{"gene":"WDR7","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2019,"finding":"WDR7 (rabconnectin3β) associates with CAPS1 (calcium-dependent activator protein for secretion) in a rabconnectin3 complex (together with DMXL2/Rbcn3α) on dense-core vesicles (DCVs) in neuroendocrine cells, as revealed by MS analysis of CAPS1 immunoprecipitates from brain membrane fractions.","method":"Co-immunoprecipitation followed by mass spectrometry (MS) from brain membrane fractions","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal IP/MS plus orthogonal cell-free binding assay and colocalization, single lab","pmids":["31004036"],"is_preprint":false},{"year":2019,"finding":"WDR7 (Rbcn3β) directly binds CAPS1 in cell-free (cell-free binding) experiments, and recruits soluble CAPS1 to membranes in cell-based assays, establishing WDR7 as the membrane anchor for CAPS1 on DCVs.","method":"Cell-free direct binding assay; membrane recruitment assay in cells","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cell-free binding plus cell-based membrane recruitment, single lab, two orthogonal methods","pmids":["31004036"],"is_preprint":false},{"year":2019,"finding":"shRNA-mediated knockdown of WDR7 (Rbcn3β) redistributes CAPS1 from DCVs to the cytosol in BON neuroendocrine cells, demonstrating that WDR7 is required for optimal DCV localization of CAPS1.","method":"shRNA knockdown with immunofluorescence microscopy to assess CAPS1 subcellular localization","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean shRNA knockdown with defined localization phenotype, single lab","pmids":["31004036"],"is_preprint":false},{"year":2019,"finding":"Knockdown of WDR7 (Rbcn3β) in neuroendocrine cells impairs rates of DCV reacidification, placing WDR7 in a pathway that regulates V-ATPase activity on DCVs via its interaction with CAPS1.","method":"shRNA knockdown with DCV reacidification assay in neuroendocrine cells","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean shRNA knockdown with defined functional (pH/V-ATPase) phenotype, single lab","pmids":["31004036"],"is_preprint":false},{"year":2019,"finding":"WDR7 (Rbcn3β) and DMXL2 (Rbcn3α) colocalize with CAPS1 on DCVs in human neuroendocrine (BON) cells, as demonstrated by immunofluorescence microscopy.","method":"Immunofluorescence colocalization microscopy in BON neuroendocrine cells","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single colocalization experiment, single lab, no functional mutagenesis","pmids":["31004036"],"is_preprint":false}],"current_model":"WDR7 (rabconnectin3β) is a membrane-associated WD-repeat protein that forms part of the rabconnectin3 complex (with DMXL2/Rbcn3α) on dense-core vesicles in neuroendocrine cells, where it directly binds and recruits the vesicle priming factor CAPS1 to DCVs and is required for V-ATPase-dependent DCV reacidification and neurotransmitter loading."},"narrative":{"mechanistic_narrative":"WDR7 (rabconnectin3β) is a membrane-associated WD-repeat protein that functions on dense-core vesicles (DCVs) in neuroendocrine cells as part of a rabconnectin3 complex with DMXL2/Rbcn3α [PMID:31004036]. It directly binds the vesicle priming factor CAPS1 and serves as its membrane anchor, recruiting soluble CAPS1 to DCV membranes [PMID:31004036]; loss of WDR7 redistributes CAPS1 from DCVs to the cytosol [PMID:31004036]. Through this interaction, WDR7 is required for V-ATPase-dependent DCV reacidification, as its knockdown impairs reacidification rates [PMID:31004036]. Beyond this CAPS1-anchoring and reacidification role on DCVs, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2019,"claim":"Established that WDR7 physically associates with the vesicle priming factor CAPS1, identifying a previously uncharacterized link between a rabconnectin3 subunit and the secretory machinery on dense-core vesicles.","evidence":"Co-immunoprecipitation followed by mass spectrometry from brain membrane fractions","pmids":["31004036"],"confidence":"Medium","gaps":["Interaction defined by IP/MS without mapping the binding interface","Does not establish stoichiometry within the rabconnectin3 complex"]},{"year":2019,"claim":"Demonstrated that the WDR7-CAPS1 interaction