{"gene":"PIGS","run_date":"2026-06-10T06:43:35","timeline":{"discoveries":[{"year":2001,"finding":"PIGS (PIG-S) is an essential subunit of the GPI transamidase complex in the endoplasmic reticulum. Homologous recombination knockout of PIGS in mouse F9 cells abolished transfer of GPI to proteins, specifically blocking formation of the carbonyl intermediates that are the hallmark of the transamidation reaction. PIGS forms a protein complex with GAA1, GPI8, and PIG-T, and the yeast ortholog is Gpi17p (YDR434W).","method":"Homologous recombination knockout in mouse F9 cells, GPI anchoring assay (carbonyl intermediate formation), co-immunoprecipitation of complex members","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal complex identification by co-IP, loss-of-function by gene knockout with specific biochemical readout (carbonyl intermediate formation), identification of yeast ortholog, multiple orthogonal methods in a single focused study","pmids":["11483512"],"is_preprint":false},{"year":2010,"finding":"The yeast ortholog of PIGS (yPIG-S, residues 38-467) adopts an elongated two-domain solution structure as determined by small-angle X-ray scattering (SAXS), with a larger domain (~10.1 nm length) and a smaller domain (~6.7 nm length) tilted relative to each other, and secondary structure comprising ~58% α-helix and ~18% β-sheet. This structural characterization places yPIG-S as an elongated subunit within the GPI transamidase complex.","method":"Small-angle X-ray scattering (SAXS), circular dichroism spectroscopy, recombinant protein production in E. coli","journal":"Journal of structural biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — low-resolution solution structure by SAXS with CD validation, single lab, yeast ortholog only, no mutagenesis or functional validation","pmids":["21134462"],"is_preprint":false}],"current_model":"PIGS (PIG-S) is an essential non-catalytic subunit of the GPI transamidase complex in the endoplasmic reticulum, where it forms a stable complex with GAA1, GPI8, and PIG-T; loss of PIGS abolishes the carbonyl intermediate step of the transamidation reaction that transfers pre-assembled GPI anchors onto substrate proteins, and structural studies of the yeast ortholog indicate it is an elongated two-domain protein within this complex."},"narrative":{"mechanistic_narrative":"PIGS (PIG-S) is an essential non-catalytic subunit of the endoplasmic reticulum GPI transamidase complex that transfers pre-assembled glycosylphosphatidylinositol (GPI) anchors onto substrate proteins [PMID:11483512]. PIGS assembles into a stable complex with GAA1, GPI8, and PIG-T, and its loss abolishes GPI transfer by specifically blocking formation of the carbonyl intermediates that are the biochemical hallmark of the transamidation reaction [PMID:11483512]. Structural characterization of the yeast ortholog (Gpi17p) indicates an elongated two-domain architecture, consistent with PIGS serving as a structural component spanning the transamidase complex [PMID:21134462]. Beyond its role as a complex subunit and the carbonyl-intermediate step, no further catalytic or regulatory mechanism for PIGS has been characterized in the available corpus.","teleology":[{"year":2001,"claim":"Established that PIGS is an essential, dedicated subunit of the GPI transamidase machinery and pinpointed which step of the transamidation reaction it enables.","evidence":"Homologous recombination knockout in mouse F9 cells with a GPI anchoring/carbonyl-intermediate assay, plus co-immunoprecipitation of complex members and identification of the yeast ortholog Gpi17p","pmids":["11483512"],"confidence":"High","gaps":["Whether PIGS contributes any catalytic activity or is purely structural/scaffolding within the complex was not resolved","The molecular role of PIGS in forming or stabilizing the carbonyl intermediate (e.g. substrate or GPI positioning) was not defined","No structural basis for how PIGS contacts GAA1, GPI8, or PIG-T was determined"]},{"year":2010,"claim":"Provided the first structural view of the PIGS subunit, showing it is an elongated two-domain protein rather than a compact globular subunit.","evidence":"Small-angle X-ray scattering and circular dichroism on recombinant yeast ortholog (residues 38-467) produced in E. coli","pmids":["21134462"],"confidence":"Medium","gaps":["Low-resolution solution envelope only; no atomic structure, no mutagenesis, and no functional validation","Performed on the yeast ortholog in isolation, not within the assembled transamidase complex or with the human protein","Does not assign which domain mediates complex assembly versus substrate handling"]},{"year":null,"claim":"The precise mechanistic contribution of PIGS to the