DYNLT2B

Review rationale: The horse protein is a one-to-one orthologue of human DYNLT2B in the DYNLT2B-specific PANTHER subfamily PTHR21255:SF7, with 91% identity over the aligned Tctex domain. Endogenous human TCTEX1D2 colocalizes with WDR60 at the ciliary base, the site where IFT dynein is loaded onto trains; the human and mouse reviews accept this location as part of the core retrograde IFT context. Transfer within the subfamily is justified because the location follows from dynein-2 membership. The horse gene has no GOA annotation on any product, so the term is novel for it. Product-level assessment: ProtNLM2 was given A0A9L0SWY1, which keeps the Tctex domain signatures (Pfam PF03645, CDD cd21459) and the human Tctex strands at residues 4-11, 89-99, 104-113 and 119-126, but ends two residues after strand 119-126 and so lacks the C-terminal Tctex beta-strand (human residues 128-140), and it adds an approximately 117-residue disordered N-terminal extension. In the human DYNLT1-DYNLT2B heterodimer crystal structure (PDB 8RGI), most DYNLT2B residues within 4 angstroms of DYNLT1 lie in the retained strands 89-112, and only residues 137, 139 and 140 of the missing strand contact DYNLT1, but that strand belongs to the core beta-sheet of the fold. Whether this truncated product folds, heterodimerizes with DYNLT1 or DYNLT3 and binds WDR60, on which ciliary-base localization, which follows from incorporation into dynein-2 through WDR60 depends, is untested, so the prediction is UNC for this product although the term is correct and novel for the gene.

Review rationale: The horse protein is a one-to-one orthologue of human DYNLT2B in the DYNLT2B-specific PANTHER subfamily PTHR21255:SF7, with 91% identity over the aligned Tctex domain. Human TCTEX1D2 forms a WDR60-TCTEX1D2-DYNLT1/DYNLT3 subcomplex mapped by immunoprecipitation, and mouse endogenous tagged TCTEX1D2 co-precipitates dynein-2 intermediate chains; PAINT places the term at the Tctex family node ancestral to SF7. This is the core molecular function in the horse gene review and in the review of the canonical horse product A0A9L0S9P8. It is an orthology inference, not a horse experiment. The horse gene has no GOA annotation on any product, so the term is novel for it. Product-level assessment: ProtNLM2 was given A0A9L0SWY1, which keeps the Tctex domain signatures (Pfam PF03645, CDD cd21459) and the human Tctex strands at residues 4-11, 89-99, 104-113 and 119-126, but ends two residues after strand 119-126 and so lacks the C-terminal Tctex beta-strand (human residues 128-140), and it adds an approximately 117-residue disordered N-terminal extension. In the human DYNLT1-DYNLT2B heterodimer crystal structure (PDB 8RGI), most DYNLT2B residues within 4 angstroms of DYNLT1 lie in the retained strands 89-112, and only residues 137, 139 and 140 of the missing strand contact DYNLT1, but that strand belongs to the core beta-sheet of the fold. Whether this truncated product folds, heterodimerizes with DYNLT1 or DYNLT3 and binds WDR60, on which this binding activity depends, is untested, so the prediction is UNC for this product although the term is correct and novel for the gene.

Review rationale: The horse protein is a one-to-one orthologue of human DYNLT2B in the DYNLT2B-specific PANTHER subfamily PTHR21255:SF7, with 91% identity over the aligned Tctex domain. Human TCTEX1D2 colocalizes with WDR60 at mitotic spindle poles by immunofluorescence; the human and mouse reviews keep this as a supported but non-core location. The term is peripheral to the ciliary dynein-2 role, and rests on a single human imaging study. The horse gene has no GOA annotation on any product, so the term is novel for it. Product-level assessment: ProtNLM2 was given A0A9L0SWY1, which keeps the Tctex domain signatures (Pfam PF03645, CDD cd21459) and the human Tctex strands at residues 4-11, 89-99, 104-113 and 119-126, but ends two residues after strand 119-126 and so lacks the C-terminal Tctex beta-strand (human residues 128-140), and it adds an approximately 117-residue disordered N-terminal extension. In the human DYNLT1-DYNLT2B heterodimer crystal structure (PDB 8RGI), most DYNLT2B residues within 4 angstroms of DYNLT1 lie in the retained strands 89-112, and only residues 137, 139 and 140 of the missing strand contact DYNLT1, but that strand belongs to the core beta-sheet of the fold. Whether this truncated product folds, heterodimerizes with DYNLT1 or DYNLT3 and binds WDR60, on which spindle-pole localization, which in human cells accompanies WDR60 depends, is untested, so the prediction is UNC for this product although the term is correct and novel for the gene.

