GPI anchor biosynthesis IV — transamidase complex (attachment to protein); PIGK/PIGS/PIGT/PIGU/GPAA1

The final step that commits a protein to a GPI anchor is transamidation: in the ER lumen the five-subunit GPI transamidase (GPI-T) complex recognises the C-terminal GPI-attachment signal peptide of a nascent protein, cleaves it, and forms an amide bond between the new C-terminus and the amino group of the bridging ethanolamine-phosphate on the third mannose of the completed GPI precursor. PIGK (GPI8) is the catalytic subunit, a cysteine-protease-like enzyme that forms the carbonyl(acyl-enzyme) intermediate; PIGT disulfide-links to and stabilises PIGK and holds the complex together; GPAA1 helps present the GPI substrate and stabilise the intermediate for amide-bond formation; PIGU assists GPI-substrate recognition; and PIGS is an indispensable but non-catalytic subunit. The product is a mature GPI-anchored protein that is then exported and remodelled. Defects across the complex cause GPI-deficiency disease with overlapping developmental/epileptic-encephalopathy, cerebellar-atrophy and hyperphosphatasia phenotypes: PIGK, PIGS, PIGT (MCAHS3 / a PNH-like phenotype), PIGU and GPAA1.

MODULE:gpi_anchor_transamidaseDRAFTMetabolic Pathwaymodules/gpi_anchor_transamidase.yaml
attachment of GPI anchor to proteinGO:0016255 GPI anchor biosynthetic processGO:0006506
GO:0016255
attachment of GPI anchor to protein
The module is grounded in attachment of GPI anchor to protein (GO:0016255): the GPI-T complex transfers the completed GPI anchor onto the protein C-terminus.
GO:0006506
GPI anchor biosynthetic process
The transamidation step is the terminal reaction of GPI anchor biosynthesis (GO:0006506).
Reactome:R-HSA-162791
Attachment of GPI anchor to uPAR
The transamidation reaction follows the human Reactome "Attachment of GPI anchor to uPAR" reaction (a representative GPI-T substrate), part of "Synthesis of GPI" (R-HSA-162710).
file:human/PIGK/PIGK-ai-review.yaml
PIGK gene review (human)
The catalytic transamidase subunit (UniProtKB:Q92643, GO:0003923) matches the completed human PIGK review.
file:human/PIGS/PIGS-ai-review.yaml
PIGS gene review (human)
The indispensable non-catalytic subunit (UniProtKB:Q96S52, GPI-T complex GO:0042765) matches the completed human PIGS review.
file:human/PIGT/PIGT-ai-review.yaml
PIGT gene review (human)
The PIGK-stabilising/GPI-anchor-binding subunit (UniProtKB:Q969N2, GO:0034235) matches the completed human PIGT review.
file:human/PIGU/PIGU-ai-review.yaml
PIGU gene review (human)
The GPI-substrate-recognition subunit (UniProtKB:Q9H490, GO:0034235) matches the completed human PIGU review.
file:human/GPAA1/GPAA1-ai-review.yaml
GPAA1 gene review (human)
The intermediate-stabilising/GPI-anchor-binding subunit (UniProtKB:O43292, GO:0034235) matches the completed human GPAA1 review.
2Nodes
1Parts
0Variant Sets
0Variants
5Annotons
0Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:gpi_anchor_transamidase 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 (5/5 grounded genes reviewed)

5 complete review(s) · 0 with deep research · 0 missing review · 5 reviewed but lacking deep research

Gene Review Complete Deep research
GPAA1 O43292 ✓ ✓ ✗
PIGK Q92643 ✓ ✓ ✗
PIGS Q96S52 ✓ ✓ ✗
PIGT Q969N2 ✓ ✓ ✗
PIGU Q9H490 ✓ ✓ ✗

Details

Context
endoplasmic reticulum membraneGO:0005789
GPI anchor transamidase complex (attachment to protein)Metabolic Pathwaygpi_anchor_transamidase
attachment of GPI anchor to proteinGO:0016255 GPI anchor biosynthetic processGO:0006506
Context
endoplasmic reticulum membraneGO:0005789

