{"gene":"GOLGA7B","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2019,"finding":"DHHC5 binds to and palmitoylates Golga7b; palmitoylation of Golga7b prevents clathrin-mediated endocytosis of DHHC5 and stabilises DHHC5 at the plasma membrane.","method":"Co-immunoprecipitation, palmitoylation assay, clathrin-mediated endocytosis inhibition experiments, and plasma membrane localisation imaging","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal binding demonstrated, direct palmitoylation shown, functional consequence (endocytosis prevention, membrane stabilisation) established with multiple orthogonal methods in a single focused study","pmids":["31402609"],"is_preprint":false},{"year":2019,"finding":"The DHHC5/Golga7b complex is required for palmitoylation of desmoglein-2 and plakophilin-3, for localisation of desmoglein-2 to the plasma membrane, for desmosomal patterning, and for cell adhesion.","method":"Proteomic analysis of DHHC5/Golga7b-associated complexes, loss-of-function knockdown, plasma membrane localisation assays, and cell adhesion functional assays","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (proteomics, KD phenotype, substrate palmitoylation, localisation) in a single rigorous focused study","pmids":["31402609"],"is_preprint":false},{"year":2023,"finding":"Golga7b improves protein stability of DHHC5 and DHHC8 (but not other members of the DHHC9 subfamily), demonstrating selectivity in accessory protein interactions; the conserved C-terminal cysteine motif (CCM) present in DHHC5 and DHHC8 is implicated in this interaction.","method":"Co-expression stability assays, size-exclusion chromatography, palmitoyl acyltransferase activity assays in vitro","journal":"Frontiers in physiology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — in vitro enzymatic and chromatography assays are rigorous but findings specific to Golga7b/DHHC5-8 come from a single lab with no independent replication reported","pmids":["37035671"],"is_preprint":false},{"year":2026,"finding":"AMPK phosphorylates ZDHHC5 at Ser296 and Ser380, which weakens ZDHHC5 association with Golga7b and promotes displacement of ZDHHC5 from the plasma membrane, thereby reducing NOD1 palmitoylation and membrane localisation.","method":"Biochemical phosphorylation assays, co-immunoprecipitation to assess Golga7b–ZDHHC5 interaction, plasma membrane localisation imaging, NOD1 signalling readouts in immune-competent cell models","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal Co-IP and biochemical assays with defined phosphorylation sites and functional readouts, but single lab with no independent replication yet","pmids":["41890956"],"is_preprint":false}],"current_model":"Golga7b is an S-acylated (palmitoylated) accessory protein that binds DHHC5 (and DHHC8) at the plasma membrane; its own palmitoylation by DHHC5 prevents clathrin-mediated endocytosis of DHHC5, stabilising the DHHC5/Golga7b complex at the membrane, which in turn palmitoylates and localises desmosomal substrates (desmoglein-2, plakophilin-3) to support cell adhesion; this membrane association is dynamically regulated by AMPK, which phosphorylates ZDHHC5 at Ser296/Ser380 to weaken its interaction with Golga7b and displace the complex from the plasma membrane, attenuating downstream innate immune (NOD1) signalling."},"narrative":{"mechanistic_narrative":"GOLGA7B is an S-acylated accessory subunit of plasma membrane palmitoyltransferase complexes that controls the stability, localization, and substrate output of DHHC5/ZDHHC5 [PMID:31402609]. DHHC5 binds and palmitoylates GOLGA7B, and this palmitoylation prevents clathrin-mediated endocytosis of DHHC5, retaining the enzyme at the plasma membrane [PMID:31402609]. GOLGA7B selectively stabilizes DHHC5 and DHHC8 — but not other DHHC9-subfamily members — through their conserved C-terminal cysteine motif, defining the specificity of the accessory interaction [PMID:37035671]. The resulting DHHC5/GOLGA7B complex palmitoylates desmosomal substrates desmoglein-2 and plakophilin-3, directing desmoglein-2 to the plasma membrane and supporting desmosomal patterning and cell adhesion [PMID:31402609]. Complex assembly is dynamically regulated: AMPK phosphorylation of ZDHHC5 at Ser296/Ser380 weakens the ZDHHC5–GOLGA7B interaction and displaces the enzyme from the plasma membrane, reducing NOD1 palmitoylation and attenuating innate immune signaling [PMID:41890956].","teleology":[{"year":2019,"claim":"Established that GOLGA7B is both a substrate and a functional partner of DHHC5, explaining how the palmitoyltransferase is retained at the plasma membrane rather than