Review rationale: The horse protein is a one-to-one orthologue of human DYNLT2B in the DYNLT2B-specific PANTHER subfamily PTHR21255:SF7, with 91% identity over the aligned Tctex domain. Human TCTEX1D2-knockout cells and patient fibroblasts show retrograde ciliary trafficking defects, and Chlamydomonas Tctex2b loss destabilizes IFT dynein; the protein contributes structure to the dynein-2 tail, which is participation in the process. This is the core process in the human and mouse reviews, and the horse review's core function places the gene in retrograde IFT by orthology. The horse gene has no GOA annotation on any product, so the term is novel for it. Product-level assessment: ProtNLM2 was given A0A9L0SWY1, which keeps the Tctex domain signatures (Pfam PF03645, CDD cd21459) and the human Tctex strands at residues 4-11, 89-99, 104-113 and 119-126, but ends two residues after strand 119-126 and so lacks the C-terminal Tctex beta-strand (human residues 128-140), and it adds an approximately 117-residue disordered N-terminal extension. In the human DYNLT1-DYNLT2B heterodimer crystal structure (PDB 8RGI), most DYNLT2B residues within 4 angstroms of DYNLT1 lie in the retained strands 89-112, and only residues 137, 139 and 140 of the missing strand contact DYNLT1, but that strand belongs to the core beta-sheet of the fold. Whether this truncated product folds, heterodimerizes with DYNLT1 or DYNLT3 and binds WDR60, on which participation in retrograde IFT as a structural dynein-2 tail subunit depends, is untested, so the prediction is UNC for this product although the term is correct and novel for the gene.

CURATION MISTAKE

Review rationale: The evidence behind this term is loss-of-function: removing TCTEX1D2 impairs retrograde IFT and destabilizes the IFT dynein motor. That shows the protein is part of the machinery that executes retrograde IFT, not a modulator of a process carried out by others. The human and mouse reviews both correct the corresponding annotations laterally to GO:0035721 intraciliary retrograde transport on exactly these grounds, which also refutes the regulation term predicted here; the prediction reproduces the upstream regulation framing. The participation term GO:0035721 is predicted separately; it is true of the gene but is scored UNC for this alternative model.

Review rationale: The horse protein is a one-to-one orthologue of human DYNLT2B in the DYNLT2B-specific PANTHER subfamily PTHR21255:SF7, with 91% identity over the aligned Tctex domain. Human TCTEX1D2 depletion caused ciliogenesis defects in one study, and in mouse the knockout disrupts sperm flagellum assembly (a descendant of cilium assembly) while somatic motile cilia appear normal. Cilium assembly is broad but true for the gene; no more specific term is annotated to the horse gene, so LSP does not apply. The human review keeps it as non-core because the effect is downstream of retrograde IFT. The horse gene has no GOA annotation on any product, so the term is novel for it. Product-level assessment: ProtNLM2 was given A0A9L0SWY1, which keeps the Tctex domain signatures (Pfam PF03645, CDD cd21459) and the human Tctex strands at residues 4-11, 89-99, 104-113 and 119-126, but ends two residues after strand 119-126 and so lacks the C-terminal Tctex beta-strand (human residues 128-140), and it adds an approximately 117-residue disordered N-terminal extension. In the human DYNLT1-DYNLT2B heterodimer crystal structure (PDB 8RGI), most DYNLT2B residues within 4 angstroms of DYNLT1 lie in the retained strands 89-112, and only residues 137, 139 and 140 of the missing strand contact DYNLT1, but that strand belongs to the core beta-sheet of the fold. Whether this truncated product folds, heterodimerizes with DYNLT1 or DYNLT3 and binds WDR60, on which the cilium-assembly role, a downstream consequence of dynein-2 function depends, is untested, so the prediction is UNC for this product although the term is correct and novel for the gene.

Review rationale: The horse protein is a one-to-one orthologue of human DYNLT2B in the DYNLT2B-specific PANTHER subfamily PTHR21255:SF7, with 91% identity over the aligned Tctex domain. Human TCTEX1D2 colocalizes with WDR60 at interphase microtubule-organizing centers (centrosomes), dependent on WDR60 and microtubules; the human and mouse reviews keep centrosome as a supported non-core location consistent with dynein-2 recruitment near the basal body. The gene-level evidence is a single human imaging study. The horse gene has no GOA annotation on any product, so the term is novel for it. Product-level assessment: ProtNLM2 was given A0A9L0SWY1, which keeps the Tctex domain signatures (Pfam PF03645, CDD cd21459) and the human Tctex strands at residues 4-11, 89-99, 104-113 and 119-126, but ends two residues after strand 119-126 and so lacks the C-terminal Tctex beta-strand (human residues 128-140), and it adds an approximately 117-residue disordered N-terminal extension. In the human DYNLT1-DYNLT2B heterodimer crystal structure (PDB 8RGI), most DYNLT2B residues within 4 angstroms of DYNLT1 lie in the retained strands 89-112, and only residues 137, 139 and 140 of the missing strand contact DYNLT1, but that strand belongs to the core beta-sheet of the fold. Whether this truncated product folds, heterodimerizes with DYNLT1 or DYNLT3 and binds WDR60, on which centrosomal localization, which in human cells depends on WDR60 depends, is untested, so the prediction is UNC for this product although the term is correct and novel for the gene.

