PIGU

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016255 attachment of GPI anchor to protein	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically-inferred annotation that PIGU participates in attachment of the GPI anchor to protein. This is the core biological process of PIGU as a subunit of the GPI transamidase complex, well supported by experimental and structural work. Reason: PIGU is an essential subunit of the ER GPI transamidase complex, whose function is to attach pre-assembled GPI anchors to the C-terminus of proprotein substrates. The IBA is at the correct level of specificity for this shared ancestral function. Supporting Evidence: PMID:34576938 Attachment of GPI to proteins is mediated by the GPI-transamidase (GPI-TA) complex, which recognizes and cleaves the C-terminal GPI attachment signal of precursor proteins PMID:12802054 posttranslationally attached to the carboxyl-terminus by GPI transamidase
GO:0042765 GPI-anchor transamidase complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically-inferred annotation that PIGU is part of the GPI-anchor transamidase complex. This is the core cellular-component annotation for PIGU. Reason: PIGU is one of the five conserved subunits of the GPI transamidase complex (PIGK, GPAA1, PIGT, PIGS, PIGU), confirmed biochemically and by cryo-EM structures. Supporting Evidence: PMID:34576938 GPI-TA consists of five subunits: PIGK, GPAA1, PIGT, PIGS, and PIGU, and the absence of any subunit leads to the loss of activity PMID:35165458 The GPIT complex is known to be composed of five subunits: PIGK, PIGU, PIGT, PIGS and GPAA1
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation (UniProt Subcellular Location mapping) placing PIGU in the ER membrane. This matches the experimentally established localization of GPI-T. Reason: PIGU is a multi-pass ER membrane protein; GPI anchoring occurs in the ER. The IEA subcellular-location mapping is correct and specific. Supporting Evidence: PMID:35551457 an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes
GO:0016020 membrane	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO electronic annotation to the generic parent term membrane. Correct but uninformative given the specific ER membrane annotation. Reason: PIGU is an integral membrane protein, so membrane is not wrong, but it is a broad parent of the more specific and better-supported endoplasmic reticulum membrane (GO:0005789) annotation. Retain as non-core. Supporting Evidence: PMID:35551457 an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes
GO:0016255 attachment of GPI anchor to protein	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation (IPR009600, PIG-U) that PIGU is involved in attachment of the GPI anchor to protein. Consistent with the core function. Reason: The InterPro PIG-U signature maps to the correct core biological process; this is the same well-supported function inferred by IBA and demonstrated experimentally. Supporting Evidence: PMID:34576938 Attachment of GPI to proteins is mediated by the GPI-transamidase (GPI-TA) complex, which recognizes and cleaves the C-terminal GPI attachment signal of precursor proteins
GO:0042765 GPI-anchor transamidase complex	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation that PIGU is part of the GPI-anchor transamidase complex, consistent with experimental evidence. Reason: The InterPro PIG-U signature correctly maps PIGU to its complex; supported by biochemistry and cryo-EM structures. Supporting Evidence: PMID:35165458 The GPIT complex is known to be composed of five subunits: PIGK, PIGU, PIGT, PIGS and GPAA1
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: IntAct annotation of a binary interaction (PIGU with KASH5/Q8N6L0) captured in the HuRI high-throughput yeast two-hybrid interactome map. protein binding is an uninformative molecular-function term and this specific interaction is not part of PIGU's established function. Reason: The generic protein binding term conveys no specific molecular function, and the single high-throughput Y2H interaction with KASH5 has no established role in GPI transamidase biology. Per curation policy this bare protein-binding IPI is marked as over-annotated rather than removed. PIGU's informative binding activity (GPI anchor binding) is captured by a separate annotation. Supporting Evidence: PMID:32296183 With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies
