosynthetic process (GO:0006506); it covers the three ethanolamine-phosphate transfers onto the GPI mannoses.
Reactome:R-HSA-162710
Synthesis of glycosylphosphatidylinositol (GPI)
Step order and intermediates follow the human Reactome "Synthesis of glycosylphosphatidylinositol (GPI)" sub-pathway (reactions R-HSA-162798 PIGN, R-HSA-162742 PIGG).
file:human/PIGN/PIGN-ai-review.yaml
PIGN gene review (human)
The first-mannose EtNP transfer (UniProtKB:O95427, GO:0051377) matches the completed human PIGN review.
file:human/PIGG/PIGG-ai-review.yaml
PIGG gene review (human)
The second-mannose EtNP transfer (UniProtKB:Q5H8A4, GO:0051377) matches the completed human PIGG review.
file:human/PIGF/PIGF-ai-review.yaml
PIGF gene review (human)
The non-catalytic PIGO/PIGG accessory-subunit role (UniProtKB:Q07326) matches the completed human PIGF review.
file:human/PIGO/PIGO-ai-review.yaml
PIGO gene review (human)
The bridging third-mannose EtNP transfer (UniProtKB:Q8TEQ8, GO:0051377) matches the completed human PIGO review.
4Nodes
3Parts
0Variant Sets
0Variants
5Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:gpi_anchor_ethanolamine_phosphate 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.

Gene-review completeness (4/4 grounded genes reviewed)

4 complete review(s) · 0 with deep research · 0 missing review · 4 reviewed but lacking deep research

Gene Review Complete Deep research
PIGF Q07326 ✓ ✓ ✗
PIGG Q5H8A4 ✓ ✓ ✗
PIGN O95427 ✓ ✓ ✗
PIGO Q8TEQ8 ✓ ✓ ✗

Details

Context
endoplasmic reticulum membraneGO:0005789
GPI anchor ethanolamine-phosphate additionsMetabolic Pathwaygpi_anchor_ethanolamine_phosphate
GPI anchor biosynthetic processGO:0006506
Context
endoplasmic reticulum membraneGO:0005789

GPI ethanolamine-phosphate-addition segment, grounded to the human enzymes PIGN (UniProtKB:O95427, GO:0051377), PIGG (Q5H8A4, GO:0051377) and PIGO (Q8TEQ8, GO:0051377), all mannose-ethanolamine phosphotransferases, plus the shared non-catalytic accessory subunit PIGF (Q07326; no PANTHER family — the InterPro family IPR009580 GPI-biosynthesis-protein Pig-F is used as its family selector). GO molecular-function/BP/location terms were taken from the completed human gene reviews and verified against the local go.db; Reactome reaction ids/titles (R-HSA-162798 PIGN, R-HSA-162742 PIGG; PIGO has no cached WT reaction so its node is grounded on its review and the umbrella pathway R-HSA-162710) were verified against the local reactome cache. Each step uses a family selector (PANTHER for PIGN/PIGG/PIGO, InterPro for PIGF); the PIGG and PIGO steps are PROTEIN_COMPLEX nodes pairing each catalytic transferase with the shared PIGF accessory subunit (modelled by its BP role, as it has no catalytic MF). All three transferases use phosphatidylethanolamine as the EtNP donor. This segment interleaves with the mannosylation module: PIGN acts on mannose-I (between PIGM and PIGV), PIGG on mannose-II (after PIGV), and PIGO adds the bridging EtNP on mannose-III (after PIGB) — the last modification before the completed GPI is transferred to protein by the GPI transamidase (PIGK/PIGS/PIGT/PIGU/GPAA1; separate module). Disorders: MCAHS1 (PIGN), HPMRS2 (PIGO), and GPIBD intellectual disability/seizures (PIGG, PIGF).

