DCC is a netrin receptor whose extracellular immunoglobulin and fibronectin domains connect guidance cues to intracellular signaling. The official human record contains one displayed 1,447-residue sequence and no alternative-products declaration. The predicted signal peptide, transmembrane segment and cytoplasmic tail are distinguished from experimentally expressed fragments and from the modeled cleavage products. The current model assigns residues 26–1290 to a membrane-retained product and 1291–1447 to the released distal tail; these are not separately encoded isoforms. The proximal apoptotic region is not the released inactive tail. UniProt P43146, Reactome R-HSA-373705.
The original receptor study establishes binding and antibody-sensitive axon outgrowth, with rat DCC, chick netrin and rat neurons; the human 293 cells are the expression host. Its author dissertation was recovered when the journal PDF was blocked. The particular turning assay inside explants was not blocked by the antibody, so outgrowth is not silently converted into a direct chemoattraction assay. The ligand-specific netrin receptor term is appropriate, and the axon-guidance synthesis also uses the actual PAINT placement and subsequent neuronal evidence. PMID:8861902(https://pubmed.ncbi.nlm.nih.gov/8861902/).
A second functional unit organizes ligand-absence apoptotic signaling. Human DCC expression, D1290 mutation and intracellular truncations support a proximal signaling role; later work connects DCC to APPL1 and state-dependent caspase association. DCC plus caspases alone does not reconstitute activation: additional S100 components are required. The signaling-adaptor interpretation therefore represents functional recruitment and coordination, not autonomous protease activity, a purified ternary complex, or a demonstrated direct caspase-9 interface. The early studies did not directly detect cleavage of native full-length DCC. PMID:9796814(https://pubmed.ncbi.nlm.nih.gov/9796814/), PMID:12011067(https://pubmed.ncbi.nlm.nih.gov/12011067/), PMID:11248093(https://pubmed.ncbi.nlm.nih.gov/11248093/), PMID:16537496(https://pubmed.ncbi.nlm.nih.gov/16537496/).
The interaction assessments distinguish the assay from the partner class. MAZ supports transcription-factor binding, CASP9 caspase binding, MYO10 myosin binding and TRIM9 ligase binding. Direct DCC P3–MYO10 contact is demonstrated with recombinant fragments and a deliberately engineered MYO10 deletion. Several database records are mutant perturbations rather than independent confirmations of wild-type binding. Human TRIM9 association is explicitly stated in the original main text even though the exact supplementary assay remained inaccessible. This is not a reason to dismiss the human result because most of that paper studies a fly homolog. PMID:11527412(https://pubmed.ncbi.nlm.nih.gov/11527412/), PMID:21642953(https://pubmed.ncbi.nlm.nih.gov/21642953/), PMID:22084112(https://pubmed.ncbi.nlm.nih.gov/22084112/).
The translation study establishes DCC association with ribosomal particles and independently demonstrates purified RPL5 contact. RPL28/RPS23 complex records are not presented as purified binary assays, and binding to a named ribosomal protein alone would not establish ribosome binding. Here the broader fractionation evidence supplies that functional context. DCC remains a receptor-associated regulator rather than a structural ribosomal subunit or constitutive translation inhibitor. PMID:20434207(https://pubmed.ncbi.nlm.nih.gov/20434207/).
Positive netrin-binding assertions remain contextual generic associations where the inspected ontology does not supply an appropriate binding-only class. Netrin receptor activity adds signal transmission, while netrin receptor binding points in the opposite direction. PSG7 and IGFBPL1 binding/SPR results are retained with extracellular-construct and avidity limits; they do not establish physiological receptor activation. Supported generic associations are retained under the standing campaign policy. PMID:19721007(https://pubmed.ncbi.nlm.nih.gov/19721007/), PMID:26190107(https://pubmed.ncbi.nlm.nih.gov/26190107/), PMID:32822567(https://pubmed.ncbi.nlm.nih.gov/32822567/).
