DYNC2I1 (WDR60) is a WD40-repeat intermediate chain of cytoplasmic dynein-2, the motor that returns intraflagellar transport components and cargo toward the ciliary base. Its C-terminal propeller contacts a dynein heavy-chain tail, while its N-terminal region associates with DYNC2I2 and dynein light chains to organize the asymmetric motor assembly. DYNC2I1 supplies binding and structural interfaces rather than ATP-driven force generation. It acts in ciliary protein trafficking and cilium assembly, with prominent ciliary-base and centrosomal pools. Biallelic variants cause skeletal ciliopathies.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000242 pericentriolar material | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conserved pericentriolar localization, with direct human experimental grounding. Reason: The literal PTN008562642 IBD is on the verified DYNC2I1 lineage and is grounded by the human target itself, as expected for PAINT. PMID:25205765 detects endogenous WDR60 around centrosomes in human RPE1 cells and shows loss of this staining after depletion. Retain this positive pericentriolar pool as contextual localization; it need not be collapsed into, or excluded by, the more specific ciliary-base pool. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN008562642 SUPPORTS TRANSFER Literal IBD on the reconstructed PTHR16022 target path; exact human sequence matches the MSA. Human target experimental grounding is legitimate descendant evidence, not circularity. The retained contextual/core disposition is explained in the reason. Supporting Evidence: PMID:25205765 (C) Cells were effectively depleted of WDR60 (shown by loss of immunoreactivity around the centrosome) file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0000242 pericentriolar material | IDA PMID:25205765 Subunit composition of the human cytoplasmic dynein-2 comple... | KEEP AS NON CORE | Summary: Endogenous human WDR60 is detected in the pericentrosomal region. Reason: PMID:25205765 reports endogenous WDR60 staining around the centrosome in human RPE1 cells, reduction after WDR60 depletion, and dependence of its pericentrosomal recruitment on giantin. This is positive localization evidence, not proof that WDR60 nucleates microtubules or occupies the Golgi. Retain the observed pool as non-core alongside its ciliary role. Supporting Evidence: PMID:25205765 The localization of WDR60, like that of WDR34, is dependent on giantin |
| GO:0000922 spindle pole | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT preserves experimentally observed spindle-pole localization. Reason: The verified PTN008562642 IBD and target path support the inheritance assertion, with human experimental grounding from PMID:25830415. That paper detects endogenous WDR60 at spindle poles in mitotic HeLa cells. Retain this positive contextual location; the examined experiments do not establish a separate mitotic mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN008562642 SUPPORTS TRANSFER Literal IBD on the reconstructed PTHR16022 target path; exact human sequence matches the MSA. Human target experimental grounding is legitimate descendant evidence, not circularity. The retained contextual/core disposition is explained in the reason. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0000922 spindle pole | IDA PMID:25830415 Tctex1d2 associates with short-rib polydactyly syndrome prot... | KEEP AS NON CORE | Summary: Human WDR60 localizes at mitotic spindle poles. Reason: PMID:25830415 reports endogenous WDR60 immunofluorescence at spindle poles during mitosis, interphase MTOCs, and centrosomal/cytokinetic regions in human HeLa cells. The source discusses possible non-ciliary functions but does not directly test a WDR60 spindle mechanism. Keep the localization without converting it into an unmeasured mitotic process. Supporting Evidence: PMID:25830415 Immunofluorescence microscopy of HeLa cells with anti-Tctex1d2 or anti-Wdr60 antibodies indicated that both proteins localized to the MTOC in interphase, the spindle poles during mitosis, and the centrosomes and cytokinetic bridge microtubules during cytokinesis |
| GO:0001673 male germ cell nucleus | NAS PMID:36973253 Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 reg... | REMOVE | Summary: The cited male-germ-cell experiment resolves dynein-1 reagents, not WDR60. Reason: The complete original PMID:36973253 and all available textual/table supplements were searched for DYNC2I1, WDR60, Q8WVS4 and historical aliases; the operative nuclear Results, Methods and caption were read. The relevant mouse-testis experiments immunoprecipitate DYNC1I1/2 and use DYNC1H1, DYNC1LI2 and p150 reagents; Supplementary Figure 4 specifically measures those dynein-1/dynactin signals at meiotic telomeres. No WDR60 target record was recovered in the original or the six surveyed PDF/workbook supplements. Supplementary Figure 2b does report mouse Wdr34 as a Y2H hit, so the paper is not devoid of dynein-2 evidence; that selected hit list is not a WDR60 nuclear-localization experiment or an exhaustive negative screen. Remove this NAS attribution on the resolved reagent/complex mismatch, not because a nuclear pool would be biologically impossible or because the title foregrounds another subunit. The inherited quotation supplies the dynein-1 telomere-movement context; the removal rests on the independently inspected reagent and complex assignment, not on that sentence or a cache search alone. Supporting Evidence: PMID:36973253 Dynein accumulates on the