{"gene":"WDTC1","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2016,"finding":"WDTC1 is a component of a DDB1-CUL4-ROC1 (CRL4) E3 ubiquitin ligase complex. Disrupting the interaction between WDTC1 and DDB1 abolishes WDTC1-mediated suppression of adipogenesis, leading to increased triglyceride accumulation and adipogenic gene expression in 3T3-L1 cells. The CRL4(WDTC1) complex promotes histone H2AK119 monoubiquitylation, implicating it in transcriptional repression during adipogenesis.","method":"Co-immunoprecipitation to identify DDB1-CUL4-ROC1 complex components; mutagenesis to disrupt WDTC1-DDB1 interaction; 3T3-L1 adipogenesis cell culture model with triglyceride accumulation and gene expression readouts; histone H2AK119 monoubiquitylation assay","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP identifying complex components, mutagenesis of interaction interface with functional adipogenesis phenotype, and histone ubiquitylation assay; single lab with multiple orthogonal methods","pmids":["27113764"],"is_preprint":false}],"current_model":"WDTC1 functions as a substrate receptor subunit of the CRL4 (DDB1-CUL4-ROC1) E3 ubiquitin ligase complex, where its interaction with DDB1 is required for suppression of adipogenesis; the CRL4(WDTC1) complex promotes histone H2AK119 monoubiquitylation, suggesting it suppresses fat accumulation through transcriptional repression."},"narrative":{"mechanistic_narrative":"WDTC1 acts as a suppressor of adipogenesis by serving as the substrate-receptor subunit of a CRL4 (DDB1-CUL4-ROC1) E3 ubiquitin ligase complex [PMID:27113764]. Its direct interaction with DDB1 is required for this function: disrupting the WDTC1-DDB1 interface abolishes suppression of fat accumulation, leading to increased triglyceride accumulation and elevated adipogenic gene expression in 3T3-L1 cells [PMID:27113764]. The CRL4(WDTC1) complex promotes histone H2AK119 monoubiquitylation, linking its activity to transcriptional repression of the adipogenic program [PMID:27113764]. Beyond this single characterization, no further mechanistic detail—including direct ubiquitylation substrates or structural basis of substrate recognition—has been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Established that WDTC1 suppresses adipogenesis as a substrate receptor of a CRL4 E3 ligase, defining a molecular mechanism (DDB1-dependent assembly and histone H2AK119 monoubiquitylation) for its anti-fat-accumulation role.","evidence":"Co-immunoprecipitation of DDB1-CUL4-ROC1 components, mutagenesis disrupting the WDTC1-DDB1 interface with triglyceride and adipogenic gene-expression readouts in 3T3-L1 cells, and an H2AK119 monoubiquitylation assay","pmids":["27113764"],"confidence":"Medium","gaps":["No direct ubiquitylation substrate of CRL4(WDTC1) was identified","The causal link between H2AK119 monoubiquitylation and specific repressed adipogenic genes was not resolved","Findings rest on a single lab and a single cell-culture model without in vivo validation"]},{"year":null,"claim":"The substrate(s) ubiquitylated by CRL4(WDTC1) and the structural basis of substrate recognition remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No protein substrate identified","No structural model of WDTC1-DDB1 or substrate engagement","Mechanism connecting histone ubiquitylation to transcriptional repression not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016874","term_label":"ligase activity","supporting_discovery_ids":[0]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0]}],"localization":[],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0]}],"complexes":["CRL4 (DDB1-CUL4-ROC1) E3 ubiquitin ligase"],"partners":["DDB1","CUL4","RBX1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8N5D0","full_name":"WD and tetratricopeptide repeats protein 1","aliases":[],"length_aa":677,"mass_kda":75.9,"function":"May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q8N5D0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/WDTC1","classification":"Not Classified","n_dependent_lines":151,"n_total_lines":1208,"dependency_fraction":0.125},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DDB1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/WDTC1","total_profiled":1310},"omim":[{"mim_id":"619763","title":"WD