GPAA1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016255 attachment of GPI anchor to protein	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred core biological process. GPAA1 orthologs across eukaryotes (yeast Gaa1p, Drosophila) are components of the GPI transamidase that attaches GPI to precursor proteins. Well supported by direct experimental evidence in human (see IDA/EXP annotations). Reason: Correct, appropriately specific core BP; matches direct experimental annotations and the phylogenetic consensus. 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 complex membership. GPAA1 is a conserved subunit of the GPI-anchor transamidase complex; this is confirmed by direct co-purification, mutagenesis and cryo-EM structures of the human complex. Reason: Core, correct complex-membership assignment consistent with experimental evidence. Supporting Evidence: PMID:34576938 GPI-TA consists of five subunits: PIGK, GPAA1, PIGT, PIGS, and PIGU
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation from the UniProt subcellular-location vocabulary. GPAA1 is a multi-pass ER membrane protein; supported directly by experimental localization studies. Reason: Correct core localization; consistent with experimental and structural evidence that GPAA1 is a multi-pass ER membrane protein. Supporting Evidence: file:human/GPAA1/GPAA1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0016020 membrane	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO electronic annotation to the generic 'membrane' term. True but uninformative: the specific and correct location is the ER membrane (GO:0005789), which is separately annotated. Reason: Redundant, low-information parent of the more specific ER membrane annotation; retained but flagged as over-annotated. Supporting Evidence: file:human/GPAA1/GPAA1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0042765 GPI-anchor transamidase complex	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation (IPR007246, Gaa1) to the transamidase complex. Correct complex membership, confirmed experimentally. Reason: Correct core complex-membership term; consistent with experimental and structural data. Supporting Evidence: PMID:34576938 GPI-TA consists of five subunits: PIGK, GPAA1, PIGT, PIGS, and PIGU
GO:0005515 protein binding	IPI PMID:10793132 Gaa1p and gpi8p are components of a glycosylphosphatidylinos...	MARK AS OVER ANNOTATED	Summary: IntAct/UniProt binary interaction with PIGK (Q92643), the catalytic subunit of the same complex. The interaction is real but the bare 'protein binding' term is uninformative; the biologically meaningful relationship is captured by GPI-anchor transamidase complex membership. Reason: Non-informative molecular-function term (bare protein binding); the underlying PIGK interaction is already represented by complex membership. Per curation policy this IPI is not removed. Supporting Evidence: PMID:10793132 Gaa1p and Gpi8p are associated with each other.
GO:0005515 protein binding	IPI PMID:11483512 PIG-S and PIG-T, essential for GPI anchor attachment to prot...	MARK AS OVER ANNOTATED	Summary: IntAct/UniProt interaction (with PIGK Q92643) supporting GPI-T complex assembly. Bare 'protein binding' is uninformative. Reason: Non-informative MF term; the relevant biology (co-complex with the other GPI-T subunits) is captured by GO:0042765. Not removed per policy. Supporting Evidence: PMID:11483512 PIG-T maintains the complex by stabilizing the expression of 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: IntAct/UniProt interaction (with PIGK Q92643) within the GPI transamidase complex, which PMID:12802054 shows is a five-subunit assembly. Bare 'protein binding' is uninformative. Reason: Non-informative MF term; complex membership is the meaningful annotation. Not removed per policy. Supporting Evidence: PMID:12802054 The mammalian GPI transamidase is a
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: High-throughput AP-MS interactome (BioPlex 2.0) binary interactions (PIGK Q92643, PIGT Q969N2, MOXD1 Q6UVY6). Bare 'protein binding' is uninformative and derives from a proteome-scale screen. Reason: Non-informative MF term from a large-scale interactome study; complex membership already captures the relevant partners. Not removed per policy. Supporting Evidence: PMID:28514442 the largest such network so far
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: High-throughput AP-MS interactome (BioPlex 3.0) interactions. Bare 'protein binding' is uninformative. Reason: Non-informative MF term from a proteome-scale interactome; not removed per policy. Supporting Evidence: PMID:33961781 we have created two proteome-scale, cell-line-specific
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: High-throughput multimodal cell-map interactome (PIGK Q92643, PIGT Q969N2). Bare 'protein binding' is uninformative. Reason: Non-informative MF term from a proteome-scale mapping study; not removed 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: UniPathway-based electronic annotation to the parent GPI-anchor biosynthesis process. GPAA1 acts in the terminal transamidation step of this pathway. Reason: Correct parent BP for GPAA1's role in GPI-anchored protein biosynthesis. Supporting Evidence: file:human/GPAA1/GPAA1-uniprot.txt PATHWAY: Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.