cytoplasmic side of the telomere-nuclear envelope attachment sites and drives the movement of the chromosomes file:human/DYNC2I1/DYNC2I1-source-guide.md |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | MODIFY | Summary: Human WDR60 associates with the independently established chaperone NUDC. Reason: The literal IntAct record for PMID:25036637 joins human WDR60 and NUDC in a FLAG-client/Renilla-NUDC LUMIER assay; both participant sequence hashes match the corresponding official sequences. PMID:21530541 independently demonstrates antiaggregation activity of purified human NUDC. GO:0051087 therefore describes the assayed partner class more informatively than generic binding. This does not assert that WDR60 itself folds proteins, that the association is a purified binary interface, or that NUDC-dependent folding of WDR60 was measured. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md file:human/DYNC2I1/DYNC2I1-source-guide.md |
| GO:0005515 protein binding | IPI PMID:26044572 TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dyst... | MODIFY | Summary: The associated partner TCTEX1D2/DYNLT2B is a dynein light chain. Reason: PMID:26044572 uses a human TCTEX1D2 SF-TAP bait in HEK293T cells and recovers endogenous WDR60. Its separate tagged verification uses mouse WDR60, a distinction retained here. Human endogenous reciprocal association and cell-free interaction assays in PMID:25830415, and human constructs in PMID:29742051, independently corroborate the gene-level light-chain interaction. Refine the partner class to dynein light chain binding without claiming an autonomous motor or a purified interface. Proposed replacements: dynein light chain binding Supporting Evidence: PMID:26044572 An interaction between TCTEX1D2 and WDR60 was verified after overexpression of Flag-tagged TCTEX1D2 and GFP-tagged WDR60 in HEK293T cells |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | MODIFY | Summary: Reciprocal affinity purification associates the two dynein-2 intermediate chains. Reason: The two literal PMID:27173435 interaction records report reciprocal human WDR60/WDR34 tandem-affinity-purification associations. The participant ROGIDs match Q8WVS4 and Q96EX3. WDR34 is the other dynein-2 intermediate chain, making GO:0045505 an evidence-backed partner-class refinement. Affinity purification permits co-complex association and does not by itself establish a purified direct interface or independent motor catalysis. Proposed replacements: dynein intermediate chain binding Supporting Evidence: PMID:31451806 dynein-2 heavy chain are contorted into different conformations by a WDR60-WDR34 heterodimer file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | MODIFY | Summary: Reciprocal WDR60βNUDC associations support chaperone binding. Reason: PMID:27173435 contains reciprocal human WDR60/NUDC tandem-affinity-purification records with sequence-matched participants. Independent purified-human-NUDC antiaggregation experiments in PMID:21530541 establish the partner as a chaperone. GO:0051087 is appropriate for this positive partner-class association; it does not require demonstrating a folding reaction by WDR60. The particular client-chaperone mechanism and purified binary interface remain unestablished. Proposed replacements: protein-folding chaperone binding Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0005515 protein binding | IPI PMID:31451806 Structure of the dynein-2 complex and its assembly with intr... | MODIFY | Summary: Human recombinant dynein-2 places WDR60 with the WDR34 intermediate-chain assembly. Reason: PMID:31451806 resolves recombinant human dynein-2 assembled in insect cells, including the WDR60/WDR34 intermediate-chain and light-chain block. WDR34 is an intermediate-chain partner, so GO:0045505 is a supported refinement of the imported association. Preserve the complex structural context rather than turning this row into an isolated binary affinity measurement or a claim that WDR60 generates force. Proposed replacements: dynein intermediate chain binding Supporting Evidence: PMID:31451806 dynein-2 heavy chain are contorted into different conformations by a WDR60-WDR34 heterodimer |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: WDR60 bait recovers WDR34 in two human-cell interaction networks. Reason: The PMID:33961781 records resolve human WDR60 bait and WDR34 prey in HEK293T and HCT116 affinity-purification mass-spectrometry experiments. Sequence-matched participants and the established WDR34 intermediate-chain identity support GO:0045505. The methods use sequence-verified human ORFs and C-terminal FLAG-HA tags; these associations do not by themselves establish a purified interface or equal interaction strength in all cells. Proposed replacements: dynein intermediate chain binding Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md file:human/DYNC2I1/DYNC2I1-source-guide.md |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: The U2OS AP-MS network contains the WDR60βWDR34 edge. Reason: The original PMID:40205054 AP-MS network contains target node 556066 (DYNC2I1; ENSG00000126870), prey node 556068 (DYNC2I2), and edge 556070. Bait metadata identifies DYNC2I1 as bait and DYNC2I2 as non-bait. The study uses sequence-validated human ORFeome constructs in U2OS cells. This positive co-complex association supports the intermediate-chain-binding class; an antibody image URL in the network is not an independent interaction experiment. Proposed replacements: dynein intermediate chain binding Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0005576 extracellular region | HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ... | KEEP AS NON CORE | Summary: WDR60 is identified in an original human tear-fluid protein table. Reason: The publisher Table II lists WDR60_HUMAN/WDR60 among proteins identified in human tear samples; the normal cache omits the table row. Retain this HDA extracellular detection as non-core, without asserting secretion, a stable extracellular pool or extracellular activity. Schirmer-strip collection and pooled detergent extraction leave the route into the sample unresolved. The paper provides no WDR60-specific peptide count. Its twofold cutoff concerns differential abundance, not the identification criterion; intracellular function alone does not establish contamination. |
