{"gene":"SGSM1","run_date":"2026-06-10T07:46:31","timeline":{"discoveries":[{"year":2007,"finding":"SGSM1 protein contains RUN and TBC domain motifs and co-precipitates with RAP and RAB subfamily members of the small G protein superfamily, indicating it functions as a modulator of RAP/RAB-mediated signaling.","method":"Immunoprecipitation assay following expression of cDNA constructs; immunofluorescence microscopy","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-IP from overexpression, single lab, consistent with domain architecture; no in vitro reconstitution or mutagenesis reported in abstract","pmids":["17509819"],"is_preprint":false},{"year":2007,"finding":"Endogenous Sgsm1 protein localizes to the trans-Golgi network in mouse Neuro2a cells, suggesting a role in vesicular transport at this compartment.","method":"Immunofluorescence microscopy of endogenous protein","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single method (immunofluorescence), no functional consequence directly demonstrated","pmids":["17509819"],"is_preprint":false},{"year":2012,"finding":"RUTBC2 (SGSM1 alias) binds Rab9A specifically both in vitro and in cultured cells (acting as a Rab9A effector) but is NOT a GAP for Rab9A; instead, RUTBC2 displays highest GAP activity toward Rab34 and Rab36 in biochemical screening.","method":"In vitro binding assay, co-immunoprecipitation in cultured cells, biochemical RabGAP activity screening","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro GAP activity assay plus cell-based co-localization and membrane-association readout, catalytically inactive mutant (R829A) used as control, multiple orthogonal methods","pmids":["22637480"],"is_preprint":false},{"year":2012,"finding":"Expression of wild-type RUTBC2 (SGSM1) decreases membrane-associated Rab36, whereas the catalytically inactive mutant RUTBC2 R829A does not, establishing that RUTBC2 acts as a Rab36 GAP in cells.","method":"Active-site mutagenesis (R829A), membrane fractionation / immunofluorescence co-localization in cultured cells","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — mutagenesis of catalytic residue with clear cellular phenotype, supported by in vitro GAP assay in the same study","pmids":["22637480"],"is_preprint":false},{"year":2018,"finding":"SGSM1 protein stability is regulated by the E3 ubiquitin ligase TRIM21, which ubiquitinates and degrades SGSM1; SHISA3 impedes this TRIM21-mediated ubiquitination, thereby stabilizing SGSM1 and suppressing MAPK pathway activation and NPC cell invasion.","method":"Co-immunoprecipitation, ubiquitination assay, siRNA knockdown of SGSM1, in vitro and in vivo invasion/metastasis assays","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — reciprocal co-IP, functional rescue by SGSM1 silencing, in vitro and in vivo readouts; single lab","pmids":["30573520"],"is_preprint":false}],"current_model":"SGSM1 (also known as RUTBC2) is a RUN- and TBC-domain-containing protein that localizes to the trans-Golgi network/endosomal system, where it acts as a Rab9A effector (binding Rab9A but not catalyzing its GTP hydrolysis) and as a GTPase-activating protein (GAP) for Rab36 (and Rab34), thereby linking Rab9A-dependent late endosome-to-TGN recycling to Rab36 inactivation; additionally, its protein stability is regulated by TRIM21-mediated ubiquitination and degradation, a process counteracted by SHISA3."},"narrative":{"mechanistic_narrative":"SGSM1 (RUTBC2) is a RUN- and TBC-domain-containing regulator of small G protein signaling that operates within the trans-Golgi network/endosomal system to couple Rab9A effector function to Rab36/Rab34 inactivation [PMID:17509819, PMID:22637480]. Endogenous SGSM1 localizes to the trans-Golgi network [PMID:17509819], where it binds Rab9A specifically as an effector without acting as a Rab9A GAP, while displaying its highest GTPase-activating activity toward Rab34 and Rab36 [PMID:22637480]. Cellular assays establish a functional GAP role: wild-type SGSM1 reduces membrane-associated Rab36, whereas the catalytically inactive R829A mutant does not [PMID:22637480]. SGSM1 protein levels are controlled post-translationally by TRIM21-mediated ubiquitination and degradation, an event antagonized by SHISA3, with consequences for MAPK pathway activation and nasopharyngeal carcinoma cell invasion [PMID:30573520].","teleology":[{"year":2007,"claim":"Established that SGSM1 is a candidate modulator of small G protein signaling