AND TETRATRICOPEPTIDE REPEATS PROTEIN 1; WDTC1","url":"https://www.omim.org/entry/619763"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Vesicles","reliability":"Supported"},{"location":"Golgi apparatus","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/WDTC1"},"hgnc":{"alias_symbol":["KIAA1037","ADP","DCAF9"],"prev_symbol":[]},"alphafold":{"accession":"Q8N5D0","domains":[{"cath_id":"2.130.10.10","chopping":"30-221_242-303_525-608","consensus_level":"medium","plddt":95.1778,"start":30,"end":608},{"cath_id":"1.25.40.10","chopping":"359-486","consensus_level":"high","plddt":95.5997,"start":359,"end":486}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N5D0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N5D0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N5D0-F1-predicted_aligned_error_v6.png","plddt_mean":81.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=WDTC1","jax_strain_url":"https://www.jax.org/strain/search?query=WDTC1"},"sequence":{"accession":"Q8N5D0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N5D0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N5D0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N5D0"}},"corpus_meta":[{"pmid":"21399626","id":"PMC_21399626","title":"Structure of mammalian AMPK and its regulation by ADP.","date":"2011","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/21399626","citation_count":736,"is_preprint":false},{"pmid":"1731253","id":"PMC_1731253","title":"Structure of the recA protein-ADP complex.","date":"1992","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/1731253","citation_count":581,"is_preprint":false},{"pmid":"1530940","id":"PMC_1530940","title":"Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase.","date":"1992","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1530940","citation_count":402,"is_preprint":false},{"pmid":"11487010","id":"PMC_11487010","title":"ADP receptors of platelets and their inhibition.","date":"2001","source":"Thrombosis and haemostasis","url":"https://pubmed.ncbi.nlm.nih.gov/11487010","citation_count":312,"is_preprint":false},{"pmid":"28190768","id":"PMC_28190768","title":"Serine ADP-Ribosylation Depends on HPF1.","date":"2017","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/28190768","citation_count":301,"is_preprint":false},{"pmid":"11461113","id":"PMC_11461113","title":"Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism.","date":"2001","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/11461113","citation_count":266,"is_preprint":false},{"pmid":"34323016","id":"PMC_34323016","title":"ADP-ribosyltransferases, an update on function and nomenclature.","date":"2021","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/34323016","citation_count":257,"is_preprint":false},{"pmid":"20105026","id":"PMC_20105026","title":"ADP-Glo: A Bioluminescent and homogeneous ADP monitoring assay for kinases.","date":"2009","source":"Assay and drug development technologies","url":"https://pubmed.ncbi.nlm.nih.gov/20105026","citation_count":234,"is_preprint":false},{"pmid":"16912299","id":"PMC_16912299","title":"Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains.","date":"2006","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/16912299","citation_count":208,"is_preprint":false},{"pmid":"25758918","id":"PMC_25758918","title":"Trapping Poly(ADP-Ribose) Polymerase.","date":"2015","source":"The Journal of pharmacology and experimental therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/25758918","citation_count":185,"is_preprint":false},{"pmid":"34671164","id":"PMC_34671164","title":"Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34671164","citation_count":170,"is_preprint":false},{"pmid":"32029451","id":"PMC_32029451","title":"(ADP-ribosyl)hydrolases: structure, function, and biology.","date":"2020","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/32029451","citation_count":168,"is_preprint":false},{"pmid":"26091340","id":"PMC_26091340","title":"The Promise of Proteomics for the Study of