GPI anchor biosynthesis V — post-attachment lipid remodeling; PGAP1/PGAP3/PGAP2

After a protein has been GPI-anchored by the transamidase, the anchor's lipid moiety is remodeled so the mature GPI-anchored protein can exit the ER, traffic through the Golgi and partition into membrane microdomains (lipid rafts). Three post-GPI-attachment factors carry out the remodeling. In the endoplasmic reticulum, PGAP1 is a GPI inositol-deacylase that removes the acyl chain from the inositol ring of the anchor (the acyl group added earlier by PIGW); this inositol-deacylation is required for efficient ER-to-Golgi transport of GPI-anchored proteins. In the Golgi, fatty-acid remodeling then exchanges the unsaturated sn-2 chain of the phosphatidylinositol for a saturated one: the GPI-specific phospholipase A2 PGAP3 first removes the sn-2 unsaturated fatty acid, and PGAP2 is required to reacylate the resulting lyso-GPI intermediate with a saturated (stearoyl) chain, generating the mature, raft-associating anchor needed for stable cell-surface expression. Inherited defects cause GPI-deficiency disease: PGAP1 (intellectual disability / encephalopathy), PGAP3 (hyperphosphatasia with mental retardation syndrome 4, HPMRS4) and PGAP2 (HPMRS3).

MODULE:gpi_anchor_remodelingDRAFTMetabolic Pathwaymodules/gpi_anchor_remodeling.yaml
GPI anchor remodellingGO:0120574 GPI anchor biosynthetic processGO:0006506
GO:0120574
GPI anchor remodelling
The module is grounded in GPI anchor remodelling (GO:0120574): post-attachment inositol-deacylation and fatty-acid remodeling of the GPI-anchored protein's lipid moiety.
Reactome:R-HSA-162710
Synthesis of glycosylphosphatidylinositol (GPI)
The inositol-deacylation step (PGAP1) follows the human Reactome reaction R-HSA-162729 (uPAR-acyl-GPI + H2O -> uPAR + long-chain fatty acid), part of "Synthesis of GPI".
file:human/PGAP1/PGAP1-ai-review.yaml
PGAP1 gene review (human)
The ER inositol-deacylation step (UniProtKB:Q75T13, GO:0160215) matches the completed human PGAP1 review.
file:human/PGAP3/PGAP3-ai-review.yaml
PGAP3 gene review (human)
The Golgi GPI-specific phospholipase-A2 (sn-2 deacylation) step (UniProtKB:Q96FM1, GO:0016788) matches the completed human PGAP3 review.
file:human/PGAP2/PGAP2-ai-review.yaml
PGAP2 gene review (human)
The Golgi reacylation (fatty-acid remodeling) step (UniProtKB:Q9UHJ9, GPI anchor remodelling GO:0120574) matches the completed human PGAP2 review.
4Nodes
3Parts
0Variant Sets
0Variants
3Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:gpi_anchor_remodeling 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 (3/3 grounded genes reviewed)

3 complete review(s) · 0 with deep research · 0 missing review · 3 reviewed but lacking deep research

Gene Review Complete Deep research
PGAP1 Q75T13 ✓ ✓ ✗
PGAP2 Q9UHJ9 ✓ ✓ ✗
PGAP3 Q96FM1 ✓ ✓ ✗

Details

Context
endoplasmic reticulum membraneGO:0005789 Golgi membraneGO:0000139
GPI anchor post-attachment lipid remodelingMetabolic Pathwaygpi_anchor_remodeling
GPI anchor remodellingGO:0120574 GPI anchor biosynthetic processGO:0006506
Context
endoplasmic reticulum membraneGO:0005789 Golgi membraneGO:0000139

