{"gene":"GIMAP2","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2010,"finding":"Crystal structures of GIMAP2 in nucleotide-free, GDP-bound, and GTP-bound states revealed that nucleotide-free and GDP-bound GIMAP2 are monomeric, with a TRAFAC-class guanine nucleotide-binding domain and a unique amphipathic helix α7 packing against switch II. GTP induces oligomerization via two distinct interfaces: switch I stabilization mediates dimerization across the nucleotide-binding site (involving the GIMAP specificity motif and nucleotide base), while structural rearrangements in switch II release α7 to allow oligomerization via a second interface. Mutagenesis confirmed the linear oligomer architecture.","method":"X-ray crystallography of multiple GIMAP2 constructs in different nucleotide states; site-directed mutagenesis to validate oligomerization interfaces","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structures at high resolution with functional mutagenesis validation in a single rigorous study","pmids":["21059949"],"is_preprint":false},{"year":2010,"finding":"GIMAP2 oligomers function at the surface of lipid droplets in a Jurkat T cell line, demonstrating a role as a GTP-dependent protein scaffold on intracellular membranes.","method":"Cellular localization assay in Jurkat T cells; biochemical fractionation linked to structural data","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment tied to functional scaffold model, single lab, supported by structural data","pmids":["21059949"],"is_preprint":false},{"year":2013,"finding":"GIMAP7, identified on lipid droplets, stimulates GTP hydrolysis by GIMAP2 via heterodimerization through an analogous mechanism to GIMAP7 homodimerization, where a catalytic arginine supplied in trans activates GTPase activity. This demonstrates that GTPase activity in the GIMAP family is controlled by homo- and heterodimerization.","method":"Crystal structure of GTP-bound GIMAP7 homodimer; in vitro GTP hydrolysis assays measuring GIMAP7-stimulated hydrolysis of GIMAP2; identification of catalytic arginine by structural analysis","journal":"Structure (London, England : 1993)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure plus in vitro enzymatic assay demonstrating trans-catalytic mechanism, single lab with multiple orthogonal methods","pmids":["23454188"],"is_preprint":false},{"year":2020,"finding":"GIMAP2 localizes to the endoplasmic reticulum and to the surface of lipid droplets in MDA-MB-436 cells, as confirmed by immunofluorescence of both endogenous and exogenous (mCherry-tagged) GIMAP2 co-stained with organelle-specific dyes imaged by super-resolution microscopy.","method":"Immunofluorescence staining of endogenous and exogenous GIMAP2-mCherry fusion protein; co-localization with organelle dyes (mitochondria, ER, lipid droplets) by super-resolution N-SIM microscopy","journal":"Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment with super-resolution imaging and orthogonal endogenous/exogenous confirmation, single lab","pmids":["32306002"],"is_preprint":false},{"year":2021,"finding":"GIMAP2 knockdown in oral squamous cell carcinoma cells caused cell cycle arrest associated with downregulation of CDK4, CDK6, and phosphorylated Rb, and upregulation of p53 and p21; additionally, knockdown affected anti-apoptotic function by upregulating Bcl-2 and downregulating Bax and Bak.","method":"siRNA-mediated GIMAP2 knockdown in OSCC cell lines; immunoblotting for CDK4, CDK6, pRb, p53, p21, Bcl-2, Bax, Bak; cell growth and apoptosis assays","journal":"Oncology letters","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single knockdown approach with pathway readout but no rescue experiment or mechanistic placement beyond correlation","pmids":["34992682"],"is_preprint":false}],"current_model":"GIMAP2 is a TRAFAC-class GTPase that exists as a monomer when GDP-bound or nucleotide-free (with amphipathic helix α7 packed against switch II) and forms linear oligomers upon GTP binding via two distinct G-domain interfaces; these oligomers serve as GTP-dependent scaffolds on the surface of lipid droplets and the endoplasmic reticulum, and GTPase activity of GIMAP2 can be stimulated in trans by heterodimerization with GIMAP7 through a catalytic arginine supplied by GIMAP7."