is direct and functions to anchor CAPS1 to membranes, answering whether WDR7 acts as the membrane recruiter for CAPS1 on DCVs.","evidence":"Cell-free direct binding assay plus membrane recruitment assay in cells","pmids":["31004036"],"confidence":"Medium","gaps":["Binding domains/residues on WDR7 and CAPS1 not mapped","Single lab, no structural characterization of the complex"]},{"year":2019,"claim":"Showed that WDR7 is required for the DCV localization of CAPS1, establishing a loss-of-function dependency rather than mere association.","evidence":"shRNA knockdown with immunofluorescence assessment of CAPS1 localization in BON neuroendocrine cells","pmids":["31004036"],"confidence":"Medium","gaps":["Knockdown phenotype not rescued by re-expression","Whether DMXL2 is required for the same anchoring not resolved"]},{"year":2019,"claim":"Linked WDR7 to organelle acidification by showing its knockdown impairs DCV reacidification, placing it in a V-ATPase-regulating pathway via CAPS1.","evidence":"shRNA knockdown with DCV reacidification assay in neuroendocrine cells","pmids":["31004036"],"confidence":"Medium","gaps":["Direct effect of WDR7 on V-ATPase assembly or activity not demonstrated","Consequences for neurotransmitter loading and secretion not measured directly"]},{"year":null,"claim":"How WDR7 mechanistically couples CAPS1 anchoring to V-ATPase regulation, and its function outside neuroendocrine DCVs, remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of WDR7 or the rabconnectin3-CAPS1 complex","No genetic or disease evidence in the available corpus","Mechanism of V-ATPase modulation not defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,2]}],"localization":[{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,4]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,3]}],"complexes":["rabconnectin3 complex"],"partners":["CAPS1","DMXL2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y4E6","full_name":"WD repeat-containing protein 7","aliases":["Rabconnectin-3 beta","TGF-beta resistance-associated protein TRAG"],"length_aa":1490,"mass_kda":163.8,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q9Y4E6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/WDR7","classification":"Common Essential","n_dependent_lines":977,"n_total_lines":1208,"dependency_fraction":0.8087748344370861},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ATP6V1G1","stoichiometry":4.0},{"gene":"ATP6V1H","stoichiometry":4.0},{"gene":"ATP6V1B2","stoichiometry":0.2},{"gene":"ATP6V1E1","stoichiometry":0.2},{"gene":"ATP6V1F","stoichiometry":0.2},{"gene":"DDOST","stoichiometry":0.2},{"gene":"OST4","stoichiometry":0.2},{"gene":"RPN1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/WDR7","total_profiled":1310},"omim":[{"mim_id":"613473","title":"WD REPEAT-CONTAINING PROTEIN 7; WDR7","url":"https://www.omim.org/entry/613473"},{"mim_id":"613214","title":"WD REPEAT-CONTAINING PROTEIN 72; WDR72","url":"https://www.omim.org/entry/613214"},{"mim_id":"606640","title":"AMYOTROPHIC LATERAL SCLEROSIS 3; ALS3","url":"https://www.omim.org/entry/606640"},{"mim_id":"105400","title":"AMYOTROPHIC LATERAL SCLEROSIS 1; ALS1","url":"https://www.omim.org/entry/105400"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/WDR7"},"hgnc":{"alias_symbol":["KIAA0541","TRAG"],"prev_symbol":[]},"alphafold":{"accession":"Q9Y4E6","domains":[{"cath_id":"-","chopping":"796-855_879-911_982-1048","consensus_level":"medium","plddt":88.9954,"start":796,"end":1048},{"cath_id":"2.130.10.10","chopping":"1358-1429_1437-1490","consensus_level":"medium","plddt":81.8987,"start":1358,"end":1490}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y4E6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y4E6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y4E6-F1-predicted_aligned_error_v6.png","plddt_mean":73.