{"gene":"GOLGA7","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2005,"finding":"GOLGA7 (GCP16) forms a protein complex with DHHC9 (ZDHHC9) that constitutes a human protein palmitoyltransferase (PAT) with specificity for H-Ras and N-Ras. DHHC9 requires GCP16 for PAT activity and protein stability. The complex co-distributes in the Golgi apparatus, consistent with the site of Ras palmitoylation in vivo. Purified DHHC9·GCP16 palmitoylates H- and N-Ras but not myristoylated proteins (Gαi1 or GAP-43).","method":"Purified enzyme reconstitution, in vitro palmitoylation assay, co-immunoprecipitation, subcellular fractionation/immunofluorescence","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — purified enzyme reconstitution with substrate specificity assay, co-IP, and localization; replicated by multiple subsequent studies","pmids":["16000296"],"is_preprint":false},{"year":2003,"finding":"GCP16 (GOLGA7) is a Golgi-localized membrane protein that interacts with GCP170 (identified by yeast two-hybrid). GCP16 is palmitoylated at Cys69 and Cys72, which is required for its Golgi membrane association and localization. A C69A/C72A mutant fails to localize to the Golgi. Overexpression of wild-type GCP16 inhibits protein transport from the Golgi to the cell surface.","method":"Yeast two-hybrid, [3H]palmitate labeling, site-directed mutagenesis, immunofluorescence microscopy, protein transport assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — metabolic labeling + mutagenesis + functional transport assay in a single study; foundational characterization paper","pmids":["14522980"],"is_preprint":false},{"year":2008,"finding":"The purified DHHC9/GCP16 complex is inhibited in vitro by 2-bromopalmitate (irreversibly) and Compound V (reversibly); both compounds block DHHC enzyme autoacylation. The palmitoylation inhibitors identified in cell-based assays do not show the selectivity predicted by those assays when tested on purified DHHC9/GCP16 with farnesylated Ras substrates.","method":"In vitro palmitoyltransferase assay with purified DHHC9/GCP16, inhibitor profiling","journal":"Journal of lipid research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — purified enzyme assay with mechanistic inhibitor characterization; single lab but multiple orthogonal assays","pmids":["18827284"],"is_preprint":false},{"year":2012,"finding":"Using the yeast ortholog Erf4 (functional equivalent of GCP16/GOLGA7), Erf4 regulates Erf2 stability via an ubiquitin-mediated pathway and is required for stable formation of the palmitoyl-Erf2 thioester intermediate (the first catalytic step). In absence of Erf4, the rate of hydrolysis of the active-site palmitoyl thioester intermediate is increased, resulting in reduced palmitoyl transfer to Ras2 substrate.","method":"Yeast genetics, in vitro palmitoylation assay, ubiquitin pathway analysis, biochemical characterization of reaction intermediates","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — mechanistic dissection of reaction intermediate stability with functional assays; yeast ortholog directly informs GCP16/GOLGA7 function","pmids":["22904317"],"is_preprint":false},{"year":2019,"finding":"GOLGA7 forms a protein complex with ZDHHC5 (distinct from the DHHC9 complex) that localizes to the plasma membrane. The ZDHHC5-GOLGA7 complex is mutually stabilizing. A catalytically active ZDHHC5-GOLGA7 complex is required for CIL56-induced nonapoptotic cell death. GOLGA7 depletion abolishes this cell death pathway.","method":"CRISPR knockout, co-immunoprecipitation, subcellular localization (immunofluorescence), functional cell death assays","journal":"Cell chemical biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP, CRISPR KO with defined phenotypic readout, localization; single lab with multiple orthogonal approaches","pmids":["31631010"],"is_preprint":false},{"year":2020,"finding":"GCP16 (GOLGA7) is an accessory protein that regulates the activity, stability, and trafficking of certain DHHC enzymes. It is described as an essential component of the S-acylation system together with GOLGA7B, huntingtin, and selenoprotein K.","method":"Review synthesizing prior experimental findings from purified-component studies","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 3 / Strong — review article summarizing established findings; no new primary experiments but synthesizes replicated results","pmids":["33203738"],"is_preprint":false},{"year":2023,"finding":"GCP16 (GOLGA7) stabilizes DHHC9 by preventing its aggregation through complex formation. Only properly folded DHHC9-GCP16 complex is enzymatically active in vitro. A conserved C-terminal cysteine motif (CCM) present in the DHHC9 subfamily (DHHC5, -8, -14, -18) is required for GCP16 interaction and DHHC9 activity. ZDHHC9 mutations linked to X-linked intellectual disability reduce protein stability and DHHC9-GCP16 complex formation. DHHC14 and DHHC18 also require GCP16 for enzymatic activity. GOLGA7B (75% identity to GCP16) stabilizes DHHC5 and DHHC8 but not other DHHC9 subfamily members.","method":"Size-exclusion chromatography, in vitro palmitoyl acyltransferase assay, site-directed mutagenesis, co-expression stability assays","journal":"Frontiers in physiology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstitution + mutagenesis + enzymatic assay; multiple DHHC paralogs tested; single lab but multiple orthogonal methods","pmids":["37035671"],"is_preprint":false},{"year":2024,"finding":"Cryo-EM structures of the human DHHC9-GCP16 complex and yeast Erf2-Erf4 complex show that GCP16 and Erf4 are not directly involved in catalysis but stabilize the architecture of DHHC9 and Erf2, respectively. Phospholipid binding to an arginine-rich region of DHHC9 and palmitoylation on DHHC9 residues C24, C25, and C288 are essential for catalytic activity. GCP16 also forms complexes with DHHC14 and DHHC18 to catalyze RAS palmitoylation.","method":"Cryo-electron microscopy structure determination, site-directed mutagenesis, in vitro palmitoylation assay, co-immunoprecipitation","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure combined with mutagenesis and functional assays; rigorous mechanistic study in single