ADP-Ribosylation.","date":"2015","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/26091340","citation_count":167,"is_preprint":false},{"pmid":"1326536","id":"PMC_1326536","title":"Histone shuttling by poly(ADP-ribosylation).","date":"1992","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1326536","citation_count":157,"is_preprint":false},{"pmid":"23290998","id":"PMC_23290998","title":"Poly(ADP-ribose): PARadigms and PARadoxes.","date":"2013","source":"Molecular aspects of medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23290998","citation_count":156,"is_preprint":false},{"pmid":"26091339","id":"PMC_26091339","title":"PARPs and ADP-Ribosylation: 50 Years … and Counting.","date":"2015","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/26091339","citation_count":156,"is_preprint":false},{"pmid":"10521355","id":"PMC_10521355","title":"ADP receptors and clinical bleeding disorders.","date":"1999","source":"Arteriosclerosis, thrombosis, and vascular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10521355","citation_count":152,"is_preprint":false},{"pmid":"24191052","id":"PMC_24191052","title":"ADP-ribosyl-acceptor hydrolase 3 regulates poly (ADP-ribose) degradation and cell death during oxidative stress.","date":"2013","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24191052","citation_count":142,"is_preprint":false},{"pmid":"37832523","id":"PMC_37832523","title":"ADP-ribosylation from molecular mechanisms to therapeutic implications.","date":"2023","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/37832523","citation_count":141,"is_preprint":false},{"pmid":"16368572","id":"PMC_16368572","title":"The role of ADP receptors in platelet function.","date":"2006","source":"Frontiers in bioscience : a journal and virtual library","url":"https://pubmed.ncbi.nlm.nih.gov/16368572","citation_count":140,"is_preprint":false},{"pmid":"31216043","id":"PMC_31216043","title":"Reversible ADP-ribosylation of RNA.","date":"2019","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/31216043","citation_count":134,"is_preprint":false},{"pmid":"15665114","id":"PMC_15665114","title":"P2Y1 and P2Y12 receptors for ADP desensitize by distinct kinase-dependent mechanisms.","date":"2005","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/15665114","citation_count":133,"is_preprint":false},{"pmid":"10544961","id":"PMC_10544961","title":"Poly(ADP-ribosylation) and apoptosis.","date":"1999","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10544961","citation_count":128,"is_preprint":false},{"pmid":"28383827","id":"PMC_28383827","title":"ADP-ribosylation: new facets of an ancient modification.","date":"2017","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/28383827","citation_count":126,"is_preprint":false},{"pmid":"25789582","id":"PMC_25789582","title":"Processing of protein ADP-ribosylation by Nudix hydrolases.","date":"2015","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/25789582","citation_count":125,"is_preprint":false},{"pmid":"23622245","id":"PMC_23622245","title":"Proteasome regulation by ADP-ribosylation.","date":"2013","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/23622245","citation_count":125,"is_preprint":false},{"pmid":"6088227","id":"PMC_6088227","title":"Poly(ADP-ribose) polymerase is a zinc metalloenzyme.","date":"1984","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/6088227","citation_count":116,"is_preprint":false},{"pmid":"20652610","id":"PMC_20652610","title":"ADP-ribosylation of arginine.","date":"2010","source":"Amino acids","url":"https://pubmed.ncbi.nlm.nih.gov/20652610","citation_count":115,"is_preprint":false},{"pmid":"8016893","id":"PMC_8016893","title":"Receptors for ADP on human blood platelets.","date":"1994","source":"Trends in pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/8016893","citation_count":113,"is_preprint":false},{"pmid":"29361132","id":"PMC_29361132","title":"Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: new insights into DNA ADP-ribosylation.","date":"2018","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/29361132","citation_count":106,"is_preprint":false},{"pmid":"8143921","id":"PMC_8143921","title":"Cyclic ADP-ribose, the ADP-ribosyl cyclase pathway and calcium signalling.","date":"1994","source":"Molecular