DCDC2

Summary: PAINT supports an inherited developmental contribution to neuronal migration, with context-dependent rodent evidence.

Reason: The current PTHR23004 tree places human DCDC2 PTN002506770 below the actual IBD node PTN002744418. The IBD sources are rat RGD:1310227 and mouse MGI:2652818; the mouse source is IGI from PMID:21689730, not an isolated Dcdc2-knockout phenotype. The rat Dcdc2 record D3ZR10 has experimental neuron-migration annotations to PMID:16278297 and PMID:18313856. These report embryonic shRNA perturbation and a partial rescue of heterotopia, not a direct assay of human neuronal migration. PMID:21689730 shows that mouse Dcdc2 deletion alone leaves constitutive and conditional migration assays grossly normal, while Dcx RNAi produces greater migration defects in the Dcdc2-mutant background. Preserve a context-dependent developmental association, without describing DCDC2 as universally essential for neuronal migration or making dyslexia a Mendelian consequence.

Summary: The Ensembl transfer reflects rodent neuron-migration experiments, a developmental context.

Reason: GO_REF:0000107 transfers from the verified rat Dcdc2 protein D3ZR10/ENSRNOP00000060289. The rat Dcdc2 record D3ZR10 has experimental neuron-migration annotations to PMID:16278297 and PMID:18313856. These report embryonic shRNA perturbation and a partial rescue of heterotopia, not a direct assay of human neuronal migration. PMID:21689730 shows that mouse Dcdc2 deletion alone leaves constitutive and conditional migration assays grossly normal, while Dcx RNAi produces greater migration defects in the Dcdc2-mutant background. Preserve a context-dependent developmental association, without describing DCDC2 as universally essential for neuronal migration or making dyslexia a Mendelian consequence.

Summary: The manual ortholog transfer retains a context-dependent developmental association.

Reason: The specified donor D3ZR10 is rat Dcdc2, as verified in the official record and its experimental GO annotation sources. The rat Dcdc2 record D3ZR10 has experimental neuron-migration annotations to PMID:16278297 and PMID:18313856. These report embryonic shRNA perturbation and a partial rescue of heterotopia, not a direct assay of human neuronal migration. PMID:21689730 shows that mouse Dcdc2 deletion alone leaves constitutive and conditional migration assays grossly normal, while Dcx RNAi produces greater migration defects in the Dcdc2-mutant background. Preserve a context-dependent developmental association, without describing DCDC2 as universally essential for neuronal migration or making dyslexia a Mendelian consequence.

Summary: The original study associates DCDC2 perturbation with neuronal migration in the developing rat cortex.

Reason: PMID:16278297 reports altered neuronal migration after RNA interference. The recovered abstract does not name the experimental organism. Rat attribution is established by the verified rat donor annotation record and the later original PMID:21689730, which explicitly identifies the earlier RNAi studies as experiments in developing rat neocortex; the human data concern expression and genetic association. The complete original body was not recovered in this session; the positive abstract statement and curator assertion are retained, with later mouse genetic results constraining generalization. The rat Dcdc2 record D3ZR10 has experimental neuron-migration annotations to PMID:16278297 and PMID:18313856. These report embryonic shRNA perturbation and a partial rescue of heterotopia, not a direct assay of human neuronal migration. PMID:21689730 shows that mouse Dcdc2 deletion alone leaves constitutive and conditional migration assays grossly normal, while Dcx RNAi produces greater migration defects in the Dcdc2-mutant background. Preserve a context-dependent developmental association, without describing DCDC2 as universally essential for neuronal migration or making dyslexia a Mendelian consequence.

Summary: DCDC2 associates with the kinesin-2 subunit KIF3A.

Reason: PMID:21698230 Figure 3 and its co-immunoprecipitation Methods establish endogenous rat Dcdc2–Kif3a association in rat hippocampal neurons, with proximity-ligation signals at cilia and in the cytoplasm. F1LQZ3 is rat Kif3a; its verified kinesin family classification and the original experiment support the more informative kinesin-binding class. The human assertion is retained with curator deference and explicit rat assay scope: the SH-SY5Y lane is an input sample, not an independent human interaction experiment. This is co-complex/proximity evidence, not a purified binary binding measurement, and does not assign motor activity or autonomous intraflagellar transport to DCDC2. The replacement is already represented by the separate ortholog-derived kinesin-binding row 50; it refines this source assertion rather than adding a NEW activity.

Proposed replacements: kinesin binding

Summary: HI-II-14 reports a construct-tested DCDC2–NIF3L1 binary interaction.

