{"gene":"SDIM1","run_date":"2026-06-10T07:46:30","timeline":{"discoveries":[{"year":2011,"finding":"SDIM1 protein localizes throughout the cytoplasm and neural processes of NT2 neurons, but is absent from the nucleus, as determined by direct localization experiments.","method":"Subcellular fractionation/immunolocalization in NT2 neurons","journal":"Molecular neurodegeneration","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment in neuronal cells, single lab, consistent with structural features (signal peptide, transmembrane domains)","pmids":["21255413"],"is_preprint":false},{"year":2011,"finding":"SDIM1 physically interacts with DNAJB4 (an HSP40 homolog and apoptosis enhancer), identified by yeast two-hybrid screening and confirmed by co-immunoprecipitation both in vitro and in vivo.","method":"Yeast two-hybrid screening and co-immunoprecipitation","journal":"Molecular neurodegeneration","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus yeast two-hybrid (two orthogonal methods), single lab","pmids":["21255413"],"is_preprint":false},{"year":2011,"finding":"Overexpression of SDIM1 in neuro-progenitor cells attenuates cell death caused by DNAJB4 overexpression, suggesting SDIM1 sequesters DNAJB4 to increase cell viability; conversely, SDIM1 knockdown accelerates OGD-induced cell death.","method":"Overexpression and siRNA knockdown in neuro-progenitor cells with cell viability assays under OGD stress","journal":"Molecular neurodegeneration","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function and gain-of-function with defined cellular phenotype, two complementary experimental approaches, single lab","pmids":["21255413"],"is_preprint":false},{"year":2011,"finding":"SDIM1 is a 146-amino-acid membrane protein containing a signal peptide and two transmembrane domains, characterizing its biochemical structure.","method":"Sequence analysis and biochemical characterization","journal":"Molecular neurodegeneration","confidence":"Low","confidence_rationale":"Tier 4 / Weak — based on computational sequence prediction, no structural validation reported in abstract","pmids":["21255413"],"is_preprint":false}],"current_model":"SDIM1 is a small neuron-enriched transmembrane protein that localizes to the cytoplasm and neural processes, promotes neuronal cell survival under stress conditions, and physically interacts with the pro-apoptotic HSP40 homolog DNAJB4 to sequester it and attenuate DNAJB4-induced cell death."},"narrative":{"mechanistic_narrative":"SDIM1 is a small neuron-enriched membrane protein that promotes neuronal survival under metabolic stress by antagonizing a pro-apoptotic chaperone [PMID:21255413]. It localizes throughout the cytoplasm and neural processes of NT2 neurons and is excluded from the nucleus [PMID:21255413]. Mechanistically, SDIM1 physically interacts with the HSP40 homolog and apoptosis enhancer DNAJB4, an association established by yeast two-hybrid screening and confirmed by reciprocal co-immunoprecipitation in vitro and in vivo [PMID:21255413]. Through this interaction SDIM1 sequesters DNAJB4: SDIM1 overexpression attenuates DNAJB4-induced cell death, while SDIM1 knockdown accelerates cell death under oxygen-glucose deprivation [PMID:21255413]. Beyond this DNAJB4-centered survival role, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2011,"claim":"Defined where SDIM1 acts in neurons, establishing it as a cytoplasmic rather than nuclear protein and constraining its possible mechanisms.","evidence":"Subcellular fractionation and immunolocalization in NT2 neurons","pmids":["21255413"],"confidence":"Medium","gaps":["Membrane compartment (ER, plasma membrane, vesicles) not resolved","Localization shown in a single neuronal cell type"]},{"year":2011,"claim":"Identified a direct binding partner for SDIM1, linking it to apoptotic machinery via the HSP40 homolog DNAJB4.","evidence":"Yeast two-hybrid screen with reciprocal co-immunoprecipitation in vitro and in vivo","pmids":["21255413"],"confidence":"Medium","gaps":["Binding interface and stoichiometry not mapped","Whether interaction is direct or bridged by other factors not resolved by Co-IP alone"]},{"year":2011,"claim":"Established the functional consequence of the SDIM1-DNAJB4 interaction, showing SDIM1 is cytoprotective against DNAJB4-driven and ischemic stress-induced death.","evidence":"Overexpression and siRNA knockdown in neuro-progenitor cells with viability assays under oxygen-glucose deprivation","pmids":["21255413"],"confidence":"Medium","gaps":["Molecular mechanism of sequestration not defined","Downstream apoptotic effectors not identified","No in vivo or animal-model validation"]},{"year":2011,"claim":"Characterized the predicted architecture of