and cellular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/8143921","citation_count":105,"is_preprint":false},{"pmid":"15868399","id":"PMC_15868399","title":"Regulation of poly(ADP-ribose) metabolism by poly(ADP-ribose) glycohydrolase: where and when?","date":"2005","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/15868399","citation_count":104,"is_preprint":false},{"pmid":"2407587","id":"PMC_2407587","title":"Aggregin: a platelet ADP receptor that mediates activation.","date":"1990","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/2407587","citation_count":98,"is_preprint":false},{"pmid":"34116477","id":"PMC_34116477","title":"ADP-ribosylation of DNA and RNA.","date":"2021","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/34116477","citation_count":94,"is_preprint":false},{"pmid":"32244383","id":"PMC_32244383","title":"The Viral Macrodomain Counters Host Antiviral ADP-Ribosylation.","date":"2020","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/32244383","citation_count":93,"is_preprint":false},{"pmid":"30991935","id":"PMC_30991935","title":"ADP-ribosylation signalling and human disease.","date":"2019","source":"Open biology","url":"https://pubmed.ncbi.nlm.nih.gov/30991935","citation_count":89,"is_preprint":false},{"pmid":"22547677","id":"PMC_22547677","title":"Histone ADP-ribosylation facilitates gene transcription by directly remodeling nucleosomes.","date":"2012","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/22547677","citation_count":88,"is_preprint":false},{"pmid":"9444477","id":"PMC_9444477","title":"ADP-induced platelet activation.","date":"1997","source":"Critical reviews in biochemistry and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/9444477","citation_count":87,"is_preprint":false},{"pmid":"15868397","id":"PMC_15868397","title":"Introduction to poly(ADP-ribose) metabolism.","date":"2005","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/15868397","citation_count":87,"is_preprint":false},{"pmid":"14566854","id":"PMC_14566854","title":"Poly(ADP-ribose) and carcinogenesis.","date":"2003","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/14566854","citation_count":85,"is_preprint":false},{"pmid":"26091344","id":"PMC_26091344","title":"RNA Regulation by Poly(ADP-Ribose) Polymerases.","date":"2015","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/26091344","citation_count":84,"is_preprint":false},{"pmid":"21518389","id":"PMC_21518389","title":"Anti-platelet therapy: ADP receptor antagonists.","date":"2011","source":"British journal of clinical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/21518389","citation_count":84,"is_preprint":false},{"pmid":"9683009","id":"PMC_9683009","title":"Role of poly(ADP-ribose)synthetase in inflammation.","date":"1998","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/9683009","citation_count":83,"is_preprint":false},{"pmid":"18508690","id":"PMC_18508690","title":"Mammalian ADP-ribosyltransferases and ADP-ribosylhydrolases.","date":"2008","source":"Frontiers in bioscience : a journal and virtual library","url":"https://pubmed.ncbi.nlm.nih.gov/18508690","citation_count":82,"is_preprint":false},{"pmid":"34314702","id":"PMC_34314702","title":"Ribosome ADP-ribosylation inhibits translation and maintains proteostasis in cancers.","date":"2021","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/34314702","citation_count":79,"is_preprint":false},{"pmid":"24508339","id":"PMC_24508339","title":"The mitochondrial fission receptor MiD51 requires ADP as a cofactor.","date":"2014","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/24508339","citation_count":79,"is_preprint":false},{"pmid":"11890553","id":"PMC_11890553","title":"The ARTT motif and a unified structural understanding of substrate recognition in ADP-ribosylating bacterial toxins and eukaryotic ADP-ribosyltransferases.","date":"2002","source":"International journal of medical microbiology : IJMM","url":"https://pubmed.ncbi.nlm.nih.gov/11890553","citation_count":77,"is_preprint":false},{"pmid":"15749861","id":"PMC_15749861","title":"CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins.","date":"2005","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/15749861","citation_count":76,"is_preprint":false},{"pmid":"25706250","id":"PMC_25706250","title":"Synthesis