{"gene":"DESI1","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2012,"finding":"DESI1 (DeSI-1) is a novel SUMO-specific isopeptidase (deSUMOylase) that catalyzes deSUMOylation but not deubiquitination of its substrate BZEL, a transcriptional repressor. It does not deSUMOylate the SENP substrates PML and ΔNp63, establishing that SENP and DeSI enzymes recognize distinct substrate sets and represent two separate classes of SUMO proteases.","method":"In vitro deSUMOylation and deubiquitination assays with BZEL, PML, and ΔNp63 as substrates; biochemical characterization of DeSI-1 enzymatic activity","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzymatic assays with defined substrates, substrate specificity benchmarked against known SENP substrates, functional distinction from existing SUMO protease family","pmids":["22370726"],"is_preprint":false},{"year":2012,"finding":"The crystal structure of DeSI-1 reveals that it forms a homodimer, with the groove between the two subunits constituting the active site containing two absolutely conserved cysteine and histidine residues that form a catalytic dyad. DeSI-1 exhibits extremely low endopeptidase activity toward precursor forms of SUMO-1 and SUMO-2, unlike SENPs.","method":"X-ray crystallography; structure-guided identification of catalytic dyad residues; in vitro endopeptidase activity assay with SUMO-1 and SUMO-2 precursors","journal":"Proteins","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure solved and catalytic dyad identified structurally; functional activity assay performed; two orthogonal methods in one study","pmids":["22498933"],"is_preprint":false},{"year":2022,"finding":"PPPDE2 (DESI1), along with structurally related PPPDE1, possesses cysteine palmitoyl thioesterase (S-depalmitoylation) activity, in addition to its known deSUMOylase function, as demonstrated using fluorescent substrates. This activity is associated with the N1pC/P60 superfamily catalytic domain.","method":"In vitro fluorescent substrate-based thioesterase activity assay; crystal structure analysis; mutational analysis of predicted catalytic residues","journal":"Science advances","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro reconstitution with fluorescent substrate for DESI1/PPPDE2, but primary focus of paper is CLN5; DESI1/PPPDE2 is a secondary finding without dedicated mutagenesis or full validation for this paralog","pmids":["35427157"],"is_preprint":false},{"year":2024,"finding":"DESI1 is required for faithful chromosome segregation during cell division. Knockdown of DESI1 accelerated mitotic progression and increased abnormal chromosome segregation, phenotypes rescued by wild-type but not catalytically inactive DESI1, establishing that the isopeptidase activity is essential. DESI1 knockdown reduced Aurora B localization at metaphase chromosomes by decreasing Aurora B expression, and reduced transcription of FoxM1 target genes (Aurora B, cyclin B1, CENP-F), implicating DESI1 in the spindle assembly checkpoint (SAC) via FoxM1 transcriptional regulation.","method":"siRNA knockdown; rescue with wild-type vs. catalytically inactive DESI1; nocodazole mitotic arrest assay; immunofluorescence for Aurora B localization; RT-qPCR/western blot for FoxM1 target genes","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD/KO with defined cellular phenotype, catalytic-dead rescue experiment, multiple downstream readouts (Aurora B localization, FoxM1 targets), single lab","pmids":["39698932"],"is_preprint":false},{"year":2024,"finding":"DESI1 (and DESI2) can be covalently engaged by activity-based probes (ABPs) IMP-2587 and IMP-2586 developed for USP30, indicating that DESI1 harbors a reactive active-site cysteine accessible to electrophilic probes in intact cells.","method":"Proteomics analysis of probe-engaged proteins in intact cells; target engagement studies with activity-based probes","journal":"RSC chemical biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single proteomics observation as an incidental finding in a study focused on USP30; no dedicated mechanistic follow-up for DESI1","pmids":["38725909"],"is_preprint":false}],"current_model":"DESI1 is a PPPDE superfamily cysteine-histidine dyad isopeptidase that functions as a deSUMOylase (removing SUMO from substrates such as BZEL) distinct from the SENP family in substrate specificity, forms a homodimer with the active site at the dimer interface, and is required for faithful chromosome segregation in mitosis by maintaining FoxM1 transcriptional activity and thereby Aurora B expression and spindle assembly checkpoint function in a catalytic-activity-dependent manner; it may also possess S-depalmitoylation (thioesterase) activity shared with other PPPDE family members."