Affinage

WDR7

WD repeat-containing protein 7 · UniProt Q9Y4E6

Length
1490 aa
Mass
163.8 kDa
Annotated
2026-06-11
42 papers in source corpus 1 papers cited in narrative 5 extracted findings
Cross-family judge faithfulness: 2/3 claims corpus-supported (67%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2019 Medium

    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

    PMID:31004036

    Open questions at the time
    • Interaction defined by IP/MS without mapping the binding interface
    • Does not establish stoichiometry within the rabconnectin3 complex
  2. 2019 Medium

    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

    PMID:31004036

    Open questions at the time
    • Binding domains/residues on WDR7 and CAPS1 not mapped
    • Single lab, no structural characterization of the complex
  3. 2019 Medium

    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

    PMID:31004036

    Open questions at the time
    • Knockdown phenotype not rescued by re-expression
    • Whether DMXL2 is required for the same anchoring not resolved
  4. 2019 Medium

    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

    PMID:31004036

    Open questions at the time
    • Direct effect of WDR7 on V-ATPase assembly or activity not demonstrated
    • Consequences for neurotransmitter loading and secretion not measured directly

Open questions

Synthesis pass · forward-looking unresolved questions
  • How WDR7 mechanistically couples CAPS1 anchoring to V-ATPase regulation, and its function outside neuroendocrine DCVs, remain unknown.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2
Localization
GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 2
Partners
CAPS1DMXL2
Complex memberships
rabconnectin3 complex

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 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. Co-immunoprecipitation followed by mass spectrometry (MS) from brain membrane fractions The Journal of biological chemistry Medium 31004036
2019 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. Cell-free direct binding assay; membrane recruitment assay in cells The Journal of biological chemistry Medium 31004036
2019 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. shRNA knockdown with immunofluorescence microscopy to assess CAPS1 subcellular localization The Journal of biological chemistry Medium 31004036
2019 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. shRNA knockdown with DCV reacidification assay in neuroendocrine cells The Journal of biological chemistry Medium 31004036
2019 WDR7 (Rbcn3β) and DMXL2 (Rbcn3α) colocalize with CAPS1 on DCVs in human neuroendocrine (BON) cells, as demonstrated by immunofluorescence microscopy. Immunofluorescence colocalization microscopy in BON neuroendocrine cells The Journal of biological chemistry Low 31004036