by linking its RUN/TBC domain architecture to physical association with RAP and RAB subfamily GTPases.","evidence":"Co-immunoprecipitation after cDNA overexpression plus immunofluorescence","pmids":["17509819"],"confidence":"Medium","gaps":["Co-IP from overexpression without in vitro reconstitution or mutagenesis","Did not distinguish effector binding from GAP activity","Specific Rab partners not resolved"]},{"year":2007,"claim":"Placed SGSM1 at the trans-Golgi network, anchoring its candidate role in vesicular transport to a defined compartment.","evidence":"Immunofluorescence of endogenous protein in mouse Neuro2a cells","pmids":["17509819"],"confidence":"Medium","gaps":["Single method, single cell line","No functional consequence of localization demonstrated","Membrane-targeting determinants unknown"]},{"year":2012,"claim":"Resolved the dual molecular logic of SGSM1: it binds Rab9A as an effector without hydrolyzing its GTP, yet acts catalytically as a GAP preferentially toward Rab34 and Rab36, defining a substrate-versus-partner distinction.","evidence":"In vitro binding and RabGAP activity screening plus cell-based co-IP, with R829A catalytic mutant control","pmids":["22637480"],"confidence":"High","gaps":["Physiological output of Rab9A binding not defined","Relative in vivo contribution of Rab34 vs Rab36 unresolved","No structural model of the Rab9A-SGSM1-Rab36 link"]},{"year":2012,"claim":"Demonstrated that SGSM1 GAP activity is functional in cells by showing wild-type but not R829A SGSM1 depletes membrane-bound Rab36.","evidence":"Active-site mutagenesis with membrane fractionation/co-localization in cultured cells","pmids":["22637480"],"confidence":"High","gaps":["Downstream trafficking consequence of Rab36 inactivation not traced","Cell-type generality untested"]},{"year":2018,"claim":"Identified post-translational control of SGSM1 abundance, showing TRIM21 ubiquitinates and degrades it while SHISA3 stabilizes it, with downstream effects on MAPK signaling and tumor cell invasion.","evidence":"Reciprocal co-IP, ubiquitination assay, siRNA knockdown, and in vitro/in vivo invasion assays","pmids":["30573520"],"confidence":"Medium","gaps":["Mechanistic link between SGSM1 GAP activity and MAPK regulation not established","Single lab","Ubiquitination site on SGSM1 not mapped"]},{"year":null,"claim":"How SGSM1 effector binding to Rab9A is mechanistically coupled to its GAP-driven inactivation of Rab36/Rab34, and how this trafficking activity connects to its TRIM21/SHISA3-regulated role in MAPK signaling, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural basis for simultaneous Rab9A binding and Rab36 GAP catalysis","Causal chain from Rab36 inactivation to MAPK output undefined","Endogenous loss-of-function trafficking phenotype not characterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,3]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[2,3]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[2,3]}],"complexes":[],"partners":["RAB9A","RAB36","RAB34","TRIM21","SHISA3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q2NKQ1","full_name":"Small G protein signaling modulator 1","aliases":["RUN and TBC1 domain-containing protein 2"],"length_aa":1148,"mass_kda":129.7,"function":"Interacts with numerous Rab family members, functioning as Rab effector for some, and as GTPase activator for others. Promotes GTP hydrolysis by RAB34 and RAB36. Probably functions as a GTPase effector with RAB9A and RAB9B; does not stimulate GTP hydrolysis with RAB9A and RAB9B","subcellular_location":"Golgi apparatus, trans-Golgi network; Cytoplasmic vesicle membrane; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q2NKQ1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SGSM1","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CETN2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SGSM1","total_profiled":1310},"omim":[{"mim_id":"619250","title":"RUN DOMAIN-CONTAINING PROTEIN 1; RUNDC1","url":"https://www.omim.org/entry/619250"},{"mim_id":"611418","title":"SMALL G PROTEIN SIGNALING MODULATOR 2; SGSM2","url":"https://www.omim.org/entry/611418"},{"mim_id":"611417","title":"SMALL G PROTEIN SIGNALING MODULATOR 1; SGSM1","url":"https://www.omim.org/entry/611417"},{"mim_id":"610440","title":"SMALL G PROTEIN SIGNALING MODULATOR 3; SGSM3","url":"https://www.omim.org/entry/610440"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"brain","ntpm":17.9},{"tissue":"heart