of dimeric ADP-ribose and its structure with human poly(ADP-ribose) glycohydrolase.","date":"2015","source":"Journal of the American Chemical Society","url":"https://pubmed.ncbi.nlm.nih.gov/25706250","citation_count":76,"is_preprint":false},{"pmid":"21482174","id":"PMC_21482174","title":"Poly(ADP-ribosyl)ation in plants.","date":"2011","source":"Trends in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/21482174","citation_count":75,"is_preprint":false},{"pmid":"26426055","id":"PMC_26426055","title":"Intracellular Mono-ADP-Ribosylation in Signaling and Disease.","date":"2015","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/26426055","citation_count":75,"is_preprint":false},{"pmid":"15313399","id":"PMC_15313399","title":"Modulation of poly(ADP-ribosylation) in apoptotic cells.","date":"2004","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/15313399","citation_count":75,"is_preprint":false},{"pmid":"14529392","id":"PMC_14529392","title":"ADP receptors--targets for developing antithrombotic agents.","date":"2003","source":"Current pharmaceutical design","url":"https://pubmed.ncbi.nlm.nih.gov/14529392","citation_count":73,"is_preprint":false},{"pmid":"27406238","id":"PMC_27406238","title":"ENPP1 processes protein ADP-ribosylation in vitro.","date":"2016","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/27406238","citation_count":72,"is_preprint":false},{"pmid":"25938242","id":"PMC_25938242","title":"ADP-ribosyltransferases and poly ADP-ribosylation.","date":"2015","source":"Current protein & peptide science","url":"https://pubmed.ncbi.nlm.nih.gov/25938242","citation_count":69,"is_preprint":false},{"pmid":"33060572","id":"PMC_33060572","title":"Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/33060572","citation_count":69,"is_preprint":false},{"pmid":"34408320","id":"PMC_34408320","title":"Molecular basis for DarT ADP-ribosylation of a DNA base.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34408320","citation_count":69,"is_preprint":false},{"pmid":"37703374","id":"PMC_37703374","title":"PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities.","date":"2023","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/37703374","citation_count":62,"is_preprint":false},{"pmid":"30712989","id":"PMC_30712989","title":"ELTA: Enzymatic Labeling of Terminal ADP-Ribose.","date":"2019","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/30712989","citation_count":62,"is_preprint":false},{"pmid":"27138857","id":"PMC_27138857","title":"Wnt pathway activation by ADP-ribosylation.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/27138857","citation_count":62,"is_preprint":false},{"pmid":"10759027","id":"PMC_10759027","title":"Cyclic ADP-ribose.","date":"2000","source":"Journal of molecular medicine (Berlin, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/10759027","citation_count":58,"is_preprint":false},{"pmid":"7898463","id":"PMC_7898463","title":"Inhibitors and activators of ADP-ribosylation reactions.","date":"1994","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/7898463","citation_count":57,"is_preprint":false},{"pmid":"7898467","id":"PMC_7898467","title":"Enzymatic and nonenzymatic ADP-ribosylation of cysteine.","date":"1994","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/7898467","citation_count":57,"is_preprint":false},{"pmid":"29199039","id":"PMC_29199039","title":"The coronavirus nucleocapsid protein is ADP-ribosylated.","date":"2017","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/29199039","citation_count":55,"is_preprint":false},{"pmid":"30658897","id":"PMC_30658897","title":"Regulating Immunity via ADP-Ribosylation: Therapeutic Implications and Beyond.","date":"2019","source":"Trends in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30658897","citation_count":55,"is_preprint":false},{"pmid":"27507885","id":"PMC_27507885","title":"ADPriboDB: The database of ADP-ribosylated proteins.","date":"2016","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/27507885","citation_count":55,"is_preprint":false},{"pmid":"7898476","id":"PMC_7898476","title":"Histone