DOCK7 is a large Rho-family guanine-nucleotide exchange factor that regulates neuronal polarity and the cytoskeleton. Its DHR2 domain catalyzes exchange on RAC1 and, under prenylated membrane-substrate conditions, CDC42. Rac signaling promotes microtubule-dependent axon formation. A separate TACC3-dependent mechanism regulates microtubule growth and interkinetic nuclear migration independently of the exchange domain. DOCK7 occupies cytosolic, axonal and centrosomal pools and associates with LRCH proteins and other cellular complexes. Its seven annotated products differ in internal segments or truncation; their functional equivalence has not been established.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000226 microtubule cytoskeleton organization | IMP PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | ACCEPT | Summary: DOCK7 regulates the neuronal microtubule cytoskeleton. Reason: The original abstract directly connects DOCK7/Rac-dependent stathmin inactivation to microtubule-dependent axon formation. Independent mouse cortical experiments in PMID:22842144 establish a separate TACC3-dependent microtubule-growth mechanism. These support cytoskeletal organization without making DOCK7 a microtubule-binding enzyme or a stathmin kinase. The full 2006 original remains unavailable; its experimental attribution is retained with curator deference. |
| GO:0005085 guanyl-nucleotide exchange factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT GEF inference is supported by target-specific biochemical evidence. Reason: The actual PTHR23317 tree places Q96N67/PTN002511220 below PTN000593987, where the literal IBD for this term is recorded; the target MSA sequence matches the current canonical sequence. Independently, purified human historical DOCK7 DHR2 fragments catalyze nucleotide exchange on prenylated RAC1 and CDC42 in liposomes. Soluble nonprenylated substrates were negative in the same study. The historical partial CDS is not an assay of every current isoform. Neither the number of donors nor target self-inclusion is used to grade the inference. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000593987 SUPPORTS TRANSFER Literal IBD and target ancestry were reconstructed from the saved family tree, MSA and IBD file. UniProtKB:Q8NF50 SUPPORTS TRANSFER Current donor record contains experimental GEF evidence; its original assay was not independently reread. FB:FBgn0031216 SUPPORTS TRANSFER The literal donor is Zir/Q9VPI9, with experimental genetic interaction annotations; the PMID:22634526 abstract supports Rac2/Cdc42 regulation. This is not a claim of a purified fly exchange assay. Supporting Evidence: |
| GO:0005085 guanyl-nucleotide exchange factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: The DOCK7-family GEF mapping is supported. Reason: IPR026791 is the target DOCK7 family assignment, and its InterPro2GO mapping is consistent with direct human DHR2 exchange assays. Current QuickGO resolves the historical Rho-GEF identifier GO:0005089 to GO:0005085, so no obsolete substrate-specific replacement is proposed. Activity on the short 632-residue natural product has not been shown. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR026791 SUPPORTS TRANSFER Official target family and literal InterPro2GO mapping inspected; target-specific exchange evidence corroborates the mapping. Supporting Evidence: |
| GO:0005096 GTPase activator activity | IDA PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | UNDECIDED | Summary: GTP hydrolysis stimulation is unresolved for this experimental assertion. Reason: GO:0005096 requires stimulation of GTP hydrolysis. Rac activation or GDP/GTP exchange does not establish that activity. The 2006 full original could not be recovered, so the curator may have inspected experiments unavailable here. The independently read 2013 nucleotide-exchange assays do not settle a GAP claim. Preserve the imported IDA and enables qualifier without converting exchange measurements into hydrolysis evidence. |
| GO:0005515 protein binding | IPI PMID:24255178 Protein interaction network of the mammalian Hippo pathway r... | KEEP AS NON CORE | Summary: DOCK7 association with LRCH4 is retained. Reason: The curated PMID:24255178 interaction records identify the human DOCK7–LRCH4 pair in anti-tag co-immunoprecipitation/affinity-purification experiments (1 matching IntAct records). This supports physical association, without establishing a purified binary interface or assigning the partner’s cellular role to DOCK7. Later targeted DOCK–LRCH studies corroborate the association. The 2013 publication cache is abstract-only and publisher recovery failed; no unseen full-text claim is made. A more specific molecular activity is not established by this pair. |