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=WDR7","jax_strain_url":"https://www.jax.org/strain/search?query=WDR7"},"sequence":{"accession":"Q9Y4E6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y4E6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y4E6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y4E6"}},"corpus_meta":[{"pmid":"9180693","id":"PMC_9180693","title":"Genetic evidence of a coupling role for the TraG protein family in bacterial conjugation.","date":"1997","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/9180693","citation_count":175,"is_preprint":false},{"pmid":"11976307","id":"PMC_11976307","title":"TraG-like proteins of DNA transfer systems and of the Helicobacter pylori type IV secretion system: inner membrane gate for exported substrates?","date":"2002","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/11976307","citation_count":130,"is_preprint":false},{"pmid":"10692358","id":"PMC_10692358","title":"TraG from RP4 and TraG and VirD4 from Ti plasmids confer relaxosome specificity to the conjugal transfer system of pTiC58.","date":"2000","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/10692358","citation_count":103,"is_preprint":false},{"pmid":"8021214","id":"PMC_8021214","title":"Essential motifs of relaxase (TraI) and TraG proteins involved in conjugative transfer of plasmid RP4.","date":"1994","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/8021214","citation_count":77,"is_preprint":false},{"pmid":"10095106","id":"PMC_10095106","title":"TRAG-3, a novel gene, isolated from a taxol-resistant ovarian carcinoma cell line.","date":"1999","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/10095106","citation_count":74,"is_preprint":false},{"pmid":"29096683","id":"PMC_29096683","title":"Calycosin inhibits the in vitro and in vivo growth of breast cancer cells through WDR7-7-GPR30 Signaling.","date":"2017","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/29096683","citation_count":67,"is_preprint":false},{"pmid":"12867445","id":"PMC_12867445","title":"TraG-like proteins of type IV secretion systems: functional dissection of the multiple activities of TraG (RP4) and TrwB (R388).","date":"2003","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/12867445","citation_count":63,"is_preprint":false},{"pmid":"17259615","id":"PMC_17259615","title":"Entry exclusion in F-like plasmids requires intact TraG in the donor that recognizes its cognate TraS in the recipient.","date":"2007","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/17259615","citation_count":58,"is_preprint":false},{"pmid":"12823814","id":"PMC_12823814","title":"Interaction between the IncHI1 plasmid R27 coupling protein and type IV secretion system: TraG associates with the coiled-coil mating pair formation protein TrhB.","date":"2003","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/12823814","citation_count":57,"is_preprint":false},{"pmid":"6310860","id":"PMC_6310860","title":"Biology of simian virus 40 (SV40) transplantation antigen (TrAg). IX. Analysis of TrAg in mouse cells synthesizing truncated SV40 large T antigen.","date":"1983","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/6310860","citation_count":56,"is_preprint":false},{"pmid":"1400217","id":"PMC_1400217","title":"Mutational analysis of essential IncP alpha plasmid transfer genes traF and traG and involvement of traF in phage sensitivity.","date":"1992","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/1400217","citation_count":55,"is_preprint":false},{"pmid":"12123451","id":"PMC_12123451","title":"Transfer origins in the conjugative Enterococcus faecalis plasmids pAD1 and pAM373: identification of the pAD1 nic site, a specific relaxase and a possible TraG-like protein.","date":"2002","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/12123451","citation_count":52,"is_preprint":false},{"pmid":"23913323","id":"PMC_23913323","title":"TraG encoded by the pIP501 type IV secretion system is a two-domain peptidoglycan-degrading enzyme essential for conjugative transfer.","date":"2013","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/23913323","citation_count":51,"is_preprint":false},{"pmid":"10998162","id":"PMC_10998162","title":"Interaction between the RP4 coupling protein TraG and the pBHR1 mobilization protein Mob.","date":"2000","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/10998162","citation_count":50,"is_preprint":false},{"pmid":"7038680","id":"PMC_7038680","title":"traG protein of the F sex factor of Escherichia coli K-12 and its role in