publication","pmids":["38182928"],"is_preprint":false},{"year":2024,"finding":"GOLGA7 depletion blocks NRAS (but not HRAS, KRAS4A, KRAS4B) translocation from the Golgi to the plasma membrane. Importantly, GOLGA7 depletion does not affect NRAS palmitoylation levels. Loss of GOLGA7 causes NRAS accumulation at the cis-Golgi. GOLGA7 depletion inhibits proliferation in NRAS-mutant cancer cell lines and attenuates NRAS(G12D)-induced oncogenic transformation in vivo.","method":"siRNA/shRNA knockdown, CRISPR knockout, fluorescence microscopy (subcellular localization), palmitoylation assay, in vivo mouse transformation assay","journal":"Cell communication and signaling : CCS","confidence":"High","confidence_rationale":"Tier 2 / Moderate — KO with defined trafficking phenotype, palmitoylation assay, in vivo functional readout; multiple orthogonal methods in single study","pmids":["38317235"],"is_preprint":false},{"year":2021,"finding":"GOLGA7 interacts with SARS-CoV-2 spike protein (confirmed by co-IP). ZDHHC5 or GOLGA7 knockout significantly decreases SARS-CoV-2 pseudovirus entry into A549 and HeLa cells, but neither ZDHHC5 nor GOLGA7 knockout significantly affects spike protein subcellular localization or palmitoylation. Spike protein interaction with ZDHHC5 is independent of ZDHHC5 enzymatic activity.","method":"Co-immunoprecipitation, CRISPR-Cas9 knockout, fluorescence microscopy, acyl-biotin exchange (ABE) palmitoylation assay, pseudovirus entry luciferase assay","journal":"Virology journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR KO with functional readout and co-IP confirmation; single lab, multiple methods","pmids":["34961524"],"is_preprint":false},{"year":2025,"finding":"Conditional knockout of Golga7 in mice drastically suppresses NRAS(G12D)-driven myeloid leukemia development. Loss of Golga7 disrupts NRAS(G12D) plasma membrane localization in bone marrow cells without altering NRAS palmitoylation levels. Golga7 is dispensable for normal adult hematopoiesis; ubiquitous Golga7 knockout in adult mice shows no detectable toxicity, though constitutive knockout causes embryonic lethality.","method":"Conditional CRISPR/Cre-mediated knockout mouse model, flow cytometry, plasma membrane localization assay, palmitoylation assay, leukemia mouse model","journal":"Advanced science","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional in vivo genetic model with defined cellular and disease phenotype, palmitoylation and localization assays; strong mechanistic dissection","pmids":["40091521"],"is_preprint":false},{"year":2025,"finding":"Cryo-EM structure of the ZDHHC5-GOLGA7 complex was determined. Key conserved residues in both ZDHHC5 and GOLGA7 required for complex formation were identified by mutagenesis. These residues are also necessary for promoting nonapoptotic cancer cell death in response to CIL56.","method":"Cryo-electron microscopy, co-immunoprecipitation, mutagenesis, functional cell death assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — cryo-EM structure with mutagenesis and functional validation; single lab but multiple rigorous orthogonal methods","pmids":["40930250"],"is_preprint":false},{"year":2026,"finding":"The ZDHHC9-GCP16 (GOLGA7) complex was used in a cell-based high-throughput screen; six small-molecule compounds that inhibit the ZDHHC9-GCP16 complex were identified with IC50 values ranging from 1.4 to 8.0 μM, demonstrating the complex is druggable.","method":"Cell-based high-throughput palmitoylation assay using APT1 fusion strategy, dose-response inhibitor profiling","journal":"Cell chemical biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional inhibitor screen with IC50 determination; single lab, single method type","pmids":["41850277"],"is_preprint":false},{"year":2025,"finding":"GOLGA7 was identified as a host factor essential for chikungunya virus (CHIKV) replication in a genome-wide CRISPR knockout screen using viral replicons, and was confirmed as required for live CHIKV replication in independent assays.","method":"Genome-wide CRISPR KO screen (replicon-based FACS), live virus replication confirmation assay","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genome-wide screen with orthogonal live virus confirmation; single study, preprint, limited mechanistic detail for GOLGA7 specifically","pmids":[],"is_preprint":true}],"current_model":"GOLGA7 (GCP16) is an accessory/scaffolding subunit that forms stable complexes with multiple DHHC S-acyltransferases—most notably DHHC9 (for H-Ras/N-Ras palmitoylation at the Golgi) and ZDHHC5 (at the plasma membrane)—where it stabilizes DHHC protein architecture and promotes formation of the catalytic palmitoyl-enzyme thioester intermediate without directly participating in catalysis; additionally, GOLGA7 controls anterograde trafficking of NRAS from the Golgi to the plasma membrane independently of palmitoylation, making it an essential regulator of NRAS oncogenic signaling."},"narrative":{"mechanistic_narrative":"GOLGA7 (GCP16) is a palmitoylated accessory subunit that partners with DHHC-family protein S-acyltransferases to control the palmitoylation and trafficking of Ras GTPases and other substrates [PMID:16000296, PMID:14522980]. As a Golgi-localized membrane protein, GOLGA7 is itself palmitoylated at Cys69 and Cys72, a modification required for its Golgi membrane association, and its overexpression impedes Golgi-to-surface transport [PMID:14522980]. It forms a stable, enzymatically active complex with DHHC9 (ZDHHC9) that constitutes an H-Ras/N-Ras palmitoyltransferase, with GOLGA7 required both for DHHC9 protein stability and for catalytic activity [PMID:16000296]. Mechanistically GOLGA7 does not participate directly in catalysis; cryo-EM of the DHHC9-GCP16 and yeast Erf2-Erf4 complexes shows that it stabilizes the architecture of the DHHC enzyme [PMID:38182928], preventing DHHC9 aggregation through a conserved C-terminal cysteine motif of the DHHC9 subfamily [PMID:37035671], and stabilizing the catalytic palmitoyl-enzyme thioester intermediate by slowing its hydrolysis [PMID:22904317]. Beyond DHHC9, GOLGA7 also stabilizes and activates DHHC14 and DHHC18 [PMID:37035671, PMID:38182928] and assembles a distinct, mutually stabilizing plasma-membrane