Reason: PMID:25416956 is represented by three IntAct records for the DCDC2–NIF3L1 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. NIF3L1 is a proposed transcriptional corepressor, but this binary association does not establish binding to a DNA-binding transcription factor or a DCDC2 transcriptional activity. Preserve the positive interaction as non-core context.

Summary: HI-II-14 reports a construct-tested DCDC2–MRFAP1 binary interaction.

Reason: PMID:25416956 is represented by three IntAct records for the DCDC2–MRFAP1 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. MRFAP1 is a MORF4-family-associated protein. The reported pair does not establish a specific catalytic, motor, receptor, or adaptor activity of DCDC2. Preserve the positive interaction as non-core context.

Summary: DCDC2 associates with the Dishevelled signaling scaffold DVL1.

Reason: PMID:25557784 reports co-immunoprecipitation of human full-length DCDC2 with human DVL1 (O14640) in NIH 3T3 cells. Curated UniProt FUNCTION/SUBUNIT descriptions, DSH family classification, and multivalent DIX/PDZ/DEP organization support the partner scaffold class; the class judgment uses the documented signaling interactions and complex organization, not a GO label or an unvetted ARBA annotation. GO:0097110 describes binding to a scaffold protein, not scaffold activity performed by DCDC2. Refine the positive association to that class while retaining the co-IP limitation: a purified direct interface and the native complex stoichiometry were not established. Disease-associated DCDC2 constructs can retain DVL association despite losing Wnt suppression, so this binding alone is not proof that DCDC2 assembles an active signaling complex or that DVL binding is sufficient for its regulatory effect.

Proposed replacements: scaffold protein binding

Summary: DCDC2 associates with the Dishevelled signaling scaffold DVL2.

Reason: PMID:25557784 reports co-immunoprecipitation of human full-length DCDC2 with human DVL2 (O14641) in NIH 3T3 cells. Curated UniProt FUNCTION/SUBUNIT descriptions, DSH family classification, and multivalent DIX/PDZ/DEP organization support the partner scaffold class; the class judgment uses the documented signaling interactions and complex organization, not a GO label or an unvetted ARBA annotation. GO:0097110 describes binding to a scaffold protein, not scaffold activity performed by DCDC2. Refine the positive association to that class while retaining the co-IP limitation: a purified direct interface and the native complex stoichiometry were not established. Disease-associated DCDC2 constructs can retain DVL association despite losing Wnt suppression, so this binding alone is not proof that DCDC2 assembles an active signaling complex or that DVL binding is sufficient for its regulatory effect.

Proposed replacements: scaffold protein binding

Summary: DCDC2 associates with the Dishevelled signaling scaffold DVL3.

Reason: PMID:25557784 reports co-immunoprecipitation of human full-length DCDC2 with human DVL3 (Q92997) in NIH 3T3 cells. Curated UniProt FUNCTION/SUBUNIT descriptions, DSH family classification, and multivalent DIX/PDZ/DEP organization support the partner scaffold class; the class judgment uses the documented signaling interactions and complex organization, not a GO label or an unvetted ARBA annotation. GO:0097110 describes binding to a scaffold protein, not scaffold activity performed by DCDC2. Refine the positive association to that class while retaining the co-IP limitation: a purified direct interface and the native complex stoichiometry were not established. Disease-associated DCDC2 constructs can retain DVL association despite losing Wnt suppression, so this binding alone is not proof that DCDC2 assembles an active signaling complex or that DVL binding is sufficient for its regulatory effect.

Proposed replacements: scaffold protein binding

Summary: HuRI reports a construct-tested DCDC2–ZNF432 binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–ZNF432 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. ZNF432 is characterized as a DNA-damage/PAR-associated recombination regulator. Its zinc-finger name does not establish the DNA-binding transcription-factor role needed for a transcription-factor-binding replacement. Preserve the positive interaction as non-core context.

Summary: HuRI reports a construct-tested DCDC2–OXT binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–OXT pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. The assayed OXT sequence is the 125-residue oxytocin-neurophysin precursor, not an isolated mature oxytocin peptide. The record does not establish mature-hormone binding or oxytocin receptor activity. Preserve the positive interaction as non-core context.

Summary: HuRI reports a construct-tested DCDC2–KRTAP5-9 binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–KRTAP5-9 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. KRTAP5-9 is a keratin-associated matrix protein rather than a keratin intermediate filament. Binding this individual protein does not demonstrate binding an intermediate filament or a role in hair-shaft formation. Preserve the positive interaction as non-core context.