| GO:0005515 protein binding | IPI PMID:24255178 Protein interaction network of the mammalian Hippo pathway r... | KEEP AS NON CORE | Summary: DOCK7 association with LRCH3 is retained. Reason: The curated PMID:24255178 interaction records identify the human DOCK7–LRCH3 pair in anti-tag co-immunoprecipitation/affinity-purification experiments (4 matching IntAct records). This supports physical association, without establishing a purified binary interface or assigning the partner’s cellular role to DOCK7. Later targeted DOCK–LRCH studies corroborate the association. The 2013 publication cache is abstract-only and publisher recovery failed; no unseen full-text claim is made. A more specific molecular activity is not established by this pair. |
| GO:0005515 protein binding | IPI PMID:24255178 Protein interaction network of the mammalian Hippo pathway r... | KEEP AS NON CORE | Summary: DOCK7 association with LRCH1 is retained. Reason: The curated PMID:24255178 interaction records identify the human DOCK7–LRCH1 pair in anti-tag co-immunoprecipitation/affinity-purification experiments (1 matching IntAct records). This supports physical association, without establishing a purified binary interface or assigning the partner’s cellular role to DOCK7. Later targeted DOCK–LRCH studies corroborate the association. The 2013 publication cache is abstract-only and publisher recovery failed; no unseen full-text claim is made. A more specific molecular activity is not established by this pair. |
| GO:0005515 protein binding | IPI PMID:27812135 Characterization and Genetic Analyses of New Genes Coding fo... | MODIFY | Summary: DOCK7 binds the NOD2 signaling receptor in heterologous assays. Reason: The initial DOCK7–NOD2 yeast two-hybrid screen and saturable BRET in HEK293T cells are positive, whereas co-immunoprecipitation in 1% Triton X-100 is negative. Original Table 1 assigns 10/0/10 points for Y2H/co-IP/BRET, total 20, without the plus sign denoting full-length Y2H reconfirmation; these are assay scores, not affinity measurements. DOCK7 did not alter the tested NOD2/NF-kB reporter after knockdown, and its BRET and expression were not stimulus-responsive in the reported tests. NOD2 is an intracellular signaling receptor, so GO:0005102 describes the bounded positive binding observation without requiring receptor agonism. No purified direct interface or native immune function is established. Both original GOA provenance contexts remain documented. Proposed replacements: signaling receptor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29187380 Nbeal2 interacts with Dock7, Sec16a, and Vac14. | KEEP AS NON CORE | Summary: DOCK7 associates with SEC16A-containing complexes. Reason: The original human HEK293T experiments recover endogenous DOCK7 in SEC16A immunoprecipitates containing an expressed NBEAL2 PH-BEACH-WD40 construct. This is complex-association evidence, not a purified DOCK7–SEC16A interface or a demonstration that DOCK7 performs ER export. The SEC16A scaffold role does not by itself define a more specific DOCK7 molecular activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29187380 Nbeal2 interacts with Dock7, Sec16a, and Vac14. | KEEP AS NON CORE | Summary: DOCK7 association with NBEAL2 is supported in human cellular contexts. Reason: Tagged NBEAL2-fragment assays, native megakaryocyte-related cell co-immunoprecipitation and human megakaryocyte proximity ligation support the association. NBEAL2 PH/BEACH-region perturbations affect DOCK7 recovery. These observations do not establish that DOCK7 directly executes NBEAL2-dependent granule biogenesis or supply a purified binary affinity measurement. Retain the physical association as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29467281 The MYO6 interactome reveals adaptor complexes coordinating ... | KEEP AS NON CORE | Summary: DOCK7–LRCH3 association contributes to the reported LRCH-associated context. Reason: The original Figure 5C co-immunoprecipitation supports this pair. The paper’s directly tested MYO6–LRCH3 interaction is distinct from DOCK7 association with the larger DISP assembly. The methods name human DOCK7 isoform 4, while fragment coordinates follow a different historical numbering convention; those constructs are not silently equated with all seven current products. The pair alone does not establish a DOCK7 adaptor or septin-binding molecular function. Supporting Evidence: PMID:29467281 both MYO6 and DOCK7 can bind to LRCH3 |