| GO:0005813 centrosome | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA supports a human centrosomal pool. Reason: The target-resolved HPA record assigns supported reliability to centrosome localization, separately from approved basal-body and supported primary-cilium localization. The additional cytosol call is uncertain and is not used to strengthen this row. Retain the observed centrosomal pool as non-core; no image pixels were independently scored and no distinct centrosomal catalytic activity is inferred. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-source-guide.md |
| GO:0005813 centrosome | IDA PMID:25830415 Tctex1d2 associates with short-rib polydactyly syndrome prot... | KEEP AS NON CORE | Summary: Human-cell immunofluorescence detects centrosomal WDR60. Reason: PMID:25830415 detects endogenous WDR60 near centrin/gamma-tubulin-marked centrosomal structures, at the interphase MTOC and at the ciliary base in the examined human cells. Retain this positive contextual localization without requiring that all centrosomal staining be a ciliary-base pool or claiming a separately measured microtubule-nucleation function. Supporting Evidence: PMID:25830415 Note that both proteins localize to the microtubule-organizing center (MTOC) in interphase |
| GO:0005813 centrosome | IDA PMID:31451806 Structure of the dynein-2 complex and its assembly with intr... | KEEP AS NON CORE | Summary: Centrosomal localization is independently well supported. Reason: The original PMID:31451806 evidence examined for this audit is recombinant structural and biochemical work; a source-specific centrosomal imaging result was not established. Nevertheless, endogenous human-cell imaging in PMID:25830415 and PMID:25205765, and the supported HPA centrosome call, positively establish the gene-level location. Retain the experimental annotation as non-core with that attribution limit rather than reject it from incomplete source localization evidence. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The UniProt centrosome mapping is experimentally grounded. Reason: The exact official SL-0048 location maps the human centrosomal pool and cites PMID:25205765. This agrees with endogenous human immunofluorescence and is retained as contextual localization, not as an inference that WDR60 catalyzes centrosome assembly. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0048 SUPPORTS TRANSFER Exact official source mapping is consistent with independently verified human evidence. |
| GO:0005868 cytoplasmic dynein complex | IBA GO_REF:0000033 | ACCEPT | Summary: The conserved family belongs to cytoplasmic dynein-2. Reason: The literal GO:0005868 IBD at PTN008562642 lies on the sequence-verified human DYNC2I1 path and is grounded by direct target experiments. Human complex purification and the recombinant human structure support the placement. The term explicitly includes IFT dyneins and is classified by dynein lineage, not by exclusion of cilia; it does not mean axonemal beating dynein. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008562642 SUPPORTS TRANSFER Literal IBD on the reconstructed PTHR16022 target path; exact human sequence matches the MSA. Human target experimental grounding is legitimate descendant evidence, not circularity. The retained contextual/core disposition is explained in the reason. Supporting Evidence: PMID:25205765 We show that the proteins encoded by the ciliopathy genes WDR34 and WDR60 are bona fide dynein-2 intermediate chains and are both required for dynein-2 function. file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0005868 cytoplasmic dynein complex | IDA PMID:25205765 Subunit composition of the human cytoplasmic dynein-2 comple... | ACCEPT | Summary: Endogenous WDR60 is part of the human dynein-2 assembly. Reason: PMID:25205765 purifies GFP-tagged human WDR34 complexes from RPE1 cells and identifies endogenous WDR60 together with dynein-2 components. Dynein-1 intermediate chains, dynactin and LIS1 were not detected in that particular preparation. The positive complex composition supports cytoplasmic dynein-2 membership without treating nondetection as universal exclusion of other interactions. Supporting Evidence: PMID:25205765 The above data indicate that both WDR34 and WDR60 are intermediate chains of the dynein-2 complex. |
| GO:0005868 cytoplasmic dynein complex | IDA PMID:25830415 Tctex1d2 associates with short-rib polydactyly syndrome prot... | ACCEPT | Summary: Human endogenous WDR60 associates with dynein-2 light chains. Reason: PMID:25830415 demonstrates reciprocal endogenous WDR60/TCTEX1D2 co-immunoprecipitation in human HEK293 cells and interaction of TCTEX1D2 with WDR60/WDR34 in cell-free translation assays. Together with the established dynein-2 architecture, these results support cytoplasmic dynein-complex membership; no independent WDR60 ATPase is asserted. Supporting Evidence: PMID:25830415 Wdr60 IPd Tctex1d2, Dync2h1, Wdr34, Dync2li1 and Dynll1 |
