id: Q8WW35 gene_symbol: DYNLT2B product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: DYNLT2B (TCTEX1D2) is a small non-catalytic Tctex-type dynein light chain and the only Tctex light chain unique to cytoplasmic dynein-2, the minus-end-directed motor that drives retrograde intraflagellar transport (IFT) from the ciliary tip back to the base. It forms a 1:1 heterodimer with the Tctex light chain DYNLT1 (or DYNLT3), and this pair binds the dynein-2 intermediate chain WDR60/DYNC2I1, forming the WDR60-TCTEX1D2-DYNLT1/DYNLT3 subcomplex of the dynein-2 tail. Endogenous protein is found at the ciliary base, centrosomal microtubule-organizing centers and mitotic spindle poles, with WDR60-dependent recruitment. Loss of DYNLT2B in human cells and of its Chlamydomonas ortholog Tctex2b impairs retrograde IFT and partially destabilizes the motor, and biallelic loss-of-function variants cause short-rib thoracic dysplasia 17 (Jeune asphyxiating thoracic dystrophy). In mouse testis the ortholog is also an axoneme component that associates with inner-dynein-arm intermediate chains and is required for sperm flagellum formation. existing_annotations: - term: id: GO:0000922 label: spindle pole evidence_type: IDA original_reference_id: PMID:25830415 qualifier: colocalizes_with review: action: KEEP_AS_NON_CORE summary: Spindle-pole localization was observed during cell division; this is a secondary localization alongside the core ciliary dynein-2 role. reason: Spindle-pole localization was observed during cell division; this is a secondary localization alongside the core ciliary dynein-2 role. supported_by: - reference_id: PMID:25830415 supporting_text: Tctex1d2 associates with Wdr34, Wdr60, and other subunits of Dync1 and Dync2 and colocalizes with Wdr60 to microtubule organizing centers during interphase, the mitotic spindle poles during cell division, and the base of the cilium in ciliated cells. - term: id: GO:0001673 label: male germ cell nucleus evidence_type: NAS original_reference_id: PMID:36973253 qualifier: located_in review: action: MARK_AS_OVER_ANNOTATED summary: Complex-level NAS from ComplexPortal; the cited paper does not examine DYNLT2B, and no study places this dynein-2 light chain in the male germ cell nucleus. reason: The cached full text of PMID:36973253 analyses DYNLRB1- and DYNLRB2-defined dynein complexes in mitotic and male meiotic spindles and does not mention DYNLT2B/TCTEX1D2. The annotation is a statement inferred from a complex description, not an observation on this protein, and nuclear residence is not consistent with what is known of dynein-2 (ciliary base, MTOC, axoneme). Mouse testis data place TCTEX1D2 in the sperm flagellar axoneme, not the nucleus. The term overstates the evidence for this gene product. supported_by: - reference_id: PMID:39827215 supporting_text: TCTEX1D2 is an axoneme component and interacts with subunits of inner dynein arm - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20195357 qualifier: enables supporting_entities: - UniProtKB:P13984 review: action: REMOVE summary: Bare protein binding to GTF2F2 from a high-throughput binary interaction screen; uninformative. reason: Generic protein binding carries no functional information. The GTF2F2 interaction comes from a proteome-scale screen, has no follow-up linking it to dynein-2 or ciliary function, and does not support a more informative molecular function term. Removal does not assert that the reported interaction is false. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25910212 qualifier: enables supporting_entities: - UniProtKB:P35609 review: action: REMOVE summary: Bare protein binding to ACTN2 from a high-throughput binary interaction screen; uninformative. reason: Generic protein binding carries no functional information. The ACTN2 interaction comes from a proteome-scale screen, has no follow-up linking it to dynein-2 or ciliary function, and does not support a more informative molecular function term. Removal does not assert that the reported interaction is false. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26044572 qualifier: enables supporting_entities: - UniProtKB:Q8WVS4 review: action: MODIFY summary: The partner is the dynein-2 intermediate chain WDR60 (DYNC2I1); the informative term is dynein intermediate chain binding. reason: Affinity purification of tagged TCTEX1D2 recovered the IFT-dynein intermediate chains WDR34 and WDR60, and follow-up work mapped the TCTEX1D2-DYNLT1/DYNLT3 dimer onto WDR60. Replace bare protein binding with dynein intermediate chain binding, which the gene already carries by IPI and IBA. supported_by: - reference_id: PMID:26044572 supporting_text: We were able to identify interactions of TCTEX1D2 with IFT dynein intermediate chains WDR34 and WDR60, and light chains DYNLT1, DYNLT3 and DYNLRB1 (Supplementary Table 7). - reference_id: PMID:29742051 supporting_text: 'We established cell lines lacking WDR60 or TCTEX1D2, both of which are dynein-2-specific subunits encoded by ciliopathy-causing genes, and found that both WDR60-knockout (KO) and TCTEX1D2-KO cells show defects in retrograde ciliary protein trafficking, with WDR60-KO cells demonstrating more severe defects probably due to failed assembly of the dynein-2 complex.' proposed_replacement_terms: - id: GO:0045505 label: dynein intermediate chain binding - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:27173435 qualifier: enables supporting_entities: - UniProtKB:P63172 review: action: MODIFY summary: The DYNLT1 partner is itself a Tctex-type dynein light chain; the specific activity is dynein light chain binding (heterodimerization with DYNLT1). reason: DYNLT2B forms an obligate 1:1 heterodimer with the Tctex light chain DYNLT1 within the dynein-2 tail, shown by affinity proteomics, binary interaction screens and an X-ray structure of the DYNLT1-DYNLT2B heterodimer. Bare protein binding should be replaced by dynein light chain binding. supported_by: - reference_id: PMID:38454149 supporting_text: X-ray crystallography structure of DYNLT1-DYNLT2B heterodimer. - reference_id: PMID:26044572 supporting_text: We were able to identify interactions of TCTEX1D2 with IFT dynein intermediate chains WDR34 and WDR60, and light chains DYNLT1, DYNLT3 and DYNLRB1 (Supplementary Table 7). proposed_replacement_terms: - id: GO:0045503 label: dynein light chain binding - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:P55273 review: action: REMOVE summary: Bare protein binding to CDKN2D from a high-throughput binary interaction screen; uninformative. reason: Generic protein binding carries no functional information. The CDKN2D interaction comes from a proteome-scale screen, has no follow-up linking it to dynein-2 or ciliary function, and does not support a more informative molecular function term. Removal does not assert that the reported interaction is false. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:P63172 review: action: MODIFY summary: The DYNLT1 partner is itself a Tctex-type dynein light chain; the specific activity is dynein light chain binding (heterodimerization with DYNLT1). reason: DYNLT2B forms an obligate 1:1 heterodimer with the Tctex light chain DYNLT1 within the dynein-2 tail, shown by affinity proteomics, binary interaction screens and an X-ray structure of the DYNLT1-DYNLT2B heterodimer. Bare protein binding should be replaced by dynein light chain binding. supported_by: - reference_id: PMID:38454149 supporting_text: X-ray crystallography structure of DYNLT1-DYNLT2B heterodimer. - reference_id: PMID:26044572 supporting_text: We were able to identify interactions of TCTEX1D2 with IFT dynein intermediate chains WDR34 and WDR60, and light chains DYNLT1, DYNLT3 and DYNLRB1 (Supplementary Table 7). proposed_replacement_terms: - id: GO:0045503 label: dynein light chain binding - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables supporting_entities: - UniProtKB:P63172 review: action: MODIFY summary: The DYNLT1 partner is itself a Tctex-type dynein light chain; the specific activity is dynein light chain binding (heterodimerization with DYNLT1). reason: DYNLT2B forms an obligate 1:1 heterodimer with the Tctex light chain DYNLT1 within the dynein-2 tail, shown by affinity proteomics, binary interaction screens and an X-ray structure of the DYNLT1-DYNLT2B heterodimer. Bare protein binding should be replaced by dynein light chain binding. supported_by: - reference_id: PMID:38454149 supporting_text: X-ray crystallography structure of DYNLT1-DYNLT2B heterodimer. - reference_id: PMID:26044572 supporting_text: We were able to identify interactions of TCTEX1D2 with IFT dynein intermediate chains WDR34 and WDR60, and light chains DYNLT1, DYNLT3 and DYNLRB1 (Supplementary Table 7). proposed_replacement_terms: - id: GO:0045503 label: dynein light chain binding - term: id: GO:0005737 label: cytoplasm evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - MGI:MGI:3045358 - MGI:MGI:98642 - MGI:MGI:98643 - PANTHER:PTN000478852 - PomBase:SPAC1805.08 - RGD:1549755 - UniProtKB:O04355 - UniProtKB:P63172 - UniProtKB:Q388R0 - UniProtKB:Q389U5 - UniProtKB:Q5JR98 - UniProtKB:Q8WW35 - WB:WBGene00017014 review: action: KEEP_AS_NON_CORE summary: Family-level IBA for cytoplasmic localization; correct, and DYNLT2B is observed at several cytoplasmic microtubule structures, but the functionally defining location is the ciliary base and cilium. reason: The PAINT node PTN000478852 spans the Tctex light-chain family (DYNLT1, DYNLT3, fly and yeast Tctex members), so cytoplasm is the level at which the family-wide claim was placed. Human TCTEX1D2 is seen at interphase MTOCs, spindle poles