PIGC (Q92535) review notes

Human PIGC / phosphatidylinositol N-acetylglucosaminyltransferase subunit C (HGNC:8960; synonym GPI2).
297 aa, multi-pass ER membrane protein (8 predicted TM helices per UniProt FT).

Core biology

PIGC is a required, non-catalytic accessory subunit of the GPI-GlcNAc transferase
(GPI-GnT) complex, which catalyses the first committed step of GPI-anchor biosynthesis:
transfer of GlcNAc from UDP-GlcNAc onto phosphatidylinositol (PI) to give GlcNAc-PI, in the
ER membrane. PIGA is the catalytic subunit; the complex also contains PIGH, PIGP, PIGQ (GPI1),
PIGY and DPM2.

• PMID:8806613 — cloning of PIG-C as a human homologue of yeast GPI2; "PIG-C protein is a 297 amino-acid membrane protein in the endoplasmic reticulum".
• PMID:9463366 — PIG-A, PIG-H, PIG-C and GPI1 (PIGQ) form the ER-membrane complex with GPI-GnT activity. IntAct IPI here is PIGC–PIGQ (Q9BRB3).
• PMID:10944123 — adds PIG-P and DPM2. IntAct IPI here is PIGC–DPM2 (O94777).
• PMID:16162815 — seventh component PIG-Y; explicitly names PIG-A as the catalytic subunit (so PIGC is accessory, not catalytic).

Molecular function in GOA

GOA carries only GO:0005515 protein binding (IPI, IntAct, x2: DPM2 and PIGQ) and a legacy
GO:0003824 catalytic activity (TAS, ProtInc, from PMID:8806613, dated 2003). There is NO
specific glycosyltransferase MF term for PIGC in the GOA. Given PIGA is the catalytic subunit
and PIGC is an accessory/structural subunit, the broad "catalytic activity" is an
over-annotation for this subunit (the catalytic activity belongs to the complex/PIGA). Per
project policy I do not invent a catalytic MF; core_functions omits function and records the
BP + location + complex membership.

Localization

ER membrane, multi-pass. PMID:8806613;
UniProt SUBCELLULAR LOCATION "Endoplasmic reticulum membrane ... Multi-pass membrane protein".

Disease

Autosomal recessive GPI biosynthesis defect 16 (GPIBD16; MIM 617816): global developmental
delay, intellectual disability, drug-responsive seizures — an inherited GPI-deficiency /
epileptic-encephalopathy phenotype.
- PMID:27694521; patient variants (L189W; L212P/R21X) reduce surface expression of GPI-anchored proteins (IMP for GPI anchor biosynthetic process).

Annotation dispositions (summary)

• GPI anchor biosynthetic process (GO:0006506): core BP. Kept across IBA/IEA/IDA/IMP/TAS.
• GPI-GnT complex (GO:0000506): core CC. Kept across IBA/IPI/IDA.
• ER membrane (GO:0005789): core CC. Kept across IEA/IDA/TAS.
• membrane (GO:0016020, IEA InterPro): correct but generic vs ER membrane -> MARK_AS_OVER_ANNOTATED.
• protein binding (GO:0005515, IPI x2): uninformative bare term -> MARK_AS_OVER_ANNOTATED (real content is complex membership, captured by GO:0000506).
• catalytic activity (GO:0003824, TAS): over-annotation for accessory subunit (PIGA is catalytic) -> MARK_AS_OVER_ANNOTATED.