Summary: HuRI reports a construct-tested DCDC2–NMU binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–NMU pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. The assayed NMU sequence is the 174-residue preproprotein, not isolated neuromedin-U-25. The pair does not demonstrate mature-neuropeptide recognition or receptor signaling by DCDC2. Preserve the positive interaction as non-core context.

Summary: HuRI reports a construct-tested DCDC2–CKS1B binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–CKS1B pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. CKS1B is a noncatalytic CDK-regulatory subunit. Binding CKS1B is not evidence that DCDC2 binds the catalytic CDK protein, catalyzes phosphorylation, or participates in cell-cycle control. Preserve the positive interaction as non-core context.

Summary: HuRI reports a construct-tested DCDC2–PTPRCAP binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–PTPRCAP pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. PTPRCAP is a protein associated with the receptor phosphatase PTPRC/CD45; it is not that catalytic phosphatase or a signaling receptor. The pair alone cannot be upgraded to phosphatase or receptor binding. Preserve the positive interaction as non-core context.

Summary: HuRI reports a DCDC2–TRMT11 binary interaction that supports enzyme binding.

Reason: PMID:32296183 supplies array, prey-pooling and validated two-hybrid records for this sequence-verified human pair. These are stages of one mapping study, not independent physiological replications. The tested proteins match 476-residue DCDC2 and 463-residue TRMT11. TRMT11 is the catalytic tRNA methyltransferase subunit and has cytoplasmic localization in the inspected official record. The positive pair and established catalytic partner class support GO:0019899 enzyme binding. This does not assign methyltransferase activity or tRNA processing to DCDC2. No pair-specific orthogonal validation or physiological role is established.

Proposed replacements: enzyme binding

Summary: HuRI reports a construct-tested DCDC2–HORMAD1 binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–HORMAD1 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. HORMAD1 has meiotic/chromosome roles, but binding this protein does not place DCDC2 in meiotic recombination or demonstrate a more specific molecular activity. Preserve the positive interaction as non-core context.

Summary: HuRI reports a construct-tested DCDC2–MICALL2 binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–MICALL2 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. MICALL2 is a Rab effector and cytoskeletal/trafficking protein, not a Rab GTPase. The binary pair does not establish GTPase binding or a DCDC2 vesicle-transport function. Preserve the positive interaction as non-core context.

Summary: HuRI reports a DCDC2–DYNLT2 binary interaction that supports dynein light chain binding.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–DYNLT2 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. DYNLT2 is a dynein light-chain protein. The exact binary pair supports the light-chain-binding term, without demonstrating association with an assembled dynein motor or DCDC2 motor activity. The replacement describes the measured binding class only; physiological relevance remains unestablished.

Proposed replacements: dynein light chain binding

Summary: HuRI reports a construct-tested DCDC2–LMO3 binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–LMO3 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. The record identifies LMO3 isoform 4, with a sufficient binding region at residues 19–163. This is a construct-bounded association with a LIM-domain protein, not evidence that DCDC2 is a transcriptional adaptor or binds an assembled transcription complex. Preserve the positive interaction as non-core context.

Summary: HuRI reports a DCDC2–DYNC2LI1 binary interaction that supports dynein light intermediate chain binding.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–DYNC2LI1 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. The assayed partner is DYNC2LI1 isoform 2, a dynein-2 light intermediate chain. Its isoform-specific sequence matches the deposited interaction checksum. The precise binding class is supported, without asserting that DCDC2 is a dynein subunit or performs retrograde intraflagellar transport. The replacement describes the measured binding class only; physiological relevance remains unestablished.

Proposed replacements: dynein light intermediate chain binding

Summary: HuRI reports a construct-tested DCDC2–POP5 binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–POP5 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. POP5 is a noncatalytic protein subunit of the RNase P/MRP ribonucleoprotein complexes. Binding POP5 alone does not establish binding an assembled ribonuclease or make DCDC2 an RNA-processing factor. Preserve the positive interaction as non-core context.

Summary: HuRI reports a DCDC2–SLC38A2 binary interaction that supports transmembrane transporter binding.

Reason: PMID:32296183 supplies array, prey-pooling and validated two-hybrid records for this sequence-verified human pair. These are stages of one mapping study, not independent physiological replications. The tested proteins match 476-residue DCDC2 and complete 506-residue SLC38A2. SLC38A2 is a sodium-coupled amino-acid transporter, matching the partner definition in GO:0044325. Its eleven transmembrane segments make native topology and membrane-context binding unresolved in a nuclear two-hybrid assay; the interface is not mapped. This limitation does not itself refute the validated positive pair. The refinement describes measured transporter-binding capacity without asserting transport, transport regulation or physiological co-localization by DCDC2. No pair-specific orthogonal validation is established.