| GO:0005515 protein binding | IPI PMID:29467281 The MYO6 interactome reveals adaptor complexes coordinating ... | KEEP AS NON CORE | Summary: DOCK7–LRCH1 association contributes to the reported LRCH-associated context. Reason: The original Figure EV4B co-immunoprecipitation supports this pair. The paper’s directly tested MYO6–LRCH3 interaction is distinct from DOCK7 association with the larger DISP assembly. The methods name human DOCK7 isoform 4, while fragment coordinates follow a different historical numbering convention; those constructs are not silently equated with all seven current products. The pair alone does not establish a DOCK7 adaptor or septin-binding molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32203420 Systems analysis of RhoGEF and RhoGAP regulatory proteins re... | KEEP AS NON CORE | Summary: DOCK7–LRCH4 association is retained with construct limits. Reason: The RhoGEF/GAP-map original reports DOCK7 co-immunoprecipitation with LRCH proteins and maps LRCH interaction to the DHR2 region. Its deposited DOCK7 library DNA translates to a construct missing the current N-terminal 362 residues and the 923–953 segment, despite a full-length/isoform-style metadata label. This deposited-sequence discrepancy does not invalidate the positive pair or identify the exact protein used in every experiment. The same study’s activity table contains no positive DOCK7 GEF-screen result; no catalytic activity is inferred from this interaction alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex supports DOCK7 association with LRCH3. Reason: Three curated matching human records link DOCK7 and LRCH3 in BioPlex anti-tag affinity-purification/co-immunoprecipitation experiments. Sequence checks authenticate the curated participant records, not all experimental splice products. AP-MS can recover an indirect complex association. Targeted LRCH studies corroborate the pair, but no more specific DOCK7 molecular role follows from this measurement. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex supports DOCK7 association with LRCH1. Reason: Three curated matching human records link DOCK7 and LRCH1 in BioPlex anti-tag affinity-purification/co-immunoprecipitation experiments. Sequence checks authenticate the curated participant records, not all experimental splice products. AP-MS can recover an indirect complex association. Targeted LRCH studies corroborate the pair, but no more specific DOCK7 molecular role follows from this measurement. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: OpenCell recovers LRCH3 with endogenous-tagged DOCK7. Reason: The public OpenCell interaction CSV has a DOCK7-bait/LRCH3-prey record at physical line 7612 including the header. The complete prey accession group is preserved in the reproducible extraction and does not identify a unique splice product. Endogenous-tag affinity purification supports cellular association but not necessarily direct contact or a distinct binding mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: OpenCell recovers LRCH1 with endogenous-tagged DOCK7. Reason: The public OpenCell interaction CSV has a DOCK7-bait/LRCH1-prey record at physical line 7610 including the header. The complete prey accession group is preserved in the reproducible extraction and does not identify a unique splice product. Endogenous-tag affinity purification supports cellular association but not necessarily direct contact or a distinct binding mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: The U2OS AP-MS map recovers DOCK7 with LRCH3. Reason: The primary public network contains edge 552514 from LRCH3 bait to DOCK7 prey. The original study uses human U2OS cells and C-terminal HA-Flag-tagged baits, with quality filtering of AP-MS associations. This source-specific positive edge is retained; network membership does not establish a purified binary interface or a more specific DOCK7 molecular activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: The U2OS AP-MS map recovers DOCK7 with LRCH1. Reason: The primary public network contains edge 554276 from LRCH1 bait to DOCK7 prey. The original study uses human U2OS cells and C-terminal HA-Flag-tagged baits, with quality filtering of AP-MS associations. This source-specific positive edge is retained; network membership does not establish a purified binary interface or a more specific DOCK7 molecular activity. Supporting Evidence: |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Summary: Focal-adhesion proteomic detection is retained as a contextual location. Reason: The original study isolated focal adhesions from human HFF1 fibroblasts and used reproducible mass-spectrometric identification. The DOCK7-specific supplementary identification row was not recovered independently, so the curator’s target assignment is retained. This contextual proteomic location is plausible for a cytoskeletal regulator but is not used as proof of an active focal-adhesion mechanism. General contamination discussion in a proteomics paper is not target-specific evidence against DOCK7. Supporting Evidence: |