GO:0180046 GPI anchored protein biosynthesis	IEA GO_REF:0000107	ACCEPT	Summary: Ortholog-based electronic annotation (Ensembl Compara, from rat Pigu) that PIGU is involved in GPI anchored protein biosynthesis. Consistent with the core function. Reason: GPI anchored protein biosynthesis is the pathway that GPI-T (and therefore PIGU) participates in; the orthology transfer is appropriate. Supporting Evidence: PMID:34576938 Attachment of GPI to proteins is mediated by the GPI-transamidase (GPI-TA) complex, which recognizes and cleaves the C-terminal GPI attachment signal of precursor proteins
GO:0006506 GPI anchor biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: UniPathway-based electronic annotation (UPA00196) to GPI anchor biosynthetic process. This is the pathway to which PIGU/GPI-T contributes. Reason: The GPI transamidase step is part of GPI-anchor biosynthesis; the UniPathway mapping is correct. Supporting Evidence: PMID:37684232 a transmembrane complex composed of five subunits: GAAP1 (Gaa1p), PIGK (Gpi8p), PIGS (Gpi17p), PIGT (Gpi16p), and PIGU (Gab1p)
GO:0005789 endoplasmic reticulum membrane	NAS PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: ComplexPortal NAS annotation placing PIGU in the ER membrane, consistent with the established ER localization of GPI-T. Reason: GPI anchoring occurs on the ER membrane and PIGU is a multi-pass ER membrane subunit; the ER membrane location is well established. Supporting Evidence: PMID:11483512 The GPI transamidase mediates GPI anchoring in the endoplasmic reticulum PMID:35551457 an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes
GO:0016255 attachment of GPI anchor to protein	NAS PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: ComplexPortal NAS annotation that PIGU is involved in attachment of the GPI anchor to protein, the core process for the GPI transamidase complex. Reason: Hong et al. established PIGU (PIG-U) as the fifth subunit of GPI transamidase, which attaches GPI anchors to proteins; this is the core function. Supporting Evidence: PMID:12802054 PIG-U and the yeast orthologue Cdc91p are the fifth component of GPI transamidase that may be involved in the recognition of either the GPI attachment signal or the lipid portion of GPI
GO:0042765 GPI-anchor transamidase complex	IPI PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: ComplexPortal IPI annotation that PIGU is part of the GPI-anchor transamidase complex, based on affinity purification of the complex containing PIG-U. Reason: The GPI transamidase complex affinity-purified from cells contained PIG-U together with the four other known components, directly demonstrating complex membership. Supporting Evidence: PMID:12802054 The GPI transamidase complex affinity-purified from cells expressing epitope-tagged-GPI8 contained PIG-U and four other known components
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:35165458 Structure of human glycosylphosphatidylinositol transamidase...	ACCEPT	Summary: Direct-assay annotation (cryo-EM structure of the human GPI transamidase) that PIGU is involved in GPI anchored protein biosynthesis. Reason: The structural study resolved PIGU as one of the five subunits of the ER GPI transamidase that is essential for maturation of GPI-anchored proteins. Supporting Evidence: PMID:35165458 Attaching GPI to the protein in the endoplasmic reticulum (ER) is catalyzed by the transmembrane GPI transamidase (GPIT) complex
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:35551457 Molecular insights into biogenesis of glycosylphosphatidylin...	ACCEPT	Summary: Direct-assay annotation (cryo-EM of the equimolar heteropentameric human GPI-T) that PIGU is involved in GPI anchored protein biosynthesis. Reason: The structure of the five-subunit ER GPI-T, including PIGU, supports its role in the biosynthesis of GPI-anchored proteins. Supporting Evidence: PMID:35551457 an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes
GO:0034235 GPI anchor binding	IDA PMID:37684232 Structures of liganded glycosylphosphatidylinositol transami...	ACCEPT	Summary: Direct-assay annotation that PIGU binds the GPI anchor. The liganded GPI-T structures show that PIGU contacts the GPI substrate, and UniProt records that PIGU binds the lipid portion of the GPI-anchor. This is the informative subunit-level molecular function of PIGU (distinct from the complex-level transamidase catalysis, which is performed by PIGK). Reason: PIGU is the subunit thought to recognise and present the lipid GPI substrate; it binds the lipid portion of the GPI-anchor. GPI anchor binding is an informative molecular-function term consistent with the structural data and PIGU's homology to lipid-handling GPI biosynthetic enzymes. Supporting Evidence: file:human/PIGU/PIGU-uniprot.txt Binds the lipid portion of GPI-anchor (PubMed:37684232). May act as an PMID:34576938 PIGU is homologous with other GPI biosynthetic enzymes (such as PIGW and PIGM), suggesting that it recognizes the lipid portion of GPI
