Essential subunit of the GPI-anchor transamidase complex (GPIT) in the endoplasmic reticulum. The complex catalyzes the terminal step of GPI anchor attachment, transferring preassembled GPI glycolipids to specific proteins at their C-terminal GPI-anchor signal sequence. Gaa1 contains a luminal domain with an M28 family metallopeptidase-like fold; while earlier work proposed this domain as the catalytic metallopeptide synthetase, the 2022 cryo-EM structure of the human complex assigns the catalytic cysteine protease to PIGK (Gpi8 ortholog) and supports a structural/substrate-positioning role for Gaa1, including substrate recruitment and GPI lipid recognition. The multi-pass transmembrane protein anchors the complex in the ER membrane and positions the catalytic machinery for GPI attachment. Direct S. pombe biochemical data are limited; functional assignments are strongly supported by orthology to the conserved Gaa1/GPAA1 family, in which a S. pombe ortholog is explicitly recognized.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016255 attachment of GPI anchor to protein | IBA GO_REF:0000033 | ACCEPT | Summary: This is the core biological process for gaa1. The protein is directly responsible for catalyzing the terminal step of GPI anchor attachment to proteins in the ER. Supporting Evidence: file:SCHPO/gaa1/gaa1-deep-research.md Gaa1 is a core component of the GPI:protein transamidase (GPIT) enzyme complex that catalyzes the final step of GPI anchor attachment to proteins in the endoplasmic reticulum file:SCHPO/gaa1/gaa1-deep-research-falcon.md gaa1 encodes a **GPI transamidase component** (Gaa1/GPAA1 family) required for efficient **attachment of GPI anchors** to secretory proteins in the ER. file:SCHPO/gaa1/gaa1-deep-research-falcon.md Cross-species sequence analysis explicitly includes **a *Schizosaccharomyces pombe* Gaa1 ortholog** and shows conservation of the function-critical proline motif in the last TM segment, supporting that *S. pombe* gaa1/Q9US48 is a true family member with conserved mechanistic features. |
| GO:0042765 GPI-anchor transamidase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Core cellular component annotation. Gaa1 is an essential structural and substrate-positioning subunit of this five-protein complex. Supporting Evidence: file:SCHPO/gaa1/gaa1-deep-research.md Gaa1 resides in the ER as an integral membrane protein and is a stable structural subunit of the GPIT enzyme complex (GO:0042765) file:SCHPO/gaa1/gaa1-deep-research-falcon.md Likely a core subunit of the **five-subunit GPI transamidase (GPIT/GPI-T)** with orthologs of PIGK/Gpi8, PIGT/Gpi16, PIGS/Gpi17, and PIGU/Gab1/Cdc91. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct localization. Gaa1 is a multi-pass transmembrane protein anchored in the ER membrane where GPI attachment occurs. Supporting Evidence: file:SCHPO/gaa1/gaa1-deep-research.md Gaa1 is an integral membrane glycoprotein of the ER. It is a multi-pass membrane protein embedded in the ER membrane as part of the GPIT complex file:SCHPO/gaa1/gaa1-deep-research-falcon.md Across systems where it has been experimentally studied, Gaa1/GPAA1 is a **multi-pass ER membrane glycoprotein**. file:SCHPO/gaa1/gaa1-deep-research-falcon.md the most defensible localization statement is **ER membrane**, inferred from conserved complex function and topology across eukaryotes. |
| GO:0006506 GPI anchor biosynthetic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: This term is correct but less specific than GO:0016255 (attachment of GPI anchor to protein). Gaa1 functions in the terminal attachment step, which is part of the broader GPI anchor biosynthetic process. Falcon notes that this final transamidation step is the commitment step producing a mature GPI-anchored protein. Supporting Evidence: file:SCHPO/gaa1/gaa1-deep-research-falcon.md This reaction occurs in the **endoplasmic reticulum (ER)** and is described as the final “commitment” step that produces a mature GPI-anchored protein. |
| GO:0016020 membrane | IEA GO_REF:0000002 | REMOVE | Summary: Too generic. The more specific term GO:0005789 (endoplasmic reticulum membrane) is already present and should be used instead. |
| GO:0042765 GPI-anchor transamidase complex | IEA GO_REF:0000002 | REMOVE | Summary: Duplicate of the IBA annotation for the same term. Accept one, remove this duplicate. |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:15003443 A sensitive predictor for potential GPI lipid modification s... | REMOVE | Summary: Duplicate of the IEA annotation for the same term. Accept one, remove this duplicate. Supporting Evidence: PMID:15003443 A sensitive predictor for potential GPI lipid modification sites in fungal protein sequences and its application to genome-wide studies for Aspergillus nidulans, Candida albicans, Neurospora crassa, Saccharomyces cerevisiae and Schizosaccharomyces pombe. |