internalized.","evidence":"Co-immunoprecipitation, palmitoylation assays, clathrin-mediated endocytosis inhibition, and membrane localization imaging","pmids":["31402609"],"confidence":"High","gaps":["Structural basis of the DHHC5–GOLGA7B interaction not resolved","Whether GOLGA7B palmitoylation sites are necessary and sufficient for endocytosis blockade not fully mapped"]},{"year":2019,"claim":"Connected the DHHC5/GOLGA7B complex to a concrete biological output by identifying desmosomal substrates and an adhesion phenotype, moving the complex beyond a self-stabilization loop.","evidence":"Proteomics of complex-associated proteins, knockdown loss-of-function, substrate palmitoylation, localization and cell adhesion assays","pmids":["31402609"],"confidence":"High","gaps":["Direct versus indirect palmitoylation of plakophilin-3 not dissected","In vivo physiological relevance to tissue adhesion not tested"]},{"year":2023,"claim":"Defined the selectivity of GOLGA7B accessory function, showing it stabilizes DHHC5 and DHHC8 specifically via their conserved C-terminal cysteine motif rather than acting as a general DHHC chaperone.","evidence":"Co-expression stability assays, size-exclusion chromatography, and in vitro palmitoyl acyltransferase activity assays","pmids":["37035671"],"confidence":"Medium","gaps":["Single lab with no independent replication","Precise residues mediating the CCM-dependent interaction not pinpointed","Quantitative effect on enzyme catalytic rate versus stability not separated"]},{"year":2026,"claim":"Identified a signaling input that dynamically regulates complex assembly, showing AMPK phosphorylation of ZDHHC5 disassembles the GOLGA7B interaction to tune innate immune palmitoylation.","evidence":"Biochemical phosphorylation assays, reciprocal Co-IP, membrane localization imaging, and NOD1 signaling readouts in immune-competent cells","pmids":["41890956"],"confidence":"Medium","gaps":["Single lab with no independent replication","Whether GOLGA7B itself is modified during this regulation untested","Upstream stimuli activating AMPK in this context not defined"]},{"year":null,"claim":"How GOLGA7B integrates its desmosomal-adhesion and innate-immune roles, and whether its own acylation state is itself a regulatory node, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the GOLGA7B–DHHC complex","No in vivo or organismal phenotype reported","Regulation of GOLGA7B abundance/turnover uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,2]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,1,3]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[3]}],"complexes":["DHHC5/GOLGA7B palmitoyltransferase complex"],"partners":["ZDHHC5","ZDHHC8"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q2TAP0","full_name":"Golgin subfamily A member 7B","aliases":[],"length_aa":167,"mass_kda":18.3,"function":"Play a role in cell adhesion by regulating the plasma membrane localization of the palmitoyltransferase ZDHHC5 (PubMed:31402609). May be involved in protein transport from Golgi to cell surface","subcellular_location":"Cell membrane; Golgi apparatus membrane","url":"https://www.uniprot.org/uniprotkb/Q2TAP0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GOLGA7B","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/GOLGA7B","total_profiled":1310},"omim":[{"mim_id":"614189","title":"GOLGIN A7 FAMILY, MEMBER B; GOLGA7B","url":"https://www.omim.org/entry/614189"},{"mim_id":"606276","title":"CARTILAGE ACIDIC PROTEIN 1; CRTAC1","url":"https://www.omim.org/entry/606276"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"brain","ntpm":55.3},{"tissue":"epididymis","ntpm":22.1}],"url":"https://www.proteinatlas.org/search/GOLGA7B"},"hgnc":{"alias_symbol":["bA459F3.4","bA451M19.3"],"prev_symbol":["C10orf133","C10orf132"]},"alphafold":{"accession":"Q2TAP0","domains":[{"cath_id":"-","chopping":"1-140","consensus_level":"medium","plddt":83.1337,"start":1,"end":140}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q2TAP0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q2TAP0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q2TAP0-F1-predicted_aligned_error_v6.png","plddt_mean":79.