},"narrative":{"mechanistic_narrative":"DESI1 (DeSI-1/PPPDE2) is a SUMO-specific isopeptidase that defines a class of deSUMOylating enzymes mechanistically and substrate-distinct from the SENP family [PMID:22370726]. It removes SUMO, but not ubiquitin, from the transcriptional repressor BZEL, and unlike SENPs does not act on the substrates PML or ΔNp63, establishing that DeSI and SENP enzymes recognize separate substrate sets [PMID:22370726]. Structurally, DESI1 functions as a homodimer in which the groove at the subunit interface forms the active site, built around a conserved cysteine–histidine catalytic dyad; consistent with its dedicated isopeptidase role it shows only minimal endopeptidase activity toward SUMO precursors, again contrasting with SENPs [PMID:22498933]. Through its catalytic activity DESI1 is required for faithful chromosome segregation: its loss accelerates mitotic progression and increases segregation errors, and rescue by wild-type but not catalytically inactive enzyme shows the isopeptidase function is essential; mechanistically DESI1 sustains FoxM1-dependent transcription of Aurora B, cyclin B1, and CENP-F, supporting Aurora B chromosomal localization and spindle assembly checkpoint integrity [PMID:39698932]. Beyond deSUMOylation, DESI1 additionally exhibits cysteine palmitoyl thioesterase (S-depalmitoylation) activity attributed to its N1pC/P60-type catalytic domain [PMID:35427157].","teleology":[{"year":2012,"claim":"Established that DESI1 is a SUMO protease of a previously unrecognized class, answering whether SUMO removal is restricted to the SENP family.","evidence":"In vitro deSUMOylation versus deubiquitination assays using BZEL, PML, and ΔNp63 substrates","pmids":["22370726"],"confidence":"High","gaps":["Substrate repertoire beyond BZEL not defined","Physiological consequences of BZEL deSUMOylation not established","No cellular or in vivo validation in this study"]},{"year":2012,"claim":"Defined the catalytic architecture, showing the active site forms at a homodimer interface around a Cys-His dyad and that DESI1 is a poor SUMO maturation enzyme, distinguishing it mechanistically from SENPs.","evidence":"X-ray crystallography with structure-guided catalytic residue identification and in vitro SUMO-1/SUMO-2 precursor endopeptidase assay","pmids":["22498933"],"confidence":"High","gaps":["No substrate-bound structure to explain specificity","Mechanism of substrate selection over SENP substrates unresolved"]},{"year":2022,"claim":"Expanded the catalytic repertoire by showing DESI1 also has S-depalmitoylation (thioesterase) activity, raising the possibility of a dual-activity enzyme.","evidence":"In vitro fluorescent substrate thioesterase assay with crystal structure and mutational analysis, as a secondary finding in a CLN5-focused study","pmids":["35427157"],"confidence":"Medium","gaps":["DESI1/PPPDE2 thioesterase activity lacks dedicated mutagenesis validation for this paralog","No cellular palmitoylation substrate identified","Relationship between deSUMOylase and thioesterase activities unknown"]},{"year":2024,"claim":"Connected DESI1 catalytic activity to a cellular function, demonstrating it is required for faithful chromosome segregation through FoxM1-dependent Aurora B expression and spindle assembly checkpoint function.","evidence":"siRNA knockdown with wild-type versus catalytic-dead rescue, nocodazole arrest, Aurora B immunofluorescence, and FoxM1 target gene RT-qPCR/western blot","pmids":["39698932"],"confidence":"Medium","gaps":["Direct SUMO substrate linking DESI1 to FoxM1 not identified","Whether FoxM1 itself is a DESI1 substrate unresolved","Single-lab finding without independent replication"]},{"year":2024,"claim":"Confirmed DESI1 has a reactive, probe-accessible active-site cysteine in cells, relevant for chemical-biology targeting.","evidence":"Proteomic target engagement with activity-based probes (IMP-2587/IMP-2586) as an incidental finding in a USP30-focused study","pmids":["38725909"],"confidence":"Low","gaps":["Single incidental proteomics observation with no dedicated DESI1 follow-up","Functional consequence of probe engagement unknown","Selectivity of probes for DESI1 not characterized"]},{"year":null,"claim":"The full substrate spectrum of DESI1 and how its deSUMOylase versus depalmitoylase activities are coordinated to control mitosis remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct deSUMOylation substrate connecting DESI1 to the FoxM1/Aurora B axis","Physiological palmitoylation substrates unidentified","No in vivo loss-of-function phenotype reported"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0016787","term_label":"hydrolase activity","supporting_discovery_ids":[0,2]}],"localization":[],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3]}],"complexes":["DESI1 homodimer"],"partners":["BZEL"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6ICB0","full_name":"Desumoylating isopeptidase 1","aliases":["PPPDE peptidase domain-containing protein 2","Palmitoyl protein thioesterase DESI1","Polyubiquitinated