DOK7 has two complementary signaling functions. Its N-terminal PH–PTB region binds phosphorylated MUSK and promotes receptor pairing and activation. Its phosphorylated tail recruits CRK and CRKL, coordinating downstream synaptic differentiation. MUSK supplies kinase catalysis; DOK7 is an activator and adaptor. The two core entries therefore represent distinct mechanisms rather than two copies of generic kinase binding.
The structural study separates its reagents carefully: human DOK7 residues 1–220 were used in solution binding and oligomerization measurements, whereas mouse PH–PTB was used for the ligand-bound crystal, lipid binding and direct kinase-activation measurements with rat MUSK. Mouse full-length Dok7 was expressed in NIH3T3 cells. The dimer-interface mutant distinguishes receptor binding from efficient activation. See Bergamin et al., 2010, Results on the Dok7–MuSK complex and stimulation of kinase activity, and Experimental Procedures.
The second mechanism is supported by the separately recovered Hallock et al., 2010 original. Figures 1–5 and the DNA constructs, cell culture, phosphopeptide affinity purification and biochemical Methods establish murine Dok7 phosphorylation, CRK/CRKL recruitment and AChR-clustering effects. The cDNA was cloned from C2 mouse muscle cells. HEK293 is an expression host, not evidence of a human construct. Phosphopeptide capture was performed from lysate; it is not a purified two-protein reconstitution. The current normal publication cache contains only the abstract, despite the successful separate original recovery. Discussion proposes Rac/Rho exchange-factor linkage; it does not directly measure that linkage.
All 16 imported annotations are preserved. The three kinase-binding assertions are refined to receptor tyrosine kinase binding. The adaptor assertion is refined to transmembrane receptor protein tyrosine kinase adaptor activity. The receptor pathway is refined to the current cell-surface receptor tyrosine-kinase pathway, and broad membrane/synapse assertions are resolved to the established postsynaptic functional pool. No new annotation is manufactured to fill a core-coverage advisory. Current GO definitions and typed ancestry were checked, including the distinction between kinase binding and kinase activation.
The postsynaptic location is an explicit ortholog-supported conclusion: mouse Q18PE0 carries IDA evidence for postsynaptic membrane from PMID:16794080. Human disease supports the neuromuscular role but is not a substitute for human localization microscopy. The 2006 paper remains abstract-only in the recovered cache, and its unavailable full Methods are not described as inspected.
The Human Protein Atlas DOK7 record also positively supports nucleoplasm and mitochondria. Both HPA059449 and HPA062780 report nucleoplasmic staining in MCF-7 and Rh30, and mitochondrial staining in Rh30; HPA059449 additionally reports U2OS nucleoplasm. Reliability is enhanced. These nonexclusive cell-context pools are retained as non-core; no mitochondrial mechanism, isoform assignment or image-pixel interpretation is inferred.
The HuRI source and literal IntAct records support the DOK7–EFEMP2 binary interaction. Records EBI-24557174, EBI-23490963 and EBI-25046471 share current canonical sequence ROGIDs for both proteins. Three records do not mean three independent physiological experiments. A signaling function for this pair is unresolved, and different usual compartments do not establish a false interaction. The positive generic binding annotation is retained as non-core under the explicit ClinGen project binding instruction.
PAINT node PTN001092033 places the human target inside the inherited clade. Its kinase-binding IBD includes human evidence legitimately; this is not circularity. The saved IBD snapshot and original GOA differ in the development donor list, which is documented without altering the imported sources. InterPro IPR037746 matches the target Dok-7 family. The exact current ARBA triggering condition remains unresolved, while the other source branches and direct target evidence support receptor binding.
The four official products reconstruct to 504, 366, 255 and 608 residues, retaining their official order and names. Product 2 removes the PH domain and changes part of PTB; product 4 changes PTB and removes the distal tail; product 3 changes the extreme C terminus. These changes do not establish activity, inactivity or functional equivalence. Engineered 1–220 fragments are not natural splice products.
Falcon research was attempted using the configured fallback. Falcon authentication failed, and the fallback returned an insufficient-quota response. No provider-authored content was invented. The initial PMID:20012313 cache request encountered HTTP429; a subsequent ordinary fetch succeeded. Existing main publication caches were protected and remain unchanged. New publication files are genuine fetched outputs with their original availability flags. The evidence guide provides source and assay locators; it is a navigation document, not independent experimental support.
The kinase-activator core is now accompanied by an explicit proposed GO:0030296 annotation. PMID:20603078 separates mouse PH-PTB direct activation from human PH-PTB binding/oligomerization with rat MUSK; the human proposal therefore uses ISS with mouse Q18PE0 rather than human IDA. MUSK catalyses phosphotransfer, while DOK7 organizes activation. No new quotation is reproduced. The synapse refinement now includes both postsynaptic membrane and neuromuscular junction. The lipid-binding explanation records the official ranked phosphoinositide preference without claiming one exclusive species. A separate phosphotyrosine-binding proposal remains a focused question because the direct peptide structural evidence is murine. DRAFT follows the repository-computed status with contextual validation warnings; project completion is counted only after a verified merge.