Proposed replacements: transmembrane transporter binding

Summary: HuRI reports a DCDC2–MGME1 binary interaction that supports enzyme binding.

Reason: PMID:32296183 supplies array, prey-pooling and validated two-hybrid records for this sequence-verified human pair. These are stages of one mapping study, not independent physiological replications. The tested proteins match 476-residue DCDC2 and complete 344-residue MGME1. MGME1 is a mitochondrial DNA nuclease, so the positive pair supports GO:0019899 enzyme binding. Its native mitochondrial location leaves a physiological encounter unresolved; no DCDC2 mitochondrial import or mtDNA-maintenance role is inferred. The term does not require the enzyme reaction to be reconstituted in the binding assay. No pair-specific orthogonal validation is established.

Proposed replacements: enzyme binding

Summary: HuRI reports a construct-tested DCDC2–CENPO binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–CENPO pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. CENPO is one component of the kinetochore-associated CENP complex. Binding a single component does not demonstrate association with an assembled kinetochore or a chromosome-segregation mechanism. Preserve the positive interaction as non-core context.

Summary: HuRI reports a DCDC2–B3GNT5 binary interaction that supports enzyme binding.

Reason: PMID:32296183 supplies array, prey-pooling and validated two-hybrid records for this sequence-verified human pair. These are stages of one mapping study, not independent physiological replications. The tested proteins match 476-residue DCDC2 and complete 378-residue B3GNT5. B3GNT5 is a glycosyltransferase, supporting GO:0019899 enzyme binding for the measured pair. Its official type-II Golgi topology places residues 36–378 in the lumen and residues 1–14 in the cytoplasm; the binding interface is unknown. Nuclear two-hybrid expression does not establish native topology or a physiological encounter, but this is not a pair-specific negative result. No glycosyltransferase activity, glycolipid-synthesis role or pair-specific orthogonal validation is assigned to DCDC2.

Proposed replacements: enzyme binding

Summary: HuRI reports a construct-tested DCDC2–KRTAP9-3 binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–KRTAP9-3 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. KRTAP9-3 is a keratin-associated matrix protein, not an assembled keratin filament. The interaction does not support intermediate-filament binding or hair-shaft physiology for DCDC2. Preserve the positive interaction as non-core context.

Summary: HuRI reports a construct-tested DCDC2–TOLLIP binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–TOLLIP pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. TOLLIP is an adaptor/ubiquitin-pathway protein. The binary pair does not show DCDC2 recruiting two partners, regulating a Toll receptor, or binding ubiquitin. Preserve the positive interaction as non-core context.

Summary: HuRI reports a DCDC2–MYG1 binary interaction that supports enzyme binding.

Reason: PMID:32296183 supplies array, prey-pooling and validated two-hybrid records for this sequence-verified human pair. These are stages of one mapping study, not independent physiological replications. The tested proteins match 476-residue DCDC2 and complete 376-residue MYG1. MYG1 is an RNA exonuclease, supporting GO:0019899 enzyme binding. Its experimentally supported nucleoplasmic and mitochondrial locations do not establish where this pair might meet physiologically. The annotation records the measured binding class, without assigning RNA processing, organelle targeting or exonuclease activity to DCDC2. No pair-specific orthogonal validation is established.

Proposed replacements: enzyme binding

Summary: HuRI reports a construct-tested DCDC2–GNL3L binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–GNL3L pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. GNL3L binds guanine nucleotides and has nucleolar/cell-cycle roles, but the inspected official functional annotation does not establish the catalytic GTPase activity needed to infer GTPase binding from this pair. Preserve the positive interaction as non-core context.

Summary: HuRI reports a construct-tested DCDC2–SIRAL2 binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–SIRAL2 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. The partner is the current official SIRAL2 entry, also named FAM118A/C22orf8. The record confirms a protein interaction, but the inspected source does not establish a specific catalytic or receptor class for a more informative binding term. Preserve the positive interaction as non-core context.

Summary: HuRI reports a construct-tested DCDC2–COMMD9 binary interaction.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–COMMD9 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. COMMD9 is a commander-complex scaffold. Its reported interaction does not demonstrate DCDC2 binding a catalytic ubiquitin ligase or carrying out commander-mediated recycling. Preserve the positive interaction as non-core context.

Summary: HuRI reports a DCDC2–C5AR2 binary interaction that supports signaling receptor binding.