transamidation chemistry and its contacts with the other transamidase subunits remain undefined.","evidence":"No further mechanistic studies present in the available corpus","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of human PIGS within the intact transamidase complex","No definition of substrate or GPI-binding determinants on PIGS","No link to disease established within this corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0]}],"complexes":["GPI transamidase complex"],"partners":["GAA1","GPI8","PIGT"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96S52","full_name":"GPI-anchor transamidase component PIGS","aliases":["Phosphatidylinositol-glycan biosynthesis class S protein"],"length_aa":555,"mass_kda":61.7,"function":"Component of the glycosylphosphatidylinositol-anchor (GPI-anchor) transamidase (GPI-T) complex that catalyzes the formation of the linkage between a proprotein and a GPI-anchor and participates in GPI anchored protein biosynthesis","subcellular_location":"Endoplasmic reticulum membrane","url":"https://www.uniprot.org/uniprotkb/Q96S52/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PIGS","classification":"Not Classified","n_dependent_lines":206,"n_total_lines":1208,"dependency_fraction":0.17052980132450332},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CANX","stoichiometry":0.2},{"gene":"TMED10","stoichiometry":0.2},{"gene":"VAPA","stoichiometry":0.2},{"gene":"CCDC47","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/PIGS","total_profiled":1310},"omim":[{"mim_id":"620944","title":"ARRESTIN DOMAIN-CONTAINING PROTEIN 5; ARRDC5","url":"https://www.omim.org/entry/620944"},{"mim_id":"620468","title":"VERTEBRAE DEVELOPMENT-ASSOCIATED GENE; VRTN","url":"https://www.omim.org/entry/620468"},{"mim_id":"620118","title":"ZINC FINGER PROTEIN 490; ZNF490","url":"https://www.omim.org/entry/620118"},{"mim_id":"619030","title":"SKELETAL MUSCLE GLYCOGEN CONTENT AND METABOLISM QUANTITATIVE TRAIT LOCUS; SMGMQTL","url":"https://www.omim.org/entry/619030"},{"mim_id":"618143","title":"DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 95; DEE95","url":"https://www.omim.org/entry/618143"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PIGS"},"hgnc":{"alias_symbol":["PIG-S"],"prev_symbol":[]},"alphafold":{"accession":"Q96S52","domains":[{"cath_id":"-","chopping":"2-42_514-549","consensus_level":"medium","plddt":76.5416,"start":2,"end":549},{"cath_id":"-","chopping":"69-203","consensus_level":"medium","plddt":86.881,"start":69,"end":203},{"cath_id":"3.40.390","chopping":"227-398","consensus_level":"high","plddt":88.3905,"start":227,"end":398}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96S52","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96S52-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96S52-F1-predicted_aligned_error_v6.png","plddt_mean":85.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PIGS","jax_strain_url":"https://www.jax.org/strain/search?query=PIGS"},"sequence":{"accession":"Q96S52","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96S52.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96S52/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96S52"}},"corpus_meta":[{"pmid":"9055854","id":"PMC_9055854","title":"Infection 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Part A, DNA mapping, sequencing, and analysis","url":"https://pubmed.ncbi.nlm.nih.gov/24810064","citation_count":17,"is_preprint":false},{"pmid":"30055014","id":"PMC_30055014","title":"Assembling multiple xenoprotective transgenes in pigs.","date":"2018","source":"Xenotransplantation","url":"https://pubmed.ncbi.nlm.nih.gov/30055014","citation_count":16,"is_preprint":false},{"pmid":"37108597","id":"PMC_37108597","title":"Distinct Transcriptional Responses of Skeletal Muscle to Short-Term Cold Exposure in Tibetan Pigs and Bama Pigs.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37108597","citation_count":15,"is_preprint":false},{"pmid":"34679989","id":"PMC_34679989","title":"A Methodology to Quantify Resilience in Growing Pigs.","date":"2021","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/34679989","citation_count":15,"is_preprint":false},{"pmid":"31302235","id":"PMC_31302235","title":"Physical inactivity and knee osteoarthritis in guinea pigs.","date":"2019","source":"Osteoarthritis and cartilage","url":"https://pubmed.ncbi.nlm.nih.gov/31302235","citation_count":15,"is_preprint":false},{"pmid":"9602732","id":"PMC_9602732","title":"Developments in transgenic techniques in pigs.","date":"1997","source":"Journal of reproduction and fertility. Supplement","url":"https://pubmed.ncbi.nlm.nih.gov/9602732","citation_count":14,"is_preprint":false},{"pmid":"14657140","id":"PMC_14657140","title":"Corynebacterium