PIGS

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016255 attachment of GPI anchor to protein	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically-inferred involvement in attachment of GPI anchor to protein. This is the accepted core biological process for PIGS as a required subunit of the GPI transamidase complex, and is well supported by direct experimental evidence in human and orthologs. Reason: IBA annotation consistent with experimental data. PIGS is an essential component of the GPI transamidase complex that attaches pre-assembled GPI anchors to the C-terminus of GPI-anchored proteins in the ER. 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.
GO:0042765 GPI-anchor transamidase complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically-inferred membership of the GPI-anchor transamidase complex. This is the core cellular component annotation for PIGS and is directly established by biochemistry and cryo-EM structures. Reason: PIGS is one of the five subunits (PIGK, GPAA1, PIGT, PIGS, PIGU) of the GPI-T complex. Supporting Evidence: PMID:11483512 Here, we report two new components of this enzyme: PIG-S and PIG-T.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation to ER membrane from the UniProt Subcellular Location mapping. This is the correct and informative location for PIGS and is supported by experimental cryo-EM structural work. Reason: PIGS is a multi-pass ER membrane protein, consistent with the ER-resident GPI-T complex. Supporting Evidence: file:human/PIGS/PIGS-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0016255 attachment of GPI anchor to protein	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (combined IEA methods, via InterPro/ortholog) to attachment of GPI anchor to protein. Consistent with the experimentally established function. Reason: Matches the well-supported core biological process; the InterPro PIG-S domain (IPR019540) is diagnostic of this family/function. Supporting Evidence: PMID:11483512 PIG-S and PIG-T, essential for GPI anchor attachment to proteins, form a complex with GAA1 and GPI8.
GO:0042765 GPI-anchor transamidase complex	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to GPI-anchor transamidase complex via combined IEA methods. Redundant with, and confirmed by, the experimental IDA/IBA complex annotations. Reason: Correct complex membership, supported by biochemistry and structure. Supporting Evidence: PMID:11483512 PIG-S and PIG-T form a protein complex with GAA1 and GPI8.
GO:0005515 protein binding	IPI PMID:11483512 PIG-S and PIG-T, essential for GPI anchor attachment to prot...	MARK AS OVER ANNOTATED	Summary: Physical interaction (IPI) with PIGT (Q969N2). PIGT is a genuine partner within the GPI-T complex, so the interaction is biologically real, but the bare 'protein binding' term is uninformative and does not capture PIGS's role as a complex subunit. Reason: Per curation guidelines, 'protein binding' (GO:0005515) is uninformative. The meaningful assertion (physical partnership with PIGT within GPI-T) is already captured by the GPI-anchor transamidase complex (GO:0042765) annotations. Retained but marked as over-annotated rather than removed, following policy on experimental IPIs. Supporting Evidence: PMID:11483512 PIG-S and PIG-T form a protein complex with GAA1 and GPI8.
GO:0005515 protein binding	IPI PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	MARK AS OVER ANNOTATED	Summary: Physical interaction (IPI) with PIGT (Q969N2) reported in the study that identified PIG-U as the fifth GPI-T subunit. Real interaction within GPI-T, but the generic term is uninformative. Reason: Bare protein binding is uninformative; the underlying biology (subunit of GPI-T) is captured by GO:0042765. Marked as over-annotated per policy rather than removed. Supporting Evidence: PMID:12802054 The mammalian GPI transamidase is a complex of at least four subunits, GPI8, GAA1, PIG-S, and PIG-T.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Interactions reported from a proteome-scale (Y2H) binary interactome map. Partners here include keratin-associated proteins (P60410/KRTAP10-8, Q6A162/KRT40, Q7Z3S9/NOTCH2NLA), which are unlikely to be biologically meaningful GPI-T partners and are characteristic sticky/false-positive hits of large-scale binary screens. Reason: Uninformative protein binding from a high-throughput interactome; partners are not established GPI-T components. Retained but marked over-annotated per policy on high-throughput IPIs. Supporting Evidence: PMID:25416956 binary protein-protein interactions
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Interactions from a reference binary human interactome map (HuRI). Includes PIGT (Q969N2), TRIP6 (Q15654) and multiple keratin-associated/NOTCH2NL proteins; only PIGT is a bona fide GPI-T partner. Reason: Generic protein binding from a large-scale binary interactome; mostly non-physiological partners. Marked over-annotated per policy. Supporting Evidence: PMID:32296183 reference map of the human binary protein interactome
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Interaction with PIGT (Q969N2) from an AP-MS proteome-scale interactome (BioPlex). The PIGT interaction is consistent with GPI-T membership, but the generic term is uninformative. Reason: Uninformative protein binding; the meaningful PIGT partnership is captured by the GPI-T complex annotation. Marked over-annotated per policy. Supporting Evidence: PMID:33961781 cell-specific remodeling of the human interactome
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Interaction with PIGT (Q969N2) from a multimodal (AP-MS/imaging) cell-map interactome study. Consistent with GPI-T assembly but reported as generic protein binding. Reason: Uninformative protein binding; underlying biology captured by GPI-T complex membership. Marked over-annotated per policy. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics.