Reason: PMID:32296183 supplies array, prey-pooling and validated two-hybrid records for this sequence-verified human pair. These are stages of one mapping study, not independent physiological replications. The tested proteins match 476-residue DCDC2 and complete 337-residue C5AR2. PMID:34582793 establishes that C5AR2 can initiate signaling: its selective agonist induces p90RSK phosphorylation in human macrophages despite C5AR1 blockade. That source establishes the receptor class; HuRI establishes the DCDC2 pair. GO:0005102 therefore describes receptor binding, not receptor agonism. The seven-transmembrane topology, binding interface and native membrane-context encounter remain unresolved in this nuclear assay. No DCDC2-driven complement signaling or pair-specific orthogonal validation is established.

Proposed replacements: signaling receptor binding

Summary: HuRI reports a DCDC2 interaction with the CYTH4 guanine-nucleotide exchange factor.

Reason: PMID:32296183 is represented by three IntAct records for the DCDC2–CYTH4 pair: two-hybrid array, prey pooling, and validated two-hybrid. All deposited participant sequence checksums match the inspected official sequences, with DCDC2 matching its 476-residue canonical product. These are assay-stage records for one pair, not three independent physiological observations. CYTH4 promotes GDP/GTP exchange on ARF1 and ARF5. The sufficient binding region is CYTH4 residues 1–118, spanning its N terminus and only part of the annotated SEC7 domain (54–241); this construct scope does not negate binding to a GEF. Current GO searches and a label/synonym audit of the retrieved GO release did not establish a bare GEF-binding or general enzyme-regulator-binding term. GO:0032794 instead requires a GTPase-activating-protein partner, which is a different regulator class. GO:0005091 requires bringing a GEF and additional proteins together, and GO:0160124/GO:1990624 require an effect on GEF activity; neither is shown by this binary assay. The mixed fragment does not establish binding specificity for one defined domain under GO:0019904. Preserve the source-specific positive interaction as non-core; a more specific supported binding term has not been established.

Summary: Cytoplasmic DCDC2 is observed, with more informative microtubule and ciliary locations available.

Reason: PMID:21698230 directly shows expressed human DCDC2 in rat neuronal cytoplasm, neurites and primary cilia, and on cytoplasmic microtubule networks in nonciliated cultured cells. These positive observations are retained. Cytoplasm is a broad ancestor of the accepted axoneme location, so TOO_GENERAL records the location hierarchy rather than denying an extra-ciliary pool. Near-centrosome staining is not evidence of centrosome occupancy. The current typed hierarchy is GO:0005930 axoneme part_of GO:0097014 ciliary plasm is_a GO:0005737 cytoplasm. This supplies the ancestor relation; the judgment does not claim that every cytoplasmic DCDC2 molecule resides in an axoneme or erase the extra-ciliary observations.

Summary: The cholangiocyte source supports cytoplasmic localization, but the compartment term is broad.

Reason: The complete PMID:27319779 abstract explicitly places normal DCDC2 in cholangiocyte cytoplasm and cilia and describes mutant cytoplasmic accumulation. Full original Methods and figures remain unavailable after bounded publisher attempts. Preserve this positive abstract and curated IDA assertion, while marking the broad cytoplasm ancestor TOO_GENERAL relative to independently established axonemal localization. The judgment does not reinterpret the mutant accumulation as the normal distribution or claim recovery of this paper’s full experiment. The current typed hierarchy is GO:0005930 axoneme part_of GO:0097014 ciliary plasm is_a GO:0005737 cytoplasm. This supplies the ancestor relation; the judgment does not claim that every cytoplasmic DCDC2 molecule resides in an axoneme or erase the extra-ciliary observations.

Summary: The deep ancestral MTOC inference is too broad for the directly observed DCDC2 compartment distribution.

Reason: The actual IBD for GO:0005815 is at PTN000543880, above human DCDC2, and uses the experimentally annotated Dictyostelium dcx donor DDB_G0277115/Q550F6 (PMID:21034843). Its single-donor basis is not itself a weakness. The decisive issue is target-specific localization: PMID:25557784 reports DCDC2 along the axoneme and spindle fibers while excluding it from the basal body in interphase and spindle poles in metaphase/anaphase. PMID:21698230 describes microtubule networks near the centrosome in nonciliated cells, which is not localization to the centrosome itself. These observations argue against inheriting the entire ancestral MTOC-localization assertion unchanged into DCDC2. Mark the inference as over-annotated rather than asserting universal absence from every MTOC in all cell states; the original Dictyostelium compartment experiment was not independently recovered.

Summary: The cytoskeleton annotation is consistent but is subsumed by retained microtubule and axoneme localizations.