substrate transporter","POST","S-depalmitoylase DESI1"],"length_aa":168,"mass_kda":18.3,"function":"Protease which deconjugates SUMO1, SUMO2 and SUMO3 from some substrate proteins. Has isopeptidase but not SUMO-processing activity (By similarity). Desumoylates ZBTB46 (By similarity). Collaborates with UBQLN4 in the export of ubiquitinated proteins from the nucleus to the cytoplasm (PubMed:29666234). Exhibits palmitoyl protein thioesterase (S-depalmitoylation) activity towards synthetic substrates 4-methylumbelliferyl-6-S-palmitoyl-beta-D-glucopyranoside and S-depalmitoylation probe 5 (DPP-5) (PubMed:35427157)","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q6ICB0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DESI1","classification":"Not Classified","n_dependent_lines":13,"n_total_lines":1208,"dependency_fraction":0.01076158940397351},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DESI1","total_profiled":1310},"omim":[{"mim_id":"614639","title":"ZINC FINGER- AND BTB DOMAIN-CONTAINING PROTEIN 46; ZBTB46","url":"https://www.omim.org/entry/614639"},{"mim_id":"614637","title":"DESUMOYLATING ISOPEPTIDASE 1; DESI1","url":"https://www.omim.org/entry/614637"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"},{"location":"Cytokinetic bridge","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DESI1"},"hgnc":{"alias_symbol":["D15Wsu75e","DESI-1","POST"],"prev_symbol":["FAM152B","PPPDE2"]},"alphafold":{"accession":"Q6ICB0","domains":[{"cath_id":"3.90.1720.30","chopping":"6-158","consensus_level":"high","plddt":96.4385,"start":6,"end":158}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ICB0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ICB0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ICB0-F1-predicted_aligned_error_v6.png","plddt_mean":93.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DESI1","jax_strain_url":"https://www.jax.org/strain/search?query=DESI1"},"sequence":{"accession":"Q6ICB0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6ICB0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6ICB0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ICB0"}},"corpus_meta":[{"pmid":"22370726","id":"PMC_22370726","title":"DeSUMOylating isopeptidase: a second class of SUMO protease.","date":"2012","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/22370726","citation_count":167,"is_preprint":false},{"pmid":"22498933","id":"PMC_22498933","title":"Crystal structure of DeSI-1, a novel deSUMOylase belonging to a putative isopeptidase superfamily.","date":"2012","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/22498933","citation_count":35,"is_preprint":false},{"pmid":"35427157","id":"PMC_35427157","title":"Cln5 represents a new type of cysteine-based S-depalmitoylase linked to neurodegeneration.","date":"2022","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/35427157","citation_count":26,"is_preprint":false},{"pmid":"36655092","id":"PMC_36655092","title":"Chemical composition of kabuli and desi chickpea (Cicer arietinum L.) cultivars grown in Xinjiang, China.","date":"2022","source":"Food science & nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/36655092","citation_count":15,"is_preprint":false},{"pmid":"36407085","id":"PMC_36407085","title":"Downregulation of hsa-miR-135b-5p Inhibits Cell Proliferation, Migration, and Invasion in Colon Adenocarcinoma.","date":"2022","source":"Genetics research","url":"https://pubmed.ncbi.nlm.nih.gov/36407085","citation_count":8,"is_preprint":false},{"pmid":"38725909","id":"PMC_38725909","title":"Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30.","date":"2024","source":"RSC chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/38725909","citation_count":8,"is_preprint":false},{"pmid":"35932303","id":"PMC_35932303","title":"Modelling reoxygenation effects in non-small cell lung cancer cell lines and showing epithelial-mesenchymal transition.","date":"2022","source":"Journal of cancer research and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35932303","citation_count":6,"is_preprint":false},{"pmid":"39698932","id":"PMC_39698932","title":"DeSUMOylating isopeptidase 1 participates in the faithful chromosome segregation and vincristine sensitivity.","date":"2024","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/39698932","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6228,"output_tokens":1532,"usd":0.020832,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8227,"output_tokens":2222,"usd":0.048342,"stage2_stop_reason":"end_turn"},"total_usd":0.069174,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"DESI1 (DeSI-1) is a novel SUMO-specific isopeptidase (deSUMOylase) that catalyzes deSUMOylation but not deubiquitination of its substrate BZEL, a transcriptional repressor. It does not deSUMOylate the SENP substrates PML and ΔNp63, establishing that SENP and DeSI enzymes recognize distinct substrate sets and represent two separate classes of SUMO proteases.