SDIM1 as a signal-peptide-bearing, two-transmembrane-domain protein.","evidence":"Sequence analysis and biochemical characterization","pmids":["21255413"],"confidence":"Low","gaps":["Based on computational prediction with no structural validation","Membrane topology not experimentally confirmed"]},{"year":null,"claim":"How SDIM1 sequestration of DNAJB4 mechanistically blocks apoptosis, and whether SDIM1 has roles beyond DNAJB4 regulation, remain unknown.","evidence":"No further studies in the available corpus","pmids":[],"confidence":"Low","gaps":["No structural model of the SDIM1-DNAJB4 complex","No identification of downstream death-pathway effectors","No in vivo survival or neurodegeneration model"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140313","term_label":"molecular sequestering activity","supporting_discovery_ids":[1,2]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[2]}],"complexes":[],"partners":["DNAJB4"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6ZPB5","full_name":"Stress-responsive DNAJB4-interacting membrane protein 1","aliases":[],"length_aa":146,"mass_kda":16.1,"function":"Promotes neuronal cells survival to stress conditions","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q6ZPB5/entry"},"depmap":{"release":"DepMap","has_data":false,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SDIM1"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SDIM1","total_profiled":1310},"omim":[{"mim_id":"621593","title":"STRESS-RESPONSIVE DNAJB4-INTERACTING MEMBRANE PROTEIN 1; SDIM1","url":"https://www.omim.org/entry/621593"}],"hpa":{"profiled":false,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"","tissue_distribution":"","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SDIM1"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q6ZPB5","domains":[{"cath_id":"-","chopping":"64-137","consensus_level":"high","plddt":32.9246,"start":64,"end":137}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZPB5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZPB5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZPB5-F1-predicted_aligned_error_v6.png","plddt_mean":30.2},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SDIM1","jax_strain_url":"https://www.jax.org/strain/search?query=SDIM1"},"sequence":{"accession":"Q6ZPB5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6ZPB5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6ZPB5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZPB5"}},"corpus_meta":[{"pmid":"21255413","id":"PMC_21255413","title":"A novel neuron-enriched protein SDIM1 is down regulated in Alzheimer's brains and attenuates cell death induced by DNAJB4 over-expression in neuro-progenitor cells.","date":"2011","source":"Molecular neurodegeneration","url":"https://pubmed.ncbi.nlm.nih.gov/21255413","citation_count":10,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2926,"output_tokens":814,"usd":0.010494,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7270,"output_tokens":1606,"usd":0.03825,"stage2_stop_reason":"end_turn"},"total_usd":0.048744,"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\": 2011,\n      \"finding\": \"SDIM1 protein localizes throughout the cytoplasm and neural processes of NT2 neurons, but is absent from the nucleus, as determined by direct localization experiments.\",\n      \"method\": \"Subcellular fractionation/immunolocalization in NT2 neurons\",\n      \"journal\": \"Molecular neurodegeneration\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment in neuronal cells, single lab, consistent with structural features (signal peptide, transmembrane domains)\",\n      \"pmids\": [\"21255413\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"SDIM1 physically interacts with DNAJB4 (an HSP40 homolog and apoptosis enhancer), identified by yeast two-hybrid screening and confirmed by co-immunoprecipitation both in vitro and in vivo.\",\n      \"method\": \"Yeast two-hybrid screening and co-immunoprecipitation\",\n      \"journal\": \"Molecular neurodegeneration\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus yeast two-hybrid (two orthogonal methods), single lab\",\n      \"pmids\": [\"21255413\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Overexpression of SDIM1 in neuro-progenitor cells attenuates cell death caused by DNAJB4 overexpression, suggesting SDIM1 sequesters DNAJB4 to increase cell viability; conversely, SDIM1 knockdown accelerates OGD-induced cell death.