and the ciliary base, all cytoplasmic microtubule structures, so the claim holds; the location defining its core role (ciliary base/cilium) is captured by separate rows. supported_by: - reference_id: PMID:25830415 supporting_text: Tctex1d2 associates with Wdr34, Wdr60, and other subunits of Dync1 and Dync2 and colocalizes with Wdr60 to microtubule organizing centers during interphase, the mitotic spindle poles during cell division, and the base of the cilium in ciliated cells. - term: id: GO:0005813 label: centrosome evidence_type: IDA original_reference_id: PMID:25830415 qualifier: colocalizes_with review: action: KEEP_AS_NON_CORE summary: Endogenous TCTEX1D2 colocalizes with WDR60 at centrosomal MTOCs; real but secondary to the ciliary-base/dynein-2 role. reason: Immunofluorescence in human cells shows the protein at MTOCs/centrosomes during interphase, depending on WDR60 and microtubules. This is consistent with recruitment of dynein-2 to the basal body region but is not itself the core functional location. supported_by: - reference_id: PMID:25830415 supporting_text: Tctex1d2 associates with Wdr34, Wdr60, and other subunits of Dync1 and Dync2 and colocalizes with Wdr60 to microtubule organizing centers during interphase, the mitotic spindle poles during cell division, and the base of the cilium in ciliated cells. - term: id: GO:0005868 label: cytoplasmic dynein complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of supporting_entities: - MGI:MGI:98642 - PANTHER:PTN000478852 - RGD:1549755 - UniProtKB:P51808 - UniProtKB:P63171 - UniProtKB:P63172 - UniProtKB:Q8WW35 review: action: ACCEPT summary: Biochemical isolation and interaction mapping place TCTEX1D2 in cytoplasmic dynein-2; this is complex membership rather than intrinsic ATPase activity. reason: Biochemical isolation and interaction mapping place TCTEX1D2 in cytoplasmic dynein-2; this is complex membership rather than intrinsic ATPase activity. supported_by: - reference_id: PMID:25205765 supporting_text: Here, we now also identify the TCTEX1D2 light chain (Tctex-2) as a light chain for dynein-2, not present in dynein-1. - term: id: GO:0005868 label: cytoplasmic dynein complex evidence_type: IDA original_reference_id: PMID:25205765 qualifier: part_of review: action: ACCEPT summary: Biochemical isolation and interaction mapping place TCTEX1D2 in cytoplasmic dynein-2; this is complex membership rather than intrinsic ATPase activity. reason: Biochemical isolation and interaction mapping place TCTEX1D2 in cytoplasmic dynein-2; this is complex membership rather than intrinsic ATPase activity. supported_by: - reference_id: PMID:25205765 supporting_text: Here, we now also identify the TCTEX1D2 light chain (Tctex-2) as a light chain for dynein-2, not present in dynein-1. - term: id: GO:0005868 label: cytoplasmic dynein complex evidence_type: IDA original_reference_id: PMID:25830415 qualifier: part_of review: action: ACCEPT summary: Biochemical isolation and interaction mapping place TCTEX1D2 in cytoplasmic dynein-2; this is complex membership rather than intrinsic ATPase activity. reason: Biochemical isolation and interaction mapping place TCTEX1D2 in cytoplasmic dynein-2; this is complex membership rather than intrinsic ATPase activity. supported_by: - reference_id: PMID:25205765 supporting_text: Here, we now also identify the TCTEX1D2 light chain (Tctex-2) as a light chain for dynein-2, not present in dynein-1. - term: id: GO:0005929 label: cilium evidence_type: NAS original_reference_id: PMID:30065109 qualifier: located_in review: action: ACCEPT summary: Dynein-2, including DYNLT2B, enters cilia on IFT trains and returns cargo from the tip; cilium is the appropriate location for the complex. reason: 'ComplexPortal NAS based on dynein-2 reviews. Independent primary evidence: TCTEX1D2 is an integral IFT-dynein subunit and its loss impairs retrograde IFT; endogenous protein is detected at the ciliary base and tagged protein in the axoneme.' supported_by: - reference_id: PMID:26044572 supporting_text: Affinity proteomics indicates that TCTEX1D2/Tctex2b is an integral component of IFT dynein. We demonstrate a retrograde IFT defect in TCTEX1D2-deficient human fibroblasts and Tctex2b-deficient Chlamydomonas cells, and find that IFT dynein is partially destabilized by loss of Tctex2b in Chlamydomonas. - term: id: GO:0005929 label: cilium evidence_type: NAS original_reference_id: PMID:32229580 qualifier: located_in review: action: ACCEPT summary: Dynein-2, including DYNLT2B, enters cilia on IFT trains and returns cargo from the tip; cilium is the appropriate location for the complex. reason: 'ComplexPortal NAS based on dynein-2 reviews. Independent primary evidence: TCTEX1D2 is an integral IFT-dynein subunit and its loss impairs retrograde IFT; endogenous protein is detected at the ciliary