muscle","ntpm":10.8}],"url":"https://www.proteinatlas.org/search/SGSM1"},"hgnc":{"alias_symbol":["KIAA1941"],"prev_symbol":["RUTBC2"]},"alphafold":{"accession":"Q2NKQ1","domains":[{"cath_id":"1.20.58.900","chopping":"4-102_120-187","consensus_level":"high","plddt":87.396,"start":4,"end":187},{"cath_id":"2.30.29.230","chopping":"242-302_309-384_417-421","consensus_level":"high","plddt":82.1332,"start":242,"end":421},{"cath_id":"1.10.472.80","chopping":"548-576_1018-1148","consensus_level":"medium","plddt":90.4866,"start":548,"end":1148},{"cath_id":"1.10.8.270","chopping":"620-680_920-1009","consensus_level":"medium","plddt":95.2197,"start":620,"end":1009}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q2NKQ1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q2NKQ1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q2NKQ1-F1-predicted_aligned_error_v6.png","plddt_mean":65.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SGSM1","jax_strain_url":"https://www.jax.org/strain/search?query=SGSM1"},"sequence":{"accession":"Q2NKQ1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q2NKQ1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q2NKQ1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q2NKQ1"}},"corpus_meta":[{"pmid":"17509819","id":"PMC_17509819","title":"Identification of three novel proteins (SGSM1, 2, 3) which modulate small G protein (RAP and RAB)-mediated signaling pathway.","date":"2007","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/17509819","citation_count":54,"is_preprint":false},{"pmid":"27670201","id":"PMC_27670201","title":"Loss of RNA expression and allele-specific expression associated with congenital heart disease.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/27670201","citation_count":49,"is_preprint":false},{"pmid":"30573520","id":"PMC_30573520","title":"Hypermethylation of SHISA3 Promotes Nasopharyngeal Carcinoma Metastasis by Reducing SGSM1 Stability.","date":"2018","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/30573520","citation_count":40,"is_preprint":false},{"pmid":"22637480","id":"PMC_22637480","title":"RUTBC2 protein, a Rab9A effector and GTPase-activating protein for Rab36.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22637480","citation_count":30,"is_preprint":false},{"pmid":"32226705","id":"PMC_32226705","title":"Dexmedetomidine alleviates postoperative cognitive dysfunction through circular RNA in aged rats.","date":"2020","source":"3 Biotech","url":"https://pubmed.ncbi.nlm.nih.gov/32226705","citation_count":18,"is_preprint":false},{"pmid":"28576919","id":"PMC_28576919","title":"Trivial role for NSMCE2 during in vitro proliferation and differentiation of male germline stem cells.","date":"2017","source":"Reproduction (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/28576919","citation_count":16,"is_preprint":false},{"pmid":"30744493","id":"PMC_30744493","title":"Small G protein signalling modulator 2 (SGSM2) is involved in oestrogen receptor-positive breast cancer metastasis through enhancement of migratory cell adhesion via interaction with E-cadherin.","date":"2019","source":"Cell adhesion & migration","url":"https://pubmed.ncbi.nlm.nih.gov/30744493","citation_count":12,"is_preprint":false},{"pmid":"15375525","id":"PMC_15375525","title":"Characterization of RUSC1 and RUSC2 genes in silico.","date":"2004","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/15375525","citation_count":8,"is_preprint":false},{"pmid":"34321704","id":"PMC_34321704","title":"Gene-Based Association Testing of Dichotomous Traits With Generalized Functional Linear Mixed Models Using Extended Pedigrees: Applications to Age-Related Macular Degeneration.","date":"2020","source":"Journal of the American Statistical Association","url":"https://pubmed.ncbi.nlm.nih.gov/34321704","citation_count":8,"is_preprint":false},{"pmid":"35738035","id":"PMC_35738035","title":"The piRNAs present in the developing testes of Chinese indigenous Xiang pigs.","date":"2022","source":"Theriogenology","url":"https://pubmed.ncbi.nlm.nih.gov/35738035","citation_count":6,"is_preprint":false},{"pmid":"34747535","id":"PMC_34747535","title":"Targeted massively parallel sequencing of candidate regions on chromosome 22q predisposing to multiple schwannomas: An analysis of 51 individuals in a single-center experience.","date":"2021","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/34747535","citation_count":5,"is_preprint":false},{"pmid":"37799139","id":"PMC_37799139","title":"Uncovering