complex with ZDHHC5 that drives CIL56-induced nonapoptotic cell death [PMID:31631010, PMID:40930250]. Independently of its palmitoyltransferase role, GOLGA7 is required for anterograde trafficking of NRAS from the cis-Golgi to the plasma membrane without affecting NRAS palmitoylation levels, and its loss selectively impairs NRAS-mutant cancer proliferation and NRAS(G12D)-driven oncogenic transformation and myeloid leukemia in vivo while sparing normal adult hematopoiesis [PMID:38317235, PMID:40091521]. GOLGA7 is also exploited as a host factor by SARS-CoV-2 and chikungunya virus entry/replication [PMID:34961524].","teleology":[{"year":2003,"claim":"Established GOLGA7/GCP16 as a Golgi membrane protein whose own palmitoylation governs its localization and whose presence influences secretory transport, defining its baseline cell biology before any enzymatic role was known.","evidence":"Yeast two-hybrid with GCP170, [3H]palmitate labeling, C69A/C72A mutagenesis, immunofluorescence and transport assay","pmids":["14522980"],"confidence":"High","gaps":["Did not connect GCP16 to any DHHC enzyme or palmitoyltransferase activity","Mechanism of the Golgi transport inhibition unresolved"]},{"year":2005,"claim":"Showed that GCP16 is an obligate partner of DHHC9, together forming the H-Ras/N-Ras palmitoyltransferase, answering how Ras becomes palmitoylated at the Golgi.","evidence":"Purified enzyme reconstitution with substrate-specificity assay, co-IP, subcellular fractionation/IF","pmids":["16000296"],"confidence":"High","gaps":["Whether GCP16 contributes to catalysis or only to stability was not resolved","Structural basis of the interaction unknown"]},{"year":2008,"claim":"Characterized the purified DHHC9/GCP16 enzyme pharmacologically, establishing that inhibitors act at the DHHC autoacylation step and exposing discrepancies between cell-based and purified-enzyme inhibitor selectivity.","evidence":"In vitro palmitoyltransferase assay with purified complex and inhibitor profiling (2-bromopalmitate, Compound V)","pmids":["18827284"],"confidence":"High","gaps":["No GCP16-specific binding site for inhibitors defined","Cell-based selectivity discrepancy left mechanistically unexplained"]},{"year":2012,"claim":"Defined the catalytic contribution of the accessory subunit: via the yeast ortholog Erf4, showed it stabilizes the palmitoyl-enzyme thioester intermediate and protects the enzyme through a ubiquitin-mediated stability pathway.","evidence":"Yeast genetics, in vitro palmitoylation assay, reaction-intermediate kinetics, ubiquitin pathway analysis","pmids":["22904317"],"confidence":"High","gaps":["Extrapolated from yeast Erf4 rather than human GCP16 directly","Identity of the ubiquitin ligase not established"]},{"year":2019,"claim":"Revealed a second, distinct GOLGA7 complex with ZDHHC5 at the plasma membrane that is required for CIL56-induced nonapoptotic cell death, broadening GOLGA7 beyond the Golgi DHHC9 axis.","evidence":"CRISPR KO, reciprocal co-IP, immunofluorescence, cell-death assays","pmids":["31631010"],"confidence":"High","gaps":["Substrate(s) of the ZDHHC5-GOLGA7 complex driving cell death not identified","Mechanism linking palmitoylation to nonapoptotic death unresolved"]},{"year":2020,"claim":"Synthesized prior work to position GCP16 as a general accessory regulator of DHHC enzyme activity, stability, and trafficking within the broader S-acylation system.","evidence":"Review synthesizing purified-component and cellular studies","pmids":["33203738"],"confidence":"Medium","gaps":["No new primary data","Scope of GOLGA7-dependent DHHC enzymes not yet experimentally bounded"]},{"year":2023,"claim":"Established the structural/biochemical basis of GCP16 selectivity, showing it stabilizes DHHC9 by preventing aggregation via a conserved C-terminal cysteine motif and extends activation to DHHC14 and DHHC18, while disease mutations in ZDHHC9 weaken complex formation.","evidence":"Size-exclusion chromatography, in vitro PAT assay, mutagenesis, co-expression stability assays","pmids":["37035671"],"confidence":"High","gaps":["Did not provide atomic structure of the interface","GOLGA7B vs GOLGA7 paralog selectivity rules incompletely mapped"]},{"year":2024,"claim":"Cryo-EM structures of human DHHC9-GCP16 and yeast Erf2-Erf4 resolved that the accessory subunit is non-catalytic and acts purely as an architectural stabilizer, while defining DHHC9 lipid binding and autopalmitoylation requirements.","evidence":"Cryo-EM structure determination, mutagenesis, in vitro palmitoylation assay, co-IP","pmids":["38182928"],"confidence":"High","gaps":["Conformational dynamics during the catalytic cycle not captured","Structural basis for substrate (Ras) recognition not resolved"]},{"year":2024,"claim":"Uncovered a palmitoylation-independent function: GOLGA7 is specifically required for NRAS anterograde transport from cis-Golgi to plasma membrane and for NRAS-mutant oncogenic phenotypes, separating its trafficking role from its enzyme-accessory role.","evidence":"siRNA/shRNA/CRISPR knockdown and KO, fluorescence localization, palmitoylation assay, in vivo mouse transformation","pmids":["38317235"],"confidence":"High","gaps":["Molecular machinery linking GOLGA7 to NRAS-selective vesicular transport unknown","Why HRAS/KRAS are unaffected not explained"]},{"year":2025,"claim":"Validated GOLGA7 as a therapeutic target in vivo: conditional knockout suppresses NRAS(G12D)-driven myeloid leukemia by disrupting NRAS plasma-membrane localization without affecting palmitoylation, while being dispensable for normal adult hematopoiesis.","evidence":"Conditional Cre-mediated knockout mouse leukemia model, flow cytometry, localization and palmitoylation assays","pmids":["40091521"],"confidence":"High","gaps":["Embryonic lethality of constitutive knockout indicates essential roles not defined here","Whether the trafficking defect is direct or secondary remains open"]},{"year":2025,"claim":"Resolved the ZDHHC5-GOLGA7 complex by cryo-EM and pinpointed interface residues required for both assembly and CIL56-induced cancer cell death, structurally completing the second GOLGA7 complex.","evidence":"Cryo-EM, co-IP, mutagenesis, functional cell-death