base and tagged protein in the axoneme.' supported_by: - reference_id: PMID:26044572 supporting_text: Affinity proteomics indicates that TCTEX1D2/Tctex2b is an integral component of IFT dynein. We demonstrate a retrograde IFT defect in TCTEX1D2-deficient human fibroblasts and Tctex2b-deficient Chlamydomonas cells, and find that IFT dynein is partially destabilized by loss of Tctex2b in Chlamydomonas. - term: id: GO:0005930 label: axoneme evidence_type: IDA original_reference_id: PMID:25830415 qualifier: colocalizes_with review: action: KEEP_AS_NON_CORE summary: Axonemal signal was observed for overexpressed tagged TCTEX1D2; the same study did not detect a clear endogenous axonemal signal. Retain the experimental localization with this limitation. reason: Axonemal signal was observed for overexpressed tagged TCTEX1D2; the same study did not detect a clear endogenous axonemal signal. Retain the experimental localization with this limitation. supported_by: - reference_id: PMID:25830415 supporting_text: overexpression of LAP(EGFP-TEV-S-Peptide)-Tctex1d2 led to the localization of LAP-Tctex1d2 to the ciliary axoneme (Fig. 3I), similar to what had been observed with Wdr60 overexpression.4 - term: id: GO:0007018 label: microtubule-based movement evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - FB:FBgn0024432 - MGI:MGI:98642 - PANTHER:PTN000478852 - PomBase:SPAC1805.08 - UniProtKB:Q8WW35 review: action: MODIFY summary: Correct family-level IBA, but for DYNLT2B the supported specific process is intraciliary retrograde transport, a descendant of microtubule-based movement that the gene already carries by IMP. reason: The PAINT node covers Tctex light chains of both dynein-1 and dynein-2, so microtubule-based movement is the right generality for the node. For this dynein-2-specific subunit the experimentally supported process is retrograde IFT (human KO fibroblasts and Chlamydomonas Tctex2b mutants), and GO:0035721 is_a descendant of microtubule-based movement. supported_by: - reference_id: PMID:26044572 supporting_text: Affinity proteomics indicates that TCTEX1D2/Tctex2b is an integral component of IFT dynein. We demonstrate a retrograde IFT defect in TCTEX1D2-deficient human fibroblasts and Tctex2b-deficient Chlamydomonas cells, and find that IFT dynein is partially destabilized by loss of Tctex2b in Chlamydomonas. proposed_replacement_terms: - id: GO:0035721 label: intraciliary retrograde transport propagation_review: root_cause: NO_FAILURE_NON_CORE failure_modes: [] source_entities: - source_id: PANTHER:PTN000478852 comment: Tctex light-chain family node spanning dynein-1 (DYNLT1/DYNLT3, fly Tctex-1, fission yeast) and dynein-2 (DYNLT2B) members; microtubule-based movement is the right generality for the node, and the target is inside the clade. The term is correct for DYNLT2B but the specific process it contributes to is intraciliary retrograde transport. source_status: SUPPORTS_TRANSFER - source_id: UniProtKB:Q8WW35 comment: Target's own retrograde-IFT loss-of-function evidence is among the descendant evidences; not circular. source_status: SUPPORTS_TRANSFER - term: id: GO:0030286 label: dynein complex evidence_type: NAS original_reference_id: PMID:30065109 qualifier: part_of review: action: MODIFY summary: Correct but general; DYNLT2B belongs to cytoplasmic dynein-2, captured by the more specific cytoplasmic dynein complex term the gene already carries by IDA. reason: The established complex is cytoplasmic dynein-2 (IFT dynein). GO:0005868 cytoplasmic dynein complex is the specific descendant supported by affinity proteomics and is already annotated to the gene. supported_by: - reference_id: PMID:25205765 supporting_text: Here, we now also identify the TCTEX1D2 light chain (Tctex-2) as a light chain for dynein-2, not present in dynein-1. proposed_replacement_terms: - id: GO:0005868 label: cytoplasmic dynein complex - term: id: GO:0030286 label: dynein complex evidence_type: NAS original_reference_id: PMID:32229580 qualifier: part_of review: action: MODIFY summary: Correct but general; DYNLT2B belongs to cytoplasmic dynein-2, captured by the more specific cytoplasmic dynein complex term the gene already carries by IDA. reason: The established complex is cytoplasmic dynein-2 (IFT dynein). GO:0005868 cytoplasmic dynein complex is the specific descendant supported by affinity proteomics and is already annotated to the gene. supported_by: - reference_id: PMID:25205765 supporting_text: Here, we now also identify the TCTEX1D2 light chain (Tctex-2) as a light chain for dynein-2, not present in dynein-1. proposed_replacement_terms: - id: GO:0005868 label: cytoplasmic dynein complex - term: id: GO:0031021 label: interphase microtubule organizing center evidence_type: IDA original_reference_id: PMID:25830415 qualifier: colocalizes_with review: action: KEEP_AS_NON_CORE summary: The interphase microtubule-organizing-center localization is directly observed, but its role is less specific than ciliary-base recruitment. reason: The interphase microtubule-organizing-center localization is directly observed, but its role is less specific than ciliary-base recruitment. supported_by: - reference_id: PMID:25830415 supporting_text: Tctex1d2 associates with Wdr34, Wdr60, and other subunits of Dync1 and Dync2 and colocalizes with Wdr60 to microtubule organizing centers during interphase, the mitotic spindle poles during cell division, and the base of the cilium in ciliated cells. - term: id: GO:0035721 label: intraciliary retrograde transport evidence_type: IMP original_reference_id: PMID:29742051 qualifier: involved_in review: action: ACCEPT summary: TCTEX1D2-KO human cells show defects in retrograde ciliary protein trafficking; DYNLT2B is a structural subunit of the motor that executes this process. reason: Direct loss-of-function evidence in human cells, corroborated by patient fibroblasts and the Chlamydomonas ortholog. DYNLT2B contributes structure to the dynein-2 tail (WDR60 arm) rather than ATPase activity, which qualifies as participation in the process. supported_by: - reference_id: PMID:29742051 supporting_text: 'We established cell lines lacking WDR60 or TCTEX1D2, both of which are dynein-2-specific subunits encoded by ciliopathy-causing genes, and found that both WDR60-knockout (KO) and TCTEX1D2-KO cells show defects in retrograde ciliary protein trafficking, with WDR60-KO cells demonstrating more severe defects probably due to failed assembly of the dynein-2 complex.' - reference_id: PMID:26044572 supporting_text: Affinity proteomics indicates that TCTEX1D2/Tctex2b is an integral component of IFT dynein. We demonstrate a retrograde IFT defect in TCTEX1D2-deficient human fibroblasts and Tctex2b-deficient Chlamydomonas cells, and find that IFT dynein is partially destabilized by loss of Tctex2b in Chlamydomonas. - term: id: GO:0035721 label: intraciliary retrograde transport evidence_type: NAS original_reference_id: PMID:31451806 qualifier: involved_in review: action: ACCEPT summary: DYNLT2B is an integral subunit of the retrograde IFT dynein; consistent with direct loss-of-function evidence. reason: ComplexPortal NAS for the dynein-2 complex. Supported independently by human TCTEX1D2-deficient fibroblasts and KO cells showing retrograde IFT defects and by Chlamydomonas Tctex2b mutants showing destabilized IFT dynein. supported_by: - reference_id: PMID:26044572 supporting_text: Affinity proteomics indicates that TCTEX1D2/Tctex2b is an integral component of IFT dynein. We demonstrate a retrograde IFT defect in TCTEX1D2-deficient human fibroblasts and Tctex2b-deficient Chlamydomonas cells, and find that IFT dynein is partially destabilized by loss of Tctex2b in Chlamydomonas. - reference_id: PMID:29742051 supporting_text: 'We established cell lines lacking WDR60 or TCTEX1D2, both of which are dynein-2-specific subunits encoded by ciliopathy-causing genes, and found that both WDR60-knockout (KO) and TCTEX1D2-KO cells show defects in retrograde ciliary protein trafficking, with WDR60-KO cells demonstrating more severe defects probably due to failed assembly of the dynein-2 complex.' - term: id: GO:0035721 label: intraciliary retrograde transport evidence_type: NAS original_reference_id: PMID:32229580 qualifier: involved_in review: action: ACCEPT summary: DYNLT2B is an integral subunit of the retrograde IFT dynein; consistent with direct loss-of-function evidence. reason: ComplexPortal NAS for the dynein-2 complex. Supported independently by human TCTEX1D2-deficient fibroblasts and KO cells showing retrograde IFT defects and by Chlamydomonas Tctex2b mutants showing destabilized IFT dynein. supported_by: - reference_id: PMID:26044572 supporting_text: Affinity proteomics indicates that TCTEX1D2/Tctex2b is an integral component of IFT dynein. We demonstrate a retrograde IFT defect in TCTEX1D2-deficient human fibroblasts and Tctex2b-deficient Chlamydomonas cells, and find that IFT dynein is partially destabilized by loss of Tctex2b in Chlamydomonas. - reference_id: PMID:29742051 supporting_text: 'We established cell lines lacking WDR60 or TCTEX1D2, both of which are dynein-2-specific subunits encoded by ciliopathy-causing genes, and found that both WDR60-knockout (KO) and TCTEX1D2-KO cells show defects in retrograde ciliary protein trafficking, with WDR60-KO cells demonstrating more severe defects probably due to failed assembly of the dynein-2 complex.' - term: id: GO:0045505 label: dynein intermediate chain binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - FB:FBgn0024432 - PANTHER:PTN000478852 - UniProtKB:Q8WW35 review: action: ACCEPT summary: The TCTEX1D2–DYNLT1/DYNLT3 dimer interacts