},"narrative":{"mechanistic_narrative":"GIMAP2 is a TRAFAC-class guanine nucleotide-binding protein that functions as a GTP-dependent, self-assembling scaffold on intracellular membranes [PMID:21059949]. Crystal structures across nucleotide states establish that nucleotide-free and GDP-bound GIMAP2 is monomeric, with a distinctive amphipathic helix α7 packed against switch II, and that GTP binding drives assembly into linear oligomers through two distinct G-domain interfaces: a switch I-stabilized dimerization interface spanning the nucleotide-binding site and a second interface exposed when switch II rearrangement releases α7 [PMID:21059949]. These GTP-loaded oligomers act as scaffolds at the surface of lipid droplets and the endoplasmic reticulum [PMID:21059949, PMID:32306002]. GIMAP2's own GTPase activity is intrinsically weak and is stimulated in trans by heterodimerization with GIMAP7, which supplies a catalytic arginine, establishing that GTP turnover in the GIMAP family is governed by homo- and heterodimerization [PMID:23454188]. Beyond this nucleotide-cycling and scaffolding mechanism, the downstream cellular consequences of GIMAP2 activity remain largely uncharacterized in the available corpus.","teleology":[{"year":2010,"claim":"Resolved how nucleotide state controls GIMAP2 conformation and self-assembly, defining it as a GTP-switch scaffold rather than a conventional signaling GTPase.","evidence":"X-ray crystallography of GIMAP2 in nucleotide-free, GDP-, and GTP-bound states with mutagenesis of oligomerization interfaces","pmids":["21059949"],"confidence":"High","gaps":["Does not identify what cargo or effectors the oligomeric scaffold recruits","Intrinsic GTPase rate and the trigger for nucleotide exchange in cells not defined"]},{"year":2010,"claim":"Placed the GTP-dependent oligomer in a cellular context, showing GIMAP2 assembles on lipid droplet surfaces in T cells.","evidence":"Cellular localization and biochemical fractionation in Jurkat T cells linked to structural data","pmids":["21059949"],"confidence":"Medium","gaps":["Functional consequence of lipid droplet scaffolding not established","Single cell type; generality across tissues untested"]},{"year":2013,"claim":"Explained how GIMAP2 GTPase activity is regulated, showing GIMAP7 acts as a trans-activating partner that supplies a catalytic arginine.","evidence":"Crystal structure of GTP-bound GIMAP7 homodimer plus in vitro GTP hydrolysis assays of GIMAP7-stimulated GIMAP2 turnover","pmids":["23454188"],"confidence":"High","gaps":["Whether GIMAP2-GIMAP7 heterodimers form at physiological levels in cells not shown","Upstream signals controlling heterodimer formation unknown"]},{"year":2020,"claim":"Confirmed GIMAP2 membrane localization in a non-lymphoid (breast cancer) cell line, extending the scaffold model beyond T cells.","evidence":"Super-resolution immunofluorescence of endogenous and mCherry-tagged GIMAP2 co-stained with ER and lipid droplet markers in MDA-MB-436 cells","pmids":["32306002"],"confidence":"Medium","gaps":["Co-localization does not establish functional role at the ER","No interaction partners identified in this system"]},{"year":2021,"claim":"First attempt to connect GIMAP2 to a cellular phenotype, linking its loss to cell cycle arrest and apoptotic pathway changes in cancer cells.","evidence":"siRNA knockdown in oral squamous cell carcinoma lines with immunoblotting of cell cycle and apoptosis markers","pmids":["34992682"],"confidence":"Low","gaps":["Correlative knockdown without rescue; off-target effects not excluded","No mechanistic link between the scaffolding/GTPase activity and the observed CDK4/6, p53/p21, or Bcl-2/Bax changes","Effects observed in a single tumor context"]},{"year":null,"claim":"The effectors and physiological substrates recruited by the GIMAP2 GTP-dependent oligomeric scaffold, and how its membrane scaffolding connects to cell cycle or apoptotic outcomes, remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No identified downstream effector bound by the oligomer","No mechanistic bridge between GTPase cycling and the cancer-cell phenotypes","Physiological function in T cells not directly tested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003924","term_label":"GTPase activity","supporting_discovery_ids":[0,2]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005811","term_label":"lipid droplet","supporting_discovery_ids":[1,3]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[3]}],"pathway":[],"complexes":[],"partners":["GIMAP7"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UG22","full_name":"GTPase