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GOLGA7B","jax_strain_url":"https://www.jax.org/strain/search?query=GOLGA7B"},"sequence":{"accession":"Q2TAP0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q2TAP0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q2TAP0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q2TAP0"}},"corpus_meta":[{"pmid":"31402609","id":"PMC_31402609","title":"S-acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate cell adhesion.","date":"2019","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/31402609","citation_count":55,"is_preprint":false},{"pmid":"33203738","id":"PMC_33203738","title":"Accessory proteins of the zDHHC family of S-acylation enzymes.","date":"2020","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/33203738","citation_count":39,"is_preprint":false},{"pmid":"31512789","id":"PMC_31512789","title":"Decreased SPTLC1 expression predicts worse outcomes in ccRCC patients.","date":"2019","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31512789","citation_count":23,"is_preprint":false},{"pmid":"37035671","id":"PMC_37035671","title":"GCP16 stabilizes the DHHC9 subfamily of protein acyltransferases through a conserved C-terminal cysteine motif.","date":"2023","source":"Frontiers in physiology","url":"https://pubmed.ncbi.nlm.nih.gov/37035671","citation_count":16,"is_preprint":false},{"pmid":"35416335","id":"PMC_35416335","title":"Golgin A7 family member B (GOLGA7B) is a plausible novel gene associating high glycaemic index diet with acne vulgaris.","date":"2022","source":"Experimental dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/35416335","citation_count":7,"is_preprint":false},{"pmid":"41890956","id":"PMC_41890956","title":"Metabolic orchestration of NOD1 signaling by AMPK-mediated phosphorylation of ZDHHC5.","date":"2026","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/41890956","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5413,"output_tokens":1176,"usd":0.016939,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7685,"output_tokens":1940,"usd":0.043463,"stage2_stop_reason":"end_turn"},"total_usd":0.060402,"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\": 2019,\n      \"finding\": \"DHHC5 binds to and palmitoylates Golga7b; palmitoylation of Golga7b prevents clathrin-mediated endocytosis of DHHC5 and stabilises DHHC5 at the plasma membrane.\",\n      \"method\": \"Co-immunoprecipitation, palmitoylation assay, clathrin-mediated endocytosis inhibition experiments, and plasma membrane localisation imaging\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding demonstrated, direct palmitoylation shown, functional consequence (endocytosis prevention, membrane stabilisation) established with multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"31402609\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The DHHC5/Golga7b complex is required for palmitoylation of desmoglein-2 and plakophilin-3, for localisation of desmoglein-2 to the plasma membrane, for desmosomal patterning, and for cell adhesion.\",\n      \"method\": \"Proteomic analysis of DHHC5/Golga7b-associated complexes, loss-of-function knockdown, plasma membrane localisation assays, and cell adhesion functional assays\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (proteomics, KD phenotype, substrate palmitoylation, localisation) in a single rigorous focused study\",\n      \"pmids\": [\"31402609\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Golga7b improves protein stability of DHHC5 and DHHC8 (but not other members of the DHHC9 subfamily), demonstrating selectivity in accessory protein interactions; the conserved C-terminal cysteine motif (CCM) present in DHHC5 and DHHC8 is implicated in this interaction.\",\n      \"method\": \"Co-expression stability assays, size-exclusion chromatography, palmitoyl acyltransferase activity assays in vitro\",\n      \"journal\": \"Frontiers in physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — in vitro enzymatic and chromatography assays are rigorous but findings specific to Golga7b/DHHC5-8 come from a single lab with no independent replication reported\",\n      \"pmids\": [\"37035671\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"AMPK phosphorylates ZDHHC5 at Ser296 and Ser380, which weakens ZDHHC5 association with Golga7b and promotes displacement of ZDHHC5 from the plasma membrane, thereby reducing NOD1 palmitoylation and membrane localisation.