GO:0006506 GPI anchor biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: Electronic annotation to GPI anchor biosynthetic process via UniPathway mapping (UPA00196). PIGS participates in the terminal (transamidation) step of GPI-anchor biosynthesis and this broader parent process is appropriate. Reason: Correct pathway-level BP; PIGS's UniProt PATHWAY is glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis. Supporting Evidence: PMID:35551457 covalent attachment of GPI at the new carboxyl terminus are catalyzed by an endoplasmic reticulum membrane GPI transamidase complex (GPI-T) conserved among all eukaryotes
GO:0005789 endoplasmic reticulum membrane	NAS PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: Non-traceable-author-statement ER membrane localization (ComplexPortal, based on the GPI-T complex). Correct and now confirmed by structural studies. Reason: ER membrane is the established, informative location for the GPI-T complex. Supporting Evidence: PMID:12582175 GPI transamidase is localized in the endoplasmic reticulum and mediates post-translational transfer of preformed GPI to proteins bearing a carboxyl-terminal GPI attachment signal.
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: NAS annotation (ComplexPortal) to attachment of GPI anchor to protein. Correct core biological process for the GPI-T complex. Reason: The GPI-T complex, of which PIGS is a subunit, attaches GPI anchors to proteins. Supporting Evidence: PMID:12802054 attaches GPI-anchors to proteins
GO:0042765 GPI-anchor transamidase complex	IPI PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: Physical-interaction-based (ComplexPortal) membership of the GPI-anchor transamidase complex. Directly supported by affinity purification identifying PIG-S among the complex components. Reason: PIG-S co-purifies as a component of the affinity-purified GPI transamidase complex. 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 (cryo-EM structure of the human GPI-T complex) supporting PIGS's involvement in GPI-anchored protein biosynthesis. The structure defines the assembly and the substrate-binding cleft of the ER GPI-T complex. Reason: Structural evidence directly supports PIGS as part of the machinery for GPI-AP biosynthesis. Supporting Evidence: PMID:35165458 Attaching GPI to the protein in the endoplasmic reticulum (ER) is catalyzed by the transmembrane GPI transamidase (GPIT) complex, which is essential for maturation of the GPI-anchored proteins.
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:35551457 Molecular insights into biogenesis of glycosylphosphatidylin...	ACCEPT	Summary: Direct assay (cryo-EM structure of human GPI-T) supporting involvement in GPI-anchored protein biosynthesis. Reveals the equimolar heteropentameric assembly including PIGS. Reason: Structural evidence directly supports PIGS's role in GPI-AP biogenesis. Supporting Evidence: PMID:35551457 revealing an equimolar heteropentameric assembly
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:11483512 PIG-S and PIG-T, essential for GPI anchor attachment to prot...	ACCEPT	Summary: Direct evidence from gene-disruption experiments (PIG-S knockout cells defective in GPI transfer) supporting involvement in GPI-anchored protein biosynthesis. Reason: Knockout of PIG-S impairs transfer of GPI to proteins, demonstrating its role in GPI-AP biosynthesis. Supporting Evidence: PMID:11483512 PIG-S and PIG-T knockout cells were defective in transfer of GPI to proteins, particularly in formation of the carbonyl intermediates.