| GO:0005868 cytoplasmic dynein complex | IDA PMID:31451806 Structure of the dynein-2 complex and its assembly with intr... | ACCEPT | Summary: The recombinant human dynein-2 structure directly includes WDR60. Reason: PMID:31451806 reconstructs the human dynein-2 assembly expressed in insect cells and resolves the WDR60 intermediate-chain architecture, including its heavy-chain-associated propeller and the light-chain block. This is direct evidence of complex membership. Docking to an algal IFT train provides contextual architecture, not a measured human IFT rate. Supporting Evidence: PMID:31451806 DHC2TAIL-A and -B, are bound by the Ξ²-propeller of WDR60 and WDR34 respectively, mainly via bundle 3 |
| GO:0005868 cytoplasmic dynein complex | IEA GO_REF:0000002 | ACCEPT | Summary: The InterPro family mapping correctly identifies cytoplasmic dynein-2 membership. Reason: IPR042505 is the verified DYNC2I1 family and integrates PTHR16022. Its explicit GO mapping includes cytoplasmic dynein complex. Independent human purification and structural evidence support the annotation, while the term definition expressly permits ciliary IFT dynein. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR042505 SUPPORTS TRANSFER The current DYNC2I1 family explicitly maps this source term; human interaction, complex and transport evidence independently supports the family assignment. |
| GO:0005929 cilium | IDA GO_REF:0000052 | ACCEPT | Summary: HPA positively localizes DYNC2I1 to primary cilia. Reason: The target HPA record separately rates primary-cilium staining as supported, centrosome as supported and basal body as approved. This provides positive support for the imported cilium location. Retain the source term while describing the measured primary-cilium context; do not infer an additional diffuse cytosolic pool from the uncertain cytosol call. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-source-guide.md |
| GO:0005929 cilium | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic cilium assertion is consistent with direct human evidence. Reason: The official human SL-0066 entry is grounded in PMID:23910462, and HPA independently supports a ciliary pool. The mouse Q8C761 record maps ENSMUSP00000047334 and carries both a direct MGI cilium annotation to PMID:22326026 and transfers from the human target. The current ARBA00028353 record does emit GO:0005929, but none of its current InterPro condition sets was fully matched to the saved human InterPro inventory; that particular rule-version join remains unresolved. This does not negate the independently grounded gene-level location or establish a wholly circular chain. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028353 UNRESOLVED Current rule emits cilium but no complete current InterPro condition set matched the saved human target inventory; the historical rule-version match is not reconstructed. Independent target localization supports the conclusion. UniProtKB:Q8C761 SUPPORTS TRANSFER Official mouse ortholog has current MGI IDA cilium annotation PMID:22326026 as well as human-source transfers; the donor paper body was not re-read. Human target imaging independently grounds the location. ensembl:ENSMUSP00000047334 SUPPORTS TRANSFER Official mouse Q8C761 cross-reference identifies ENSMUSP00000047334.7; the isolated QuickGO accession route returned 400, retained as an access failure rather than a missing gene claim. UniProtKB-SubCell:SL-0066 SUPPORTS TRANSFER Exact official source mapping is consistent with independently verified human evidence. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-source-guide.md |
| GO:0005929 cilium | NAS PMID:30065109 Emerging mechanisms of dynein transport in the cytoplasm ver... | ACCEPT | Summary: The review places WDR60 in the ciliary dynein-2 machinery. Reason: PMID:30065109 explicitly identifies WDR60 as a dynein-2 intermediate chain and reviews the IFT motor assembly. Direct human ciliary-base and HPA localization independently ground the cellular-component assertion. The review is supporting synthesis, not a new primary WDR60 imaging experiment. |
| GO:0005929 cilium | NAS PMID:32229580 Cytoplasmic dynein-2 at a glance. | ACCEPT | Summary: Ciliary localization is well supported despite abstract-only access to this review. Reason: The authentic PMID:32229580 abstract describes dynein-2 as the intraciliary transport complex. The paper body was not independently accessed here. Direct human WDR60 localization and complex evidence from PMID:23910462, PMID:25205765 and HPA make the imported location clearly correct, while the review-specific access limit is preserved. |