IMAP family member 2","aliases":["Immunity-associated protein 2","hIMAP2"],"length_aa":337,"mass_kda":38.0,"function":"The heterodimer formed by GIMAP2 and GIMAP7 has GTPase activity. In contrast, GIMAP2 has no GTPase activity by itself","subcellular_location":"Lipid droplet","url":"https://www.uniprot.org/uniprotkb/Q9UG22/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GIMAP2","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/GIMAP2","total_profiled":1310},"omim":[{"mim_id":"616961","title":"GTPase, IMAP FAMILY, MEMBER 7; GIMAP7","url":"https://www.omim.org/entry/616961"},{"mim_id":"616960","title":"GTPase, IMAP FAMILY, MEMBER 6; GIMAP6","url":"https://www.omim.org/entry/616960"},{"mim_id":"608087","title":"GTPase, IMAP FAMILY, MEMBER 4; GIMAP4","url":"https://www.omim.org/entry/608087"},{"mim_id":"608085","title":"GTPase, IMAP FAMILY, MEMBER 2; GIMAP2","url":"https://www.omim.org/entry/608085"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Lipid droplets","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":73.4}],"url":"https://www.proteinatlas.org/search/GIMAP2"},"hgnc":{"alias_symbol":["DKFZp586D0824","HIMAP2","IMAP2","IAN12"],"prev_symbol":[]},"alphafold":{"accession":"Q9UG22","domains":[{"cath_id":"3.40.50.300","chopping":"22-228","consensus_level":"high","plddt":94.209,"start":22,"end":228},{"cath_id":"1.20.5","chopping":"229-330","consensus_level":"medium","plddt":89.7102,"start":229,"end":330}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UG22","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UG22-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UG22-F1-predicted_aligned_error_v6.png","plddt_mean":88.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GIMAP2","jax_strain_url":"https://www.jax.org/strain/search?query=GIMAP2"},"sequence":{"accession":"Q9UG22","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UG22.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UG22/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UG22"}},"corpus_meta":[{"pmid":"23041938","id":"PMC_23041938","title":"Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease.","date":"2012","source":"Annals of the rheumatic diseases","url":"https://pubmed.ncbi.nlm.nih.gov/23041938","citation_count":93,"is_preprint":false},{"pmid":"21059949","id":"PMC_21059949","title":"Structural basis of oligomerization in septin-like GTPase of immunity-associated protein 2 (GIMAP2).","date":"2010","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/21059949","citation_count":51,"is_preprint":false},{"pmid":"23454188","id":"PMC_23454188","title":"Structural insights into the mechanism of GTPase activation in the GIMAP family.","date":"2013","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/23454188","citation_count":42,"is_preprint":false},{"pmid":"21686278","id":"PMC_21686278","title":"GTP-dependent scaffold formation in the GTPase of Immunity Associated Protein family.","date":"2011","source":"Small GTPases","url":"https://pubmed.ncbi.nlm.nih.gov/21686278","citation_count":11,"is_preprint":false},{"pmid":"34992682","id":"PMC_34992682","title":"Aberrant GIMAP2 expression affects oral squamous cell carcinoma progression by promoting cell cycle and inhibiting apoptosis.","date":"2021","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/34992682","citation_count":5,"is_preprint":false},{"pmid":"20516611","id":"PMC_20516611","title":"Purification, crystallization and preliminary X-ray analysis of human GIMAP2.","date":"2010","source":"Acta crystallographica. Section F, Structural biology and crystallization communications","url":"https://pubmed.ncbi.nlm.nih.gov/20516611","citation_count":5,"is_preprint":false},{"pmid":"32306002","id":"PMC_32306002","title":"[Subcellular localization of GTPase of immunity-associated protein 2].","date":"2020","source":"Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32306002","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5671,"output_tokens":1444,"usd":0.019336,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8180,"output_tokens":2074,"usd":0.046375,"stage2_stop_reason":"end_turn"},"total_usd":0.065711,"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\": 2010,\n      \"finding\": \"Crystal structures of GIMAP2 in nucleotide-free, GDP-bound, and GTP-bound states revealed that nucleotide-free and GDP-bound GIMAP2 are monomeric, with a TRAFAC-class guanine nucleotide-binding domain and a unique amphipathic helix α7 packing against switch II. GTP induces oligomerization via two distinct interfaces: switch I stabilization mediates dimerization across the nucleotide-binding site (involving the GIMAP specificity motif and nucleotide base), while structural rearrangements in switch II release α7 to allow oligomerization via a second interface. Mutagenesis confirmed the linear oligomer architecture.