GO:0016255 attachment of GPI anchor to protein	IDA PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: Direct-assay annotation that PIGU is involved in attachment of the GPI anchor to protein. Class U (PIGU-deficient) cells lack GPI transamidase activity and cannot cleave the GPI attachment signal peptide. Reason: Loss of PIGU abolishes GPI transamidase activity in cells, directly demonstrating that PIGU is required for attachment of the GPI anchor to protein. Supporting Evidence: PMID:12802054 The class U cells accumulated mature and immature GPI and did not have in vitro GPI transamidase activity
GO:0016255 attachment of GPI anchor to protein	IDA PMID:31353022 Mutations in PIGU Impair the Function of the GPI Transamidas...	ACCEPT	Summary: Direct-assay annotation from the disease study that PIGU is involved in attachment of the GPI anchor to protein; PIGU is described as an essential component of the GPI transamidase complex, and pathogenic variants impair GPI-anchored protein surface expression. Reason: Functional characterization of NEDBSS variants showed reduced GPI-anchored protein expression, confirming PIGU's essential role in GPI anchor attachment. Supporting Evidence: PMID:31353022 An essential component of the GPI transamidase complex is PIGU, along with PIGK, PIGS, PIGT, and GPAA1, all of which link GPI-anchored proteins (GPI-APs) onto the GPI anchor in the endoplasmic reticulum (ER)
GO:0016255 attachment of GPI anchor to protein	IDA PMID:34576938 Functional Analysis of the GPI Transamidase Complex by Scree...	ACCEPT	Summary: Direct-assay annotation that PIGU is involved in attachment of the GPI anchor to protein; mutagenesis of PIGU residues (Leu375/Trp376) reduced GPI-TA rescue activity, and loss of PIGU abolishes activity of the complex. Reason: Functional analysis of GPI-TA subunits demonstrated that PIGU is required for transamidase activity and identified functionally important PIGU residues. Supporting Evidence: PMID:34576938 Lacking PIGU, other subunits (PIGK, GPAA1, PIGT and PIGS) still form a complex, but have no activity
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:31353022 Mutations in PIGU Impair the Function of the GPI Transamidas...	ACCEPT	Summary: Direct-assay annotation from the disease study that PIGU is involved in GPI anchored protein biosynthesis; variant cells show reduced surface GPI-anchored proteins. Reason: PIGU is required for biosynthesis/surface expression of GPI-anchored proteins, and biallelic PIGU variants cause an inherited GPI-anchor deficiency. Supporting Evidence: PMID:31353022 An essential component of the GPI transamidase complex is PIGU, along with PIGK, PIGS, PIGT, and GPAA1, all of which link GPI-anchored proteins (GPI-APs) onto the GPI anchor in the endoplasmic reticulum (ER)
GO:0016255 attachment of GPI anchor to protein	IDA PMID:37684232 Structures of liganded glycosylphosphatidylinositol transami...	ACCEPT	Summary: Direct-assay annotation (liganded GPI-T structures) that PIGU is involved in attachment of the GPI anchor to protein, as a subunit of the transmembrane complex that adds GPI to proproteins. Reason: The substrate- and product-bound GPI-T structures include PIGU as one of the five subunits that together carry out the transamidation reaction. Supporting Evidence: PMID:37684232 a transmembrane complex composed of five subunits: GAAP1 (Gaa1p), PIGK (Gpi8p), PIGS (Gpi17p), PIGT (Gpi16p), and PIGU (Gab1p)
GO:0042765 GPI-anchor transamidase complex	IDA PMID:37684232 Structures of liganded glycosylphosphatidylinositol transami...	ACCEPT	Summary: Direct-assay annotation (cryo-EM) that PIGU is part of the GPI-anchor transamidase complex. Reason: The liganded GPI-T structures resolve PIGU as an integral subunit of the five-subunit complex. Supporting Evidence: PMID:37684232 a transmembrane complex composed of five subunits: GAAP1 (Gaa1p), PIGK (Gpi8p), PIGS (Gpi17p), PIGT (Gpi16p), and PIGU (Gab1p)
GO:0016255 attachment of GPI anchor to protein	IDA PMID:35165458 Structure of human glycosylphosphatidylinositol transamidase...	ACCEPT	Summary: Direct-assay annotation (cryo-EM structure) that PIGU is involved in attachment of the GPI anchor to protein. Reason: The human GPI-T structure, including PIGU, defines the transmembrane GPI substrate-binding cleft and supports the complex's role in attaching GPI to proteins. Supporting Evidence: PMID:35165458 Transmembrane helices constitute a widely opened cleft, which is located underneath PIGK, serving as a GPI substrate-binding site
