Long dystrophin connects cytoskeletal networks to the sarcolemmal dystrophin-associated glycoprotein complex (DGC) and helps organize membrane-associated proteins. Human dystrophin fragment binding to a rabbit beta-dystroglycan tail and direct keratin-19 binding support complementary sides of this linkage PMID:7592992(https://pubmed.ncbi.nlm.nih.gov/7592992/), PMID:16000376(https://pubmed.ncbi.nlm.nih.gov/16000376/). The compact core describes this integrated anchor and organization mechanism without assigning one core to every recovered partner.
The historical human WW/EF-like fragment bound to a dystroglycan peptide is distinct from newer native complexes. Native rabbit and mouse cryo-EM structures place beta-dystroglycan near the dystrophin ZZ region and include additional cytoplasmic partners; unresolved flexible regions and fitted models limit atomic claims. Neither native ortholog structure measures all human natural products PMID:10932245(https://pubmed.ncbi.nlm.nih.gov/10932245/), PMID:39663457(https://pubmed.ncbi.nlm.nih.gov/39663457/), PMID:39663450(https://pubmed.ncbi.nlm.nih.gov/39663450/). The human 1DXX N-terminal construct is an apo 246-residue fragment carrying C10S/C188S relative to current canonical sequence, not a full-length wild-type actin-bound complex PMID:10801490(https://pubmed.ncbi.nlm.nih.gov/10801490/).
Seventeen official human sequences were reconstructed independently. Accessions and displayed product names are not ordinal equivalents. Long Dp427 products contain the N-terminal actin-binding region; Dp260, Dp140, Dp116, Dp71-related and Dp40 products have different retained regions. Sequence shortening alone establishes neither equivalence nor inactivity. Historical molecular-mass bands, splice names and engineered deletions cannot be assigned indiscriminately to current accessions. Controlled human mitochondrial fractions support a Dp71-related pool but do not resolve a matrix-facing inner-membrane location or every natural product PMID:34575126(https://pubmed.ncbi.nlm.nih.gov/34575126/).
The source of a localization observation is retained when selecting a more precise term. Rat brain postsynaptic-density fractionation supports a PSD pool, not a synaptic-vesicle pool; the original journal pages are 11642–11644 PMID:1454857(https://pubmed.ncbi.nlm.nih.gov/1454857/). Glial material can complicate brain PSD interpretation PMID:10545507(https://pubmed.ncbi.nlm.nih.gov/10545507/). Unavailable platelet originals leave specific filopodium and binding assertions unresolved rather than disproved PMID:16803572(https://pubmed.ncbi.nlm.nih.gov/16803572/).
Targeted mouse transgene experiments restore and co-isolate dystrobrevin/syntrophin assemblies with dystrophin lacking exons 71–74. This supports performed organization of the DGC, while the exact stoichiometric arrangement remains a model PMID:9214383(https://pubmed.ncbi.nlm.nih.gov/9214383/). In contrast, RyR/calstabin destabilization and its pharmacological rescue demonstrate downstream calcium-handling consequences of dystrophin deficiency, not a direct DMD-catalyzed assembly reaction PMID:19198614(https://pubmed.ncbi.nlm.nih.gov/19198614/), PMID:20080623(https://pubmed.ncbi.nlm.nih.gov/20080623/). Cardiac sodium-current density and additional utrophin-dependent gating effects are distinguished PMID:21677768(https://pubmed.ncbi.nlm.nih.gov/21677768/).
nNOS association has both direct-fragment and mediated-recruitment evidence. A purified R16–17/nNOS-PDZ BLI assay reports an equilibrium dissociation constant near 50 micromolar; kinetics are multiphasic and atomic contacts are modeled PMID:26378238(https://pmc.ncbi.nlm.nih.gov/articles/PMC4705953/). Human repeat peptides capture syntrophins from mouse muscle, and microdystrophin restores nNOS at the mouse sarcolemma only in the presence of alpha-syntrophin PMID:29790927(https://pmc.ncbi.nlm.nih.gov/articles/PMC6097012/). The latter study does not repeat the BLI assay and therefore does not directly invalidate it. Human atrial co-immunoprecipitation separately establishes native association PMID:27225184(https://pubmed.ncbi.nlm.nih.gov/27225184/). The unresolved question is how much direct contact contributes within the native human complex. Kir-channel-tail experiments attribute their PDZ recognition to syntrophin, so they do not independently establish DMD–PDZ recognition PMID:15024025(https://pubmed.ncbi.nlm.nih.gov/15024025/).
Positive generic interactions are retained as non-core under the scoped project instruction when a more informative role is unestablished. Untargeted binary hits and AP-MS associations are not treated as proof of a partner's physiological function. Independent targeted scaffold evidence justifies selected syntrophin/alpha-catulin refinements; short beta-dystrobrevin product identity remains a separate limitation PMID:21115837(https://pubmed.ncbi.nlm.nih.gov/21115837/). The source guide gives public pair identifiers, assay features, literal phylogenetic nodes, matched rule branches and positive Reactome paths.
All 166 imported annotation source objects are preserved. PAINT conclusions are evaluated on actual ancestral placement, not donor count or the presence of target self-evidence. Broad annotations are refined using supported specific terms, with pleiotropic roles retained where appropriate. No new annotation is manufactured merely to duplicate the integrated core. Eighteen unresolved assertions retain their positive evidence and exact limits.
Normal source fetching succeeded. The default Falcon research attempt returned an authentication failure, and the configured fallback returned a quota/authentication failure; neither produced a research report. Manual source research is documented here and in the evidence guide. Cached publication text, UniProt, GOA and failed provider receipts remain unmodified. A full-text cache flag is not a claim that a complete original was read: the guide records abstract-only access, independently recovered original windows and the incomplete PMID:30280653 cache separately.
The peptide-biosynthesis verdict (GO:0043043 / IDA / PMID:16000376) is corrected to REMOVE after re-reading the original Methods and Results. The expression system produces the constructs; the tested dystrophin domain performs binding and structural organization. This is a source-specific judgment from the recovered original, not from its abstract alone. Positive functions from that study remain represented.
The K19 interaction now refines to GO:0019215, intermediate filament binding. The original Figures 1–3 and 6 distinguish cellular K8/K19 filaments from purified-subunit binding. For synemin, the complete abstract establishes direct human-domain binding and colocalization, but the full original remains unavailable. GO:0019215 names an assembled filament, so that separate pair retains GO:0008092, cytoskeletal protein binding; neither a filament assay nor its absence is inferred from unseen text.
All eight Reactome cytosol annotations are retained as KEEP_AS_NON_CORE. The source guide's 16 positive participant paths still resolve to human P11532 residues 1–3685. These are broad model compartments compatible with membrane attachment, not evidence that DMD performs myosin ATP hydrolysis or extracellular ligand recognition. The R-NUL-9913739 event retains its human-dystrophin/bovine-actin distinction. The single integrated anchor core remains at the sarcolemmal DGC; its description now explicitly connects the complementary cytoskeletal and DGC-facing contacts.
Both cytoskeleton refinements retain GO:0030863, cortical cytoskeleton, in addition to the previously supported anatomical terms. Its current is_a/part_of ancestry includes GO:0005856; costamere does not have that ancestry. This preserves the cortical cytoskeletal claim while retaining the independently supported costameric distribution and the separate neuronal pool. These are refinements of existing assertions, not new annotations.
All 166 imported source objects, 17 product records, reference assessments and nine existing quotations remain unchanged. No new quotations were added. Earlier notes and the source guide remain intact; this dated appendix supersedes the earlier action categorization only where specified above.