\",\n      \"method\": \"X-ray crystallography of multiple GIMAP2 constructs in different nucleotide states; site-directed mutagenesis to validate oligomerization interfaces\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structures at high resolution with functional mutagenesis validation in a single rigorous study\",\n      \"pmids\": [\"21059949\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"GIMAP2 oligomers function at the surface of lipid droplets in a Jurkat T cell line, demonstrating a role as a GTP-dependent protein scaffold on intracellular membranes.\",\n      \"method\": \"Cellular localization assay in Jurkat T cells; biochemical fractionation linked to structural data\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment tied to functional scaffold model, single lab, supported by structural data\",\n      \"pmids\": [\"21059949\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"GIMAP7, identified on lipid droplets, stimulates GTP hydrolysis by GIMAP2 via heterodimerization through an analogous mechanism to GIMAP7 homodimerization, where a catalytic arginine supplied in trans activates GTPase activity. This demonstrates that GTPase activity in the GIMAP family is controlled by homo- and heterodimerization.\",\n      \"method\": \"Crystal structure of GTP-bound GIMAP7 homodimer; in vitro GTP hydrolysis assays measuring GIMAP7-stimulated hydrolysis of GIMAP2; identification of catalytic arginine by structural analysis\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure plus in vitro enzymatic assay demonstrating trans-catalytic mechanism, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"23454188\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"GIMAP2 localizes to the endoplasmic reticulum and to the surface of lipid droplets in MDA-MB-436 cells, as confirmed by immunofluorescence of both endogenous and exogenous (mCherry-tagged) GIMAP2 co-stained with organelle-specific dyes imaged by super-resolution microscopy.\",\n      \"method\": \"Immunofluorescence staining of endogenous and exogenous GIMAP2-mCherry fusion protein; co-localization with organelle dyes (mitochondria, ER, lipid droplets) by super-resolution N-SIM microscopy\",\n      \"journal\": \"Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment with super-resolution imaging and orthogonal endogenous/exogenous confirmation, single lab\",\n      \"pmids\": [\"32306002\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"GIMAP2 knockdown in oral squamous cell carcinoma cells caused cell cycle arrest associated with downregulation of CDK4, CDK6, and phosphorylated Rb, and upregulation of p53 and p21; additionally, knockdown affected anti-apoptotic function by upregulating Bcl-2 and downregulating Bax and Bak.\",\n      \"method\": \"siRNA-mediated GIMAP2 knockdown in OSCC cell lines; immunoblotting for CDK4, CDK6, pRb, p53, p21, Bcl-2, Bax, Bak; cell growth and apoptosis assays\",\n      \"journal\": \"Oncology letters\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single knockdown approach with pathway readout but no rescue experiment or mechanistic placement beyond correlation\",\n      \"pmids\": [\"34992682\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GIMAP2 is a TRAFAC-class GTPase that exists as a monomer when GDP-bound or nucleotide-free (with amphipathic helix α7 packed against switch II) and forms linear oligomers upon GTP binding via two distinct G-domain interfaces; these oligomers serve as GTP-dependent scaffolds on the surface of lipid droplets and the endoplasmic reticulum, and GTPase activity of GIMAP2 can be stimulated in trans by heterodimerization with GIMAP7 through a catalytic arginine supplied by GIMAP7.