conjugation.","date":"1981","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/7038680","citation_count":49,"is_preprint":false},{"pmid":"1348105","id":"PMC_1348105","title":"Characterization of the F plasmid bifunctional conjugation gene, traG.","date":"1992","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/1348105","citation_count":45,"is_preprint":false},{"pmid":"15838018","id":"PMC_15838018","title":"The DotL protein, a member of the TraG-coupling protein family, is essential for Viability of Legionella pneumophila strain Lp02.","date":"2005","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/15838018","citation_count":45,"is_preprint":false},{"pmid":"17573467","id":"PMC_17573467","title":"Determinants of entry exclusion within Eex and TraG are cytoplasmic.","date":"2007","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/17573467","citation_count":41,"is_preprint":false},{"pmid":"16272373","id":"PMC_16272373","title":"Conjugative plasmid DNA transfer in Helicobacter pylori mediated by chromosomally encoded relaxase and TraG-like proteins.","date":"2005","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/16272373","citation_count":40,"is_preprint":false},{"pmid":"9696755","id":"PMC_9696755","title":"Both the fipA gene of pKM101 and the pifC gene of F inhibit conjugal transfer of RP1 by an effect on traG.","date":"1998","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/9696755","citation_count":31,"is_preprint":false},{"pmid":"12738743","id":"PMC_12738743","title":"Identification of HLA-A*0201-restricted cytotoxic T lymphocyte epitope from TRAG-3 antigen.","date":"2003","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/12738743","citation_count":31,"is_preprint":false},{"pmid":"11205240","id":"PMC_11205240","title":"TRAG-3, a novel cancer/testis antigen, is overexpressed in the majority of melanoma cell lines and malignant melanoma.","date":"2000","source":"Anticancer research","url":"https://pubmed.ncbi.nlm.nih.gov/11205240","citation_count":27,"is_preprint":false},{"pmid":"15120907","id":"PMC_15120907","title":"Epigenetic regulation of the taxol resistance-associated gene TRAG-3 in human tumors.","date":"2004","source":"Cancer genetics and cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/15120907","citation_count":25,"is_preprint":false},{"pmid":"16272378","id":"PMC_16272378","title":"Subcellular localization and functional domains of the coupling protein, TraG, from IncHI1 plasmid R27.","date":"2005","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/16272378","citation_count":23,"is_preprint":false},{"pmid":"23378511","id":"PMC_23378511","title":"Mating pair formation homologue TraG is a variable membrane protein essential for contact-independent type IV secretion of chromosomal DNA by Neisseria gonorrhoeae.","date":"2013","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/23378511","citation_count":22,"is_preprint":false},{"pmid":"17216190","id":"PMC_17216190","title":"Taxol-resistance-associated gene-3 (TRAG-3/CSAG2) expression is predictive for clinical outcome in ovarian carcinoma patients.","date":"2007","source":"Virchows Archiv : an international journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/17216190","citation_count":20,"is_preprint":false},{"pmid":"6316651","id":"PMC_6316651","title":"Biology of simian virus 40 (SV40) transplantation antigen (TrAg). X. Tumorigenic potential of mouse cells transformed by SV40 in high responder C57BL/6 mice and correlation with the persistence of SV40 TrAg, early proteins and sequences.","date":"1983","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/6316651","citation_count":20,"is_preprint":false},{"pmid":"17259614","id":"PMC_17259614","title":"Interaction between the co-inherited TraG coupling protein and the TraJ membrane-associated protein of the H-plasmid conjugative DNA transfer system resembles chromosomal DNA translocases.","date":"2007","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/17259614","citation_count":17,"is_preprint":false},{"pmid":"31004036","id":"PMC_31004036","title":"The priming factor CAPS1 regulates dense-core vesicle acidification by interacting with rabconnectin3β/WDR7 in neuroendocrine