Review rationale: The horse protein is a one-to-one orthologue of human DYNLT2B in the DYNLT2B-specific PANTHER subfamily PTHR21255:SF7, with 91% identity over the aligned Tctex domain. Mouse sperm fractionation recovers endogenous tagged TCTEX1D2 in the axonemal fraction and the authors conclude it is an axoneme component; tagged human TCTEX1D2 also localizes to the ciliary axoneme when overexpressed. The mouse review accepts axoneme as a core location for the flagellar role. Transfer within SF7 is justified, though the strongest evidence is from sperm flagella. The horse gene has no GOA annotation on any product, so the term is novel for it. Product-level assessment: ProtNLM2 was given A0A9L0SWY1, which keeps the Tctex domain signatures (Pfam PF03645, CDD cd21459) and the human Tctex strands at residues 4-11, 89-99, 104-113 and 119-126, but ends two residues after strand 119-126 and so lacks the C-terminal Tctex beta-strand (human residues 128-140), and it adds an approximately 117-residue disordered N-terminal extension. In the human DYNLT1-DYNLT2B heterodimer crystal structure (PDB 8RGI), most DYNLT2B residues within 4 angstroms of DYNLT1 lie in the retained strands 89-112, and only residues 137, 139 and 140 of the missing strand contact DYNLT1, but that strand belongs to the core beta-sheet of the fold. Whether this truncated product folds, heterodimerizes with DYNLT1 or DYNLT3 and binds WDR60, on which axonemal localization as a dynein-2 component depends, is untested, so the prediction is UNC for this product although the term is correct and novel for the gene.

Review rationale: The horse protein is a one-to-one orthologue of human DYNLT2B in the DYNLT2B-specific PANTHER subfamily PTHR21255:SF7, with 91% identity over the aligned Tctex domain. Human TCTEX1D2 colocalizes with WDR60 at microtubule-organizing centers during interphase; the human and mouse reviews keep this as a supported non-core location. The gene-level evidence is a single human imaging study. The horse gene has no GOA annotation on any product, so the term is novel for it. Product-level assessment: ProtNLM2 was given A0A9L0SWY1, which keeps the Tctex domain signatures (Pfam PF03645, CDD cd21459) and the human Tctex strands at residues 4-11, 89-99, 104-113 and 119-126, but ends two residues after strand 119-126 and so lacks the C-terminal Tctex beta-strand (human residues 128-140), and it adds an approximately 117-residue disordered N-terminal extension. In the human DYNLT1-DYNLT2B heterodimer crystal structure (PDB 8RGI), most DYNLT2B residues within 4 angstroms of DYNLT1 lie in the retained strands 89-112, and only residues 137, 139 and 140 of the missing strand contact DYNLT1, but that strand belongs to the core beta-sheet of the fold. Whether this truncated product folds, heterodimerizes with DYNLT1 or DYNLT3 and binds WDR60, on which MTOC localization, which in human cells depends on WDR60 depends, is untested, so the prediction is UNC for this product although the term is correct and novel for the gene.

Review rationale: The horse protein is a one-to-one orthologue of human DYNLT2B in the DYNLT2B-specific PANTHER subfamily PTHR21255:SF7, with 91% identity over the aligned Tctex domain. TCTEX1D2 depletion in human cells increases cilia length, a typical retrograde IFT phenotype, which supports a role in controlling cilium assembly; the human and mouse reviews keep this term as non-core because it is a downstream consequence of the protein's dynein-2 subunit role rather than a dedicated regulatory activity. The term is of limited informativeness. The horse gene has no GOA annotation on any product, so the term is novel for it. Product-level assessment: ProtNLM2 was given A0A9L0SWY1, which keeps the Tctex domain signatures (Pfam PF03645, CDD cd21459) and the human Tctex strands at residues 4-11, 89-99, 104-113 and 119-126, but ends two residues after strand 119-126 and so lacks the C-terminal Tctex beta-strand (human residues 128-140), and it adds an approximately 117-residue disordered N-terminal extension. In the human DYNLT1-DYNLT2B heterodimer crystal structure (PDB 8RGI), most DYNLT2B residues within 4 angstroms of DYNLT1 lie in the retained strands 89-112, and only residues 137, 139 and 140 of the missing strand contact DYNLT1, but that strand belongs to the core beta-sheet of the fold. Whether this truncated product folds, heterodimerizes with DYNLT1 or DYNLT3 and binds WDR60, on which the cilium-length phenotype, a downstream consequence of dynein-2 function depends, is untested, so the prediction is UNC for this product although the term is correct and novel for the gene.