| GO:0005929 cilium | TAS Reactome:R-HSA-5624949 | ACCEPT | Summary: Reactome contains full-length WDR60 in a ciliary dynein-2 state. Reason: The saved Reactome R-HSA-5624949 event traces through its dynein-2 components to Q8WVS4 residues 1β1066 in the cilium. This is an explicit model entity, corroborated by independent human localization and complex data. The reaction context does not assign autonomous motor activity to WDR60; anterograde carriage of dynein-2 is distinct from the retrograde force-generating role of its heavy chains. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0005929 cilium | TAS Reactome:R-HSA-5625416 | ACCEPT | Summary: Reactome contains full-length WDR60 in a ciliary dynein-2 state. Reason: The saved Reactome R-HSA-5625416 event traces through its dynein-2 components to Q8WVS4 residues 1β1066 in the cilium. This is an explicit model entity, corroborated by independent human localization and complex data. The reaction context does not assign autonomous motor activity to WDR60; anterograde carriage of dynein-2 is distinct from the retrograde force-generating role of its heavy chains. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0005929 cilium | TAS Reactome:R-HSA-5625424 | ACCEPT | Summary: Reactome contains full-length WDR60 in a ciliary dynein-2 state. Reason: The saved Reactome R-HSA-5625424 event traces through its dynein-2 components to Q8WVS4 residues 1β1066 in the cilium. This is an explicit model entity, corroborated by independent human localization and complex data. The reaction context does not assign autonomous motor activity to WDR60; anterograde carriage of dynein-2 is distinct from the retrograde force-generating role of its heavy chains. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0005929 cilium | TAS Reactome:R-HSA-5625426 | ACCEPT | Summary: Reactome contains full-length WDR60 in a ciliary dynein-2 state. Reason: The saved Reactome R-HSA-5625426 event traces through its dynein-2 components to Q8WVS4 residues 1β1066 in the cilium. This is an explicit model entity, corroborated by independent human localization and complex data. The reaction context does not assign autonomous motor activity to WDR60; anterograde carriage of dynein-2 is distinct from the retrograde force-generating role of its heavy chains. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0030286 dynein complex | NAS PMID:30065109 Emerging mechanisms of dynein transport in the cytoplasm ver... | MODIFY | Summary: The reviewed complex is specifically cytoplasmic dynein-2. Reason: PMID:30065109 explicitly distinguishes WDR60-containing dynein-2 from dynein-1 and axonemal dyneins. Refine the broad dynein-complex term to GO:0005868, whose definition includes the ciliary IFT motor lineage. This is complex specificity, not a claim of a diffuse cytoplasmic pool. Proposed replacements: cytoplasmic dynein complex |
| GO:0030286 dynein complex | NAS PMID:32229580 Cytoplasmic dynein-2 at a glance. | MODIFY | Summary: The review and independent structure identify the cytoplasmic dynein-2 class. Reason: The accessible PMID:32229580 abstract specifically concerns cytoplasmic dynein-2, and the human complex is directly established by PMID:25205765 and PMID:31451806. Refine broad dynein complex to GO:0005868 without claiming the review body was read or equating cytoplasmic-dynein classification with subcellular location. Proposed replacements: cytoplasmic dynein complex |
| GO:0031021 interphase microtubule organizing center | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT retains the experimentally observed interphase MTOC association. Reason: The literal PTN008562642 IBD is on the verified target lineage and is supported by the target human localization study PMID:25830415. Retain the interphase MTOC localization as contextual evidence. The finding does not demonstrate that WDR60 organizes or nucleates microtubules, and source relationship fields are left unchanged. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN008562642 SUPPORTS TRANSFER Literal IBD on the reconstructed PTHR16022 target path; exact human sequence matches the MSA. Human target experimental grounding is legitimate descendant evidence, not circularity. The retained contextual/core disposition is explained in the reason. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0031021 interphase microtubule organizing center | IDA PMID:25830415 Tctex1d2 associates with short-rib polydactyly syndrome prot... | KEEP AS NON CORE | Summary: WDR60 is observed at the interphase MTOC in human cells. Reason: PMID:25830415 reports endogenous WDR60 immunostaining at the interphase MTOC in HeLa cells, alongside its mitotic and ciliary-base distributions. Retain the observed location as non-core rather than infer a distinct MTOC-organizing activity from localization alone. Supporting Evidence: PMID:25830415 Note that both proteins localize to the microtubule-organizing center (MTOC) in interphase |
| GO:0035721 intraciliary retrograde transport | IDA PMID:29742051 Interaction of WDR60 intermediate chain with TCTEX1D2 light ... | ACCEPT | Summary: WDR60 structurally supports retrograde ciliary trafficking. Reason: PMID:29742051 uses human WDR60 constructs and RPE1 knockout/rescue experiments. WDR60 loss produces ciliary IFT88/IFT140 and receptor-trafficking defects; deleting the 473β522 light-chain-binding region impairs selected rescue endpoints. This supports participation of the intermediate chain in retrograde transport. TIRF velocity measurements in that paper concern the TCTEX1D2-knockout comparison, not a quantitative WDR60-knockout velocity assay. WDR60 does not itself hydrolyze ATP to generate movement. Supporting Evidence: PMID:29742051 These observations indicate that retrograde trafficking of the IFT machinery is severely impaired in the absence of WDR60. |