Reason: The UniProt subcellular-location mapping SL-0090 asserts a genuine broad cytoskeletal localization. GO:0005856 is an is_a/part_of ancestor of the microtubule and axoneme terms retained elsewhere in this review. The broad term is therefore true but adds little anatomical precision; this does not reject the mapped location.

Summary: DCDC2 is a microtubule-associated protein, consistent with the ancestral PAINT localization.

Reason: The actual GO:0005874 IBD at PTN000543880 precedes the human target in the PTHR23004 tree. Its source list includes worm rpi-1/WBGene00012332/Q69Z08 and Dictyostelium dcx/DDB_G0277115/Q550F6. The worm paper PMID:27930654 explicitly reports RPI-1::GFP on ciliary and cytoplasmic microtubules; its experimental GO:0005879 and GO:0005881 terms are typed descendants of GO:0005874, so the lack of an exact-term donor row is not absence of support. Human HPA independently reports microtubule localization. This supports the conservative cellular-component term without transferring worm-specific sensory functions or assigning a motor activity.

Summary: Human DCDC2 expressed in rat neurons localizes to primary cilia.

Reason: PMID:21698230 directly shows tagged human DCDC2 in primary rat hippocampal neuronal cilia and NIH 3T3 cilia, using ciliary markers. The source is positive. Retain its evidence while using TOO_GENERAL for the broad cilium location because the annotation set already captures the more precise axoneme and kinocilium locations. This does not make all observed primary cilia sensory kinocilia and does not imply ciliary membrane-receptor activity.

Summary: DCDC2 occupies sensory kinocilia and supporting-cell primary cilia.

Reason: The recovered PMID:25601850 original shows endogenous rodent DCDC2 in sensory kinocilia and supporting-cell primary cilia, and human DCDC2-GFP in both structures in rat organotypic cultures. Both observations are retained. At gene level, cilium is a broad parent of the independently established axoneme location; kinocilium additionally records sensory specialization. TOO_GENERAL is therefore based on the combination of the axoneme and kinocilium assertions, not on replacing every cilium with a kinocilium. This does not claim that the supporting-cell experiment alone resolved an axonemal subcompartment, and no direct human cochlear imaging is claimed.

Summary: Normal cholangiocyte DCDC2 has a positive ciliary localization assertion.

Reason: PMID:27319779 explicitly reports normal cholangiocyte ciliary localization in its complete abstract. Its full Methods/figures were not recovered. Retain that positive information and curator deference; the broad cilium term is TOO_GENERAL relative to the independently established axoneme location. The independent human renal/cholangiocyte localization in PMID:25557784 corroborates the gene-level location without substituting for recovery of the 2016 experiment.

Summary: The positive UniProt cilium location is broad relative to the supported axoneme and kinocilium locations.

Reason: SL-0066 maps the official UniProt cilium location, supported by original DCDC2 studies PMID:25601850 and PMID:27319779 and independently established axonemal localization in PMID:25557784. Retain the positive localization while marking the broad cilium term TOO_GENERAL beside the more specific axoneme and kinocilium terms. This does not restrict all observed cilia to sensory kinocilia: the original experiments also include supporting-cell primary cilia.

Summary: PAINT places axonemal localization in the DCDC2 ancestral clade.

Reason: The actual IBD for GO:0005930 is at PTN002744418, above human DCDC2. Human Q9UHG0 is the descendant experimental source: its presence in WITH/FROM is expected PAINT grounding, not circular evidence. Preserve the inherited localization together with the original target axoneme experiments.

Summary: DCDC2 localizes to the axoneme of human epithelial cilia.

Reason: PMID:25557784 Results and Figure 1G describe DCDC2 colocalization with acetylated tubulin in the axoneme of human renal-tubule and cholangiocyte cilia. Additional cell-cycle localization distinguishes axonemal and spindle fibers from basal bodies and spindle poles. Accept this specific location without assigning microtubule-organizing-center occupancy or motor activity.

Summary: The curated cholangiocyte axoneme assertion agrees with independently demonstrated DCDC2 localization.

Reason: The complete PMID:27319779 abstract establishes normal cholangiocyte ciliary localization, but its precise axoneme staining and original Methods could not be independently inspected. Defer to the curated IDA for that source-specific detail because the same gene’s human cholangiocyte and renal axonemal localization is directly established in the recovered PMID:25557784 original. This is acceptance of a clearly supported gene-level location with a stated access limit, not a claim to have recovered the 2016 axoneme assay.

Summary: The UniProt mapping records the specific axonemal localization.

Reason: SL-0304 maps the official cilium-axoneme location to GO:0005930, supported in UniProt by PMID:25557784 and PMID:27319779. The mapping and target experiments agree; it does not establish ciliary membrane localization or an independent motor function.