shuttling by poly ADP-ribosylation.","date":"1994","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/7898476","citation_count":54,"is_preprint":false},{"pmid":"30910692","id":"PMC_30910692","title":"Mitotic functions of poly(ADP-ribose) polymerases.","date":"2019","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/30910692","citation_count":52,"is_preprint":false},{"pmid":"8527483","id":"PMC_8527483","title":"ADP-ribosylation reactions.","date":"1995","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/8527483","citation_count":52,"is_preprint":false},{"pmid":"34025930","id":"PMC_34025930","title":"ADP-ribosylation systems in bacteria and viruses.","date":"2021","source":"Computational and structural biotechnology journal","url":"https://pubmed.ncbi.nlm.nih.gov/34025930","citation_count":51,"is_preprint":false},{"pmid":"29397193","id":"PMC_29397193","title":"The poly (ADP ribose) polymerase inhibitor niraparib: Management of toxicities.","date":"2018","source":"Gynecologic oncology","url":"https://pubmed.ncbi.nlm.nih.gov/29397193","citation_count":51,"is_preprint":false},{"pmid":"19105632","id":"PMC_19105632","title":"Proteomic investigation of phosphorylation sites in poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase.","date":"2009","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/19105632","citation_count":51,"is_preprint":false},{"pmid":"31930280","id":"PMC_31930280","title":"ADP-ribosylation: from molecular mechanisms to human disease.","date":"2019","source":"Genetics and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/31930280","citation_count":49,"is_preprint":false},{"pmid":"15959554","id":"PMC_15959554","title":"Poly(ADP-ribosylation) and genomic stability.","date":"2005","source":"Biochemistry and cell biology = Biochimie et biologie cellulaire","url":"https://pubmed.ncbi.nlm.nih.gov/15959554","citation_count":48,"is_preprint":false},{"pmid":"27002155","id":"PMC_27002155","title":"Scabin, a Novel DNA-acting ADP-ribosyltransferase from Streptomyces scabies.","date":"2016","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27002155","citation_count":46,"is_preprint":false},{"pmid":"26091348","id":"PMC_26091348","title":"SnapShot: ADP-Ribosylation Signaling.","date":"2015","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/26091348","citation_count":45,"is_preprint":false},{"pmid":"18076209","id":"PMC_18076209","title":"ADP receptor antagonism: what's in the pipeline?","date":"2007","source":"American journal of cardiovascular drugs : drugs, devices, and other interventions","url":"https://pubmed.ncbi.nlm.nih.gov/18076209","citation_count":45,"is_preprint":false},{"pmid":"16515502","id":"PMC_16515502","title":"The platelet ATP and ADP receptors.","date":"2006","source":"Current pharmaceutical design","url":"https://pubmed.ncbi.nlm.nih.gov/16515502","citation_count":45,"is_preprint":false},{"pmid":"35084332","id":"PMC_35084332","title":"Legionella pneumophila modulates host energy metabolism by ADP-ribosylation of ADP/ATP translocases.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35084332","citation_count":45,"is_preprint":false},{"pmid":"23714734","id":"PMC_23714734","title":"Poly(ADP-ribosyl)ation in carcinogenesis.","date":"2013","source":"Molecular aspects of medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23714734","citation_count":43,"is_preprint":false},{"pmid":"25263235","id":"PMC_25263235","title":"Proteomics approaches to identify mono-(ADP-ribosyl)ated and poly(ADP-ribosyl)ated proteins.","date":"2014","source":"Proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/25263235","citation_count":42,"is_preprint":false},{"pmid":"9193679","id":"PMC_9193679","title":"ADP-ribose in glycation and glycoxidation reactions.","date":"1997","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/9193679","citation_count":41,"is_preprint":false},{"pmid":"21697277","id":"PMC_21697277","title":"ADP-ribosylarginine hydrolase regulates cell proliferation and tumorigenesis.","date":"2011","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/21697277","citation_count":41,"is_preprint":false},{"pmid":"35130321","id":"PMC_35130321","title":"Poly(ADP-ribose) potentiates ZAP antiviral activity.","date":"2022","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/35130321","citation_count":40,"is_preprint":false},{"pmid":"25477523","id":"PMC_25477523","title":"C3larvin toxin, an ADP-ribosyltransferase from Paenibacillus larvae.