with the dynein-2 intermediate chain WDR60. This is a specific functional interaction. reason: The TCTEX1D2–DYNLT1/DYNLT3 dimer interacts with the dynein-2 intermediate chain WDR60. This is a specific functional interaction. supported_by: - reference_id: PMID:29742051 supporting_text: 'Utilizing the visible immunoprecipitation assay, we demonstrated the interaction modes among the dynein-2 subunits, including previously undefined interactions, such as that between WDR60 and the TCTEX1D2-DYNLT1/DYNLT3 dimer. The dynein-2 complex can be divided into three subcomplexes, namely DYNC2H1-DYNC2LI1, WDR34-DYNLL1/DYNLL2-DYNLRB1/DYNLRB2, and WDR60-TCTEX1D2-DYNLT1/DYNLT3.' - term: id: GO:0045505 label: dynein intermediate chain binding evidence_type: IPI original_reference_id: PMID:25830415 qualifier: enables supporting_entities: - UniProtKB:Q8WVS4 review: action: ACCEPT summary: The TCTEX1D2–DYNLT1/DYNLT3 dimer interacts with the dynein-2 intermediate chain WDR60. This is a specific functional interaction. reason: The TCTEX1D2–DYNLT1/DYNLT3 dimer interacts with the dynein-2 intermediate chain WDR60. This is a specific functional interaction. supported_by: - reference_id: PMID:29742051 supporting_text: 'Utilizing the visible immunoprecipitation assay, we demonstrated the interaction modes among the dynein-2 subunits, including previously undefined interactions, such as that between WDR60 and the TCTEX1D2-DYNLT1/DYNLT3 dimer. The dynein-2 complex can be divided into three subcomplexes, namely DYNC2H1-DYNC2LI1, WDR34-DYNLL1/DYNLL2-DYNLRB1/DYNLRB2, and WDR60-TCTEX1D2-DYNLT1/DYNLT3.' - term: id: GO:0045505 label: dynein intermediate chain binding evidence_type: IPI original_reference_id: PMID:25830415 qualifier: enables supporting_entities: - UniProtKB:Q96EX3 review: action: ACCEPT summary: The TCTEX1D2–DYNLT1/DYNLT3 dimer interacts with the dynein-2 intermediate chain WDR60. This is a specific functional interaction. reason: The TCTEX1D2–DYNLT1/DYNLT3 dimer interacts with the dynein-2 intermediate chain WDR60. This is a specific functional interaction. supported_by: - reference_id: PMID:29742051 supporting_text: 'Utilizing the visible immunoprecipitation assay, we demonstrated the interaction modes among the dynein-2 subunits, including previously undefined interactions, such as that between WDR60 and the TCTEX1D2-DYNLT1/DYNLT3 dimer. The dynein-2 complex can be divided into three subcomplexes, namely DYNC2H1-DYNC2LI1, WDR34-DYNLL1/DYNLL2-DYNLRB1/DYNLRB2, and WDR60-TCTEX1D2-DYNLT1/DYNLT3.' - term: id: GO:0060271 label: cilium assembly evidence_type: IMP original_reference_id: PMID:25830415 qualifier: involved_in review: action: KEEP_AS_NON_CORE summary: Depletion impairs ciliogenesis in human cells; consistent with dynein-2/IFT being required for cilium assembly, but this is a downstream consequence of the core retrograde-IFT role. reason: Intraciliary transport is part of cilium assembly in GO and the IMP is curator-made from full text (siRNA depletion reduced ciliogenesis in that study). Other studies found milder effects (TCTEX1D2-depleted cells still form cilia but they are longer, PMID:25205765; mild trafficking defects in KO cells, PMID:29742051), so this is a context-dependent downstream outcome of the core retrograde-IFT role and is kept as non-core. supported_by: - reference_id: PMID:25830415 supporting_text: 'Tctex1d2 and Wdr60 localize to the base of the cilium and their depletion causes defects in ciliogenesis.' - term: id: GO:0097546 label: ciliary base evidence_type: IDA original_reference_id: PMID:25830415 qualifier: colocalizes_with review: action: ACCEPT summary: Human microscopy places endogenous TCTEX1D2 at the ciliary base, consistent with dynein-2 recruitment. reason: Human microscopy places endogenous TCTEX1D2 at the ciliary base, consistent with dynein-2 recruitment. supported_by: - reference_id: PMID:25830415 supporting_text: Tctex1d2 associates with Wdr34, Wdr60, and other subunits of Dync1 and Dync2 and colocalizes with Wdr60 to microtubule organizing centers during interphase, the mitotic spindle poles during cell division, and the base of the cilium in ciliated cells. - term: id: GO:0120293 label: dynein axonemal particle evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0542 review: action: UNDECIDED summary: SubCell mapping from a curator-inferred UniProt location (ECO:0000305). No study tested DYNLT2B residence in dynein axonemal particles; mouse and Chlamydomonas data suggest an inner-arm axonemal role that makes it plausible but unshown. reason: Dynein axonemal particles are cytoplasmic preassembly foci for axonemal dyneins. The mouse study reports TCTEX1D2 as a sperm axoneme component interacting with inner-dynein-arm intermediate chains WDR63 and WDR78, and Chlamydomonas Tctex2b is an inner-arm light chain, so