assay","pmids":["40930250"],"confidence":"High","gaps":["Substrate engaged by the complex during cell death not defined","Generalizability of interface residues to other DHHC-GOLGA7 pairs untested"]},{"year":2026,"claim":"Demonstrated the ZDHHC9-GCP16 complex is druggable, identifying six small-molecule inhibitors with low-micromolar potency in a cell-based assay.","evidence":"Cell-based high-throughput palmitoylation assay (APT1 fusion), dose-response IC50 determination","pmids":["41850277"],"confidence":"Medium","gaps":["Binding sites and selectivity of compounds not defined","Whether compounds act on GCP16, DHHC9, or the interface unknown"]},{"year":2025,"claim":"Implicated GOLGA7 as a host dependency factor for viral infection, expanding its functional reach beyond Ras biology.","evidence":"Genome-wide CRISPR KO replicon screen with live chikungunya virus confirmation (preprint)","pmids":[],"confidence":"Medium","gaps":["Mechanism of GOLGA7 requirement in CHIKV replication unknown","Preprint, not yet peer-reviewed"]},{"year":null,"claim":"The molecular basis by which GOLGA7 selectively chaperones NRAS Golgi-to-membrane transport independently of palmitoylation, and how this connects to its DHHC-accessory function, remains unresolved.","evidence":"No direct experimental evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No identified trafficking machinery or adaptor linking GOLGA7 to NRAS vesicles","Cause of constitutive-knockout embryonic lethality uncharacterized","Substrates of ZDHHC5-GOLGA7 in cell death not identified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,6,7]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,3,6,7]},{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[6,7]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,1,8]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[4,11]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,6,7]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[8,10]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[8,10]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[4,11]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[8,9,10]}],"complexes":["DHHC9-GCP16 (ZDHHC9-GOLGA7) palmitoyltransferase","ZDHHC5-GOLGA7 complex","DHHC14-GCP16 complex","DHHC18-GCP16 complex"],"partners":["ZDHHC9","ZDHHC5","ZDHHC14","ZDHHC18","GCP170","NRAS"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q7Z5G4","full_name":"Golgin subfamily A member 7","aliases":["Golgi complex-associated protein of 16 kDa"],"length_aa":137,"mass_kda":15.8,"function":"May be involved in protein transport from Golgi to cell surface. The ZDHHC9-GOLGA7 complex is a palmitoyltransferase specific for HRAS and NRAS","subcellular_location":"Golgi apparatus membrane","url":"https://www.uniprot.org/uniprotkb/Q7Z5G4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GOLGA7","classification":"Not Classified","n_dependent_lines":35,"n_total_lines":1208,"dependency_fraction":0.028973509933774833},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000147533","cell_line_id":"CID000870","localizations":[{"compartment":"membrane","grade":3},{"compartment":"vesicles","grade":3}],"interactors":[{"gene":"CLDND1","stoichiometry":0.2},{"gene":"ZDHHC5","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000870","total_profiled":1310},"omim":[{"mim_id":"620963","title":"ZDHHC PALMITOYLTRANSFERASE 18; ZDHHC18","url":"https://www.omim.org/entry/620963"},{"mim_id":"614189","title":"GOLGIN A7 FAMILY, MEMBER B; GOLGA7B","url":"https://www.omim.org/entry/614189"},{"mim_id":"609453","title":"GOLGIN A7; GOLGA7","url":"https://www.omim.org/entry/609453"},{"mim_id":"300646","title":"ZDHHC PALMITOYLTRANSFERASE 9; ZDHHC9","url":"https://www.omim.org/entry/300646"}],"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/GOLGA7"},"hgnc":{"alias_symbol":["GCP16","HSPC041","GOLGA3AP1","GOLGA7A"],"prev_symbol":[]},"alphafold":{"accession":"Q7Z5G4","domains":[{"cath_id":"-","chopping":"7-59_85-127","consensus_level":"high","plddt":96.0932,"start":7,"end":127}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z5G4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z5G4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z5G4-F1-predicted_aligned_error_v6.png","plddt_mean":88.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GOLGA7","jax_strain_url":"https://www.jax.org/strain/search?query=GOLGA7"},"sequence":{"accession":"Q7Z5G4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7Z5G4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7Z5G4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z5G4"}},"corpus_meta":[{"pmid":"16000296","id":"PMC_16000296","title":"DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16000296","citation_count":290,"is_preprint":false},{"pmid":"18827284","id":"PMC_18827284","title":"2-Bromopalmitate and 2-(2-hydroxy-5-nitro-benzylidene)-benzo[b]thiophen-3-one inhibit DHHC-mediated palmitoylation in vitro.","date":"2008","source":"Journal of lipid research","url":"https://pubmed.ncbi.nlm.nih.gov/18827284","citation_count":179,"is_preprint":false},{"pmid":"31631010","id":"PMC_31631010","title":"A ZDHHC5-GOLGA7 Protein Acyltransferase Complex Promotes Nonapoptotic Cell Death.","date":"2019","source":"Cell chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/31631010","citation_count":55,"is_preprint":false},{"pmid":"14522980","id":"PMC_14522980","title":"Identification and characterization of GCP16, a novel acylated Golgi protein that interacts with GCP170.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/14522980","citation_count":46,"is_preprint":false},{"pmid":"23885124","id":"PMC_23885124","title":"Fission yeast MOZART1/Mzt1 is an essential γ-tubulin complex component required for complex recruitment to the microtubule organizing center, but not its assembly.","date":"2013","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/23885124","citation_count":41,"is_preprint":false},{"pmid":"22904317","id":"PMC_22904317","title":"The Erf4 subunit of the yeast Ras palmitoyl acyltransferase is required for stability of the Acyl-Erf2 intermediate and palmitoyl transfer to a Ras2 substrate.