structural variants associated with body weight and obesity risk in labrador retrievers: a genome-wide study.","date":"2023","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/37799139","citation_count":4,"is_preprint":false},{"pmid":"34114396","id":"PMC_34114396","title":"Epigenetic mechanisms involved in the neuroprotective effect of scorpion extract in a Parkinson's disease murine model based on multi-omics 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cattle.","date":"2024","source":"Veterinary world","url":"https://pubmed.ncbi.nlm.nih.gov/39829673","citation_count":2,"is_preprint":false},{"pmid":"42021739","id":"PMC_42021739","title":"Endothelial NOX1 Drives Obesity via Skeletal Muscle Mitochondrial Dysfunction.","date":"2026","source":"Circulation research","url":"https://pubmed.ncbi.nlm.nih.gov/42021739","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11409,"output_tokens":1242,"usd":0.026429,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7807,"output_tokens":1963,"usd":0.044055,"stage2_stop_reason":"end_turn"},"total_usd":0.070484,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"SGSM1 protein contains RUN and TBC domain motifs and co-precipitates with RAP and RAB subfamily members of the small G protein superfamily, indicating it functions as a modulator of RAP/RAB-mediated signaling.\",\n      \"method\": \"Immunoprecipitation assay following expression of cDNA constructs; immunofluorescence microscopy\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-IP from overexpression, single lab, consistent with domain architecture; no in vitro reconstitution or mutagenesis reported in abstract\",\n      \"pmids\": [\"17509819\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Endogenous Sgsm1 protein localizes to the trans-Golgi network in mouse Neuro2a cells, suggesting a role in vesicular transport at this compartment.\",\n      \"method\": \"Immunofluorescence microscopy of endogenous protein\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (immunofluorescence), no functional consequence directly demonstrated\",\n      \"pmids\": [\"17509819\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"RUTBC2 (SGSM1 alias) binds Rab9A specifically both in vitro and in cultured cells (acting as a Rab9A effector) but is NOT a GAP for Rab9A; instead, RUTBC2 displays highest GAP activity toward Rab34 and Rab36 in biochemical screening.\",\n      \"method\": \"In vitro binding assay, co-immunoprecipitation in cultured cells, biochemical RabGAP activity screening\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro GAP activity assay plus cell-based co-localization and membrane-association readout, catalytically inactive mutant (R829A) used as control, multiple orthogonal methods\",\n      \"pmids\": [\"22637480\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Expression of wild-type RUTBC2 (SGSM1) decreases membrane-associated Rab36, whereas the catalytically inactive mutant RUTBC2 R829A does not, establishing that RUTBC2 acts as a Rab36 GAP in cells.\",\n      \"method\": \"Active-site mutagenesis (R829A), membrane fractionation / immunofluorescence co-localization in cultured cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — mutagenesis of catalytic residue with clear cellular phenotype, supported by in vitro GAP assay in the same study\",\n      \"pmids\": [\"22637480\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SGSM1 protein stability is regulated by the E3 ubiquitin ligase TRIM21, which ubiquitinates and degrades SGSM1; SHISA3 impedes this TRIM21-mediated ubiquitination, thereby stabilizing SGSM1 and suppressing MAPK pathway activation and NPC cell invasion.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, siRNA knockdown of SGSM1, in vitro and in vivo invasion/metastasis assays\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — reciprocal co-IP, functional rescue by SGSM1 silencing, in vitro and in vivo readouts; single lab\",\n      \"pmids\": [\"30573520\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SGSM1 (also known as RUTBC2) is a RUN- and TBC-domain-containing protein that localizes to the trans-Golgi network/endosomal system, where it acts as a Rab9A effector (binding Rab9A but not catalyzing its GTP hydrolysis) and as a GTPase-activating protein (GAP) for Rab36 (and Rab34), thereby linking Rab9A-dependent late endosome-to-TGN recycling to Rab36 inactivation; additionally, its protein stability is regulated by TRIM21-mediated ubiquitination and degradation, a process counteracted by SHISA3.