cells.","date":"2019","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31004036","citation_count":15,"is_preprint":false},{"pmid":"28219792","id":"PMC_28219792","title":"Conjugative type IV secretion in Gram-positive pathogens: TraG, a lytic transglycosylase and endopeptidase, interacts with translocation channel protein TraM.","date":"2017","source":"Plasmid","url":"https://pubmed.ncbi.nlm.nih.gov/28219792","citation_count":14,"is_preprint":false},{"pmid":"15556294","id":"PMC_15556294","title":"MM-TRAG (MGC4175), a novel intracellular mitochondrial protein, is associated with the taxol- and doxorubicin-resistant phenotype in human cancer cell lines.","date":"2004","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/15556294","citation_count":13,"is_preprint":false},{"pmid":"16888034","id":"PMC_16888034","title":"Spontaneous CD4+ T cell responses against TRAG-3 in patients with melanoma and breast cancers.","date":"2006","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/16888034","citation_count":12,"is_preprint":false},{"pmid":"17919288","id":"PMC_17919288","title":"Interaction of Bacteroides fragilis pLV22a relaxase and transfer DNA with Escherichia coli RP4-TraG coupling protein.","date":"2007","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/17919288","citation_count":12,"is_preprint":false},{"pmid":"15580499","id":"PMC_15580499","title":"Spontaneous T-cell responses against peptides derived from the Taxol resistance-associated gene-3 (TRAG-3) protein in cancer patients.","date":"2004","source":"Cancer immunology, immunotherapy : CII","url":"https://pubmed.ncbi.nlm.nih.gov/15580499","citation_count":12,"is_preprint":false},{"pmid":"6446656","id":"PMC_6446656","title":"Characterisation of a lambda transducing phage carrying the F conjugation gene traG.","date":"1980","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/6446656","citation_count":12,"is_preprint":false},{"pmid":"16685391","id":"PMC_16685391","title":"Expression of the TRAG-3 gene in human esophageal cancer: the frequent synchronous expression of MAGE-3 gene.","date":"2006","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/16685391","citation_count":11,"is_preprint":false},{"pmid":"30834262","id":"PMC_30834262","title":"traG Gene Is Conserved across Mesorhizobium spp. Able to Nodulate the Same Host Plant and Expressed in Response to Root Exudates.","date":"2019","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/30834262","citation_count":7,"is_preprint":false},{"pmid":"36590369","id":"PMC_36590369","title":"Solution characterization of the dynamic conjugative entry exclusion protein TraG.","date":"2022","source":"Structural dynamics (Melville, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/36590369","citation_count":6,"is_preprint":false},{"pmid":"11572456","id":"PMC_11572456","title":"Screening for trbB- and traG-like sequences by PCR for the detection of conjugative plasmids in bacterial soil isolates.","date":"2001","source":"Microbiological research","url":"https://pubmed.ncbi.nlm.nih.gov/11572456","citation_count":4,"is_preprint":false},{"pmid":"32128092","id":"PMC_32128092","title":"WDR7 up-regulation upon knocking down of neighboring non-coding RNA using siRNAs encapsulated in polyamidoamine dendrimers.","date":"2019","source":"Iranian journal of basic medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32128092","citation_count":3,"is_preprint":false},{"pmid":"15733385","id":"PMC_15733385","title":"[In vitro induction of immune response by dendritic cells pulsed with TRAG-3-derived cytotoxic T lymphocyte epitope].","date":"2004","source":"Zhonghua zhong liu za zhi [Chinese journal of oncology]","url":"https://pubmed.ncbi.nlm.nih.gov/15733385","citation_count":1,"is_preprint":false},{"pmid":"19271540","id":"PMC_19271540","title":"[Identification and detection of trag: a new infection-related gene expressed in vivo from isolates of Streptococcus suis].","date":"2008","source":"Wei sheng wu xue bao = Acta microbiologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/19271540","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.13.688259","title":"Adaptive evolution of  <i>Plasmodium vivax</i>  in Duffy-negative