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22904317","citation_count":40,"is_preprint":false},{"pmid":"33203738","id":"PMC_33203738","title":"Accessory proteins of the zDHHC family of S-acylation 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and intellectual disability.","date":"2016","source":"Taiwanese journal of obstetrics & gynecology","url":"https://pubmed.ncbi.nlm.nih.gov/28040133","citation_count":5,"is_preprint":false},{"pmid":"30895958","id":"PMC_30895958","title":"[Splicing Pattern of mRNA in Thymus Epithelial Cells Limitsthe Transcriptome Available for Negative Selection of Autoreactive T Cells].","date":"2019","source":"Molekuliarnaia biologiia","url":"https://pubmed.ncbi.nlm.nih.gov/30895958","citation_count":4,"is_preprint":false},{"pmid":"40091521","id":"PMC_40091521","title":"Loss of Golga7 Suppresses Oncogenic Nras-Driven Leukemogenesis without Detectable Toxicity in Adult Mice.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/40091521","citation_count":2,"is_preprint":false},{"pmid":"40930250","id":"PMC_40930250","title":"Functional dissection of the zDHHC palmitoyltransferase 5-golgin A7 palmitoylation complex.","date":"2025","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/40930250","citation_count":2,"is_preprint":false},{"pmid":"39121087","id":"PMC_39121087","title":"RNAseq analysis of oocyte maturation from the germinal vesicle stage to metaphase II in pig and human.","date":"2024","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/39121087","citation_count":1,"is_preprint":false},{"pmid":"41850277","id":"PMC_41850277","title":"Control of the signaling of RAS proteins by modulating their palmitoylation.","date":"2026","source":"Cell chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/41850277","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.04.28.651057","title":"Functional Dissection of the Zdhhc5-GOLGA7 Protein Palmitoylation Complex","date":"2025-04-29","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.28.651057","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.09.632058","title":"Genome-wide CRISPR knockout screening with viral replicons for identification of host factors involved in viral replication","date":"2025-01-11","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.09.632058","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16615,"output_tokens":3861,"usd":0.05388,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11493,"output_tokens":4651,"usd":0.08687,"stage2_stop_reason":"end_turn"},"total_usd":0.14075,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"GOLGA7 (GCP16) forms a protein complex with DHHC9 (ZDHHC9) that constitutes a human protein palmitoyltransferase (PAT) with specificity for H-Ras and N-Ras. DHHC9 requires GCP16 for PAT activity and protein stability. The complex co-distributes in the Golgi apparatus, consistent with the site of Ras palmitoylation in vivo. Purified DHHC9·GCP16 palmitoylates H- and N-Ras but not myristoylated proteins (Gαi1 or GAP-43).\",\n      \"method\": \"Purified enzyme reconstitution, in vitro palmitoylation assay, co-immunoprecipitation, subcellular fractionation/immunofluorescence\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — purified enzyme reconstitution with substrate specificity assay, co-IP, and localization; replicated by multiple subsequent studies\",\n      \"pmids\": [\"16000296\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"GCP16 (GOLGA7) is a Golgi-localized membrane protein that interacts with GCP170 (identified by yeast two-hybrid). GCP16 is palmitoylated at Cys69 and Cys72, which is required for its Golgi membrane association and localization. A C69A/C72A mutant fails to localize to the Golgi. Overexpression of wild-type GCP16 inhibits protein transport from the Golgi to the cell surface.\",\n      \"method\": \"Yeast two-hybrid, [3H]palmitate labeling, site-directed mutagenesis, immunofluorescence microscopy, protein transport assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — metabolic labeling + mutagenesis + functional transport assay in a single study; foundational characterization paper\",\n      \"pmids\": [\"14522980\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"The purified DHHC9/GCP16 complex is inhibited in vitro by 2-bromopalmitate (irreversibly) and Compound V (reversibly); both compounds block DHHC enzyme autoacylation. The palmitoylation inhibitors identified in cell-based assays do not show the selectivity predicted by those assays when tested on purified DHHC9/GCP16 with farnesylated Ras substrates.\",\n      \"method\": \"In vitro palmitoyltransferase assay with purified DHHC9/GCP16, inhibitor profiling\",\n      \"journal\": \"Journal of lipid research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — purified enzyme assay with mechanistic inhibitor characterization; single lab but multiple orthogonal assays\",\n      \"pmids\": [\"18827284\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Using the yeast ortholog Erf4 (functional equivalent of GCP16/GOLGA7), Erf4 regulates Erf2 stability via an ubiquitin-mediated pathway and is required for stable formation of the palmitoyl-Erf2 thioester intermediate (the first catalytic step). In absence of Erf4, the rate of hydrolysis of the active-site palmitoyl thioester intermediate is increased, resulting in reduced palmitoyl transfer to Ras2 substrate.\",\n      \"method\": \"Yeast genetics, in vitro palmitoylation assay, ubiquitin pathway analysis, biochemical characterization of reaction intermediates\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — mechanistic dissection of reaction intermediate stability with functional assays; yeast ortholog directly informs GCP16/GOLGA7 function\",\n      \"pmids\": [\"22904317\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"GOLGA7 forms a protein complex with ZDHHC5 (distinct from the DHHC9 complex) that localizes to the plasma membrane. The ZDHHC5-GOLGA7 complex is mutually stabilizing. A catalytically active ZDHHC5-GOLGA7 complex is required for CIL56-induced nonapoptotic cell death. GOLGA7 depletion abolishes this cell death pathway.