DOCK7 has two experimentally separable mechanisms. Its DHR2 domain promotes nucleotide exchange on Rho-family GTPases, whereas its interaction with TACC3 regulates microtubule growth and interkinetic nuclear migration independently of DHR2. The latter distinction is supported by deletion/rescue experiments in mouse cortical radial glia; human neuroblastoma cells separately show endogenous DOCK7/TACC3 centrosomal colocalization. PMID:23718289(https://pmc.ncbi.nlm.nih.gov/articles/PMC3752685/), PMID:22842144(https://pubmed.ncbi.nlm.nih.gov/22842144/)
The 2013 biochemical experiments resolve an apparent substrate contradiction: purified human historical DHR2 fragments activate prenylated, membrane-associated RAC1 and CDC42, while soluble nonprenylated substrates show little or no exchange. The broad CDC42-negative sentence in the curated protein summary therefore does not cover every tested condition. These exchange measurements do not establish GTP hydrolysis stimulation. The imported GAP assertion remains unresolved because the complete 2006 original was unavailable. Positive Rho signaling is the supported signed refinement; the independent Rac-specific assertion remains. PMID:23718289(https://pmc.ncbi.nlm.nih.gov/articles/PMC3752685/), PMID:16982419(https://pubmed.ncbi.nlm.nih.gov/16982419/)
Seven official products are preserved. Their sequences were reconstructed from UniProt alternative-sequence features and checked against the official FASTAs. The historical 1,992-residue human template used for biochemical fragments is a partial CDS, not an exact current full-length natural product. The 2020 deposited library sequence also differs from its product-style label. Neither discrepancy invalidates a positive interaction or proves which construct was used in every experiment. The short 632-residue product lacks the tested DHR2 region; its own activity remains unresolved. Construct analysis
LRCH association is repeatedly supported by targeted cellular experiments, BioPlex, OpenCell and the U2OS AP-MS map. The public dataset analysis preserves the opposite bait directions across studies and complete accession groups. For NOD2, positive two-hybrid/BRET results and a negative co-immunoprecipitation result are both retained. Its signaling-receptor class supports a narrower binding term without establishing a native DOCK7 immune pathway. PMID:27812135(https://pmc.ncbi.nlm.nih.gov/articles/PMC5094585/), interaction extraction
The septin-ring observation comes from LRCH3/DOCK7-fragment coexpression. The proposed connection to GEF activity remains a model, not an endogenous loss-of-function or catalytic-dead result. COP9 association retains its imported colocalizes_with qualifier. Focal-adhesion proteomic detection is retained as contextual evidence; failure to recover its target-resolved supplementary row is not evidence of contamination. The mouse thermogenesis phenotype and human smooth-muscle migration are context-dependent functions rather than additional catalytic cores. PMID:29467281(https://pmc.ncbi.nlm.nih.gov/articles/PMC5891429/), PMID:18850735(https://pmc.ncbi.nlm.nih.gov/articles/PMC2676908/), PMID:21423176(https://pmc.ncbi.nlm.nih.gov/articles/PMC3279191/), PMID:23553822(https://pmc.ncbi.nlm.nih.gov/articles/PMC3743939/), PMID:22158624(https://pmc.ncbi.nlm.nih.gov/articles/PMC3281737/)
The 40 raw GOA contexts produce 39 source assertions. The NOD2 pair has two provider/provenance contexts collapsed by normal seeding; neither is discarded from the saved source record. All source qualifiers and supporting entities remain unchanged. PAINT target self-inclusion is valid experimental grounding, and the actual tree/IBD placement was inspected. No NEW annotation is proposed.
Positive generic associations without a supported finer molecular role are retained as non-core under the project curation instructions. Expected generic-binding advisories do not invalidate the retained positive experiments. Falcon research failed with an authorization response and the configured fallback failed with a quota response; no provider report was manufactured. Manual primary-source research supplies the evidence summarized here.
The source guide distinguishes normal cache access from separately recovered originals and supplies public assay locators. Four short excerpts appear once each in the YAML, totaling 12, 6, 5 and 8 words from their respective publications; no publication excerpt is duplicated here.
This entry supersedes the earlier retention of negative cold-induced thermogenesis regulation. The Misty mouse study distinguishes altered brown-fat function from compensatory cold-induced white-fat browning. Compensation does not identify DOCK7 as the agent of negative thermogenic regulation, so that ISS assertion is now over-annotated. This is not a uniform reversal of regulatory sign across tissues, and no positive-thermogenesis replacement is inferred. The mouse phenotype and donor identity remain valid. PMID:23553822(https://pmc.ncbi.nlm.nih.gov/articles/PMC3743939/)
The septin assertion remains non-core on the observed controlled phenotype. Figure 6D compares DHR2 and mock expression in parental and stable-LRCH3 RPE cells; LRCH3 plus DHR2 produces rings in approximately 80% of cells. The proposed GEF mechanism remains unresolved. The NOD2 binding refinement also remains, with all contrary assays explicit: initial Y2H and saturable BRET are positive, detergent co-IP is negative, and Table 1 gives 10/0/10 points without a full-length Y2H reconfirmation flag. The tested signaling and expression responses do not establish a native DOCK7 immune function. A signaling-receptor binding class does not imply receptor agonism. PMID:29467281, Figure 6, PMID:27812135, Table 1
The GEF core now includes the already supported axonal location. The complete 2006 abstract reports axonal enrichment and Rac-dependent axon formation; its detailed organism and construct Methods remain unavailable. Cytosol is retained from the curated target-resolved model, and liposome biochemistry is not treated as native plasma-membrane localization. The source-specific GAP and neuroblast-polarity questions remain unresolved. PMID:16982419(https://pubmed.ncbi.nlm.nih.gov/16982419/)
The positive-Rho replacement for the broad small-GTPase assertion is a supported role correction, not a claim that the replacement is its strict ontology descendant. It retains coverage of both RAC1 and conditionally tested CDC42. The categorical CDC42 exclusion in the curated protein summary warrants qualification by the historical fragment, substrate prenylation and membrane conditions. It should not be replaced by a universal claim about all natural products or endogenous pathways. The machine record remains unchanged. PMID:23718289(https://pmc.ncbi.nlm.nih.gov/articles/PMC3752685/), source guide
All 39 imported source objects, seven products, previous evidence excerpts and reproducible analyses are unchanged. No new annotation or source quotation is added.