Source papers

Stage 0 corpus · 42 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Genetic evidence of a coupling role for the TraG protein family in bacterial conjugation. Molecular & general genetics : MGG 175 9180693
2002 TraG-like proteins of DNA transfer systems and of the Helicobacter pylori type IV secretion system: inner membrane gate for exported substrates? Journal of bacteriology 130 11976307
2000 TraG from RP4 and TraG and VirD4 from Ti plasmids confer relaxosome specificity to the conjugal transfer system of pTiC58. Journal of bacteriology 103 10692358
1994 Essential motifs of relaxase (TraI) and TraG proteins involved in conjugative transfer of plasmid RP4. Journal of bacteriology 77 8021214
1999 TRAG-3, a novel gene, isolated from a taxol-resistant ovarian carcinoma cell line. Gene 74 10095106
2017 Calycosin inhibits the in vitro and in vivo growth of breast cancer cells through WDR7-7-GPR30 Signaling. Journal of experimental & clinical cancer research : CR 67 29096683
2003 TraG-like proteins of type IV secretion systems: functional dissection of the multiple activities of TraG (RP4) and TrwB (R388). Journal of bacteriology 63 12867445
2007 Entry exclusion in F-like plasmids requires intact TraG in the donor that recognizes its cognate TraS in the recipient. Microbiology (Reading, England) 58 17259615
2003 Interaction between the IncHI1 plasmid R27 coupling protein and type IV secretion system: TraG associates with the coiled-coil mating pair formation protein TrhB. Molecular microbiology 57 12823814
1983 Biology of simian virus 40 (SV40) transplantation antigen (TrAg). IX. Analysis of TrAg in mouse cells synthesizing truncated SV40 large T antigen. Virology 56 6310860
1992 Mutational analysis of essential IncP alpha plasmid transfer genes traF and traG and involvement of traF in phage sensitivity. Journal of bacteriology 55 1400217
2002 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. Molecular microbiology 52 12123451
2013 TraG encoded by the pIP501 type IV secretion system is a two-domain peptidoglycan-degrading enzyme essential for conjugative transfer. Journal of bacteriology 51 23913323
2000 Interaction between the RP4 coupling protein TraG and the pBHR1 mobilization protein Mob. Molecular microbiology 50 10998162
1981 traG protein of the F sex factor of Escherichia coli K-12 and its role in conjugation. Proceedings of the National Academy of Sciences of the United States of America 49 7038680
2005 The DotL protein, a member of the TraG-coupling protein family, is essential for Viability of Legionella pneumophila strain Lp02. Journal of bacteriology 45 15838018
1992 Characterization of the F plasmid bifunctional conjugation gene, traG. Molecular & general genetics : MGG 45 1348105
2007 Determinants of entry exclusion within Eex and TraG are cytoplasmic. Journal of bacteriology 41 17573467
2005 Conjugative plasmid DNA transfer in Helicobacter pylori mediated by chromosomally encoded relaxase and TraG-like proteins. Microbiology (Reading, England) 40 16272373
2003 Identification of HLA-A*0201-restricted cytotoxic T lymphocyte epitope from TRAG-3 antigen. Clinical cancer research : an official journal of the American Association for Cancer Research 31 12738743
1998 Both the fipA gene of pKM101 and the pifC gene of F inhibit conjugal transfer of RP1 by an effect on traG. Journal of bacteriology 31 9696755
2000 TRAG-3, a novel cancer/testis antigen, is overexpressed in the majority of melanoma cell lines and malignant melanoma. Anticancer research 27 11205240
2004 Epigenetic regulation of the taxol resistance-associated gene TRAG-3 in human tumors. Cancer genetics and cytogenetics 25 15120907
2005 Subcellular localization and functional domains of the coupling protein, TraG, from IncHI1 plasmid R27. Microbiology (Reading, England) 23 16272378
2013 Mating pair formation homologue TraG is a variable membrane protein essential for contact-independent type IV secretion of chromosomal DNA by Neisseria gonorrhoeae. Journal of bacteriology 22 23378511
2007 Taxol-resistance-associated gene-3 (TRAG-3/CSAG2) expression is predictive for clinical outcome in ovarian carcinoma patients. Virchows Archiv : an international journal of pathology 20 17216190
1983 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. Virology 20 6316651
2007 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. Microbiology (Reading, England) 17 17259614
2019 The priming factor CAPS1 regulates dense-core vesicle acidification by interacting with rabconnectin3β/WDR7 in neuroendocrine cells. The Journal of biological chemistry 15 31004036
2017 Conjugative type IV secretion in Gram-positive pathogens: TraG, a lytic transglycosylase and endopeptidase, interacts with translocation channel protein TraM. Plasmid 14 28219792
2004 MM-TRAG (MGC4175), a novel intracellular mitochondrial protein, is associated with the taxol- and doxorubicin-resistant phenotype in human cancer cell lines. Gene 13 15556294
2007 Interaction of Bacteroides fragilis pLV22a relaxase and transfer DNA with Escherichia coli RP4-TraG coupling protein. Molecular microbiology 12 17919288
2006 Spontaneous CD4+ T cell responses against TRAG-3 in patients with melanoma and breast cancers. Journal of immunology (Baltimore, Md. : 1950) 12 16888034
2004 Spontaneous T-cell responses against peptides derived from the Taxol resistance-associated gene-3 (TRAG-3) protein in cancer patients. Cancer immunology, immunotherapy : CII 12 15580499
1980 Characterisation of a lambda transducing phage carrying the F conjugation gene traG. Molecular & general genetics : MGG 12 6446656
2006 Expression of the TRAG-3 gene in human esophageal cancer: the frequent synchronous expression of MAGE-3 gene. Oncology reports 11 16685391
2019 traG Gene Is Conserved across Mesorhizobium spp. Able to Nodulate the Same Host Plant and Expressed in Response to Root Exudates. BioMed research international 7 30834262
2022 Solution characterization of the dynamic conjugative entry exclusion protein TraG. Structural dynamics (Melville, N.Y.) 6 36590369
2001 Screening for trbB- and traG-like sequences by PCR for the detection of conjugative plasmids in bacterial soil isolates. Microbiological research 4 11572456
2019 WDR7 up-regulation upon knocking down of neighboring non-coding RNA using siRNAs encapsulated in polyamidoamine dendrimers. Iranian journal of basic medical sciences 3 32128092
2004 [In vitro induction of immune response by dendritic cells pulsed with TRAG-3-derived cytotoxic T lymphocyte epitope]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 1 15733385
2008 [Identification and detection of trag: a new infection-related gene expressed in vivo from isolates of Streptococcus suis]. Wei sheng wu xue bao = Acta microbiologica Sinica 0 19271540

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