| GO:0016255 attachment of GPI anchor to protein | NAS PMID:15003443 A sensitive predictor for potential GPI lipid modification s... | REMOVE | Summary: Duplicate of the IBA annotation for the same term. Accept one, remove this duplicate. Supporting Evidence: PMID:15003443 A sensitive predictor for potential GPI lipid modification sites in fungal protein sequences and its application to genome-wide studies for Aspergillus nidulans, Candida albicans, Neurospora crassa, Saccharomyces cerevisiae and Schizosaccharomyces pombe. |
| GO:0031505 fungal-type cell wall organization | NAS PMID:15003443 A sensitive predictor for potential GPI lipid modification s... | MARK AS OVER ANNOTATED | Summary: While GPI-anchored proteins contribute to cell wall organization in fungi, this is an indirect downstream effect. The direct function of gaa1 is GPI anchor attachment, not cell wall organization itself; this annotation overshoots the gene's direct role and is marked as over-annotated. Supporting Evidence: file:SCHPO/gaa1/gaa1-deep-research.md In S. pombe (and other fungi), numerous cell wall enzymes and adhesins are GPI-anchored; therefore, Gaa1 is indirectly critical for cell wall assembly and integrity PMID:15003443 A sensitive predictor for potential GPI lipid modification sites in fungal protein sequences and its application to genome-wide studies for Aspergillus nidulans, Candida albicans, Neurospora crassa, Saccharomyces cerevisiae and Schizosaccharomyces pombe. file:SCHPO/gaa1/gaa1-deep-research-falcon.md In yeast and fungal systems, GPI anchoring is a major contributor to **cell wall protein display** and surface proteome composition. |
| GO:0042765 GPI-anchor transamidase complex | NAS PMID:15003443 A sensitive predictor for potential GPI lipid modification s... | REMOVE | Summary: Duplicate of the IBA annotation for the same term. Accept one, remove this duplicate. Supporting Evidence: PMID:15003443 A sensitive predictor for potential GPI lipid modification sites in fungal protein sequences and its application to genome-wide studies for Aspergillus nidulans, Candida albicans, Neurospora crassa, Saccharomyces cerevisiae and Schizosaccharomyces pombe. |
| GO:0003923 GPI-anchor transamidase activity | TAS PMID:26563290 Biosynthesis of GPI-anchored proteins: special emphasis on G... | ACCEPT | Summary: Core molecular function. GO:0003923 is the complex-level catalytic activity of the GPI transamidase complex that gaa1 is part of, and the annotation is retained as core for gaa1 as a subunit. Note on mechanism: earlier modeling (Eisenhaber 2014; Su 2020) proposed that the M28-family-like luminal domain of Gaa1/GPAA1 is itself the peptide-bond-forming metallopeptide synthetase. Falcon deep research flags that this has been revised by the 2022 near-atomic cryo-EM structure of human GPI-T, which assigns the catalytic cysteine protease to PIGK (the Gpi8 ortholog) and indicates Gaa1/GPAA1 is more likely a structural/substrate-positioning subunit contributing to substrate recruitment and GPI lipid recognition rather than the principal catalyst. The complex-level GO:0003923 annotation remains appropriate for gaa1 as an essential subunit, but it should not be read as asserting that Gaa1 alone performs the peptide-bond chemistry. Supporting Evidence: file:SCHPO/gaa1/gaa1-deep-research.md structural and bioinformatic studies revealed that Gaa1's luminal domain is homologous to M28 family metallo-peptidases, suggesting that Gaa1 itself is the enzyme that catalyzes the second step of the transamidation PMID:26563290 Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling. PMID:35551457 Structure-based mutagenesis suggests a legumain-like mechanism for the recognition and cleavage of proprotein substrates, and an endogenous GPI in the structure defines a composite cavity for the lipid substrate. file:SCHPO/gaa1/gaa1-deep-research-falcon.md In the literature, the **precise catalytic assignment** for GPAA1/Gaa1 has evolved. A 2022 near-atomic cryo-EM structure of human GPI-T supports **PIGK** as the catalytic cysteine protease (with an essential catalytic dyad) and provides evidence that GPAA1’s luminal domain—despite a protease-like fold—may be more **structural/substrate-positioning** rather than the main catalytic center (based on mutagenesis and a cell-surface CD59 reporter assay). file:SCHPO/gaa1/gaa1-deep-research-falcon.md proproteins can bind Gaa1 even when the catalytic subunit Gpi8/PIGK is absent, consistent with a **substrate-recruitment** role for Gaa1. file:SCHPO/gaa1/gaa1-deep-research-falcon.md The last transmembrane segment of Gaa1 is implicated in **GPI recognition**: truncations and point mutations (including a conserved proline) disrupt GPI co-precipitation while preserving assembly and proprotein binding, indicating a role in binding/presenting the lipid substrate. |
| GO:0005783 endoplasmic reticulum | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: Correct but less specific than GO:0005789 (endoplasmic reticulum membrane). Since gaa1 is a transmembrane protein, the membrane term is more accurate. Supporting Evidence: PMID:16823372 ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe. |
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