The actual PTHR44170 tree, target alignment and five on-path IBDs were reconstructed. The deep cell-adhesion node is not judged by donor count or pairwise similarity. Its current sources include positive experimental annotations to verified children of cell-cell adhesion; an exact-term-only query would miss these. The ancestral adhesion assertion is retained as contextual, without inventing direct human homophilic adhesion. The current guidance IBD includes an additional zebrafish donor absent from the old seeded source; the imported source fields remain literal.
Mouse spinal accessory neuron experiments quantify Dcc-dependent cell-body migration and axon trajectories. The synaptic study combines mouse conditional deletion and Schaffer-collateral physiology with adult-rat PSD fractionation and immunoelectron microscopy. Its genuine author thesis Chapter 3 was recovered and selected Methods/Results were read; neither this nor the mouse ortholog annotation is represented as a direct human synapse experiment. PMID:16267219(https://pubmed.ncbi.nlm.nih.gov/16267219/), PMID:23291093(https://pubmed.ncbi.nlm.nih.gov/23291093/), PMID:9331350(https://pubmed.ncbi.nlm.nih.gov/9331350/). The Neogenin/Lrig2 paper is used only as PAINT donor context. PMID:26651291(https://pubmed.ncbi.nlm.nih.gov/26651291/).
Three precise negative developmental assertions remain undecided. The BCL11A paper explicitly reports DCC-overexpression rescue, so there is positive target evidence and no wrong-gene claim. Its accessible abstract does not identify which DCC rescue measurements support the separate neuron-projection, collateral-sprouting and dendrite-development terms. Bounded original-access attempts did not resolve this. PMID:19616629(https://pubmed.ncbi.nlm.nih.gov/19616629/).
All 51 seeded source dictionaries are preserved: term, evidence, reference, qualifier and supporting entities. No NEW annotation is proposed. The source evidence guide gives public source locators, actual interaction identifiers, product/construct boundaries and source-specific limitations. It is an authored navigation aid, not an independent experiment.
The 18 Reactome source events were traced through 118 objects and 45 typed paths to human DCC. The receptor can be a signal-receiving component, a recruitment platform or a regulated substrate; membership in a kinase, GEF or caspase event does not transfer the catalytic activity to DCC. The Siah-related cached source explicitly concerns DCC regulation as a substrate. Its cache declares full text but contains abstract/Discussion rather than the complete original, and no complete-paper read is claimed. PMID:9334332(https://pubmed.ncbi.nlm.nih.gov/9334332/).
Independent consultations assessed seven primary/core rows and thirteen interaction rows. Their original recoveries and selected passage readings are attributed separately from the owner's remaining source review. The core proposal and interaction refinements were read and independently reproduced before integration. The initial draft has 24 ACCEPT, 11 MODIFY, 12 KEEP_AS_NON_CORE, three UNDECIDED and one TOO_GENERAL decision.
The genuine normal fetch and publication caching completed in an isolated exact-tooling workspace. Falcon authentication failed and its configured Perplexity-lite fallback returned insufficient quota; no provider report was fabricated. Existing caches, GOA, UniProt and family sources were retained exactly. An additional-reference qualification script initially failed at parse time while a subsequent shell line started the isolated fetch; the corrected qualification found no pending source collision, and the preexisting cache was authenticated and skipped by the fetch. The failed script and actual sequence of receipts are preserved. No canonical source was modified.
The distinct PAINT variant in pending PR4576 is excluded. A later pending family-review proposal in PR5078 is also context only; the accepted main source boundary remains the one used for this review. These ownership constraints are qualified again at publication, without importing pending scientific content.
The frozen scientific candidate and its archived source inputs were preserved during handover. Re-executing the saved science checker reconstructed the target sequence, on-path PAINT assertions, electronic-rule conditions, literal interactions and typed Reactome paths. Comparing the public guide to the raw ARBA branch corrected the formatting of its three FunFam identifiers to their literal FF: form. The HPA entry now explicitly distinguishes inspection of the data record from inspection of its underlying microscopy images. These documentation corrections do not change an annotation decision. Independent review of the remaining 31 annotation rows is tracked separately from the earlier core and interaction consultations.