Summary: The source distinguishes the RU2AS antigen from the sense RU2S/DCDC2 product and does not demonstrate a DCDC2 defense effector function.

Reason: The original full Results in PMID:10601354 identify cDNA4.1 as an antisense RU2AS message encoding an 84-amino-acid antigenic product, while sense cDNAI.1 is the longer RU2S/DCDC2 transcript. The HLA-B7-restricted LPRWPPPQL epitope sensitizes target cells to CTL lysis. This is positive evidence about a distinct antisense product, not an immune effector activity of the 476- or 229-residue DCDC2 products. Moreover, being the antigen recognized by cytotoxic lymphocytes does not itself mean performing the cellular defense response. GO:0006968 denotes the response mediated by cells. Removal follows the explicit transcript/product distinction and the role of the antigen in the assay, not the paper title or missing full text.

Summary: DCDC2-dependent ciliary integrity is relevant to sensory hearing.

Reason: PMID:25601850 combines a segregating human p.Gln424Pro variant with human DCDC2-GFP effects in rat sensory epithelia and zebrafish dcdc2b knockdown producing abnormal hair cells and impaired auditory microphonic responses. These support the contextual hearing phenotype, but do not show DCDC2 as a mechanotransduction channel or establish that the human variant was directly assayed for hearing in vivo. The zebrafish morpholino has developmental and dose limitations, and the supporting-cell/kinocilium effects are context dependent. Retain hearing as non-core organismal context for the ciliary role.

Summary: The ortholog transfer supports binding the kinesin-2 machinery.

Reason: The mapped source D3ZR10 is rat Dcdc2. Its current direct annotation is kinesin binding, IPI to PMID:21698230 with rat Kif3a RGD:621536; the human protein-binding row cites the corresponding experiment and partner F1LQZ3. Retain this specific binding class with the original assay and construct limits, without assigning DCDC2 kinesin motor activity or autonomous intraflagellar transport.

Summary: DCDC2 suppresses canonical beta-catenin-dependent Wnt output.

Reason: PMID:25557784 shows increased beta-catenin/TCF reporter output after Dcdc2 knockdown and reduced output with human wild-type DCDC2 overexpression; three patient-derived constructs lose this suppression. This establishes negative regulation of the canonical branch, so GO:0090090 is more informative than undirected Wnt regulation. The current typed is_a/part_of ancestry places it below GO:0030111. DVL co-IP and rescue of ciliation by a Wnt inhibitor are supporting context, not proof of a particular physical inhibitory mechanism. PMID:21698230 independently reports a knockdown effect rescued by human DCDC2, while overexpression alone has no effect in that neuronal assay. Neither experiment establishes DCDC2 adaptor, kinase, or motor activity.

Proposed replacements: negative regulation of canonical Wnt signaling pathway

Summary: A generic doublecortin-domain mapping is insufficient to establish DCDC2 as an intracellular signal-transduction component.

Reason: Both source mappings, IPR003533 and IPR036572, genuinely assign GO:0035556 and match the DCDC2 canonical sequence. Their descriptions span doublecortin-family cytoskeletal proteins and kinase-containing relatives; DCDC2 domain matches alone do not establish the passing and downstream propagation of an intracellular signal required by the GO definition. DCDC2 can influence cilium-dependent Wnt and Smoothened signaling, but those specific regulation terms are not is_a/part_of descendants of GO:0035556 and are assessed separately using the target experiments. The mapping overstates what can be inferred from the common structural domain; this does not deny the experimentally reported regulatory effects.

Summary: DCDC2 overexpression enhances a Hedgehog pathway reporter in cultured neurons.

Reason: PMID:21698230 transfects primary rat cortical neurons with human DCDC2 constructs and a Shh-responsive reporter. Full-length overexpression increases reporter output, whereas the deletion constructs and knockdown do not. Retain the positive regulation annotation as a measured, context-specific output rather than a central molecular activity. KIF3A-mediated Smoothened trafficking is proposed by the authors, not directly demonstrated in these assays; no intrinsic motor function or direct Smoothened binding is inferred. The original reports a statistically significant full-length gain-of-function effect in three independent luciferase experiments, each using at least five parallel wells. The absence of a knockdown effect limits an endogenous requirement claim but does not negate the measured increase under overexpression. GO:0045880 describes increased pathway output; KEEP_AS_NON_CORE preserves that restricted result without claiming direct Smoothened regulation or an established normal physiological role. This differs from the MTOC assertion, for which a separate original explicitly excludes localization at the relevant structures.

Summary: PAINT supports kinociliary localization within the DCDC2 clade.