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:30269814 Mutations in PIGS, Encoding a GPI Transamidase, Cause a Neur...	ACCEPT	Summary: Direct evidence from patient/cell studies (GPIBD18) showing PIGS loss of function produces a GPI-AP deficiency profile, supporting its role in GPI-anchored protein biosynthesis. Reason: Human loss-of-function causes GPI-AP deficiency, directly implicating PIGS in GPI-AP biosynthesis. Supporting Evidence: PMID:30269814 Flow-cytometry analyses demonstrated that the individuals with PIGS mutations show a GPI-AP deficiency profile.
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:34576938 Functional Analysis of the GPI Transamidase Complex by Scree...	ACCEPT	Summary: Direct functional assay (rescue of GPI-AP surface expression in PIGS-KO cells) supporting PIGS's role in GPI-anchored protein biosynthesis; PIGS is indispensable for GPI-T activity. Reason: Functional complementation in PIGS-KO cells directly supports involvement in GPI-AP biosynthesis. Supporting Evidence: PMID:34576938 PIGS is an indispensable subunit of GPI-TA activity, although its role is unclear.
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 evidence (affinity purification / in vitro transamidase assays with the five-subunit complex) supporting PIGS's involvement in attachment of GPI anchor to protein. Reason: The affinity-purified complex containing PIG-S mediates GPI attachment; loss of subunits abolishes transamidase activity. Supporting Evidence: PMID:12802054 attaches GPI-anchors to proteins
GO:0016255 attachment of GPI anchor to protein	IDA PMID:34576938 Functional Analysis of the GPI Transamidase Complex by Scree...	ACCEPT	Summary: Direct functional assay supporting involvement in attachment of GPI anchor to protein; PIGS is required for GPI-T activity (loss of any subunit abolishes activity). Reason: Mutagenesis/complementation confirms PIGS is required for GPI attachment activity. 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:0016255 attachment of GPI anchor to protein	IDA PMID:37684232 Structures of liganded glycosylphosphatidylinositol transami...	ACCEPT	Summary: Direct evidence from liganded (substrate/product-bound) cryo-EM structures of human GPI-T illuminating the transamidation/GPI-attachment mechanism. Reason: Substrate- and product-bound structures directly define the GPI-attachment reaction of the complex containing PIGS. Supporting Evidence: PMID:37684232 The transmembrane complex GPI-T recognizes diverse proproteins at a signal peptide region that lacks consensus sequence and replaces it with GPI via a transamidation reaction.
GO:0042765 GPI-anchor transamidase complex	IDA PMID:37684232 Structures of liganded glycosylphosphatidylinositol transami...	ACCEPT	Summary: Direct structural evidence (liganded cryo-EM structures, PDB 8IMX/8IMY) for PIGS as a subunit of the GPI-anchor transamidase complex. Reason: PIGS is resolved as a subunit in the cryo-EM structures of the human GPI-T complex. Supporting Evidence: PMID:37684232 substrates- and products-bound human GPI-T structures
GO:0016255 attachment of GPI anchor to protein	IDA PMID:35165458 Structure of human glycosylphosphatidylinositol transamidase...	ACCEPT	Summary: Direct evidence (cryo-EM structure) supporting involvement in attachment of GPI anchor to protein; the structure identifies the catalytic triad and GPI substrate-binding cleft of the complex. Reason: Structural work directly supports the GPI-attachment function of the complex containing PIGS. Supporting Evidence: PMID:35165458 Attaching GPI to the protein in the endoplasmic reticulum (ER) is catalyzed by the transmembrane GPI transamidase (GPIT) complex
GO:0016255 attachment of GPI anchor to protein	IDA PMID:35551457 Molecular insights into biogenesis of glycosylphosphatidylin...	ACCEPT	Summary: Direct evidence (cryo-EM structure) supporting involvement in attachment of GPI anchor to protein; structure-based mutagenesis supports the transamidation mechanism. Reason: Structural evidence directly supports the GPI-attachment function of the GPI-T complex that includes PIGS. Supporting Evidence: PMID:35551457 The removal of a hydrophobic signal peptide and covalent attachment of GPI at the new carboxyl terminus are catalyzed by an endoplasmic reticulum membrane GPI transamidase complex (GPI-T)