\",\n      \"method\": \"CRISPR knockout, co-immunoprecipitation, subcellular localization (immunofluorescence), functional cell death assays\",\n      \"journal\": \"Cell chemical biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP, CRISPR KO with defined phenotypic readout, localization; single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"31631010\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"GCP16 (GOLGA7) is an accessory protein that regulates the activity, stability, and trafficking of certain DHHC enzymes. It is described as an essential component of the S-acylation system together with GOLGA7B, huntingtin, and selenoprotein K.\",\n      \"method\": \"Review synthesizing prior experimental findings from purified-component studies\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Strong — review article summarizing established findings; no new primary experiments but synthesizes replicated results\",\n      \"pmids\": [\"33203738\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"GCP16 (GOLGA7) stabilizes DHHC9 by preventing its aggregation through complex formation. Only properly folded DHHC9-GCP16 complex is enzymatically active in vitro. A conserved C-terminal cysteine motif (CCM) present in the DHHC9 subfamily (DHHC5, -8, -14, -18) is required for GCP16 interaction and DHHC9 activity. ZDHHC9 mutations linked to X-linked intellectual disability reduce protein stability and DHHC9-GCP16 complex formation. DHHC14 and DHHC18 also require GCP16 for enzymatic activity. GOLGA7B (75% identity to GCP16) stabilizes DHHC5 and DHHC8 but not other DHHC9 subfamily members.\",\n      \"method\": \"Size-exclusion chromatography, in vitro palmitoyl acyltransferase assay, site-directed mutagenesis, co-expression stability assays\",\n      \"journal\": \"Frontiers in physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstitution + mutagenesis + enzymatic assay; multiple DHHC paralogs tested; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"37035671\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Cryo-EM structures of the human DHHC9-GCP16 complex and yeast Erf2-Erf4 complex show that GCP16 and Erf4 are not directly involved in catalysis but stabilize the architecture of DHHC9 and Erf2, respectively. Phospholipid binding to an arginine-rich region of DHHC9 and palmitoylation on DHHC9 residues C24, C25, and C288 are essential for catalytic activity. GCP16 also forms complexes with DHHC14 and DHHC18 to catalyze RAS palmitoylation.\",\n      \"method\": \"Cryo-electron microscopy structure determination, site-directed mutagenesis, in vitro palmitoylation assay, co-immunoprecipitation\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure combined with mutagenesis and functional assays; rigorous mechanistic study in single publication\",\n      \"pmids\": [\"38182928\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"GOLGA7 depletion blocks NRAS (but not HRAS, KRAS4A, KRAS4B) translocation from the Golgi to the plasma membrane. Importantly, GOLGA7 depletion does not affect NRAS palmitoylation levels. Loss of GOLGA7 causes NRAS accumulation at the cis-Golgi. GOLGA7 depletion inhibits proliferation in NRAS-mutant cancer cell lines and attenuates NRAS(G12D)-induced oncogenic transformation in vivo.\",\n      \"method\": \"siRNA/shRNA knockdown, CRISPR knockout, fluorescence microscopy (subcellular localization), palmitoylation assay, in vivo mouse transformation assay\",\n      \"journal\": \"Cell communication and signaling : CCS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO with defined trafficking phenotype, palmitoylation assay, in vivo functional readout; multiple orthogonal methods in single study\",\n      \"pmids\": [\"38317235\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"GOLGA7 interacts with SARS-CoV-2 spike protein (confirmed by co-IP). ZDHHC5 or GOLGA7 knockout significantly decreases SARS-CoV-2 pseudovirus entry into A549 and HeLa cells, but neither ZDHHC5 nor GOLGA7 knockout significantly affects spike protein subcellular localization or palmitoylation. Spike protein interaction with ZDHHC5 is independent of ZDHHC5 enzymatic activity.\",\n      \"method\": \"Co-immunoprecipitation, CRISPR-Cas9 knockout, fluorescence microscopy, acyl-biotin exchange (ABE) palmitoylation assay, pseudovirus entry luciferase assay\",\n      \"journal\": \"Virology journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR KO with functional readout and co-IP confirmation; single lab, multiple methods\",\n      \"pmids\": [\"34961524\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Conditional knockout of Golga7 in mice drastically suppresses NRAS(G12D)-driven myeloid leukemia development. Loss of Golga7 disrupts NRAS(G12D) plasma membrane localization in bone marrow cells without altering NRAS palmitoylation levels. Golga7 is dispensable for normal adult hematopoiesis; ubiquitous Golga7 knockout in adult mice shows no detectable toxicity, though constitutive knockout causes embryonic lethality.\",\n      \"method\": \"Conditional CRISPR/Cre-mediated knockout mouse model, flow cytometry, plasma membrane localization assay, palmitoylation assay, leukemia mouse model\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional in vivo genetic model with defined cellular and disease phenotype, palmitoylation and localization assays; strong mechanistic dissection\",\n      \"pmids\": [\"40091521\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cryo-EM structure of the ZDHHC5-GOLGA7 complex was determined. Key conserved residues in both ZDHHC5 and GOLGA7 required for complex formation were identified by mutagenesis. These residues are also necessary for promoting nonapoptotic cancer cell death in response to CIL56.\",\n      \"method\": \"Cryo-electron microscopy, co-immunoprecipitation, mutagenesis, functional cell death assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cryo-EM structure with mutagenesis and functional validation; single lab but multiple rigorous orthogonal methods\",\n      \"pmids\": [\"40930250\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"The ZDHHC9-GCP16 (GOLGA7) complex was used in a cell-based high-throughput screen; six small-molecule compounds that inhibit the ZDHHC9-GCP16 complex were identified with IC50 values ranging from 1.4 to 8.0 μM, demonstrating the complex is druggable.