Affinage

WDTC1

WD and tetratricopeptide repeats protein 1 · UniProt Q8N5D0

Length
677 aa
Mass
75.9 kDa
Annotated
2026-06-11
100 papers in source corpus 1 papers cited in narrative 1 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 3/3 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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.

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 2016 Medium

    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

    PMID:27113764

    Open questions at the time
    • 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

Open questions

Synthesis pass · forward-looking unresolved questions
  • The substrate(s) ubiquitylated by CRL4(WDTC1) and the structural basis of substrate recognition remain unknown.
  • No protein substrate identified
  • No structural model of WDTC1-DDB1 or substrate engagement
  • Mechanism connecting histone ubiquitylation to transcriptional repression not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Pathway
R-HSA-392499 Metabolism of proteins 1
Partners
CUL4DDB1RBX1
Complex memberships
CRL4 (DDB1-CUL4-ROC1) E3 ubiquitin ligase

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 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. 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 EMBO reports Medium 27113764

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Structure of mammalian AMPK and its regulation by ADP. Nature 736 21399626
1992 Structure of the recA protein-ADP complex. Nature 581 1731253
1992 Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase. The Journal of biological chemistry 402 1530940
2001 ADP receptors of platelets and their inhibition. Thrombosis and haemostasis 312 11487010
2017 Serine ADP-Ribosylation Depends on HPF1. Molecular cell 301 28190768
2001 Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism. Experimental cell research 266 11461113
2021 ADP-ribosyltransferases, an update on function and nomenclature. The FEBS journal 257 34323016
2009 ADP-Glo: A Bioluminescent and homogeneous ADP monitoring assay for kinases. Assay and drug development technologies 234 20105026
2006 Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains. Journal of virology 208 16912299
2015 Trapping Poly(ADP-Ribose) Polymerase. The Journal of pharmacology and experimental therapeutics 185 25758918
2021 Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11. Nature 170 34671164
2020 (ADP-ribosyl)hydrolases: structure, function, and biology. Genes & development 168 32029451
2015 The Promise of Proteomics for the Study of ADP-Ribosylation. Molecular cell 167 26091340
1992 Histone shuttling by poly(ADP-ribosylation). The Journal of biological chemistry 157 1326536
2015 PARPs and ADP-Ribosylation: 50 Years … and Counting. Molecular cell 156 26091339
2013 Poly(ADP-ribose): PARadigms and PARadoxes. Molecular aspects of medicine 156 23290998
1999 ADP receptors and clinical bleeding disorders. Arteriosclerosis, thrombosis, and vascular biology 152 10521355
2013 ADP-ribosyl-acceptor hydrolase 3 regulates poly (ADP-ribose) degradation and cell death during oxidative stress. Proceedings of the National Academy of Sciences of the United States of America 142 24191052
2023 ADP-ribosylation from molecular mechanisms to therapeutic implications. Cell 141 37832523
2006 The role of ADP receptors in platelet function. Frontiers in bioscience : a journal and virtual library 140 16368572
2019 Reversible ADP-ribosylation of RNA. Nucleic acids research 134 31216043
2005 P2Y1 and P2Y12 receptors for ADP desensitize by distinct kinase-dependent mechanisms. Blood 133 15665114
1999 Poly(ADP-ribosylation) and apoptosis. Molecular and cellular biochemistry 128 10544961
2017 ADP-ribosylation: new facets of an ancient modification. The FEBS journal 126 28383827
2015 Processing of protein ADP-ribosylation by Nudix hydrolases. The Biochemical journal 125 25789582
2013 Proteasome regulation by ADP-ribosylation. Cell 125 23622245