hosts: insights from East African genomes","date":"2025-11-13","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.13.688259","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.04.17.649302","title":"Cellularly-Retained Fluorogenic Probes for Sensitive Cell-Resolved Bioactivity Imaging","date":"2025-04-20","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.17.649302","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":23509,"output_tokens":1553,"usd":0.046911,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7716,"output_tokens":1587,"usd":0.039128,"stage2_stop_reason":"end_turn"},"total_usd":0.086039,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the 44 papers, I need to identify which ones are about the human/mammalian gene WDR7 (also known as KIAA0541, TRAG). \n\nThe vast majority of papers (papers 1-20, 24-25, 28, 30, 33, 35, 37-39, 42, 44) describe bacterial TraG proteins involved in conjugative plasmid transfer — these are symbol collisions with bacterial genes, not orthologs of human WDR7.\n\nPapers 5, 21-23, 26, 31-32, 34, 36, 41 describe TRAG-3 (CSAG2/CSAG1), which is a cancer-testis antigen — this is a different gene entirely (TRAG-3 maps to Xq28), NOT WDR7/KIAA0541/TRAG.\n\nPaper 6 describes \"WDR7-7\" which is explicitly a lncRNA — excluded as non-protein product.\n\nPaper 10, 27 describe SV40 TrAg (transplantation antigen) — unrelated.\n\nPaper 40 mentions WDR7 as a gene adjacent to lincRNA-RoR, but only reports expression changes with no mechanistic experiment on WDR7 protein itself.\n\nPaper 43 describes Plasmodium TRAg — symbol collision, unrelated.\n\nPaper 44 describes \"TrappableGreen (TraG)\" — a synthetic fluorogenic probe, not the gene.\n\nPaper 29 (PMID: 31004036) is clearly about the mammalian WDR7 protein (WD repeat domain 7, rabconnectin3β) in a neuroendocrine cell context — this is the canonical human WDR7.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"WDR7 (rabconnectin3β) associates with CAPS1 (calcium-dependent activator protein for secretion) in a rabconnectin3 complex (together with DMXL2/Rbcn3α) on dense-core vesicles (DCVs) in neuroendocrine cells, as revealed by MS analysis of CAPS1 immunoprecipitates from brain membrane fractions.\",\n      \"method\": \"Co-immunoprecipitation followed by mass spectrometry (MS) from brain membrane fractions\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal IP/MS plus orthogonal cell-free binding assay and colocalization, single lab\",\n      \"pmids\": [\"31004036\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"WDR7 (Rbcn3β) directly binds CAPS1 in cell-free (cell-free binding) experiments, and recruits soluble CAPS1 to membranes in cell-based assays, establishing WDR7 as the membrane anchor for CAPS1 on DCVs.\",\n      \"method\": \"Cell-free direct binding assay; membrane recruitment assay in cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cell-free binding plus cell-based membrane recruitment, single lab, two orthogonal methods\",\n      \"pmids\": [\"31004036\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"shRNA-mediated knockdown of WDR7 (Rbcn3β) redistributes CAPS1 from DCVs to the cytosol in BON neuroendocrine cells, demonstrating that WDR7 is required for optimal DCV localization of CAPS1.\",\n      \"method\": \"shRNA knockdown with immunofluorescence microscopy to assess CAPS1 subcellular localization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean shRNA knockdown with defined localization phenotype, single lab\",\n      \"pmids\": [\"31004036\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Knockdown of WDR7 (Rbcn3β) in neuroendocrine cells impairs rates of DCV reacidification, placing WDR7 in a pathway that regulates V-ATPase activity on DCVs via its interaction with CAPS1.\",\n      \"method\": \"shRNA knockdown with DCV reacidification assay in neuroendocrine cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean shRNA knockdown with defined functional (pH/V-ATPase) phenotype, single lab\",\n      \"pmids\": [\"31004036\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"WDR7 (Rbcn3β) and DMXL2 (Rbcn3α) colocalize with CAPS1 on DCVs in human neuroendocrine (BON) cells, as demonstrated by immunofluorescence microscopy.