\",\n      \"method\": \"Cell-based high-throughput palmitoylation assay using APT1 fusion strategy, dose-response inhibitor profiling\",\n      \"journal\": \"Cell chemical biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional inhibitor screen with IC50 determination; single lab, single method type\",\n      \"pmids\": [\"41850277\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GOLGA7 was identified as a host factor essential for chikungunya virus (CHIKV) replication in a genome-wide CRISPR knockout screen using viral replicons, and was confirmed as required for live CHIKV replication in independent assays.\",\n      \"method\": \"Genome-wide CRISPR KO screen (replicon-based FACS), live virus replication confirmation assay\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genome-wide screen with orthogonal live virus confirmation; single study, preprint, limited mechanistic detail for GOLGA7 specifically\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"GOLGA7 (GCP16) is an accessory/scaffolding subunit that forms stable complexes with multiple DHHC S-acyltransferases—most notably DHHC9 (for H-Ras/N-Ras palmitoylation at the Golgi) and ZDHHC5 (at the plasma membrane)—where it stabilizes DHHC protein architecture and promotes formation of the catalytic palmitoyl-enzyme thioester intermediate without directly participating in catalysis; additionally, GOLGA7 controls anterograde trafficking of NRAS from the Golgi to the plasma membrane independently of palmitoylation, making it an essential regulator of NRAS oncogenic signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GOLGA7 (GCP16) is a palmitoylated accessory subunit that partners with DHHC-family protein S-acyltransferases to control the palmitoylation and trafficking of Ras GTPases and other substrates [#0, #1]. As a Golgi-localized membrane protein, GOLGA7 is itself palmitoylated at Cys69 and Cys72, a modification required for its Golgi membrane association, and its overexpression impedes Golgi-to-surface transport [#1]. It forms a stable, enzymatically active complex with DHHC9 (ZDHHC9) that constitutes an H-Ras/N-Ras palmitoyltransferase, with GOLGA7 required both for DHHC9 protein stability and for catalytic activity [#0]. Mechanistically GOLGA7 does not participate directly in catalysis; cryo-EM of the DHHC9-GCP16 and yeast Erf2-Erf4 complexes shows that it stabilizes the architecture of the DHHC enzyme [#7], preventing DHHC9 aggregation through a conserved C-terminal cysteine motif of the DHHC9 subfamily [#6], and stabilizing the catalytic palmitoyl-enzyme thioester intermediate by slowing its hydrolysis [#3]. Beyond DHHC9, GOLGA7 also stabilizes and activates DHHC14 and DHHC18 [#6, #7] and assembles a distinct, mutually stabilizing plasma-membrane complex with ZDHHC5 that drives CIL56-induced nonapoptotic cell death [#4, #11]. Independently of its palmitoyltransferase role, GOLGA7 is required for anterograde trafficking of NRAS from the cis-Golgi to the plasma membrane without affecting NRAS palmitoylation levels, and its loss selectively impairs NRAS-mutant cancer proliferation and NRAS(G12D)-driven oncogenic transformation and myeloid leukemia in vivo while sparing normal adult hematopoiesis [#8, #10]. GOLGA7 is also exploited as a host factor by SARS-CoV-2 and chikungunya virus entry/replication [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Established GOLGA7/GCP16 as a Golgi membrane protein whose own palmitoylation governs its localization and whose presence influences secretory transport, defining its baseline cell biology before any enzymatic role was known.\",\n      \"evidence\": \"Yeast two-hybrid with GCP170, [3H]palmitate labeling, C69A/C72A mutagenesis, immunofluorescence and transport assay\",\n      \"pmids\": [\"14522980\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not connect GCP16 to any DHHC enzyme or palmitoyltransferase activity\", \"Mechanism of the Golgi transport inhibition unresolved\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Showed that GCP16 is an obligate partner of DHHC9, together forming the H-Ras/N-Ras palmitoyltransferase, answering how Ras becomes palmitoylated at the Golgi.\",\n      \"evidence\": \"Purified enzyme reconstitution with substrate-specificity assay, co-IP, subcellular fractionation/IF\",\n      \"pmids\": [\"16000296\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether GCP16 contributes to catalysis or only to stability was not resolved\", \"Structural basis of the interaction unknown\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Characterized the purified DHHC9/GCP16 enzyme pharmacologically, establishing that inhibitors act at the DHHC autoacylation step and exposing discrepancies between cell-based and purified-enzyme inhibitor selectivity.\",\n      \"evidence\": \"In vitro palmitoyltransferase assay with purified complex and inhibitor profiling (2-bromopalmitate, Compound V)\",\n      \"pmids\": [\"18827284\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No GCP16-specific binding site for inhibitors defined\", \"Cell-based selectivity discrepancy left mechanistically unexplained\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Defined the catalytic contribution of the accessory subunit: via the yeast ortholog Erf4, showed it stabilizes the palmitoyl-enzyme thioester intermediate and protects the enzyme through a ubiquitin-mediated stability pathway.\",\n      \"evidence\": \"Yeast genetics, in vitro palmitoylation assay, reaction-intermediate kinetics, ubiquitin pathway analysis\",\n      \"pmids\": [\"22904317\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Extrapolated from yeast Erf4 rather than human GCP16 directly\", \"Identity of the ubiquitin ligase not established\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Revealed a second, distinct GOLGA7 complex with ZDHHC5 at the plasma membrane that is required for CIL56-induced nonapoptotic cell death, broadening GOLGA7 beyond the Golgi DHHC9 axis.