Reason: The actual IBD for GO:0060091 is placed at PTN002744418, an ancestor of human DCDC2. Its source RGD:1310227 maps to rat Dcdc2/D3ZR10, whose direct IDA annotation cites PMID:25601850. Retain the conserved sensory-cilium localization, while distinguishing the rodent localization experiment from a direct human cochlear assay.

Summary: The combined electronic methods consistently map DCDC2 to the kinocilium.

Reason: The source row combines the verified rat Dcdc2 ortholog D3ZR10/ENSRNOP00000060289 with UniProt location SL-0460. The official human kinocilium location itself traces to rat D3ZR10, whose direct localization source is PMID:25601850. These are related propagation paths to the same underlying observation, not several independent experiments. Retain the location without overcounting the evidence.

Summary: The manual ortholog transfer preserves the Dcdc2 kinociliary localization.

Reason: The specified donor D3ZR10 is rat Dcdc2 and has a direct IDA kinocilium annotation to PMID:25601850. The transfer is biologically consistent with DCDC2 ciliary localization, but the originating species and sensory-cell context remain explicit.

Summary: PAINT supports a conserved contribution to cilium assembly within the DCDC2 clade.

Reason: The current IBD places GO:0060271 at PTN002744418, above the human target, and uses human Q9UHG0 experimental evidence. This self appearance is normal descendant evidence supporting the ancestral assertion. Retain the conservative assembly contribution in conjunction with the target experiments; it does not make DCDC2 a motor, enzyme, or universally indispensable component of every cilium.

Summary: DCDC2 supports normal epithelial cilium assembly.

Reason: The complete PMID:27319779 abstract reports DCDC2 variants in four affected children, loss of mutant protein from cholangiocyte cilia, and a ciliogenesis defect. The original Methods/figures remain unavailable, so defer to the curated IMP for its exact experiment. Independent recovered PMID:25557784 demonstrates reduced ciliation after two mouse Dcdc2 siRNAs in IMCD3 spheroids and rescue by human wild-type DCDC2, but not the tested disease truncations. Together these support an assembly contribution without asserting that DCDC2 is universally indispensable in every cell type or that the protein itself is a ciliary motor.

Summary: HPA reports DCDC2 at the mitotic spindle in human cells.

Reason: The actual HPA subcellular record and antibody/cell-line table report supported mitotic-spindle localization with HPA031582 and HPA031584 in RPTEC/TERT1 cells. This agrees with the GO_REF:0000052 immunofluorescence annotation. The record and table were inspected, but individual image pixels were not reviewed. Preserve this cell-cycle-dependent localization as non-core context without inferring a specific spindle-assembly or chromosome-segregation mechanism.

Summary: PAINT supports a conserved role in regulating ciliary assembly and length.

Reason: The actual GO:1902017 IBD at PTN002744418 is ancestral to the target and is supported by human Q9UHG0 descendant experimental evidence. Keep this normal phylogenetic inference together with the original ciliary length-regulation experiment; the target occurring among the sources is not circularity.

Summary: DCDC2 regulates ciliary growth and organization in sensory epithelia.

Reason: The recovered PMID:25601850 original tests human variant-1 DCDC2-GFP and p.Gln424Pro in postnatal rat hair and supporting cells. Wild-type expression alters cilium length, and the mutant has greater length and branching/multiplicity effects; these effects were not reproduced in MDCK-II or COS7 primary cilia. Methods identify NP_001182539.1 and the human variant-1 construct, consistent with the long Q9UHG0-1 product. Retain regulation of cilium assembly with these cell-type and overexpression limits; do not equate all mutant phenotypes with the normal protein’s action or transfer the activity to the 229-aa product.

Summary: Expressed human DCDC2 co-pellets with polymerized microtubules in a controlled binding assay.

Reason: Figure S1 of PMID:21698230 incubates polymerized microtubules with NIH/3T3 cell lysates expressing human full-length DCDC2-V5 or engineered doublecortin-domain deletion constructs. DCDC2 co-pellets with microtubules but remains unpelleted in microtubule-omission controls; LacZ-V5 stays in the supernatant and an anti-tubulin blot confirms microtubule pelleting. This is evidence for microtubule binding beyond colocalization, but lysate co-pelleting does not establish a purified binary contact, binding kinetics or microtubule stabilization. It does not establish activity of the natural short product. No existing source row or proposed replacement records this microtubule-binding assay; the generic protein-binding rows concern distinct protein partners. The user ancestry restriction is stated for NEW process terms, so it does not preclude this independently supported missing molecular function. The addition records the same directly supported activity used in the core synthesis without repurposing another assay.