| GO:0007264 small GTPase-mediated signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: DOCK7 positively regulates Rho-family signaling through nucleotide exchange. Reason: The DOCK7-family mapping is sound. Target-specific Rac activation and purified human historical DHR2-fragment exchange on prenylated RAC1 and CDC42 support positive regulation of Rho-family signaling. GO:0035025 is a target-supported role correction rather than a claimed strict descendant of GO:0007264; it captures the activating direction while covering both tested GTPases. CDC42 exchange is conditional on the membrane/prenylation reconstitution and does not establish an endogenous CDC42 pathway in every cell type. The independent Rac-specific assertion is retained. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR026791 SUPPORTS TRANSFER Valid target-family mapping; positive Rho-family regulation is supported by target Rac biology and defined human-fragment exchange assays. Proposed replacements: positive regulation of Rho protein signal transduction |
| GO:0007409 axonogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: The axonogenesis IBA has valid target-grounded ancestry. Reason: The literal IBD at PTN002762137 is on the DOCK7 lineage and is experimentally grounded in the target’s axonogenesis annotation. Target self-inclusion is expected in PAINT and is not circular. The original abstract reports that DOCK7 depletion prevents axon formation and overexpression induces multiple axons; the full 2006 paper remains unavailable, so detailed assay species/constructs are not invented. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002762137 SUPPORTS TRANSFER Actual ancestral placement and path to Q96N67 verified. UniProtKB:Q96N67 SUPPORTS TRANSFER Target experimental grounding of the ancestral IBD is legitimate, not circular. Supporting Evidence: |
| GO:0007409 axonogenesis | IMP PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | ACCEPT | Summary: DOCK7 promotes axon formation. Reason: The source abstract explicitly reports loss of axon formation following DOCK7 knockdown and multiple axons after overexpression, linking the phenotype to Rac/stathmin-dependent microtubule regulation. These findings support the imported experimental claim. Full original methods remain unavailable; detailed construct or species claims are not inferred from the abstract. Supporting Evidence: |
| GO:0008180 COP9 signalosome | IDA PMID:18850735 Characterization of the human COP9 signalosome complex using... | KEEP AS NON CORE | Summary: Association with COP9 signalosome is retained with its original colocalizes_with qualifier. Reason: Human CSN5-tag purification and independent immunoblotting recover endogenous DOCK7 with the COP9 complex compared with a tagged control. This supports association with the complex; it does not make DOCK7 a constitutive COP9 structural subunit or a deneddylase. The imported colocalizes_with relation is therefore preserved and the contextual complex association remains non-core. Supporting Evidence: |
| GO:0016601 Rac protein signal transduction | IMP PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | ACCEPT | Summary: Rac signaling is a central DOCK7 function. Reason: The source abstract links DOCK7-dependent Rac activation to stathmin phosphorylation and axon formation. Defined human historical DHR2 fragments independently catalyze RAC1 nucleotide exchange in a membrane reconstitution. These support Rac signaling while keeping exchange distinct from GTP hydrolysis stimulation and without assigning kinase activity to DOCK7. |
| GO:0022027 interkinetic nuclear migration | ISS GO_REF:0000024 | ACCEPT | Summary: The interkinetic nuclear migration inference is supported by the mouse ortholog mechanism. Reason: Actual mouse cortical experiments show that DOCK7 depletion accelerates basal-to-apical nuclear migration and that a DHR2-deleted construct rescues the phenotype, whereas a TACC3-binding-deficient construct does not. This supports a GEF-independent role in microtubule/centrosome–nucleus regulation. Human SK-N-BE cells separately show DOCK7/TACC3 centrosomal colocalization; they do not provide a human cortical migration assay. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8R1A4 SUPPORTS TRANSFER Mouse ortholog identity and direct cortical migration/TACC3 experiments support transfer; human centrosome evidence is separate. Supporting Evidence: |
| GO:0030424 axon | IEA GO_REF:0000044 | ACCEPT | Summary: The axonal location mapping agrees with target literature. Reason: The UniProt subcellular-location mapping to axon is supported by the 2006 report of selective DOCK7 enrichment in developing axons. This is the neuronal pool relevant to its polarity function; it is not a universal location of all splice products or cell types. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0279 SUPPORTS TRANSFER The literal subcellular-location mapping and independent target axonal observation agree. Supporting Evidence: |
| GO:0030424 axon | TAS PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | ACCEPT | Summary: DOCK7 is enriched in developing axons. Reason: The source abstract explicitly reports selective axonal expression after asymmetric distribution in unpolarized hippocampal neurons. The finer microscopy/construct details are not claimed without the full original. Other cytosolic and centrosomal pools do not contradict this neuronal location. Supporting Evidence: PMID:16982419 selectively expressed in the axon |