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SGSM1 (RUTBC2) is a RUN- and TBC-domain-containing regulator of small G protein signaling that operates within the trans-Golgi network/endosomal system to couple Rab9A effector function to Rab36/Rab34 inactivation [#0, #2]. Endogenous SGSM1 localizes to the trans-Golgi network [#1], where it binds Rab9A specifically as an effector without acting as a Rab9A GAP, while displaying its highest GTPase-activating activity toward Rab34 and Rab36 [#2]. Cellular assays establish a functional GAP role: wild-type SGSM1 reduces membrane-associated Rab36, whereas the catalytically inactive R829A mutant does not [#3]. SGSM1 protein levels are controlled post-translationally by TRIM21-mediated ubiquitination and degradation, an event antagonized by SHISA3, with consequences for MAPK pathway activation and nasopharyngeal carcinoma cell invasion [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established that SGSM1 is a candidate modulator of small G protein signaling by linking its RUN/TBC domain architecture to physical association with RAP and RAB subfamily GTPases.\",\n      \"evidence\": \"Co-immunoprecipitation after cDNA overexpression plus immunofluorescence\",\n      \"pmids\": [\"17509819\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-IP from overexpression without in vitro reconstitution or mutagenesis\", \"Did not distinguish effector binding from GAP activity\", \"Specific Rab partners not resolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Placed SGSM1 at the trans-Golgi network, anchoring its candidate role in vesicular transport to a defined compartment.\",\n      \"evidence\": \"Immunofluorescence of endogenous protein in mouse Neuro2a cells\",\n      \"pmids\": [\"17509819\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single method, single cell line\", \"No functional consequence of localization demonstrated\", \"Membrane-targeting determinants unknown\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Resolved the dual molecular logic of SGSM1: it binds Rab9A as an effector without hydrolyzing its GTP, yet acts catalytically as a GAP preferentially toward Rab34 and Rab36, defining a substrate-versus-partner distinction.\",\n      \"evidence\": \"In vitro binding and RabGAP activity screening plus cell-based co-IP, with R829A catalytic mutant control\",\n      \"pmids\": [\"22637480\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological output of Rab9A binding not defined\", \"Relative in vivo contribution of Rab34 vs Rab36 unresolved\", \"No structural model of the Rab9A-SGSM1-Rab36 link\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Demonstrated that SGSM1 GAP activity is functional in cells by showing wild-type but not R829A SGSM1 depletes membrane-bound Rab36.\",\n      \"evidence\": \"Active-site mutagenesis with membrane fractionation/co-localization in cultured cells\",\n      \"pmids\": [\"22637480\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream trafficking consequence of Rab36 inactivation not traced\", \"Cell-type generality untested\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identified post-translational control of SGSM1 abundance, showing TRIM21 ubiquitinates and degrades it while SHISA3 stabilizes it, with downstream effects on MAPK signaling and tumor cell invasion.\",\n      \"evidence\": \"Reciprocal co-IP, ubiquitination assay, siRNA knockdown, and in vitro/in vivo invasion assays\",\n      \"pmids\": [\"30573520\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between SGSM1 GAP activity and MAPK regulation not established\", \"Single lab\", \"Ubiquitination site on SGSM1 not mapped\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SGSM1 effector binding to Rab9A is mechanistically coupled to its GAP-driven inactivation of Rab36/Rab34, and how this trafficking activity connects to its TRIM21/SHISA3-regulated role in MAPK signaling, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural basis for simultaneous Rab9A binding and Rab36 GAP catalysis\", \"Causal chain from Rab36 inactivation to MAPK output undefined\", \"Endogenous loss-of-function trafficking phenotype not characterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"RAB9A\", \"RAB36\", \"RAB34\", \"TRIM21\", \"SHISA3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}