1984 Poly(ADP-ribose) polymerase is a zinc metalloenzyme. European journal of biochemistry 116 6088227
2010 ADP-ribosylation of arginine. Amino acids 115 20652610
1994 Receptors for ADP on human blood platelets. Trends in pharmacological sciences 113 8016893
2018 Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: new insights into DNA ADP-ribosylation. Nucleic acids research 106 29361132
1994 Cyclic ADP-ribose, the ADP-ribosyl cyclase pathway and calcium signalling. Molecular and cellular endocrinology 105 8143921
2005 Regulation of poly(ADP-ribose) metabolism by poly(ADP-ribose) glycohydrolase: where and when? Cellular and molecular life sciences : CMLS 104 15868399
1990 Aggregin: a platelet ADP receptor that mediates activation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 98 2407587
2021 ADP-ribosylation of DNA and RNA. DNA repair 94 34116477
2020 The Viral Macrodomain Counters Host Antiviral ADP-Ribosylation. Viruses 93 32244383
2019 ADP-ribosylation signalling and human disease. Open biology 89 30991935
2012 Histone ADP-ribosylation facilitates gene transcription by directly remodeling nucleosomes. Molecular and cellular biology 88 22547677
2005 Introduction to poly(ADP-ribose) metabolism. Cellular and molecular life sciences : CMLS 87 15868397
1997 ADP-induced platelet activation. Critical reviews in biochemistry and molecular biology 87 9444477
2003 Poly(ADP-ribose) and carcinogenesis. Genes, chromosomes & cancer 85 14566854
2015 RNA Regulation by Poly(ADP-Ribose) Polymerases. Molecular cell 84 26091344
2011 Anti-platelet therapy: ADP receptor antagonists. British journal of clinical pharmacology 84 21518389
1998 Role of poly(ADP-ribose)synthetase in inflammation. European journal of pharmacology 83 9683009
2008 Mammalian ADP-ribosyltransferases and ADP-ribosylhydrolases. Frontiers in bioscience : a journal and virtual library 82 18508690
2021 Ribosome ADP-ribosylation inhibits translation and maintains proteostasis in cancers. Cell 79 34314702
2014 The mitochondrial fission receptor MiD51 requires ADP as a cofactor. Structure (London, England : 1993) 79 24508339
2002 The ARTT motif and a unified structural understanding of substrate recognition in ADP-ribosylating bacterial toxins and eukaryotic ADP-ribosyltransferases. International journal of medical microbiology : IJMM 77 11890553
2015 Synthesis of dimeric ADP-ribose and its structure with human poly(ADP-ribose) glycohydrolase. Journal of the American Chemical Society 76 25706250
2005 CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins. Journal of immunology (Baltimore, Md. : 1950) 76 15749861
2015 Intracellular Mono-ADP-Ribosylation in Signaling and Disease. Cells 75 26426055
2011 Poly(ADP-ribosyl)ation in plants. Trends in plant science 75 21482174
2004 Modulation of poly(ADP-ribosylation) in apoptotic cells. Biochemical pharmacology 75 15313399
2003 ADP receptors--targets for developing antithrombotic agents. Current pharmaceutical design 73 14529392
2016 ENPP1 processes protein ADP-ribosylation in vitro. The FEBS journal 72 27406238
2021 Molecular basis for DarT ADP-ribosylation of a DNA base. Nature 69 34408320
2020 Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins. Nature communications 69 33060572
2015 ADP-ribosyltransferases and poly ADP-ribosylation. Current protein & peptide science 69 25938242
2023 PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities. Science advances 62 37703374
2019 ELTA: Enzymatic Labeling of Terminal ADP-Ribose. Molecular cell 62 30712989
2016 Wnt pathway activation by ADP-ribosylation. Nature communications 62 27138857
2000 Cyclic ADP-ribose. Journal of molecular medicine (Berlin, Germany) 58 10759027
1994 Inhibitors and activators of ADP-ribosylation reactions. Molecular and cellular biochemistry 57 7898463
1994 Enzymatic and nonenzymatic ADP-ribosylation of cysteine. Molecular and cellular biochemistry 57 7898467
2019 Regulating Immunity via ADP-Ribosylation: Therapeutic Implications and Beyond. Trends in immunology 55 30658897