Connections

pign_step -> pigg_step Provides Input For
The GPI intermediate EtNP-modified on mannose-I is further EtNP-modified on mannose-II by PIGG/PIGF.
pigg_step -> pigo_step Provides Input For
The GPI intermediate is completed by the bridging EtNP on mannose-III added by PIGO/PIGF.
Part 1: EtNP on the first mannose
ethanolamine-phosphate added to mannose-IReactionpign_step

Annotons

PIGN: GPI ethanolamine phosphate transferase 1
pign_activity
Participant: Family: GPI ethanolamine-phosphate transferase family (PIGN)
Family:
GPI ethanolamine-phosphate transferase family (PIGN)PANTHER:PTHR12250
Representative Members: PIGN (human)UniProtKB:O95427

Function

mannose-ethanolamine phosphotransferase activityGO:0051377
Substrates: Man1-GlcN-(acyl)PI GPI intermediate phosphatidylethanolamine
Products: EtNP-Man1 GPI intermediate diacylglycerol

Locations

endoplasmic reticulum membraneGO:0005789

Adds EtNP to mannose-I; deficiency = MCAHS1.

Part 2: EtNP on the second mannose (side-branch)
ethanolamine-phosphate added to mannose-IIProtein Complexpigg_step

Annotons

PIGG: GPI ethanolamine phosphate transferase 2 (catalytic)
pigg_activity
Participant: Family: GPI ethanolamine-phosphate transferase family (PIGG)
Family:
GPI ethanolamine-phosphate transferase family (PIGG)PANTHER:PTHR23072
Representative Members: PIGG (human)UniProtKB:Q5H8A4

Function

mannose-ethanolamine phosphotransferase activityGO:0051377
Substrates: Man2 GPI intermediate phosphatidylethanolamine
Products: EtNP-Man2 GPI intermediate diacylglycerol

Locations

endoplasmic reticulum membraneGO:0005789

Catalytic EtNP transferase for mannose-II.

PIGF: accessory subunit (with PIGG)
pigf_activity_g
Participant: Family: GPI biosynthesis protein Pig-F family
Family:
GPI biosynthesis protein Pig-F familyInterPro:IPR009580
Representative Members: PIGF (human)UniProtKB:Q07326

Processes

GPI anchor biosynthetic processGO:0006506

Locations

endoplasmic reticulum membraneGO:0005789

Non-catalytic accessory subunit that stabilises PIGG.

file:human/PIGF/PIGF-ai-review.yaml
non-catalytic accessory subunit required to stabilise the EtNP transferases PIGG and PIGO
Part 3: bridging EtNP on the third mannose (protein-attachment site)
bridging ethanolamine-phosphate added to mannose-IIIProtein Complexpigo_step

Annotons

PIGO: GPI ethanolamine phosphate transferase 3 (catalytic)
pigo_activity
Participant: Family: GPI ethanolamine-phosphate transferase family (PIGO)
Family:
GPI ethanolamine-phosphate transferase family (PIGO)PANTHER:PTHR23071
Representative Members: PIGO (human)UniProtKB:Q8TEQ8

Function

mannose-ethanolamine phosphotransferase activityGO:0051377
Substrates: Man3 GPI intermediate phosphatidylethanolamine
Products: EtNP-Man3 (bridging EtNP) GPI intermediate diacylglycerol

Locations

endoplasmic reticulum membraneGO:0005789

Catalytic EtNP transferase for the third mannose; supplies the bridging EtNP for protein attachment. Deficiency = HPMRS2.

PIGF: accessory subunit (with PIGO)
pigf_activity_o
Participant: Family: GPI biosynthesis protein Pig-F family
Family:
GPI biosynthesis protein Pig-F familyInterPro:IPR009580
Representative Members: PIGF (human)UniProtKB:Q07326

Processes

GPI anchor biosynthetic processGO:0006506

Locations

endoplasmic reticulum membraneGO:0005789

Non-catalytic accessory subunit that stabilises PIGO.

file:human/PIGF/PIGF-ai-review.yaml
non-catalytic accessory subunit required to stabilise the EtNP transferases PIGO and PIGG