\",\n      \"method\": \"In vitro deSUMOylation and deubiquitination assays with BZEL, PML, and ΔNp63 as substrates; biochemical characterization of DeSI-1 enzymatic activity\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzymatic assays with defined substrates, substrate specificity benchmarked against known SENP substrates, functional distinction from existing SUMO protease family\",\n      \"pmids\": [\"22370726\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The crystal structure of DeSI-1 reveals that it forms a homodimer, with the groove between the two subunits constituting the active site containing two absolutely conserved cysteine and histidine residues that form a catalytic dyad. DeSI-1 exhibits extremely low endopeptidase activity toward precursor forms of SUMO-1 and SUMO-2, unlike SENPs.\",\n      \"method\": \"X-ray crystallography; structure-guided identification of catalytic dyad residues; in vitro endopeptidase activity assay with SUMO-1 and SUMO-2 precursors\",\n      \"journal\": \"Proteins\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure solved and catalytic dyad identified structurally; functional activity assay performed; two orthogonal methods in one study\",\n      \"pmids\": [\"22498933\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PPPDE2 (DESI1), along with structurally related PPPDE1, possesses cysteine palmitoyl thioesterase (S-depalmitoylation) activity, in addition to its known deSUMOylase function, as demonstrated using fluorescent substrates. This activity is associated with the N1pC/P60 superfamily catalytic domain.\",\n      \"method\": \"In vitro fluorescent substrate-based thioesterase activity assay; crystal structure analysis; mutational analysis of predicted catalytic residues\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro reconstitution with fluorescent substrate for DESI1/PPPDE2, but primary focus of paper is CLN5; DESI1/PPPDE2 is a secondary finding without dedicated mutagenesis or full validation for this paralog\",\n      \"pmids\": [\"35427157\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DESI1 is required for faithful chromosome segregation during cell division. Knockdown of DESI1 accelerated mitotic progression and increased abnormal chromosome segregation, phenotypes rescued by wild-type but not catalytically inactive DESI1, establishing that the isopeptidase activity is essential. DESI1 knockdown reduced Aurora B localization at metaphase chromosomes by decreasing Aurora B expression, and reduced transcription of FoxM1 target genes (Aurora B, cyclin B1, CENP-F), implicating DESI1 in the spindle assembly checkpoint (SAC) via FoxM1 transcriptional regulation.\",\n      \"method\": \"siRNA knockdown; rescue with wild-type vs. catalytically inactive DESI1; nocodazole mitotic arrest assay; immunofluorescence for Aurora B localization; RT-qPCR/western blot for FoxM1 target genes\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD/KO with defined cellular phenotype, catalytic-dead rescue experiment, multiple downstream readouts (Aurora B localization, FoxM1 targets), single lab\",\n      \"pmids\": [\"39698932\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DESI1 (and DESI2) can be covalently engaged by activity-based probes (ABPs) IMP-2587 and IMP-2586 developed for USP30, indicating that DESI1 harbors a reactive active-site cysteine accessible to electrophilic probes in intact cells.\",\n      \"method\": \"Proteomics analysis of probe-engaged proteins in intact cells; target engagement studies with activity-based probes\",\n      \"journal\": \"RSC chemical biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single proteomics observation as an incidental finding in a study focused on USP30; no dedicated mechanistic follow-up for DESI1\",\n      \"pmids\": [\"38725909\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DESI1 is a PPPDE superfamily cysteine-histidine dyad isopeptidase that functions as a deSUMOylase (removing SUMO from substrates such as BZEL) distinct from the SENP family in substrate specificity, forms a homodimer with the active site at the dimer interface, and is required for faithful chromosome segregation in mitosis by maintaining FoxM1 transcriptional activity and thereby Aurora B expression and spindle assembly checkpoint function in a catalytic-activity-dependent manner; it may also possess S-depalmitoylation (thioesterase) activity shared with other PPPDE family members.