\",\n      \"method\": \"Overexpression and siRNA knockdown in neuro-progenitor cells with cell viability assays under OGD stress\",\n      \"journal\": \"Molecular neurodegeneration\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function and gain-of-function with defined cellular phenotype, two complementary experimental approaches, single lab\",\n      \"pmids\": [\"21255413\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"SDIM1 is a 146-amino-acid membrane protein containing a signal peptide and two transmembrane domains, characterizing its biochemical structure.\",\n      \"method\": \"Sequence analysis and biochemical characterization\",\n      \"journal\": \"Molecular neurodegeneration\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — based on computational sequence prediction, no structural validation reported in abstract\",\n      \"pmids\": [\"21255413\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SDIM1 is a small neuron-enriched transmembrane protein that localizes to the cytoplasm and neural processes, promotes neuronal cell survival under stress conditions, and physically interacts with the pro-apoptotic HSP40 homolog DNAJB4 to sequester it and attenuate DNAJB4-induced cell death.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SDIM1 is a small neuron-enriched membrane protein that promotes neuronal survival under metabolic stress by antagonizing a pro-apoptotic chaperone [#2]. It localizes throughout the cytoplasm and neural processes of NT2 neurons and is excluded from the nucleus [#0]. Mechanistically, SDIM1 physically interacts with the HSP40 homolog and apoptosis enhancer DNAJB4, an association established by yeast two-hybrid screening and confirmed by reciprocal co-immunoprecipitation in vitro and in vivo [#1]. Through this interaction SDIM1 sequesters DNAJB4: SDIM1 overexpression attenuates DNAJB4-induced cell death, while SDIM1 knockdown accelerates cell death under oxygen-glucose deprivation [#2]. Beyond this DNAJB4-centered survival role, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined where SDIM1 acts in neurons, establishing it as a cytoplasmic rather than nuclear protein and constraining its possible mechanisms.\",\n      \"evidence\": \"Subcellular fractionation and immunolocalization in NT2 neurons\",\n      \"pmids\": [\n        \"21255413\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Membrane compartment (ER, plasma membrane, vesicles) not resolved\",\n        \"Localization shown in a single neuronal cell type\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Identified a direct binding partner for SDIM1, linking it to apoptotic machinery via the HSP40 homolog DNAJB4.\",\n      \"evidence\": \"Yeast two-hybrid screen with reciprocal co-immunoprecipitation in vitro and in vivo\",\n      \"pmids\": [\n        \"21255413\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Binding interface and stoichiometry not mapped\",\n        \"Whether interaction is direct or bridged by other factors not resolved by Co-IP alone\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Established the functional consequence of the SDIM1-DNAJB4 interaction, showing SDIM1 is cytoprotective against DNAJB4-driven and ischemic stress-induced death.\",\n      \"evidence\": \"Overexpression and siRNA knockdown in neuro-progenitor cells with viability assays under oxygen-glucose deprivation\",\n      \"pmids\": [\n        \"21255413\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular mechanism of sequestration not defined\",\n        \"Downstream apoptotic effectors not identified\",\n        \"No in vivo or animal-model validation\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Characterized the predicted architecture of SDIM1 as a signal-peptide-bearing, two-transmembrane-domain protein.\",\n      \"evidence\": \"Sequence analysis and biochemical characterization\",\n      \"pmids\": [\n        \"21255413\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Based on computational prediction with no structural validation\",\n        \"Membrane topology not experimentally confirmed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SDIM1 sequestration of DNAJB4 mechanistically blocks apoptosis, and whether SDIM1 has roles beyond DNAJB4 regulation, remain unknown.\",\n      \"evidence\": \"No further studies in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of the SDIM1-DNAJB4 complex\",\n        \"No identification of downstream death-pathway effectors\",\n        \"No in vivo survival or neurodegeneration model\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0140313\",\n        \"supporting_discovery_ids\": [\n          1,\n          2\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005829\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-5357801\",\n        \"supporting_discovery_ids\": [\n          2\n        ]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"DNAJB4\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}