2017 The coronavirus nucleocapsid protein is ADP-ribosylated. Virology 55 29199039
2016 ADPriboDB: The database of ADP-ribosylated proteins. Nucleic acids research 55 27507885
1994 Histone shuttling by poly ADP-ribosylation. Molecular and cellular biochemistry 54 7898476
2019 Mitotic functions of poly(ADP-ribose) polymerases. Biochemical pharmacology 52 30910692
1995 ADP-ribosylation reactions. Biochimie 52 8527483
2021 ADP-ribosylation systems in bacteria and viruses. Computational and structural biotechnology journal 51 34025930
2018 The poly (ADP ribose) polymerase inhibitor niraparib: Management of toxicities. Gynecologic oncology 51 29397193
2009 Proteomic investigation of phosphorylation sites in poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase. Journal of proteome research 51 19105632
2019 ADP-ribosylation: from molecular mechanisms to human disease. Genetics and molecular biology 49 31930280
2005 Poly(ADP-ribosylation) and genomic stability. Biochemistry and cell biology = Biochimie et biologie cellulaire 48 15959554
2016 Scabin, a Novel DNA-acting ADP-ribosyltransferase from Streptomyces scabies. The Journal of biological chemistry 46 27002155
2022 Legionella pneumophila modulates host energy metabolism by ADP-ribosylation of ADP/ATP translocases. eLife 45 35084332
2015 SnapShot: ADP-Ribosylation Signaling. Molecular cell 45 26091348
2007 ADP receptor antagonism: what's in the pipeline? American journal of cardiovascular drugs : drugs, devices, and other interventions 45 18076209
2006 The platelet ATP and ADP receptors. Current pharmaceutical design 45 16515502
2013 Poly(ADP-ribosyl)ation in carcinogenesis. Molecular aspects of medicine 43 23714734
2014 Proteomics approaches to identify mono-(ADP-ribosyl)ated and poly(ADP-ribosyl)ated proteins. Proteomics 42 25263235
2011 ADP-ribosylarginine hydrolase regulates cell proliferation and tumorigenesis. Cancer research 41 21697277
1997 ADP-ribose in glycation and glycoxidation reactions. Advances in experimental medicine and biology 41 9193679
2022 Truncated PARP1 mediates ADP-ribosylation of RNA polymerase III for apoptosis. Cell discovery 40 35039483
2022 Poly(ADP-ribose) potentiates ZAP antiviral activity. PLoS pathogens 40 35130321
2014 C3larvin toxin, an ADP-ribosyltransferase from Paenibacillus larvae. The Journal of biological chemistry 40 25477523
2001 ADP-dependent phosphofructokinases in mesophilic and thermophilic methanogenic archaea. Journal of bacteriology 40 11717273
2016 The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase. EMBO reports 39 27113764
2024 DELTEX E3 ligases ubiquitylate ADP-ribosyl modification on nucleic acids. Nucleic acids research 38 38000390
2021 TARG1 protects against toxic DNA ADP-ribosylation. Nucleic acids research 36 34508355
2004 Platelet ADP receptor antagonists: ticlopidine and clopidogrel. Best practice & research. Clinical haematology 36 15171957
2023 A viral ADP-ribosyltransferase attaches RNA chains to host proteins. Nature 35 37587340
2021 A molecular toolbox for ADP-ribosyl binding proteins. Cell reports methods 34 34786571
2016 Inhibiting poly(ADP-ribosylation) improves axon regeneration. eLife 34 27697151
2020 Nudix Hydrolase NUDT16 Regulates 53BP1 Protein by Reversing 53BP1 ADP-Ribosylation. Cancer research 33 31911551
2016 Players in ADP-ribosylation: Readers and Erasers. Current protein & peptide science 33 27090904
2012 Expression and role in glycolysis of human ADP-dependent glucokinase. Molecular and cellular biochemistry 33 22219026
2002 Pancreatic beta-cell death, regeneration and insulin secretion: roles of poly(ADP-ribose) polymerase and cyclic ADP-ribose. International journal of experimental diabetes research 33 11991201
2023 Regulation of Biomolecular Condensates by Poly(ADP-ribose). Chemical reviews 32 37115110
2004 Poly(ADP-ribosyl)ation and aging. Experimental gerontology 32 15582275

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