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) assignment of the GPI-anchor transamidase complex to the ER membrane. Consistent with direct experimental localization of GPAA1. Reason: Correct core localization; corroborated by experimental evidence. Supporting Evidence: PMID:12582175 GPI transamidase is localized in the
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) assignment of the transamidase complex process to GPAA1. Correct core BP, confirmed by experimental data. Reason: Correct core BP; consistent with the direct experimental annotations. Supporting Evidence: PMID:12802054 GPI transamidase that 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: Affinity-purification evidence that GPAA1 is part of the GPI transamidase complex; this paper established PIG-U as the fifth subunit alongside GAA1, GPI8, PIG-S and PIG-T. Reason: Correct core complex-membership annotation, experimentally supported. 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:0005783 endoplasmic reticulum	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas immunofluorescence localizes GPAA1 to the endoplasmic reticulum. Consistent with its role as an ER-membrane transamidase subunit; the ER membrane (GO:0005789) is the more precise location. Reason: Correct localization to the ER (parent of ER membrane); consistent with all other localization data. Supporting Evidence: file:human/GPAA1/GPAA1-uniprot.txt GO:0005783; C:endoplasmic reticulum; IDA:HPA.
GO:0005789 endoplasmic reticulum membrane	EXP PMID:11483512 PIG-S and PIG-T, essential for GPI anchor attachment to prot...	ACCEPT	Summary: Experimental localization of the GAA1-containing transamidase to the ER membrane, where it mediates GPI anchoring. Reason: Correct core localization, directly supported. Supporting Evidence: PMID:11483512 The GPI transamidase mediates GPI anchoring in the endoplasmic reticulum
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:35165458 Structure of human glycosylphosphatidylinositol transamidase...	ACCEPT	Summary: Cryo-EM structure of the human GPI transamidase (PIGK/PIGU/PIGT/PIGS/GPAA1) demonstrating its role in maturation of GPI-anchored proteins. Reason: Correct core BP, directly supported by the structural characterization of the complex containing GPAA1. Supporting Evidence: PMID:35165458 composed of five subunits: PIGK, PIGU, PIGT, PIGS and GPAA1
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:35551457 Molecular insights into biogenesis of glycosylphosphatidylin...	ACCEPT	Summary: Cryo-EM structure of the human GPI-T heteropentamer including GPAA1, illuminating GPI-anchored protein biogenesis. Reason: Correct core BP; directly supported by structural data on the GPAA1- containing complex. Supporting Evidence: PMID:35551457 GPI-T at a global 2.53-Å resolution, revealing an equimolar
GO:0016255 attachment of GPI anchor to protein	IDA PMID:29100095 Mutations in GPAA1, Encoding a GPI Transamidase Complex Prot...	ACCEPT	Summary: Functional evidence that GPAA1 is essential for attaching GPI to precursor proteins: patient cells with biallelic GPAA1 variants show reduced surface levels of GPI-anchored proteins. Reason: Correct core BP, supported by loss-of-function disease evidence. Supporting Evidence: PMID:29100095 This complex orchestrates the attachment of the GPI anchor to the
GO:0016255 attachment of GPI anchor to protein	IDA PMID:9468317 Molecular cloning of human homolog of yeast GAA1 which is re...	ACCEPT	Summary: Original cloning of human GAA1; antisense knockdown reduced production of a reporter GPI-anchored protein, implicating GPAA1 in GPI attachment. Reason: Correct core BP; supported by functional knockdown evidence. Supporting Evidence: PMID:9468317 Overexpression of antisense hGAA1 in human K562 cells significantly reduced the production of a reporter GPI-anchored protein
GO:0042765 GPI-anchor transamidase complex	IDA PMID:9468317 Molecular cloning of human homolog of yeast GAA1 which is re...	ACCEPT	Summary: GPAA1 identified as a component of the putative transamidase machinery. Reason: Correct core complex-membership annotation. Supporting Evidence: PMID:9468317 We have isolated a component of the putative transamidase