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25477523","citation_count":40,"is_preprint":false},{"pmid":"35039483","id":"PMC_35039483","title":"Truncated PARP1 mediates ADP-ribosylation of RNA polymerase III for apoptosis.","date":"2022","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/35039483","citation_count":40,"is_preprint":false},{"pmid":"11717273","id":"PMC_11717273","title":"ADP-dependent phosphofructokinases in mesophilic and thermophilic methanogenic archaea.","date":"2001","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/11717273","citation_count":40,"is_preprint":false},{"pmid":"27113764","id":"PMC_27113764","title":"The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase.","date":"2016","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/27113764","citation_count":39,"is_preprint":false},{"pmid":"38000390","id":"PMC_38000390","title":"DELTEX E3 ligases ubiquitylate ADP-ribosyl modification on nucleic acids.","date":"2024","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/38000390","citation_count":38,"is_preprint":false},{"pmid":"34508355","id":"PMC_34508355","title":"TARG1 protects against toxic DNA ADP-ribosylation.","date":"2021","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/34508355","citation_count":36,"is_preprint":false},{"pmid":"15171957","id":"PMC_15171957","title":"Platelet ADP receptor antagonists: ticlopidine and clopidogrel.","date":"2004","source":"Best practice & research. Clinical haematology","url":"https://pubmed.ncbi.nlm.nih.gov/15171957","citation_count":36,"is_preprint":false},{"pmid":"37587340","id":"PMC_37587340","title":"A viral ADP-ribosyltransferase attaches RNA chains to host proteins.","date":"2023","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/37587340","citation_count":35,"is_preprint":false},{"pmid":"34786571","id":"PMC_34786571","title":"A molecular toolbox for ADP-ribosyl binding proteins.","date":"2021","source":"Cell reports methods","url":"https://pubmed.ncbi.nlm.nih.gov/34786571","citation_count":34,"is_preprint":false},{"pmid":"27697151","id":"PMC_27697151","title":"Inhibiting poly(ADP-ribosylation) improves axon regeneration.","date":"2016","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/27697151","citation_count":34,"is_preprint":false},{"pmid":"27090904","id":"PMC_27090904","title":"Players in ADP-ribosylation: Readers and Erasers.","date":"2016","source":"Current protein & peptide science","url":"https://pubmed.ncbi.nlm.nih.gov/27090904","citation_count":33,"is_preprint":false},{"pmid":"22219026","id":"PMC_22219026","title":"Expression and role in glycolysis of human ADP-dependent glucokinase.","date":"2012","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22219026","citation_count":33,"is_preprint":false},{"pmid":"31911551","id":"PMC_31911551","title":"Nudix Hydrolase NUDT16 Regulates 53BP1 Protein by Reversing 53BP1 ADP-Ribosylation.","date":"2020","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/31911551","citation_count":33,"is_preprint":false},{"pmid":"11991201","id":"PMC_11991201","title":"Pancreatic beta-cell death, regeneration and insulin secretion: roles of poly(ADP-ribose) polymerase and cyclic ADP-ribose.","date":"2002","source":"International journal of experimental diabetes research","url":"https://pubmed.ncbi.nlm.nih.gov/11991201","citation_count":33,"is_preprint":false},{"pmid":"15582275","id":"PMC_15582275","title":"Poly(ADP-ribosyl)ation and aging.","date":"2004","source":"Experimental gerontology","url":"https://pubmed.ncbi.nlm.nih.gov/15582275","citation_count":32,"is_preprint":false},{"pmid":"37115110","id":"PMC_37115110","title":"Regulation of Biomolecular Condensates by Poly(ADP-ribose).","date":"2023","source":"Chemical reviews","url":"https://pubmed.ncbi.nlm.nih.gov/37115110","citation_count":32,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":42778,"output_tokens":619,"usd":0.068809,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6751,"output_tokens":1100,"usd":0.030627,"stage2_stop_reason":"end_turn"},"total_usd":0.099436,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the 100 abstracts, I need to identify papers specifically about WDTC1 (also known as KIAA1037, ADP, DCAF9).