| GO:0030426 growth cone | TAS PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | UNDECIDED | Summary: The growth-cone-specific location remains unresolved. Reason: Axonal enrichment is directly described in the accessible abstract, but it does not by itself establish the migrating growth cone. The full original needed to inspect this finer location was not recovered. Preserve the imported TAS assertion without treating it as wrong or inferring growth-cone localization merely from axon formation. Supporting Evidence: |
| GO:0031106 septin ring organization | NAS PMID:29467281 The MYO6 interactome reveals adaptor complexes coordinating ... | KEEP AS NON CORE | Summary: The LRCH3/DOCK7 overexpression study supports a bounded septin-organization context. Reason: Figure 6D compares mock and DHR2 expression in parental RPE cells and stable LRCH3 cells, counting more than 100 cells per condition in three experiments. LRCH3 plus DOCK7 DHR2 produces septin rings in approximately 80% of cells; DHR2 alone does not reproduce this large redistribution. Figure 6B also immunostains DOCK7 at LRCH3-induced rings. This controlled organization phenotype supports the NAS term as non-core. The proposed GEF-to-septin mechanism remains speculative: endogenous loss-of-function dependence, a catalytic-dead requirement and direct septin binding were not established. The engineered fragment result is not generalized to all natural products. Supporting Evidence: |
| GO:0031175 neuron projection development | IMP PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | MODIFY | Summary: Axonogenesis is the specific projection-development outcome established by this source. Reason: The original abstract directly establishes DOCK7-dependent axon formation. Current typed GO ancestry places axonogenesis below neuron projection development. Refining this source assertion to the already represented axonogenesis term preserves its demonstrated outcome; it does not add a new annotation or deny other DOCK7 neuronal roles. Proposed replacements: axonogenesis Supporting Evidence: |
| GO:0031267 small GTPase binding | IDA PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | ACCEPT | Summary: Small-GTPase binding is directly supported. Reason: The original experimental attribution is retained with curator deference, and independent purified human historical DHR2-fragment assays directly recover RAC1/CDC42 in nucleotide-state-dependent binding experiments. The larger DHR2s fragment binds activated GTPase forms, whereas the shorter fragment has different binding behavior. This supports the broad small-GTPase binding function without universal product or substrate-state equivalence. |
| GO:0035023 regulation of Rho protein signal transduction | IBA GO_REF:0000033 | MODIFY | Summary: The valid ancestral regulatory inference can be refined to positive regulation. Reason: The literal PTN000593987 IBD is grounded in fly Zir/FBgn0031216, and Q96N67 descends from that node. The fly genetic evidence supports the ancestral regulatory role; independent human DOCK7 exchange assays and target Rac signaling establish an activating direction. GO:0035025 is a current descendant of the imported regulation term. The refinement combines that valid ancestry with target evidence, without transferring fly immune physiology or asserting a native human CDC42 pathway from a liposome assay. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000593987 SUPPORTS TRANSFER Literal IBD and target descent established. FB:FBgn0031216 SUPPORTS TRANSFER Zir donor identity and IGI annotations verified; the primary abstract supports Rac2/Cdc42 genetic interaction, with no independently recovered full assay methods. Proposed replacements: positive regulation of Rho protein signal transduction |
| GO:0043005 neuron projection | TAS PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | MODIFY | Summary: Axon is the more informative neuronal location supported by this source. Reason: The 2006 abstract specifically describes selective axonal localization, which refines the broad neuron-projection term. This source-specific replacement points to an existing axonal assertion and does not erase independently supported centrosomal or cytosolic pools. Proposed replacements: axon Supporting Evidence: |
| GO:0045178 basal part of cell | TAS PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | UNDECIDED | Summary: The source-specific basal-cell location is unresolved. Reason: GO:0045178 describes the region near a cell base. The accessible source describes neuronal asymmetry and axonal enrichment, but the finer basal-cell localization cannot be evaluated without its original figures and methods. No contradictory localization is inferred from that access limit. Supporting Evidence: |