passage through DAPs is plausible for this axonemal pool. No experiment localizes the protein to DAPs, so the call is left open. supported_by: - reference_id: PMID:39827215 supporting_text: TCTEX1D2 is an axoneme component and interacts with subunits of inner dynein arm - term: id: GO:1902017 label: regulation of cilium assembly evidence_type: IMP original_reference_id: PMID:25205765 qualifier: involved_in review: action: KEEP_AS_NON_CORE summary: TCTEX1D2 depletion lengthens cilia without blocking their formation; a downstream consequence of impaired retrograde IFT, retained as non-core. reason: In the cited study TCTEX1D2 depletion did not prevent ciliogenesis but significantly increased cilia length, a phenotype typical of impaired retrograde IFT. The curator-made IMP is not contradicted and fits a ciliary-length (assembly control) effect, but it is a downstream consequence of the gene's role as a dynein-2 subunit rather than a dedicated regulatory activity, so it is non-core. supported_by: - reference_id: PMID:25205765 supporting_text: In all cases, we can detect a statistically significant increase in cilia length following TCTEX1D2 depletion. - reference_id: PMID:25205765 supporting_text: Of note, TCTEX1D2-depleted cells still form cilia. - term: id: GO:1905799 label: regulation of intraciliary retrograde transport evidence_type: IMP original_reference_id: PMID:26044572 qualifier: involved_in review: action: MODIFY summary: DYNLT2B is a subunit of the IFT dynein that performs retrograde IFT; its loss impairs the process itself, so participation (intraciliary retrograde transport) is the appropriate term rather than regulation. reason: Loss of TCTEX1D2/Tctex2b impairs retrograde IFT and partially destabilizes the IFT dynein motor. That is evidence that the protein is part of the machinery executing the process, not that it modulates the rate of a process carried out by others. Lateral correction to GO:0035721, which the gene already carries by IMP. supported_by: - reference_id: PMID:26044572 supporting_text: Affinity proteomics indicates that TCTEX1D2/Tctex2b is an integral component of IFT dynein. We demonstrate a retrograde IFT defect in TCTEX1D2-deficient human fibroblasts and Tctex2b-deficient Chlamydomonas cells, and find that IFT dynein is partially destabilized by loss of Tctex2b in Chlamydomonas. proposed_replacement_terms: - id: GO:0035721 label: intraciliary retrograde transport references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: PMID:20195357 title: A comprehensive resource of interacting protein regions for refining human transcription factor networks. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interaction screen; source of a GO:0005515 IPI row. DYNLT1 partner rows are refined to dynein light chain binding; other partners removed as uninformative. - id: PMID:25205765 title: Subunit composition of the human cytoplasmic dynein-2 complex. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: 'Primary: dynein-2 subunit composition; TCTEX1D2 as dynein-2-specific light chain.' - id: PMID:25830415 title: Tctex1d2 associates with short-rib polydactyly syndrome proteins and is required for ciliogenesis. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: 'Primary: localization (MTOC, spindle pole, ciliary base; tagged protein in axoneme) and ciliogenesis knockdown phenotype.' - id: PMID:25910212 title: Widespread macromolecular interaction perturbations in human genetic disorders. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interaction screen; source of a GO:0005515 IPI row. DYNLT1 partner rows are refined to dynein light chain binding; other partners removed as uninformative. - id: PMID:26044572 title: TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: 'Primary: affinity proteomics placing TCTEX1D2 in IFT dynein; retrograde IFT defect in patient fibroblasts and Chlamydomonas Tctex2b mutants; SRTD17/JATD variants.' - id: PMID:27173435 title: An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interaction screen; source of a GO:0005515 IPI row. DYNLT1 partner rows are refined to dynein light chain binding; other partners removed as uninformative. - id: PMID:29742051 title: Interaction of WDR60 intermediate chain with TCTEX1D2 light chain of the dynein-2 complex is crucial for ciliary protein trafficking. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: 'Primary: TCTEX1D2-KO human cells; WDR60-TCTEX1D2-DYNLT1/DYNLT3 subcomplex mapping.' - id: PMID:30065109 title: Emerging mechanisms of dynein transport in the cytoplasm versus the cilium. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Dynein-2 review/structure paper cited by ComplexPortal NAS rows; complex-level evidence, primary support quoted from PMID:26044572 and PMID:29742051. - id: PMID:31451806 title: Structure of the dynein-2 complex and its assembly with intraflagellar transport trains. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Dynein-2 review/structure paper cited by ComplexPortal NAS rows; complex-level evidence, primary support quoted from PMID:26044572 and PMID:29742051. - id: PMID:32229580 title: Cytoplasmic dynein-2 at a glance. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Dynein-2 review/structure paper cited by ComplexPortal NAS rows; complex-level evidence, primary support quoted from PMID:26044572 and PMID:29742051. - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interaction screen; source of a GO:0005515 IPI row. DYNLT1 partner rows are refined to dynein light chain binding; other partners removed as uninformative. - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interaction screen; source of a GO:0005515 IPI row. DYNLT1 partner rows are refined to dynein light chain binding; other partners removed as uninformative. - id: PMID:36973253 title: Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity. findings: [] reference_review: relevance: NONE correctness: MISCITED review_notes: 'Full text cached and searched: DYNLRB1/DYNLRB2 dynein complexes in mitotic and male meiotic spindles; DYNLT2B/TCTEX1D2 is not mentioned. Cited only as the source of a ComplexPortal NAS male germ cell nucleus row, which is marked as over-annotated.' - id: PMID:39827215 title: TCTEX1D2 is essential for sperm flagellum formation in mice. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: 'Mouse ortholog (Q9CQ66, same PANTHER subfamily SF7): sperm flagellum formation, axoneme component, co-IP with inner-arm intermediate chains WDR63/WDR78. Not transferred as a human annotation.' - id: PMID:38454149 title: Structure and tethering mechanism of dynein-2 intermediate chains in intraflagellar transport. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: 'Structural: crystal structure of the DYNLT1-DYNLT2B heterodimer; dynein-2 intermediate-chain tethering.' core_functions: - description: 'Structural light-chain subunit of cytoplasmic dynein-2: as a heterodimer with DYNLT1/DYNLT3 it binds the WDR60 intermediate chain in the dynein-2 tail and is required for stable motor function in retrograde intraflagellar transport.' molecular_function: id: GO:0045505 label: dynein intermediate chain binding in_complex: id: GO:0005868 label: cytoplasmic dynein complex directly_involved_in: - id: GO:0035721 label: intraciliary retrograde transport locations: - id: GO:0097546 label: ciliary base - id: GO:0005929 label: cilium supported_by: - reference_id: PMID:29742051 supporting_text: 'Utilizing the visible immunoprecipitation assay, we demonstrated the interaction modes among the dynein-2 subunits, including previously undefined interactions, such as that between WDR60 and the TCTEX1D2-DYNLT1/DYNLT3 dimer. The dynein-2 complex can be divided into three subcomplexes, namely DYNC2H1-DYNC2LI1, WDR34-DYNLL1/DYNLL2-DYNLRB1/DYNLRB2, and WDR60-TCTEX1D2-DYNLT1/DYNLT3.' - reference_id: PMID:29742051 supporting_text: 'We established cell lines lacking WDR60 or TCTEX1D2, both of which are dynein-2-specific subunits encoded by ciliopathy-causing genes, and found that both WDR60-knockout (KO) and TCTEX1D2-KO cells show defects in retrograde ciliary protein trafficking, with WDR60-KO cells demonstrating more severe defects probably due to failed assembly of the dynein-2 complex.' - reference_id: PMID:26044572 supporting_text: Affinity proteomics indicates that TCTEX1D2/Tctex2b is an integral component of IFT dynein. We demonstrate a retrograde IFT defect in TCTEX1D2-deficient human fibroblasts and Tctex2b-deficient Chlamydomonas cells, and find that IFT dynein is partially destabilized by loss of Tctex2b in Chlamydomonas. - description: Heterodimerization with the Tctex light chain DYNLT1 (dynein light chain binding), forming the light-chain pair that docks onto the dynein-2 intermediate chains. molecular_function: id: GO:0045503 label: dynein light chain binding in_complex: id: GO:0005868 label: cytoplasmic dynein complex supported_by: - reference_id: PMID:38454149 supporting_text: X-ray crystallography structure of DYNLT1-DYNLT2B heterodimer. suggested_questions: - question: Does human DYNLT2B, like the mouse ortholog in sperm, also act as an inner-dynein-arm light chain in motile cilia or flagella, and does it pass through dynein axonemal particles during preassembly? - question: Does the DYNLT2B N-terminal extension bind any specific ciliary cargo, or is the subunit purely structural within dynein-2? suggested_experiments: - description: Endogenous tagging of DYNLT2B in human multiciliated airway cells or spermatids with co-staining for DNAAF markers of dynein axonemal particles and for inner-arm dynein subunits, combined with immunoprecipitation of DNAH/WDR63/WDR78 complexes.