GPI-anchor post-attachment lipid-remodeling segment, grounded to the human enzymes PGAP1 (UniProtKB:Q75T13, GO:0160215 deacylase activity; ER) and the Golgi fatty-acid-remodeling pair PGAP3 (Q96FM1, GO:0016788 ester-bond hydrolase / GPI-specific phospholipase A2) and PGAP2 (Q9UHJ9; no catalytic MF in GOA — modelled by its GPI anchor remodelling BP role). GO molecular-function/BP/location terms were taken from the completed human gene reviews and verified against the local go.db; the PGAP1 reaction (R-HSA-162729) and parent pathway (R-HSA-162710) were verified against the local reactome cache. Each step uses a PANTHER family selector with the human enzyme as representative. Note the two-compartment organisation: PGAP1 inositol-deacylation is an ER-membrane step required for ER exit, whereas the PGAP3/PGAP2 fatty-acid remodeling (sn-2 unsaturated -> saturated) occurs in the Golgi and confers lipid-raft association / stable surface expression. Upstream is the GPI-transamidase module (PIGK/PIGS/PIGT/PIGU/GPAA1) that attaches the anchor; this remodeling module completes GPI-anchor maturation. This is the FIFTH and final module of the GPI-anchor biosynthesis series (GnT -> core glycan -> EtNP additions -> transamidase -> remodeling). Disorders: PGAP1 GPI-deficiency (intellectual disability/encephalopathy), PGAP3 HPMRS4, PGAP2 HPMRS3.

Connections

pgap1_step -> pgap3_step Provides Input For
The inositol-deacylated GPI-anchored protein (ER exit competent) undergoes Golgi fatty-acid remodeling, beginning with PGAP3 sn-2 deacylation.
pgap3_step -> pgap2_step Provides Input For
The lyso-GPI intermediate from PGAP3 is reacylated by PGAP2 with a saturated chain.
Part 1: ER inositol-deacylation
removal of the inositol-linked acyl chain from the GPI anchorReactionpgap1_step

Annotons

PGAP1: GPI inositol-deacylase
pgap1_activity
Participant: Family: PGAP1 GPI inositol-deacylase family
Family:
PGAP1 GPI inositol-deacylase familyPANTHER:PTHR15495
Representative Members: PGAP1 (human)UniProtKB:Q75T13

Function

deacylase activityGO:0160215
Substrates: inositol-acylated GPI-anchored protein H2O
Products: inositol-deacylated GPI-anchored protein long-chain fatty acid

Locations

endoplasmic reticulum membraneGO:0005789

Removes the inositol acyl chain in the ER; required for ER exit of GPI-anchored proteins. Deficiency = GPIBD (intellectual disability/encephalopathy).

Part 2: Golgi sn-2 deacylation (fatty-acid remodeling step 1)
removal of the sn-2 unsaturated fatty acid from the GPI anchorReactionpgap3_step

Annotons

PGAP3: GPI-specific phospholipase A2
pgap3_activity
Participant: Family: PGAP3/CREST GPI phospholipase family
Family:
PGAP3/CREST GPI phospholipase familyPANTHER:PTHR13148
Representative Members: PGAP3 (human)UniProtKB:Q96FM1

Function

hydrolase activity, acting on ester bondsGO:0016788
Substrates: GPI-anchored protein (sn-2 unsaturated acyl-PI) H2O
Products: lyso-GPI-anchored protein unsaturated fatty acid

Locations

Golgi membraneGO:0000139

Removes the sn-2 unsaturated fatty acid in the Golgi (fatty-acid remodeling step 1). Deficiency = HPMRS4.

Part 3: Golgi reacylation (fatty-acid remodeling step 2)
reacylation of the lyso-GPI anchor with a saturated fatty acidReactionpgap2_step

Annotons

PGAP2: GPI fatty-acid reacylation factor
pgap2_activity
Participant: Family: PGAP2 family
Family:
PGAP2 familyPANTHER:PTHR12892
Representative Members: PGAP2 (human)UniProtKB:Q9UHJ9

Processes

GPI anchor remodellingGO:0120574

Locations

Golgi membraneGO:0000139

Reacylates the lyso-GPI anchor with a saturated fatty acid (remodeling step 2), producing the mature raft-associating anchor. Deficiency = HPMRS3. (GOA carries no catalytic MF for PGAP2 — its precise catalytic vs accessory role is debated — so it is represented by its GPI-remodelling BP role.)

file:human/PGAP2/PGAP2-ai-review.yaml
required for reacylation of the lyso-GPI intermediate with a saturated (stearoyl) chain after PGAP3; generates the mature raft-associating anchor; deficiency = HPMRS3