| GO:0045200 establishment of neuroblast polarity | IMP PMID:16982419 The Rac activator DOCK7 regulates neuronal polarity through ... | UNDECIDED | Summary: Neuroblast apicobasal polarity is not resolved by the accessible neuronal-polarity evidence. Reason: The current term specifically describes apicobasal polarity of a central-nervous-system progenitor. Axon–dendrite polarity of a differentiating neuron is not automatically the same claim. The original full text remains inaccessible, so the imported experimental annotation is not removed or declared misattributed. The separate TACC3 study supports progenitor nuclear migration but does not itself establish this polarity endpoint. |
| GO:0050767 regulation of neurogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: DOCK7 regulates cortical progenitor differentiation in the ortholog study. Reason: Mouse in utero perturbation and rescue experiments show that DOCK7 balances radial-glial proliferation and neuronal differentiation through its TACC3-dependent nuclear-migration mechanism. Rescue by a DHR2-deleted construct separates this from its catalytic GEF unit. Retain the ISS claim with explicit mouse developmental scope and no assertion of equivalent activity for every human splice product. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8R1A4 SUPPORTS TRANSFER Verified mouse ortholog and direct cortical differentiation experiments support the conserved role; human functional equivalence of all products was not tested. Supporting Evidence: |
| GO:0120163 negative regulation of cold-induced thermogenesis | ISS PMID:23553822 Altered thermogenesis and impaired bone remodeling in Misty ... | MARK AS OVER ANNOTATED | Summary: Compensatory white-fat browning does not establish a negative thermogenic regulatory role for DOCK7. Reason: Misty Dock7-mutant mice show altered brown-fat thermogenic function and sympathetic innervation, while retaining a beta-3-agonist response. Their cold-induced white-fat browning program is interpreted as compensation. These different tissue responses are valid observations, but the compensatory program does not establish that DOCK7 itself negatively regulates cold-induced thermogenesis. The imported ISS assertion therefore overstates the supported regulatory role. This is not a simple reversal of sign across tissues and does not justify substituting positive thermogenesis regulation or asserting an experimentally demonstrated human heat-production function. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:Q8R1A4 SOURCE WEAK OR INFERRED Mouse cold-response and tissue-compensation phenotypes are supported; inferring that DOCK7 performs negative thermogenic regulation from compensatory white-fat browning exceeds that source evidence. Supporting Evidence: |
| GO:1904754 positive regulation of vascular associated smooth muscle cell migration | IMP PMID:22158624 Bone morphogenetic protein 4 promotes vascular smooth muscle... | KEEP AS NON CORE | Summary: Human vascular smooth-muscle migration is a supported context-dependent outcome. Reason: In primary human pulmonary arterial smooth-muscle cells, DOCK7 knockdown reduces scratch migration; the paper distinguishes DOCK7 from DOCK4/5 because DOCK7 depletion does not alter contraction or contractile-gene expression. Human DOCK7 re-expression in rat PAC1 cells is a separate experiment. Retain the migration role without transferring the paper’s contractility headline or interpreting Rac pull-downs as a purified DOCK7 exchange assay. Supporting Evidence: |
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Download this section (compressed HTML)Q: Does DOCK7 stimulate GTP hydrolysis in any context, as distinct from its established nucleotide-exchange activity?
Q: How should the categorical CDC42 exclusion in the curated protein summary be qualified to reflect positive exchange by historical human DHR2 fragments on prenylated, membrane-associated CDC42, and which endogenous contexts and natural products use this substrate?
Q: How does the DOCK7–TACC3 interaction alter microtubule growth independently of DHR2, and which natural products retain this mechanism?
Q: Does endogenous DOCK7 regulate septin organization independently of the LRCH3/fragment coexpression system?
Experiment: Compare sequence-authenticated natural products and catalytic controls in separate nucleotide-exchange and GTP-hydrolysis assays using prenylated membrane-associated and soluble RAC1/CDC42.
Hypothesis: Membrane context and product composition determine exchange specificity without implying GAP activity.
Type: Biochemical substrate and product comparison
Experiment: Combine endogenous DOCK7 perturbation with TACC3-binding-deficient and DHR2-deficient rescue, measuring microtubule growth and nuclear migration separately from Rac activation.
Hypothesis: The TACC3-dependent nuclear-migration mechanism is separable from nucleotide exchange.
Type: Mechanistic separation-of-function rescue
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