\",\n      \"method\": \"Biochemical phosphorylation assays, co-immunoprecipitation to assess Golga7b–ZDHHC5 interaction, plasma membrane localisation imaging, NOD1 signalling readouts in immune-competent cell models\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal Co-IP and biochemical assays with defined phosphorylation sites and functional readouts, but single lab with no independent replication yet\",\n      \"pmids\": [\"41890956\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Golga7b is an S-acylated (palmitoylated) accessory protein that binds DHHC5 (and DHHC8) at the plasma membrane; its own palmitoylation by DHHC5 prevents clathrin-mediated endocytosis of DHHC5, stabilising the DHHC5/Golga7b complex at the membrane, which in turn palmitoylates and localises desmosomal substrates (desmoglein-2, plakophilin-3) to support cell adhesion; this membrane association is dynamically regulated by AMPK, which phosphorylates ZDHHC5 at Ser296/Ser380 to weaken its interaction with Golga7b and displace the complex from the plasma membrane, attenuating downstream innate immune (NOD1) signalling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GOLGA7B is an S-acylated accessory subunit of plasma membrane palmitoyltransferase complexes that controls the stability, localization, and substrate output of DHHC5/ZDHHC5 [#0, #1]. DHHC5 binds and palmitoylates GOLGA7B, and this palmitoylation prevents clathrin-mediated endocytosis of DHHC5, retaining the enzyme at the plasma membrane [#0]. GOLGA7B selectively stabilizes DHHC5 and DHHC8 — but not other DHHC9-subfamily members — through their conserved C-terminal cysteine motif, defining the specificity of the accessory interaction [#2]. The resulting DHHC5/GOLGA7B complex palmitoylates desmosomal substrates desmoglein-2 and plakophilin-3, directing desmoglein-2 to the plasma membrane and supporting desmosomal patterning and cell adhesion [#1]. Complex assembly is dynamically regulated: AMPK phosphorylation of ZDHHC5 at Ser296/Ser380 weakens the ZDHHC5–GOLGA7B interaction and displaces the enzyme from the plasma membrane, reducing NOD1 palmitoylation and attenuating innate immune signaling [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Established that GOLGA7B is both a substrate and a functional partner of DHHC5, explaining how the palmitoyltransferase is retained at the plasma membrane rather than internalized.\",\n      \"evidence\": \"Co-immunoprecipitation, palmitoylation assays, clathrin-mediated endocytosis inhibition, and membrane localization imaging\",\n      \"pmids\": [\"31402609\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the DHHC5–GOLGA7B interaction not resolved\", \"Whether GOLGA7B palmitoylation sites are necessary and sufficient for endocytosis blockade not fully mapped\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connected the DHHC5/GOLGA7B complex to a concrete biological output by identifying desmosomal substrates and an adhesion phenotype, moving the complex beyond a self-stabilization loop.\",\n      \"evidence\": \"Proteomics of complex-associated proteins, knockdown loss-of-function, substrate palmitoylation, localization and cell adhesion assays\",\n      \"pmids\": [\"31402609\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct versus indirect palmitoylation of plakophilin-3 not dissected\", \"In vivo physiological relevance to tissue adhesion not tested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined the selectivity of GOLGA7B accessory function, showing it stabilizes DHHC5 and DHHC8 specifically via their conserved C-terminal cysteine motif rather than acting as a general DHHC chaperone.\",\n      \"evidence\": \"Co-expression stability assays, size-exclusion chromatography, and in vitro palmitoyl acyltransferase activity assays\",\n      \"pmids\": [\"37035671\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab with no independent replication\", \"Precise residues mediating the CCM-dependent interaction not pinpointed\", \"Quantitative effect on enzyme catalytic rate versus stability not separated\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Identified a signaling input that dynamically regulates complex assembly, showing AMPK phosphorylation of ZDHHC5 disassembles the GOLGA7B interaction to tune innate immune palmitoylation.\",\n      \"evidence\": \"Biochemical phosphorylation assays, reciprocal Co-IP, membrane localization imaging, and NOD1 signaling readouts in immune-competent cells\",\n      \"pmids\": [\"41890956\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab with no independent replication\", \"Whether GOLGA7B itself is modified during this regulation untested\", \"Upstream stimuli activating AMPK in this context not defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How GOLGA7B integrates its desmosomal-adhesion and innate-immune roles, and whether its own acylation state is itself a regulatory node, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the GOLGA7B–DHHC complex\", \"No in vivo or organismal phenotype reported\", \"Regulation of GOLGA7B abundance/turnover uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\"DHHC5/GOLGA7B palmitoyltransferase complex\"],\n    \"partners\": [\"ZDHHC5\", \"ZDHHC8\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}