| GO:0035721 intraciliary retrograde transport | IDA PMID:30649997 Interactions of the dynein-2 intermediate chain WDR34 with t... | ACCEPT | Summary: The WDR60 comparison directly supports retrograde transport. Reason: Although PMID:30649997 foregrounds WDR34, it explicitly assays the established human RPE1 WDR60-knockout line. WDR60 loss increases ciliary IFT88/IFT140 and disrupts SMO/GPR161 trafficking, providing direct target evidence. These accumulation and receptor-localization endpoints support retrograde transport participation but are not measurements of WDR60 motor speed or an isolated catalytic activity. Supporting Evidence: PMID:30649997 whereas WDR60-KO cells demonstrated slight but significant accumulation of IFT140 within cilia |
| GO:0035721 intraciliary retrograde transport | NAS PMID:31451806 Structure of the dynein-2 complex and its assembly with intr... | ACCEPT | Summary: Human dynein-2 structure supports the intermediate chainβs retrograde-transport role. Reason: PMID:31451806 resolves WDR60 in the human intermediate-chain/light-chain scaffold of the retrograde IFT motor. Cellular studies independently establish WDR60-dependent ciliary trafficking. The human structure was docked into an algal IFT train, so loading cooperativity and tip activation remain mechanistic models rather than measured human transport kinetics. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-deep-research-falcon.md Dynein-2 powers transport from the ciliary tip toward the base along axonemal microtubules. |
| GO:0035721 intraciliary retrograde transport | NAS PMID:32229580 Cytoplasmic dynein-2 at a glance. | ACCEPT | Summary: Retrograde IFT is a well-grounded function of the WDR60-containing complex. Reason: The authentic PMID:32229580 abstract reviews the ciliary dynein-2 motor; the full review body was not independently read. Direct human WDR60 knockout/rescue and structural evidence establish its participation in retrograde IFT. Accept the clearly correct gene-level process while retaining the source-specific access limitation and the distinction between structural participation and ATPase force generation. |
| GO:0042073 intraciliary transport | IEA GO_REF:0000002 | MODIFY | Summary: The family participates specifically in retrograde intraciliary transport. Reason: The current IPR042505 family description and the human WDR60 perturbation/assembly experiments support specifically the retrograde dynein-2 transport role. Refine to GO:0035721. The inherited PMID:30320547 excerpt describes the broader consequence for bidirectional IFT; PMID:29742051 provides the WDR60-specific retrograde-trafficking anchor. A disruption affecting both directions does not imply that WDR60 supplies both motor activities. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR042505 SUPPORTS TRANSFER The current DYNC2I1 family explicitly maps this source term; human interaction, complex and transport evidence independently supports the family assignment. Proposed replacements: intraciliary retrograde transport Supporting Evidence: PMID:30320547 Both proteins are required to maintain a functional transition zone and for efficient bidirectional intraflagellar transport. file:human/DYNC2I1/DYNC2I1-source-guide.md |
| GO:0045503 dynein light chain binding | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved light-chain binding is grounded in human target experiments. Reason: The GO:0045503 IBD at PTN008562642 is on the verified DYNC2I1 path and legitimately uses the human target as an experimental descendant. PMID:25830415 establishes TCTEX1D2 association, and PMID:29742051 maps the human WDR60 region needed for binding the TCTEX1D2βDYNLT1/3 light-chain module. This is not circular inference or a donor-count argument. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008562642 SUPPORTS TRANSFER Literal IBD on the reconstructed PTHR16022 target path; exact human sequence matches the MSA. Human target experimental grounding is legitimate descendant evidence, not circularity. The retained contextual/core disposition is explained in the reason. Supporting Evidence: PMID:29742051 Although WDR60 did not demonstrate a binary interaction with any other subunit (Figure 1B), we found that it interacts with the TCTEX1D2βDYNLT1/DYNLT3 dimer via its conserved region upstream of the WD40 domain file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0045503 dynein light chain binding | IEA GO_REF:0000002 | ACCEPT | Summary: The InterPro light-chain-binding mapping has direct mechanistic support. Reason: IPR042505 is the actual DYNC2I1 family and explicitly maps GO:0045503. Human association and deletion-mapping experiments establish WDR60 as a binding scaffold for dynein-2 light chains. The annotation denotes binding, not light-chain catalysis or autonomous motor activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR042505 SUPPORTS TRANSFER The current DYNC2I1 family explicitly maps this source term; human interaction, complex and transport evidence independently supports the family assignment. |
| GO:0045503 dynein light chain binding | IPI PMID:25830415 Tctex1d2 associates with short-rib polydactyly syndrome prot... | ACCEPT | Summary: Human WDR60 associates with the TCTEX1D2/DYNLT2B light chain. Reason: PMID:25830415 demonstrates reciprocal endogenous association in human HEK293 cells and interaction in cell-free translation assays, with the TCTEX1D2 C-terminal region sufficient in the tested assay. The official Q8WW35 partner is a dynein light chain. Accept the binding class without overstating cell-free translation as a purified binary-binding measurement. Supporting Evidence: PMID:25830415 Reciprocal co-IPs of endogenous Tctex1d2 and Wdr60 from ciliated hTERT-RPE cells, using anti-Tctex1d2 or anti-Wdr60 antibodies. |