The six supported generic-binding assertions follow the user's explicit instruction for the ClinGen campaign: preserve a biologically supported association as KEEP_AS_NON_CORE when no evidence-backed narrower replacement has been established, and use UNDECIDED for inaccessible or unadjudicated evidence. The project curation instructions record that scoped instruction at immutable tracker commit f60d148872b916a941f699aab90ab06597ca9bf8 in pending PR #5053. This is user-authorized project scope, not a repository-wide policy change, an external maintainer sign-off, or a claim that the tracker branch has merged. It takes precedence over the general skill recommendation; the six automated binding advisories remain disclosed. The earlier shorthand “standing campaign policy” refers to this instruction. No supported interaction is removed to silence that advisory.
The APPL1-specific IPI assertion remains a pair-binding assessment. The earlier second-core adaptor assignment is corrected: the core now records receptor-associated proapoptotic recruitment, retaining GO:0097192 and plasma-membrane location while omitting GO:0035591. PMID11248093 demonstrates state-dependent caspase association and CASP9-dependent CASP3 activation in cell extracts. Additional S100 components were required, and the allocation of coordinated binding between DCC and other adaptors remains unresolved. The existing core description therefore does not assign a distinct adaptor molecular function. A focused question records that mechanistic uncertainty. No NEW adaptor assertion is proposed. PMID:11248093(https://pmc.ncbi.nlm.nih.gov/articles/PMC30668/), PMID:12011067(https://doi.org/10.1074/jbc.M204679200), PMID:16537496(https://pmc.ncbi.nlm.nih.gov/articles/PMC1449658/).
The NEW assessment checked typed is_a ancestry: GO:0035591 is neither an ancestor nor a descendant of any of the nine existing/proposed molecular functions. Redundancy is not the reason for its omission. Complete current human QuickGO inventories for FAS/P25445 (111 records), TNFRSF1A/P19438 (139) and NGFR/P08138 (107) contain no adaptor term or descendant; ancestry of every comparator MF was checked. These noncatalytic receptor comparators suggest that receptor-associated recruitment should not automatically be recast as a separate adaptor annotation. They do not establish a universal rule, and lack of autonomous reconstitution alone would not exclude an adaptor. Together with the unresolved allocation of coordinating work, they warrant a conservative core description and no NEW row here. This is a scientific correction of the earlier core interpretation, not a warning-removal rationale. FAS, TNFRSF1A, NGFR, GO:0035591.
The MAZ and ribosome refinements use a consistent entity distinction. DNA-binding transcription-factor binding classifies a protein partner, whereas ribosome binding names a ribosomal particle. MAZ's verified class supports the former; a ribosomal protein name alone cannot establish the latter. The translation paper independently measures DCC with ribosomal subunits and 80S particles, while its purified RPL5 contact experiment is a separate observation. None of these refinements makes DCC a transcription factor or structural ribosomal subunit. PMID:11527412(https://pubmed.ncbi.nlm.nih.gov/11527412/), PMID:20434207(https://pmc.ncbi.nlm.nih.gov/articles/PMC2881594/).
GO:0005042 remains the functional netrin-receptor refinement supported by receptor signaling/outgrowth evidence. It is not substituted into each ligand-binding tuple: the fourth fibronectin-domain ELISA, other extracellular constructs and spoke-expanded pair records have narrower assay scopes. GO:0005042 includes transmission across a membrane; an isolated extracellular binding fragment cannot establish that entire activity. The three positive netrin pair annotations remain contextual under the same explicit project instruction, with their original construct and physiological limits. The cytosolic 1291–1447 product remains a modeled cleavage state, with no invented encoded isoform or PRO identifier.
The biological description now names the candidate tumor-suppressor interpretation cautiously and omits the defensive kinase/protease comparison. The candidate framing comes from the ligand-absence apoptosis study; it does not assert that these experiments alone establish a universal tumor-suppressor role. PMID:9796814(https://pubmed.ncbi.nlm.nih.gov/9796814/). The counts remain 24 ACCEPT, 11 MODIFY, 12 KEEP_AS_NON_CORE, three UNDECIDED, one TOO_GENERAL, two core functions and zero NEW annotations.