GO:0016255 attachment of GPI anchor to protein	IDA PMID:35551457 Molecular insights into biogenesis of glycosylphosphatidylin...	ACCEPT	Summary: Direct-assay annotation (cryo-EM structure) that PIGU is involved in attachment of the GPI anchor to protein, as a subunit of the ER GPI transamidase. Reason: The equimolar heteropentameric GPI-T structure, including PIGU, supports its role in attaching GPI anchors to proproteins in the ER. Supporting Evidence: PMID:35551457 an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes
GO:0042765 GPI-anchor transamidase complex	IDA PMID:35165458 Structure of human glycosylphosphatidylinositol transamidase...	ACCEPT	Summary: Direct-assay annotation (cryo-EM) that PIGU is part of the GPI-anchor transamidase complex. Reason: The human GPI-T structure directly resolves PIGU as one of the five subunits of the complex. Supporting Evidence: PMID:35165458 The GPIT complex is known to be composed of five subunits: PIGK, PIGU, PIGT, PIGS and GPAA1
GO:0042765 GPI-anchor transamidase complex	IDA PMID:35551457 Molecular insights into biogenesis of glycosylphosphatidylin...	ACCEPT	Summary: Direct-assay annotation (cryo-EM) that PIGU is part of the GPI-anchor transamidase complex, an equimolar heteropentamer. Reason: The structure reveals an equimolar heteropentameric assembly that includes PIGU. Supporting Evidence: PMID:35551457 revealing an equimolar heteropentameric assembly
GO:0042765 GPI-anchor transamidase complex	IDA PMID:34576938 Functional Analysis of the GPI Transamidase Complex by Scree...	ACCEPT	Summary: Direct-assay annotation that PIGU is part of the GPI-anchor transamidase complex, which was purified with all five subunits including PIGU. Reason: GPI-TA consists of five subunits including PIGU, and the purified complex contained all five; PIGU is a bona fide member. Supporting Evidence: PMID:34576938 GPI-TA consists of five subunits: PIGK, GPAA1, PIGT, PIGS, and PIGU, and the absence of any subunit leads to the loss of activity
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: High-throughput proteomics (membrane proteome of an NK-like cell line) detected PIGU in the membrane fraction. Correct but non-specific relative to the ER membrane annotation. Reason: Consistent with PIGU being an integral membrane protein, but membrane is a broad parent term; the specific ER membrane location is better supported. Retain as non-core. Supporting Evidence: PMID:19946888 Mass spectrometric analysis identified 1843 proteins with high confidence scores
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-162836	ACCEPT	Summary: Reactome traceable-author-statement annotation placing PIGU in the ER membrane in the context of the GPI-anchor attachment reaction. Consistent with the established localization. Reason: GPI anchoring occurs on the ER membrane; the Reactome pathway correctly localizes PIGU there. Supporting Evidence: PMID:35551457 an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes
GO:0016255 attachment of GPI anchor to protein	IMP PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: Mutant-phenotype annotation: PIGU-deficient (class U) cells cannot attach GPI anchors to proteins and lack transamidase activity, demonstrating PIGU's requirement in this process. Reason: Class U cells accumulate GPI and lack GPI transamidase activity, and cannot cleave the GPI attachment signal peptide, directly implicating PIGU in GPI anchor attachment. Supporting Evidence: PMID:12802054 The class U cells accumulated mature and immature GPI and did not have in vitro GPI transamidase activity
GO:0034235 GPI anchor binding	IMP PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: Mutant-phenotype annotation (contributes_to) that PIGU contributes to GPI anchor binding within the transamidase complex. Hong et al. proposed that PIG-U/Cdc91p is involved in recognition of the lipid portion of GPI. Reason: The contributes_to qualifier is appropriate for an accessory subunit: PIGU is proposed to recognise the lipid portion of the GPI substrate as part of the complex, consistent with later structural evidence that PIGU binds the lipid portion of the GPI-anchor. Supporting Evidence: PMID:12802054 PIG-U and the yeast orthologue Cdc91p are the fifth component of GPI transamidase that may be involved in the recognition of either the GPI attachment signal or the lipid portion of GPI