| GO:0045504 dynein heavy chain binding | IEA GO_REF:0000002 | ACCEPT | Summary: WDR60 contacts the dynein heavy-chain assembly. Reason: The exact IPR042505 mapping includes heavy-chain binding. Human subunit association assays in PMID:29742051 and the human recombinant structure in PMID:31451806 support WDR60βs heavy-chain-associated architecture. The former uses a DYNC2H1 tail construct in an assembled subunit context; the latter resolves the propeller contact. Neither makes WDR60 the force-generating ATPase. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR042505 SUPPORTS TRANSFER The current DYNC2I1 family explicitly maps this source term; human interaction, complex and transport evidence independently supports the family assignment. Supporting Evidence: PMID:31451806 DHC2TAIL-A and -B, are bound by the Ξ²-propeller of WDR60 and WDR34 respectively, mainly via bundle 3 |
| GO:0048704 embryonic skeletal system morphogenesis | IMP PMID:23910462 Short-rib polydactyly and Jeune syndromes are caused by muta... | KEEP AS NON CORE | Summary: Human variants connect WDR60 to embryonic skeletal morphogenesis. Reason: PMID:23910462 identifies biallelic WDR60 variants in skeletal ciliopathies and shows cellular ciliogenesis and GLI2-distribution defects. Retain the developmental process as a clinically and experimentally supported downstream context of ciliary dysfunction. The direct molecular role is dynein-2 assembly/transport, not a separately demonstrated skeletal morphogenetic activity. Supporting Evidence: PMID:23910462 These findings show that WDR60 mutations can cause skeletal ciliopathies and suggest a role for WDR60 in ciliogenesis. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited cilium-assembly annotation is experimentally grounded. Reason: The verified PTN008562642 IBD is grounded by human target ciliation experiments and lies on the actual DYNC2I1 lineage. WDR60 structurally organizes the retrograde transport machinery that returns IFT components, supporting ciliary formation and maintenance. Later cells can retain axonemes with transport defects, so assembly participation is accepted without claiming that WDR60 absence universally abolishes cilium initiation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008562642 SUPPORTS TRANSFER Literal IBD on the reconstructed PTHR16022 target path; exact human sequence matches the MSA. Human target experimental grounding is legitimate descendant evidence, not circularity. The retained contextual/core disposition is explained in the reason. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0060271 cilium assembly | IGI PMID:25205765 Subunit composition of the human cytoplasmic dynein-2 comple... | ACCEPT | Summary: WDR34/WDR60 perturbation supports a shared cilium-assembly pathway. Reason: PMID:25205765 shows reduced ciliation after WDR60 depletion and a nonadditive phenotype when WDR34 is also depleted, supporting their participation in a shared dynein-2 pathway. The human intermediate-chain association and complex role support the IGI assertion. Retain the source partner and distinguish this assay from proof of complete ciliogenesis loss in every knockout context. Supporting Evidence: PMID:25205765 Of note, double depletion of both WDR34 and WDR60 did not further exacerbate the cilia phenotypes seen |
| GO:0060271 cilium assembly | IMP PMID:23910462 Short-rib polydactyly and Jeune syndromes are caused by muta... | ACCEPT | Summary: Patient-cell defects support cilium assembly, with contextual limits. Reason: PMID:23910462 reports markedly reduced ciliation and abnormal basal IFT/GLI2 accumulations in patient fibroblasts, alongside WDR60 localization at the ciliary base in human chondrocytes. Residual cilia and the acknowledged control-age limitation are retained. Independent perturbation and complex evidence support assembly participation; no universal all-or-none requirement for initiation is inferred. Supporting Evidence: PMID:23910462 analysis of fibroblasts from affected individuals revealed a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme |
| GO:0060271 cilium assembly | IMP PMID:25205765 Subunit composition of the human cytoplasmic dynein-2 comple... | ACCEPT | Summary: WDR60 depletion perturbs ciliation in human RPE1 cells. Reason: PMID:25205765 directly measures reduced ciliation after WDR60 depletion; the cilia that remain are longer in that experimental context. This supports participation in ciliary assembly/homeostasis through dynein-2. It does not establish that every WDR60-deficient cell lacks an axoneme or that WDR60 is a polymerizing enzyme. Supporting Evidence: PMID:25205765 labeling showed either longer cilia (example shown for WDR60 |
| GO:0060271 cilium assembly | IMP PMID:25830415 Tctex1d2 associates with short-rib polydactyly syndrome prot... | ACCEPT | Summary: WDR60 depletion compromises ciliogenesis and basal light-chain recruitment. Reason: PMID:25830415 reports reduced ciliation after WDR60 depletion in RPE cells and impaired basal recruitment of TCTEX1D2, while CEP164 and TTBK2 localization is retained. The source supports structural participation in cilium assembly, not assignment of the earliest initiation step or an independent motor chemistry. Supporting Evidence: PMID:25830415 Tctex1d2 and Wdr60 localize to the base of the cilium and their depletion causes defects in ciliogenesis. |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5624952 | ACCEPT | Summary: Reactome explicitly places WDR60 in a ciliary-tip transport state. Reason: The saved R-HSA-5624952 reaction explicitly traces to WDR60/Q8WVS4 residues 1β1066 in the ciliary-tip dynein-2 entity R-HSA-5625409. The tip is the turnaround state of the primary IFT transport cycle, so it is core-relevant localization. Preserve the conserved pathway-model provenance: this is not a new human WDR60 imaging measurement, residence-time determination, or independent biochemical activity. Those measurement limits do not make the positive location non-core. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5625416 | ACCEPT | Summary: Reactome explicitly places WDR60 in a ciliary-tip transport state. Reason: The saved R-HSA-5625416 reaction explicitly traces to WDR60/Q8WVS4 residues 1β1066 in the ciliary-tip dynein-2 entity R-HSA-5625409. The tip is the turnaround state of the primary IFT transport cycle, so it is core-relevant localization. Preserve the conserved pathway-model provenance: this is not a new human WDR60 imaging measurement, residence-time determination, or independent biochemical activity. Those measurement limits do not make the positive location non-core. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5625421 | ACCEPT | Summary: Reactome explicitly places WDR60 in a ciliary-tip transport state. Reason: The saved R-HSA-5625421 reaction explicitly traces to WDR60/Q8WVS4 residues 1β1066 in the ciliary-tip dynein-2 entity R-HSA-5625409. The tip is the turnaround state of the primary IFT transport cycle, so it is core-relevant localization. Preserve the conserved pathway-model provenance: this is not a new human WDR60 imaging measurement, residence-time determination, or independent biochemical activity. Those measurement limits do not make the positive location non-core. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5625426 | ACCEPT | Summary: Reactome explicitly places WDR60 in a ciliary-tip transport state. Reason: The saved R-HSA-5625426 reaction explicitly traces to WDR60/Q8WVS4 residues 1β1066 in the ciliary-tip dynein-2 entity R-HSA-5625409. The tip is the turnaround state of the primary IFT transport cycle, so it is core-relevant localization. Preserve the conserved pathway-model provenance: this is not a new human WDR60 imaging measurement, residence-time determination, or independent biochemical activity. Those measurement limits do not make the positive location non-core. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0097546 ciliary base | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved ciliary-base localization is grounded directly in human WDR60. Reason: The literal GO:0097546 IBD at PTN008562642 lies on the verified target path and includes legitimate human target experimental grounding. PMID:23910462 and PMID:25830415 localize endogenous WDR60 at the base of primary cilia. The broad ciliary-base term respects imaging resolution rather than assigning a particular transition-zone or basal-body substructure without evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008562642 SUPPORTS TRANSFER Literal IBD on the reconstructed PTHR16022 target path; exact human sequence matches the MSA. Human target experimental grounding is legitimate descendant evidence, not circularity. The retained contextual/core disposition is explained in the reason. Supporting Evidence: file:human/DYNC2I1/DYNC2I1-bioinformatics/evidence-audit/RESULTS.md |
| GO:0097546 ciliary base | IDA PMID:23910462 Short-rib polydactyly and Jeune syndromes are caused by muta... | ACCEPT | Summary: Endogenous WDR60 localizes at the primary-cilium base in human chondrocytes. Reason: PMID:23910462 directly detects WDR60 at the base of primary cilia in human C28/I2 chondrocytes. This is positive target localization, separate from patient-cell perturbation phenotypes. The ciliary-base term preserves the resolution of the assay without asserting a more precise transition-zone structure. Supporting Evidence: PMID:23910462 We further show that WDR60 localizes at the base of the primary cilium in wild-type human chondrocytes |
| GO:0097546 ciliary base | IDA PMID:25830415 Tctex1d2 associates with short-rib polydactyly syndrome prot... | ACCEPT | Summary: Human-cell imaging confirms the WDR60 ciliary-base pool. Reason: PMID:25830415 detects endogenous WDR60 at the base of primary cilia in RPE cells, near the mother centriole and appendage markers. Endogenous axonemal staining was not detected in that particular assay, which does not negate independently observed ciliary pools. Accept ciliary-base localization without claiming that every signal belongs to a single subcompartment. Supporting Evidence: PMID:25830415 Tctex1d2 and Wdr60 localize to the base of the cilium and their depletion causes defects in ciliogenesis. |
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Download this section (compressed HTML)Q: Do WDR60 and TCTEX1D2 have a genuine non-ciliary role with dynein-1 at spindle poles and MTOCs in cycling cells, as suggested by their mitotic localization?
Q: Why did WDR60 knockout permit axoneme extension whereas WDR34 knockout impaired extension in the human RPE1 experiments of PMID:30320547, and how do allele and experimental-context differences, including those examined in PMID:30649997, affect that distinction?
Experiment: In WDR60-knockout HeLa or RPE1 cells, quantify spindle assembly, spindle-pole focusing and mitotic timing, and test whether WDR60 co-purifies with dynein-1 heavy chain in mitotic extracts.
Hypothesis: WDR60 contributes to mitotic dynein-1 function independently of dynein-2.
Type: knockout phenotyping and biochemistry
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