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DESI1 (DeSI-1/PPPDE2) is a SUMO-specific isopeptidase that defines a class of deSUMOylating enzymes mechanistically and substrate-distinct from the SENP family [#0]. It removes SUMO, but not ubiquitin, from the transcriptional repressor BZEL, and unlike SENPs does not act on the substrates PML or \\u0394Np63, establishing that DeSI and SENP enzymes recognize separate substrate sets [#0]. Structurally, DESI1 functions as a homodimer in which the groove at the subunit interface forms the active site, built around a conserved cysteine\\u2013histidine catalytic dyad; consistent with its dedicated isopeptidase role it shows only minimal endopeptidase activity toward SUMO precursors, again contrasting with SENPs [#1]. Through its catalytic activity DESI1 is required for faithful chromosome segregation: its loss accelerates mitotic progression and increases segregation errors, and rescue by wild-type but not catalytically inactive enzyme shows the isopeptidase function is essential; mechanistically DESI1 sustains FoxM1-dependent transcription of Aurora B, cyclin B1, and CENP-F, supporting Aurora B chromosomal localization and spindle assembly checkpoint integrity [#3]. Beyond deSUMOylation, DESI1 additionally exhibits cysteine palmitoyl thioesterase (S-depalmitoylation) activity attributed to its N1pC/P60-type catalytic domain [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established that DESI1 is a SUMO protease of a previously unrecognized class, answering whether SUMO removal is restricted to the SENP family.\",\n      \"evidence\": \"In vitro deSUMOylation versus deubiquitination assays using BZEL, PML, and \\u0394Np63 substrates\",\n      \"pmids\": [\"22370726\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Substrate repertoire beyond BZEL not defined\",\n        \"Physiological consequences of BZEL deSUMOylation not established\",\n        \"No cellular or in vivo validation in this study\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Defined the catalytic architecture, showing the active site forms at a homodimer interface around a Cys-His dyad and that DESI1 is a poor SUMO maturation enzyme, distinguishing it mechanistically from SENPs.\",\n      \"evidence\": \"X-ray crystallography with structure-guided catalytic residue identification and in vitro SUMO-1/SUMO-2 precursor endopeptidase assay\",\n      \"pmids\": [\"22498933\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No substrate-bound structure to explain specificity\",\n        \"Mechanism of substrate selection over SENP substrates unresolved\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Expanded the catalytic repertoire by showing DESI1 also has S-depalmitoylation (thioesterase) activity, raising the possibility of a dual-activity enzyme.\",\n      \"evidence\": \"In vitro fluorescent substrate thioesterase assay with crystal structure and mutational analysis, as a secondary finding in a CLN5-focused study\",\n      \"pmids\": [\"35427157\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"DESI1/PPPDE2 thioesterase activity lacks dedicated mutagenesis validation for this paralog\",\n        \"No cellular palmitoylation substrate identified\",\n        \"Relationship between deSUMOylase and thioesterase activities unknown\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Connected DESI1 catalytic activity to a cellular function, demonstrating it is required for faithful chromosome segregation through FoxM1-dependent Aurora B expression and spindle assembly checkpoint function.\",\n      \"evidence\": \"siRNA knockdown with wild-type versus catalytic-dead rescue, nocodazole arrest, Aurora B immunofluorescence, and FoxM1 target gene RT-qPCR/western blot\",\n      \"pmids\": [\"39698932\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct SUMO substrate linking DESI1 to FoxM1 not identified\",\n        \"Whether FoxM1 itself is a DESI1 substrate unresolved\",\n        \"Single-lab finding without independent replication\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Confirmed DESI1 has a reactive, probe-accessible active-site cysteine in cells, relevant for chemical-biology targeting.\",\n      \"evidence\": \"Proteomic target engagement with activity-based probes (IMP-2587/IMP-2586) as an incidental finding in a USP30-focused study\",\n      \"pmids\": [\"38725909\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single incidental proteomics observation with no dedicated DESI1 follow-up\",\n        \"Functional consequence of probe engagement unknown\",\n        \"Selectivity of probes for DESI1 not characterized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The full substrate spectrum of DESI1 and how its deSUMOylase versus depalmitoylase activities are coordinated to control mitosis remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct deSUMOylation substrate connecting DESI1 to the FoxM1/Aurora B axis\",\n        \"Physiological palmitoylation substrates unidentified\",\n        \"No in vivo loss-of-function phenotype reported\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0016787\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"DESI1 homodimer\"\n    ],\n    \"partners\": [\n      \"BZEL\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}