GPI-transamidase (attachment-to-protein) segment, grounded to the human GPI-T complex (GO:0042765): catalytic PIGK (UniProtKB:Q92643, GO:0003923) plus PIGT (Q969N2), GPAA1 (O43292) and PIGU (Q9H490) — all carrying GPI anchor binding (GO:0034235) as their informative subunit-level MF — and the indispensable non-catalytic PIGS (Q96S52). GO molecular-function/BP/location terms were taken from the completed human gene reviews and verified against the local go.db; the reaction (R-HSA-162791) and parent pathway (R-HSA-162710) were verified against the local reactome cache. Modelled as a single PROTEIN_COMPLEX node: only PIGK carries a catalytic MF (GPI-anchor transamidase activity); PIGT/GPAA1/PIGU carry GPI-anchor-binding, and PIGS (no MF) is represented by its BP role. The complex cleaves the C-terminal GPI-attachment signal of nascent proteins and transfers the completed GPI precursor (from the mannosylation + EtNP modules) onto the new C-terminus. Downstream, the GPI-anchored protein is remodelled (PGAP1 inositol deacylation; PGAP2/PGAP3 fatty-acid remodelling — a separate module) and exported. Disorders across the complex: GPIBD/developmental-epileptic encephalopathy (PIGK, PIGS, PIGU), MCAHS3 / PNH-like (PIGT) and GPIBD with cerebellar atrophy (GPAA1).

Part 1: transamidation (GPI anchor attachment to protein)
transfer of the completed GPI anchor onto the protein C-terminusProtein Complexgpi_transamidase_step

Annotons

PIGK (GPI8): catalytic transamidase subunit
pigk_activity
Participant: Family: GPI transamidase GPI8/PIGK family
Family:
GPI transamidase GPI8/PIGK familyPANTHER:PTHR48067
Representative Members: PIGK (human)UniProtKB:Q92643

Function

GPI-anchor transamidase activityGO:0003923
Substrates: completed GPI precursor (EtNP-Man3 GPI) pro-protein bearing C-terminal GPI-attachment signal
Products: GPI-anchored protein cleaved C-terminal signal peptide

Locations

endoplasmic reticulum membraneGO:0005789

Catalytic subunit of the GPI transamidase complex.

PIGT: PIGK-stabilising / GPI-anchor-binding subunit
pigt_activity
Participant: Family: GPI transamidase PIG-T family
Family:
GPI transamidase PIG-T familyPANTHER:PTHR12959
Representative Members: PIGT (human)UniProtKB:Q969N2

Function

GPI anchor bindingGO:0034235
Substrates: GPI precursor (lipid moiety)
Products: complex-bound GPI substrate

Locations

endoplasmic reticulum membraneGO:0005789

Stabilises the catalytic PIGK and binds the GPI substrate.

GPAA1 (GAA1): intermediate-stabilising / GPI-anchor-binding subunit
gpaa1_activity
Participant: Family: GPI transamidase GAA1/GPAA1 family
Family:
GPI transamidase GAA1/GPAA1 familyPANTHER:PTHR13304
Representative Members: GPAA1 (human)UniProtKB:O43292

Function

GPI anchor bindingGO:0034235
Substrates: GPI precursor
Products: presented GPI substrate for amide-bond formation

Locations

endoplasmic reticulum membraneGO:0005789

Presents the GPI substrate and stabilises the reaction intermediate.

PIGU: GPI-substrate-recognition subunit
pigu_activity
Participant: Family: GPI transamidase PIG-U family
Family:
GPI transamidase PIG-U familyPANTHER:PTHR13121
Representative Members: PIGU (human)UniProtKB:Q9H490

Function

GPI anchor bindingGO:0034235
Substrates: GPI precursor (lipid moiety)
Products: recognised GPI substrate

Locations

endoplasmic reticulum membraneGO:0005789

Assists recognition/binding of the lipid GPI substrate.

PIGS: indispensable non-catalytic subunit
pigs_activity
Participant: Family: GPI transamidase PIG-S family
Family:
GPI transamidase PIG-S familyPANTHER:PTHR21072
Representative Members: PIGS (human)UniProtKB:Q96S52

Processes

attachment of GPI anchor to proteinGO:0016255

Locations

endoplasmic reticulum membraneGO:0005789

Indispensable non-catalytic subunit of the complex.

file:human/PIGS/PIGS-ai-review.yaml
indispensable but non-catalytic subunit of the GPI-T complex (role unclear); deficiency = GPIBD18