suicordis sp. nov., from pigs.","date":"2003","source":"International journal of systematic and evolutionary microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/14657140","citation_count":14,"is_preprint":false},{"pmid":"30223793","id":"PMC_30223793","title":"Role of AMPK signalling pathway during compensatory growth in pigs.","date":"2018","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/30223793","citation_count":13,"is_preprint":false},{"pmid":"31928416","id":"PMC_31928416","title":"Transcriptomic comparison of liver tissue between Anqing six-end-white pigs and Yorkshire pigs based on RNA sequencing.","date":"2020","source":"Genome","url":"https://pubmed.ncbi.nlm.nih.gov/31928416","citation_count":13,"is_preprint":false},{"pmid":"32787931","id":"PMC_32787931","title":"Thymol modulates the endocannabinoid system and gut chemosensing of weaning pigs.","date":"2020","source":"BMC veterinary research","url":"https://pubmed.ncbi.nlm.nih.gov/32787931","citation_count":13,"is_preprint":false},{"pmid":"28130881","id":"PMC_28130881","title":"Transplantation of hepatocytes from genetically engineered pigs into baboons.","date":"2017","source":"Xenotransplantation","url":"https://pubmed.ncbi.nlm.nih.gov/28130881","citation_count":13,"is_preprint":false},{"pmid":"35739841","id":"PMC_35739841","title":"Change of Gut Microbiota in PRRSV-Resistant Pigs and PRRSV-Susceptible Pigs from Tongcheng Pigs and Large White Pigs Crossed Population upon PRRSV Infection.","date":"2022","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/35739841","citation_count":12,"is_preprint":false},{"pmid":"21741782","id":"PMC_21741782","title":"Microarray and cytokine analyses of field cases of pigs with diarrhoea.","date":"2011","source":"Veterinary microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/21741782","citation_count":12,"is_preprint":false},{"pmid":"6663631","id":"PMC_6663631","title":"Postnatal DNA-syntheses and mitoses in hearts of dwarf pigs.","date":"1983","source":"Journal of molecular and cellular cardiology","url":"https://pubmed.ncbi.nlm.nih.gov/6663631","citation_count":12,"is_preprint":false},{"pmid":"21134462","id":"PMC_21134462","title":"Structural insight into the glycosylphosphatidylinositol transamidase subunits PIG-K and PIG-S from yeast.","date":"2010","source":"Journal of structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/21134462","citation_count":12,"is_preprint":false},{"pmid":"24650890","id":"PMC_24650890","title":"Experimental teschovirus encephalomyelitis in gnotobiotic pigs.","date":"2013","source":"Journal of comparative pathology","url":"https://pubmed.ncbi.nlm.nih.gov/24650890","citation_count":12,"is_preprint":false},{"pmid":"28801552","id":"PMC_28801552","title":"Gene Location, Expression, and Function of FNDC5 in Meishan Pigs.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28801552","citation_count":11,"is_preprint":false},{"pmid":"22067442","id":"PMC_22067442","title":"Expression and imprinting analysis of the NESP55 gene in pigs.","date":"2011","source":"Gene expression patterns : GEP","url":"https://pubmed.ncbi.nlm.nih.gov/22067442","citation_count":11,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":47178,"output_tokens":881,"usd":0.077374,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7093,"output_tokens":1331,"usd":0.03437,"stage2_stop_reason":"end_turn"},"total_usd":0.111744,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about the human/mammalian gene PIGS (also known as PIG-S), which encodes a subunit of the GPI transamidase complex involved in glycosylphosphatidylinositol (GPI) anchor attachment to proteins.\n\nRelevant papers:\n- [7] PMID:11483512 - Directly about PIG-S and PIG-T as components of GPI transamidase\n- [97] PMID:21134462 - Structural study of yeast PIG-S (ortholog)\n\nAll other papers are about pigs (the animal, Sus scrofa) or guinea pigs, not the PIGS gene. These are symbol collisions.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"PIGS (PIG-S) is an essential subunit of the GPI transamidase complex in the endoplasmic reticulum. Homologous recombination knockout of PIGS in mouse F9 cells abolished transfer of GPI to proteins, specifically blocking formation of the carbonyl intermediates that are the hallmark of the transamidation reaction. PIGS forms a protein complex with GAA1, GPI8, and PIG-T, and the yeast ortholog is Gpi17p (YDR434W).