\n\nOnly paper [88] is directly about WDTC1/Adp. All other papers are about ADP (adenosine diphosphate) the molecule, PARP enzymes, platelet ADP receptors, or other unrelated proteins. Paper [88] describes mechanistic findings about WDTC1 protein.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"WDTC1 is a component of a DDB1-CUL4-ROC1 (CRL4) E3 ubiquitin ligase complex. Disrupting the interaction between WDTC1 and DDB1 abolishes WDTC1-mediated suppression of adipogenesis, leading to increased triglyceride accumulation and adipogenic gene expression in 3T3-L1 cells. The CRL4(WDTC1) complex promotes histone H2AK119 monoubiquitylation, implicating it in transcriptional repression during adipogenesis.\",\n      \"method\": \"Co-immunoprecipitation to identify DDB1-CUL4-ROC1 complex components; mutagenesis to disrupt WDTC1-DDB1 interaction; 3T3-L1 adipogenesis cell culture model with triglyceride accumulation and gene expression readouts; histone H2AK119 monoubiquitylation assay\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP identifying complex components, mutagenesis of interaction interface with functional adipogenesis phenotype, and histone ubiquitylation assay; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"27113764\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"WDTC1 functions as a substrate receptor subunit of the CRL4 (DDB1-CUL4-ROC1) E3 ubiquitin ligase complex, where its interaction with DDB1 is required for suppression of adipogenesis; the CRL4(WDTC1) complex promotes histone H2AK119 monoubiquitylation, suggesting it suppresses fat accumulation through transcriptional repression.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"WDTC1 acts as a suppressor of adipogenesis by serving as the substrate-receptor subunit of a CRL4 (DDB1-CUL4-ROC1) E3 ubiquitin ligase complex [#0]. Its direct interaction with DDB1 is required for this function: disrupting the WDTC1-DDB1 interface abolishes suppression of fat accumulation, leading to increased triglyceride accumulation and elevated adipogenic gene expression in 3T3-L1 cells [#0]. The CRL4(WDTC1) complex promotes histone H2AK119 monoubiquitylation, linking its activity to transcriptional repression of the adipogenic program [#0]. Beyond this single characterization, no further mechanistic detail—including direct ubiquitylation substrates or structural basis of substrate recognition—has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Established that WDTC1 suppresses adipogenesis as a substrate receptor of a CRL4 E3 ligase, defining a molecular mechanism (DDB1-dependent assembly and histone H2AK119 monoubiquitylation) for its anti-fat-accumulation role.\",\n      \"evidence\": \"Co-immunoprecipitation of DDB1-CUL4-ROC1 components, mutagenesis disrupting the WDTC1-DDB1 interface with triglyceride and adipogenic gene-expression readouts in 3T3-L1 cells, and an H2AK119 monoubiquitylation assay\",\n      \"pmids\": [\"27113764\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct ubiquitylation substrate of CRL4(WDTC1) was identified\",\n        \"The causal link between H2AK119 monoubiquitylation and specific repressed adipogenic genes was not resolved\",\n        \"Findings rest on a single lab and a single cell-culture model without in vivo validation\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The substrate(s) ubiquitylated by CRL4(WDTC1) and the structural basis of substrate recognition remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No protein substrate identified\",\n        \"No structural model of WDTC1-DDB1 or substrate engagement\",\n        \"Mechanism connecting histone ubiquitylation to transcriptional repression not established\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"CRL4 (DDB1-CUL4-ROC1) E3 ubiquitin ligase\"],\n    \"partners\": [\"DDB1\", \"CUL4\", \"RBX1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}