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:29100095 Mutations in GPAA1, Encoding a GPI Transamidase Complex Prot...	ACCEPT	Summary: GPAA1 as an essential component of the transamidase complex in GPI-anchored protein biosynthesis; loss of function reduces surface GPI-APs. Reason: Correct core BP, supported by disease/functional evidence. Supporting Evidence: PMID:29100095 GPI-anchored proteins had decreased cell-surface abundance in
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:34576938 Functional Analysis of the GPI Transamidase Complex by Scree...	ACCEPT	Summary: Mutational screen of GPI-TA subunits confirming GPAA1 function in GPI anchoring (GPAA1 D250A reduces activity). Reason: Correct core BP, directly supported by functional mutagenesis. Supporting Evidence: PMID:34576938 The D250A construct reduced GPI-TA activity without changing the protein stability
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:37684232 Structures of liganded glycosylphosphatidylinositol transami...	ACCEPT	Summary: Liganded GPI-T structures showing GPAA1 within the complex engaged in GPI-anchored protein biogenesis (GPI substrate bound). Reason: Correct core BP, directly supported by structural data on the substrate- and product-bound complex. Supporting Evidence: PMID:37684232 EtNP2 is fixed by GPAA1 Gln355 and Ser51
GO:0180046 GPI anchored protein biosynthesis	IDA PMID:9468317 Molecular cloning of human homolog of yeast GAA1 which is re...	ACCEPT	Summary: GPAA1 functionally implicated in production of GPI-anchored proteins via antisense knockdown. Reason: Correct core BP; functional knockdown evidence. Supporting Evidence: PMID:9468317 Overexpression of antisense hGAA1 in human K562 cells significantly reduced the production of a reporter GPI-anchored protein
GO:0034235 GPI anchor binding	IDA PMID:37684232 Structures of liganded glycosylphosphatidylinositol transami...	ACCEPT	Summary: Liganded cryo-EM structures directly show GPAA1 binding the GPI lipid substrate: GPAA1 residues coordinate the three ethanolamine-phosphate arms of GPI (EtNP1-His354 via Mg2+, EtNP2-Gln355/Ser51, EtNP3-Ser51/Asn53). This is GPAA1's specific molecular function within the complex. Reason: Well-supported, informative core molecular function (GPI lipid-substrate binding), established by liganded structures. Supporting Evidence: PMID:37684232 EtNP1 interacts with GPAA1 His354 through metal coordination (modeled as Mg2+) PMID:37684232 Finally, EtNP3 interacts with GPAA1 Ser51 and Asn53
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 for the transamidase complex (containing GAA1) attaching GPI anchors to proteins. Reason: Correct core BP, experimentally supported. Supporting Evidence: PMID:12802054 GPI transamidase that 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: Functional analysis of GPI-TA subunits including GPAA1, confirming its role in GPI attachment; GPAA1 is proposed to catalyse formation of the amide bond between the substrate omega-site and the bridging EtNP. Reason: Correct core BP, supported by mutagenesis and functional rescue assays. Supporting Evidence: PMID:34576938 GPAA1 is proposed to catalyze the formation of an amide bond between the
GO:0016255 attachment of GPI anchor to protein	IDA PMID:37684232 Structures of liganded glycosylphosphatidylinositol transami...	ACCEPT	Summary: Substrate/product-bound GPI-T structures directly visualise the attachment reaction, with GPAA1 binding the GPI substrate. Reason: Correct core BP, directly supported by structural data. Supporting Evidence: PMID:37684232 EtNP2 is fixed by GPAA1 Gln355 and Ser51
GO:0042765 GPI-anchor transamidase complex	IDA PMID:37684232 Structures of liganded glycosylphosphatidylinositol transami...	ACCEPT	Summary: Cryo-EM structures of the GPI-T complex including GPAA1 (light blue subunit) with PIGK, PIGT, PIGS and PIGU. Reason: Correct core complex-membership annotation, structurally confirmed. Supporting Evidence: PMID:37684232 a Interactions between the product ULBP2* and GPI-T (GPAA1, light blue; PIGK, marine blue; PIGT, purple; PGIS, cyan).