\",\n      \"method\": \"Homologous recombination knockout in mouse F9 cells, GPI anchoring assay (carbonyl intermediate formation), co-immunoprecipitation of complex members\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal complex identification by co-IP, loss-of-function by gene knockout with specific biochemical readout (carbonyl intermediate formation), identification of yeast ortholog, multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"11483512\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The yeast ortholog of PIGS (yPIG-S, residues 38-467) adopts an elongated two-domain solution structure as determined by small-angle X-ray scattering (SAXS), with a larger domain (~10.1 nm length) and a smaller domain (~6.7 nm length) tilted relative to each other, and secondary structure comprising ~58% α-helix and ~18% β-sheet. This structural characterization places yPIG-S as an elongated subunit within the GPI transamidase complex.\",\n      \"method\": \"Small-angle X-ray scattering (SAXS), circular dichroism spectroscopy, recombinant protein production in E. coli\",\n      \"journal\": \"Journal of structural biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — low-resolution solution structure by SAXS with CD validation, single lab, yeast ortholog only, no mutagenesis or functional validation\",\n      \"pmids\": [\"21134462\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PIGS (PIG-S) is an essential non-catalytic subunit of the GPI transamidase complex in the endoplasmic reticulum, where it forms a stable complex with GAA1, GPI8, and PIG-T; loss of PIGS abolishes the carbonyl intermediate step of the transamidation reaction that transfers pre-assembled GPI anchors onto substrate proteins, and structural studies of the yeast ortholog indicate it is an elongated two-domain protein within this complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PIGS (PIG-S) is an essential non-catalytic subunit of the endoplasmic reticulum GPI transamidase complex that transfers pre-assembled glycosylphosphatidylinositol (GPI) anchors onto substrate proteins [#0]. PIGS assembles into a stable complex with GAA1, GPI8, and PIG-T, and its loss abolishes GPI transfer by specifically blocking formation of the carbonyl intermediates that are the biochemical hallmark of the transamidation reaction [#0]. Structural characterization of the yeast ortholog (Gpi17p) indicates an elongated two-domain architecture, consistent with PIGS serving as a structural component spanning the transamidase complex [#1]. Beyond its role as a complex subunit and the carbonyl-intermediate step, no further catalytic or regulatory mechanism for PIGS has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established that PIGS is an essential, dedicated subunit of the GPI transamidase machinery and pinpointed which step of the transamidation reaction it enables.\",\n      \"evidence\": \"Homologous recombination knockout in mouse F9 cells with a GPI anchoring/carbonyl-intermediate assay, plus co-immunoprecipitation of complex members and identification of the yeast ortholog Gpi17p\",\n      \"pmids\": [\"11483512\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether PIGS contributes any catalytic activity or is purely structural/scaffolding within the complex was not resolved\",\n        \"The molecular role of PIGS in forming or stabilizing the carbonyl intermediate (e.g. substrate or GPI positioning) was not defined\",\n        \"No structural basis for how PIGS contacts GAA1, GPI8, or PIG-T was determined\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Provided the first structural view of the PIGS subunit, showing it is an elongated two-domain protein rather than a compact globular subunit.\",\n      \"evidence\": \"Small-angle X-ray scattering and circular dichroism on recombinant yeast ortholog (residues 38-467) produced in E. coli\",\n      \"pmids\": [\"21134462\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Low-resolution solution envelope only; no atomic structure, no mutagenesis, and no functional validation\",\n        \"Performed on the yeast ortholog in isolation, not within the assembled transamidase complex or with the human protein\",\n        \"Does not assign which domain mediates complex assembly versus substrate handling\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise mechanistic contribution of PIGS to the transamidation chemistry and its contacts with the other transamidase subunits remain undefined.\",\n      \"evidence\": \"No further mechanistic studies present in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No high-resolution structure of human PIGS within the intact transamidase complex\",\n        \"No definition of substrate or GPI-binding determinants on PIGS\",\n        \"No link to disease established within this corpus\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"GPI transamidase complex\"],\n    \"partners\": [\"GAA1\", \"GPI8\", \"PIGT\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}