\",\n      \"method\": \"Immunofluorescence colocalization microscopy in BON neuroendocrine cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single colocalization experiment, single lab, no functional mutagenesis\",\n      \"pmids\": [\"31004036\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"WDR7 (rabconnectin3β) is a membrane-associated WD-repeat protein that forms part of the rabconnectin3 complex (with DMXL2/Rbcn3α) on dense-core vesicles in neuroendocrine cells, where it directly binds and recruits the vesicle priming factor CAPS1 to DCVs and is required for V-ATPase-dependent DCV reacidification and neurotransmitter loading.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"WDR7 (rabconnectin3β) is a membrane-associated WD-repeat protein that functions on dense-core vesicles (DCVs) in neuroendocrine cells as part of a rabconnectin3 complex with DMXL2/Rbcn3α [#0]. It directly binds the vesicle priming factor CAPS1 and serves as its membrane anchor, recruiting soluble CAPS1 to DCV membranes [#1]; loss of WDR7 redistributes CAPS1 from DCVs to the cytosol [#2]. Through this interaction, WDR7 is required for V-ATPase-dependent DCV reacidification, as its knockdown impairs reacidification rates [#3]. Beyond this CAPS1-anchoring and reacidification role on DCVs, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Established that WDR7 physically associates with the vesicle priming factor CAPS1, identifying a previously uncharacterized link between a rabconnectin3 subunit and the secretory machinery on dense-core vesicles.\",\n      \"evidence\": \"Co-immunoprecipitation followed by mass spectrometry from brain membrane fractions\",\n      \"pmids\": [\"31004036\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interaction defined by IP/MS without mapping the binding interface\",\n        \"Does not establish stoichiometry within the rabconnectin3 complex\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Demonstrated that the WDR7-CAPS1 interaction is direct and functions to anchor CAPS1 to membranes, answering whether WDR7 acts as the membrane recruiter for CAPS1 on DCVs.\",\n      \"evidence\": \"Cell-free direct binding assay plus membrane recruitment assay in cells\",\n      \"pmids\": [\"31004036\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Binding domains/residues on WDR7 and CAPS1 not mapped\",\n        \"Single lab, no structural characterization of the complex\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showed that WDR7 is required for the DCV localization of CAPS1, establishing a loss-of-function dependency rather than mere association.\",\n      \"evidence\": \"shRNA knockdown with immunofluorescence assessment of CAPS1 localization in BON neuroendocrine cells\",\n      \"pmids\": [\"31004036\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Knockdown phenotype not rescued by re-expression\",\n        \"Whether DMXL2 is required for the same anchoring not resolved\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Linked WDR7 to organelle acidification by showing its knockdown impairs DCV reacidification, placing it in a V-ATPase-regulating pathway via CAPS1.\",\n      \"evidence\": \"shRNA knockdown with DCV reacidification assay in neuroendocrine cells\",\n      \"pmids\": [\"31004036\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct effect of WDR7 on V-ATPase assembly or activity not demonstrated\",\n        \"Consequences for neurotransmitter loading and secretion not measured directly\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How WDR7 mechanistically couples CAPS1 anchoring to V-ATPase regulation, and its function outside neuroendocrine DCVs, remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structure of WDR7 or the rabconnectin3-CAPS1 complex\",\n        \"No genetic or disease evidence in the available corpus\",\n        \"Mechanism of V-ATPase modulation not defined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"complexes\": [\"rabconnectin3 complex\"],\n    \"partners\": [\"CAPS1\", \"DMXL2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":2,"faith_total":3,"faith_pct":66.66666666666667}}