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GIMAP2 is a TRAFAC-class guanine nucleotide-binding protein that functions as a GTP-dependent, self-assembling scaffold on intracellular membranes [#0, #1]. Crystal structures across nucleotide states establish that nucleotide-free and GDP-bound GIMAP2 is monomeric, with a distinctive amphipathic helix \\u03b17 packed against switch II, and that GTP binding drives assembly into linear oligomers through two distinct G-domain interfaces: a switch I-stabilized dimerization interface spanning the nucleotide-binding site and a second interface exposed when switch II rearrangement releases \\u03b17 [#0]. These GTP-loaded oligomers act as scaffolds at the surface of lipid droplets and the endoplasmic reticulum [#1, #3]. GIMAP2's own GTPase activity is intrinsically weak and is stimulated in trans by heterodimerization with GIMAP7, which supplies a catalytic arginine, establishing that GTP turnover in the GIMAP family is governed by homo- and heterodimerization [#2]. Beyond this nucleotide-cycling and scaffolding mechanism, the downstream cellular consequences of GIMAP2 activity remain largely uncharacterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Resolved how nucleotide state controls GIMAP2 conformation and self-assembly, defining it as a GTP-switch scaffold rather than a conventional signaling GTPase.\",\n      \"evidence\": \"X-ray crystallography of GIMAP2 in nucleotide-free, GDP-, and GTP-bound states with mutagenesis of oligomerization interfaces\",\n      \"pmids\": [\"21059949\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not identify what cargo or effectors the oligomeric scaffold recruits\",\n        \"Intrinsic GTPase rate and the trigger for nucleotide exchange in cells not defined\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Placed the GTP-dependent oligomer in a cellular context, showing GIMAP2 assembles on lipid droplet surfaces in T cells.\",\n      \"evidence\": \"Cellular localization and biochemical fractionation in Jurkat T cells linked to structural data\",\n      \"pmids\": [\"21059949\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of lipid droplet scaffolding not established\",\n        \"Single cell type; generality across tissues untested\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Explained how GIMAP2 GTPase activity is regulated, showing GIMAP7 acts as a trans-activating partner that supplies a catalytic arginine.\",\n      \"evidence\": \"Crystal structure of GTP-bound GIMAP7 homodimer plus in vitro GTP hydrolysis assays of GIMAP7-stimulated GIMAP2 turnover\",\n      \"pmids\": [\"23454188\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether GIMAP2-GIMAP7 heterodimers form at physiological levels in cells not shown\",\n        \"Upstream signals controlling heterodimer formation unknown\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Confirmed GIMAP2 membrane localization in a non-lymphoid (breast cancer) cell line, extending the scaffold model beyond T cells.\",\n      \"evidence\": \"Super-resolution immunofluorescence of endogenous and mCherry-tagged GIMAP2 co-stained with ER and lipid droplet markers in MDA-MB-436 cells\",\n      \"pmids\": [\"32306002\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Co-localization does not establish functional role at the ER\",\n        \"No interaction partners identified in this system\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"First attempt to connect GIMAP2 to a cellular phenotype, linking its loss to cell cycle arrest and apoptotic pathway changes in cancer cells.\",\n      \"evidence\": \"siRNA knockdown in oral squamous cell carcinoma lines with immunoblotting of cell cycle and apoptosis markers\",\n      \"pmids\": [\"34992682\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Correlative knockdown without rescue; off-target effects not excluded\",\n        \"No mechanistic link between the scaffolding/GTPase activity and the observed CDK4/6, p53/p21, or Bcl-2/Bax changes\",\n        \"Effects observed in a single tumor context\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The effectors and physiological substrates recruited by the GIMAP2 GTP-dependent oligomeric scaffold, and how its membrane scaffolding connects to cell cycle or apoptotic outcomes, remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No identified downstream effector bound by the oligomer\",\n        \"No mechanistic bridge between GTPase cycling and the cancer-cell phenotypes\",\n        \"Physiological function in T cells not directly tested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005811\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"GIMAP7\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":4,"faith_pct":75.0}}