\",\n      \"evidence\": \"CRISPR KO, reciprocal co-IP, immunofluorescence, cell-death assays\",\n      \"pmids\": [\"31631010\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Substrate(s) of the ZDHHC5-GOLGA7 complex driving cell death not identified\", \"Mechanism linking palmitoylation to nonapoptotic death unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Synthesized prior work to position GCP16 as a general accessory regulator of DHHC enzyme activity, stability, and trafficking within the broader S-acylation system.\",\n      \"evidence\": \"Review synthesizing purified-component and cellular studies\",\n      \"pmids\": [\"33203738\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No new primary data\", \"Scope of GOLGA7-dependent DHHC enzymes not yet experimentally bounded\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Established the structural/biochemical basis of GCP16 selectivity, showing it stabilizes DHHC9 by preventing aggregation via a conserved C-terminal cysteine motif and extends activation to DHHC14 and DHHC18, while disease mutations in ZDHHC9 weaken complex formation.\",\n      \"evidence\": \"Size-exclusion chromatography, in vitro PAT assay, mutagenesis, co-expression stability assays\",\n      \"pmids\": [\"37035671\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not provide atomic structure of the interface\", \"GOLGA7B vs GOLGA7 paralog selectivity rules incompletely mapped\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Cryo-EM structures of human DHHC9-GCP16 and yeast Erf2-Erf4 resolved that the accessory subunit is non-catalytic and acts purely as an architectural stabilizer, while defining DHHC9 lipid binding and autopalmitoylation requirements.\",\n      \"evidence\": \"Cryo-EM structure determination, mutagenesis, in vitro palmitoylation assay, co-IP\",\n      \"pmids\": [\"38182928\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Conformational dynamics during the catalytic cycle not captured\", \"Structural basis for substrate (Ras) recognition not resolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Uncovered a palmitoylation-independent function: GOLGA7 is specifically required for NRAS anterograde transport from cis-Golgi to plasma membrane and for NRAS-mutant oncogenic phenotypes, separating its trafficking role from its enzyme-accessory role.\",\n      \"evidence\": \"siRNA/shRNA/CRISPR knockdown and KO, fluorescence localization, palmitoylation assay, in vivo mouse transformation\",\n      \"pmids\": [\"38317235\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular machinery linking GOLGA7 to NRAS-selective vesicular transport unknown\", \"Why HRAS/KRAS are unaffected not explained\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Validated GOLGA7 as a therapeutic target in vivo: conditional knockout suppresses NRAS(G12D)-driven myeloid leukemia by disrupting NRAS plasma-membrane localization without affecting palmitoylation, while being dispensable for normal adult hematopoiesis.\",\n      \"evidence\": \"Conditional Cre-mediated knockout mouse leukemia model, flow cytometry, localization and palmitoylation assays\",\n      \"pmids\": [\"40091521\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Embryonic lethality of constitutive knockout indicates essential roles not defined here\", \"Whether the trafficking defect is direct or secondary remains open\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Resolved the ZDHHC5-GOLGA7 complex by cryo-EM and pinpointed interface residues required for both assembly and CIL56-induced cancer cell death, structurally completing the second GOLGA7 complex.\",\n      \"evidence\": \"Cryo-EM, co-IP, mutagenesis, functional cell-death assay\",\n      \"pmids\": [\"40930250\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Substrate engaged by the complex during cell death not defined\", \"Generalizability of interface residues to other DHHC-GOLGA7 pairs untested\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Demonstrated the ZDHHC9-GCP16 complex is druggable, identifying six small-molecule inhibitors with low-micromolar potency in a cell-based assay.\",\n      \"evidence\": \"Cell-based high-throughput palmitoylation assay (APT1 fusion), dose-response IC50 determination\",\n      \"pmids\": [\"41850277\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding sites and selectivity of compounds not defined\", \"Whether compounds act on GCP16, DHHC9, or the interface unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Implicated GOLGA7 as a host dependency factor for viral infection, expanding its functional reach beyond Ras biology.\",\n      \"evidence\": \"Genome-wide CRISPR KO replicon screen with live chikungunya virus confirmation (preprint)\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of GOLGA7 requirement in CHIKV replication unknown\", \"Preprint, not yet peer-reviewed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular basis by which GOLGA7 selectively chaperones NRAS Golgi-to-membrane transport independently of palmitoylation, and how this connects to its DHHC-accessory function, remains unresolved.\",\n      \"evidence\": \"No direct experimental evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No identified trafficking machinery or adaptor linking GOLGA7 to NRAS vesicles\", \"Cause of constitutive-knockout embryonic lethality uncharacterized\", \"Substrates of ZDHHC5-GOLGA7 in cell death not identified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 6, 7]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 3, 6, 7]},\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [6, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 1, 8]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [4, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 6, 7]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [8, 10]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [8, 10]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [4, 11]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [8, 9, 10]}\n    ],\n    \"complexes\": [\n      \"DHHC9-GCP16 (ZDHHC9-GOLGA7) palmitoyltransferase\",\n      \"ZDHHC5-GOLGA7 complex\",\n      \"DHHC14-GCP16 complex\",\n      \"DHHC18-GCP16 complex\"\n    ],\n    \"partners\": [\n      \"ZDHHC9\",\n      \"ZDHHC5\",\n      \"ZDHHC14\",\n      \"ZDHHC18\",\n      \"GCP170\",\n      \"NRAS\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":7,"faith_total":7,"faith_pct":100.0}}