GO:0016255 attachment of GPI anchor to protein	IDA PMID:35165458 Structure of human glycosylphosphatidylinositol transamidase...	ACCEPT	Summary: Cryo-EM structure of the human GPI transamidase catalysing GPI attachment to proteins in the ER. Reason: Correct core BP, structurally supported. Supporting Evidence: PMID:35165458 composed of five subunits: PIGK, PIGU, PIGT, PIGS and GPAA1
GO:0016255 attachment of GPI anchor to protein	IDA PMID:35551457 Molecular insights into biogenesis of glycosylphosphatidylin...	ACCEPT	Summary: Cryo-EM structure of the human GPI-T heteropentamer engaged in the removal of the signal peptide and covalent attachment of GPI. Reason: Correct core BP, structurally supported. Supporting Evidence: PMID:35551457 covalent attachment of GPI at the new carboxyl terminus
GO:0042765 GPI-anchor transamidase complex	IDA PMID:35165458 Structure of human glycosylphosphatidylinositol transamidase...	ACCEPT	Summary: Cryo-EM structure demonstrating GPAA1 as one of the five subunits of the human GPI transamidase complex. Reason: Correct core complex-membership annotation, structurally confirmed. Supporting Evidence: PMID:35165458 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: Cryo-EM structure of the equimolar heteropentameric GPI-T complex including GPAA1. Reason: Correct core complex-membership annotation, structurally confirmed. Supporting Evidence: PMID:35551457 GPI-T at a global 2.53-Å resolution, revealing an equimolar
GO:0042765 GPI-anchor transamidase complex	IDA PMID:12582175 Two subunits of glycosylphosphatidylinositol transamidase, G...	ACCEPT	Summary: Biochemical evidence that the human GPI transamidase is a multimeric complex of five components (including GAA1) sufficient to hold the substrate protein. Reason: Correct core complex-membership annotation. Supporting Evidence: PMID:12582175 indicating that these five components are sufficient to
GO:0042765 GPI-anchor transamidase complex	IDA PMID:34576938 Functional Analysis of the GPI Transamidase Complex by Scree...	ACCEPT	Summary: Purified human GPI-TA containing GPAA1 with the four other subunits. Reason: Correct core complex-membership annotation, experimentally supported. Supporting Evidence: PMID:34576938 GPI-TA consists of five subunits: PIGK, GPAA1, PIGT, PIGS, and PIGU
GO:0016255 attachment of GPI anchor to protein	IMP PMID:14660601 A conserved proline in the last transmembrane segment of Gaa...	ACCEPT	Summary: Mutation of a conserved proline in the last TM segment of GAA1 abolishes GPI recognition/binding by the transamidase, impairing GPI attachment. Reason: Correct core BP, supported by mutational (IMP) evidence linking GAA1 to the attachment reaction. Supporting Evidence: PMID:14660601 required for glycosylphosphatidylinositol (GPI) recognition by GPI transamidase
GO:0042765 GPI-anchor transamidase complex	IDA PMID:12802054 Human PIG-U and yeast Cdc91p are the fifth subunit of GPI tr...	ACCEPT	Summary: Affinity-purified GPI transamidase complex containing GAA1 and the four other subunits. Reason: Correct core complex-membership annotation. 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: GAA1 shown to form a protein complex with GPI8, PIG-S and PIG-T. Reason: Correct core complex-membership annotation, experimentally supported. Supporting Evidence: PMID:11483512 PIG-S and PIG-T form a protein complex with GAA1 and GPI8
GO:0042765 GPI-anchor transamidase complex	IDA PMID:14660601 A conserved proline in the last transmembrane segment of Gaa...	ACCEPT	Summary: GAA1 shown to be part of the multisubunit human GPI transamidase (Gaa1, Gpi8, PIG-S, PIG-T, PIG-U). Reason: Correct core complex-membership annotation. Supporting Evidence: PMID:14660601 Human GPIT is a multisubunit membrane-bound protein complex