GO:0042765 GPI-anchor transamidase complex	IDA PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: Direct-assay annotation that PIGU is part of the GPI-anchor transamidase complex, based on affinity purification of the complex containing PIG-U and four other components. Reason: The affinity-purified GPI transamidase complex contained PIG-U together with the four other known subunits, directly demonstrating complex membership. Supporting Evidence: PMID:12802054 The GPI transamidase complex affinity-purified from cells expressing epitope-tagged-GPI8 contained PIG-U and four other known components
GO:0005886 plasma membrane	IDA PMID:15034568 CDC91L1 (PIG-U) is a newly discovered oncogene in human blad...	MARK AS OVER ANNOTATED	Summary: Annotation to plasma membrane from the bladder-cancer oncogene study of overexpressed CDC91L1 (PIG-U). PIGU is an ER-resident, multi-pass ER membrane protein; its established site of action is the ER membrane, not the plasma membrane. Reason: Later biochemical and structural work firmly localizes PIGU/GPI-T to the ER membrane, where GPI anchoring occurs; the plasma membrane localization does not represent PIGU's core function and likely reflects the overexpression/oncogene context. Per curation policy this experimental annotation is marked as over-annotated rather than removed. Supporting Evidence: PMID:35551457 an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes PMID:15034568 a transamidase complex unit in the glycosylphosphatidylinositol (GPI) anchoring pathway
GO:0006506 GPI anchor biosynthetic process	IDA PMID:15034568 CDC91L1 (PIG-U) is a newly discovered oncogene in human blad...	ACCEPT	Summary: Annotation that PIGU is involved in GPI anchor biosynthetic process, from the bladder-cancer study describing PIG-U as a transamidase-complex unit in the GPI anchoring pathway. Consistent with PIGU's core role. Reason: PIG-U is described as a transamidase-complex unit in the GPI anchoring pathway; this is the correct, core biosynthetic process, corroborated by all subsequent work. Supporting Evidence: PMID:15034568 a transamidase complex unit in the glycosylphosphatidylinositol (GPI) anchoring pathway
GO:0046425 regulation of receptor signaling pathway via JAK-STAT	IDA PMID:15034568 CDC91L1 (PIG-U) is a newly discovered oncogene in human blad...	MARK AS OVER ANNOTATED	Summary: Annotation derived from the bladder-cancer study, where PIG-U overexpression upregulated the GPI-anchored urokinase receptor (uPAR) and increased STAT-3 phosphorylation. This is a downstream, indirect consequence of aberrant PIGU overexpression, not a core direct molecular activity of PIGU. Reason: PIGU has no direct role in JAK-STAT signaling; the observed STAT-3 phosphorylation is an indirect effect of increased surface uPAR (a GPI-anchored protein) upon PIG-U overexpression in cancer cells. This reflects a pathological overexpression phenotype rather than PIGU's normal function, so it is marked as over-annotated (kept, not removed, per policy for experimental annotations). Supporting Evidence: PMID:15034568 Overexpression of CDC91L1 also resulted in upregulation of the urokinase receptor (uPAR), a GPI-anchored protein, and in turn increased STAT-3 phosphorylation in bladder cancer cells
GO:0016255 attachment of GPI anchor to protein	TAS PMID:11483512 PIG-S and PIG-T, essential for GPI anchor attachment to prot...	ACCEPT	Summary: Traceable-author-statement annotation that PIGU is involved in attachment of the GPI anchor to protein. This paper describes the GPI transamidase complex (GAA1, GPI8, PIG-S, PIG-T) that mediates GPI anchoring in the ER; PIGU was later identified as the fifth subunit. Reason: The GPI transamidase attaches GPI anchors to proteins in the ER by replacing the C-terminal GPI attachment signal peptide with a pre-assembled GPI; PIGU is an essential subunit of this complex. The core process is correct. Supporting Evidence: PMID:11483512 The GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by replacing a protein's C-terminal GPI attachment signal peptide with a pre-assembled GPI

Gene Description

Existing Annotations Review

Core Functions

As a non-catalytic accessory subunit of the ER GPI transamidase (GPI-T) complex, PIGU binds the lipid portion of the GPI substrate and contributes to attachment of the pre-assembled GPI anchor to the C-terminus of proprotein substrates, generating mature GPI-anchored proteins.

References

📚 Additional Documentation

Notes

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