GO:0042765 GPI-anchor transamidase complex	IDA PMID:35165458 Structure of human glycosylphosphatidylinositol transamidase...	ACCEPT	Summary: Direct structural evidence (cryo-EM, PDB 7W72) for PIGS as one of the five subunits of the GPI-anchor transamidase complex. Reason: PIGS is resolved as a subunit of the human GPI-T complex in the cryo-EM structure. 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 structural evidence (cryo-EM) for PIGS as a subunit of the equimolar heteropentameric GPI-anchor transamidase complex. Reason: PIGS is a subunit of the human GPI-T heteropentamer. Supporting Evidence: PMID:35551457 revealing an equimolar heteropentameric assembly
GO:0042765 GPI-anchor transamidase complex	IDA PMID:12582175 Two subunits of glycosylphosphatidylinositol transamidase, G...	ACCEPT	Summary: Direct evidence for PIGS as part of the multimeric GPI transamidase complex; this study on the GPI8-PIG-T disulfide bridge confirms an inactive five-component complex holds the substrate protein. Reason: Biochemistry places PIG-S among the five components of the mammalian GPI transamidase complex. Supporting Evidence: PMID:12582175 an inactive human GPI transamidase complex that consists of non-functional GPI8 and four other components
GO:0042765 GPI-anchor transamidase complex	IDA PMID:34576938 Functional Analysis of the GPI Transamidase Complex by Scree...	ACCEPT	Summary: Direct evidence (co-purification of all five subunits confirmed by mass spectrometry) for PIGS as a subunit of the GPI-anchor transamidase complex. Reason: All five GPI-TA subunits, including PIGS, co-purify as the assembled complex. 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:0042765 GPI-anchor transamidase complex	IDA PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: Direct evidence (affinity purification of the complex) for PIGS as a component of the GPI-anchor transamidase complex. Reason: PIG-S is a component of the affinity-purified GPI transamidase complex. 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:0042765 GPI-anchor transamidase complex	IDA PMID:11483512 PIG-S and PIG-T, essential for GPI anchor attachment to prot...	ACCEPT	Summary: Direct evidence for PIG-S as a component of the GPI transamidase complex, forming a complex with GAA1, GPI8 (PIGK) and PIG-T. Reason: Foundational biochemical identification of PIG-S as a GPI-T subunit. Supporting Evidence: PMID:11483512 PIG-S and PIG-T form a protein complex with GAA1 and GPI8.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: High-throughput proteomics detected PIGS in the membrane proteome of an NK-like cell line. This localizes PIGS to a membrane but is far less informative than the established ER membrane annotation. Reason: GO:0016020 (membrane) is a correct but unspecific parent; the informative location is endoplasmic reticulum membrane (GO:0005789). Retained but marked as over-annotated. Supporting Evidence: PMID:19946888 define the composition of the membrane proteome of the Natural Killer (NK) like cell line YTS
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-162836	ACCEPT	Summary: Traceable-author-statement (Reactome) localization to the ER membrane, in the context of GPI-anchor attachment reactions. Correct and consistent with all other evidence. Reason: ER membrane is the established location of the GPI-T complex. Supporting Evidence: file:human/PIGS/PIGS-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
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 to attachment of GPI anchor to protein, from the paper identifying PIG-S as essential for GPI anchor attachment. Reason: Core, well-supported biological process for PIGS. Supporting Evidence: PMID:11483512 PIG-S and PIG-T, essential for GPI anchor attachment to proteins, form a complex with GAA1 and GPI8.
GO:0042765 GPI-anchor transamidase complex	TAS PMID:15713669 Endoplasmic reticulum localization of Gaa1 and PIG-T, subuni...	ACCEPT	Summary: Traceable-author-statement for PIGS as one of the five subunits of the ER-localized GPI transamidase complex. Reason: Consistent with the established five-subunit GPI-T complex membership. Supporting Evidence: PMID:15713669 two of the five subunits of the ER-localized glycosylphosphatidylinositol transamidase complex

Gene Description

Existing Annotations Review

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References

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