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: High-throughput mass-spectrometry identification of GPAA1 in an NK-cell membrane proteome. Generic 'membrane' term; the specific location is the ER membrane. Reason: Uninformative parent term from a proteome-scale membrane fractionation; the specific ER membrane location is annotated separately. Supporting Evidence: PMID:19946888 define the composition of the membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-162836	ACCEPT	Summary: Reactome traceable assignment of GPAA1 (as part of the GPI transamidase reaction) to the ER membrane. Reason: Correct core localization, consistent with all other evidence. Supporting Evidence: file:human/GPAA1/GPAA1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0034235 GPI anchor binding	IMP PMID:14660601 A conserved proline in the last transmembrane segment of Gaa...	ACCEPT	Summary: Truncation of GAA1's C-terminal TM span, or mutation of a conserved proline within it, prevents the transamidase complex from co-immunoprecipitating GPI while leaving assembly intact - showing GAA1 contributes to GPI binding by the complex. Reason: Correct, informative core molecular function; the contributes_to qualifier appropriately captures that GPI binding is a property of the complex to which GAA1 contributes. Supporting Evidence: PMID:14660601 abrogate the ability of the resulting GPIT complex to co-immunoprecipitate GPI
GO:0006621 protein retention in ER lumen	NAS PMID:12052837 Structural requirements for the recruitment of Gaa1 into a f...	MARK AS OVER ANNOTATED	Summary: The cited paper describes how GAA1 itself is retained in the ER (a signalless, passive mechanism) and how its cytoplasmic N terminus may act as a membrane-sorting determinant for GAA1 and associated GPIT subunits. It does not show that GPAA1 retains other proteins in the ER lumen, and GPAA1 is not a KDEL-receptor-type lumenal-retention factor. The GO term 'protein retention in ER lumen' is therefore a poor fit for GPAA1's biology. Reason: Term/paper mismatch: PMID:12052837 concerns retention of GAA1 (and its own complex) in the ER membrane, not retention of substrate proteins in the ER lumen. NAS evidence; not experimentally supported for this process. Supporting Evidence: PMID:12052837 the cytoplasmic N terminus of Gaa1 is not required for formation of a functional GPIT complex but may act as a membrane-sorting determinant directing Gaa1 and associated GPIT subunits to an endoplasmic reticulum membrane domain.
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 assertion that the GAA1-containing transamidase attaches GPI to the C-terminus of precursor proteins in the ER. Reason: Correct core BP, consistent with all experimental evidence. 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:0016255 attachment of GPI anchor to protein	NAS PMID:9468317 Molecular cloning of human homolog of yeast GAA1 which is re...	ACCEPT	Summary: Non-traceable assertion that human GAA1 is required for attachment of GPI to proteins (original cloning paper). Reason: Correct core BP; corroborated by later direct experimental evidence. Supporting Evidence: PMID:9468317 required for attachment of glycosylphosphatidylinositols to proteins
GO:0005515 protein binding	IPI PMID:15713669 Endoplasmic reticulum localization of Gaa1 and PIG-T, subuni...	MARK AS OVER ANNOTATED	Summary: IntAct/UniProt interaction (with PIGT Q969N2) within the ER-localized GPI transamidase complex. Bare 'protein binding' is uninformative. Reason: Non-informative MF term; the PIGT interaction is captured by complex membership (GO:0042765). Not removed per policy. Supporting Evidence: PMID:15713669 human Gaa1 and PIG-T, two of the five subunits
GO:0042765 GPI-anchor transamidase complex	TAS PMID:15713669 Endoplasmic reticulum localization of Gaa1 and PIG-T, subuni...	ACCEPT	Summary: Traceable assertion that GAA1 is one of the five subunits of the ER-localized GPI transamidase complex. Reason: Correct core complex-membership annotation. Supporting Evidence: PMID:15713669 human Gaa1 and PIG-T, two of the five subunits

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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