TTC21B

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003682 chromatin binding	IEA GO_REF:0000107	REMOVE	Summary: Chromatin binding, transferred electronically from mouse via Ensembl Compara. Reason: TTC21B is a ciliary IFT-A subunit with no known DNA- or chromatin-binding domain or nuclear role; reported effects of ciliopathy proteins on gene expression are indirect. There is no biological basis for a chromatin binding molecular function. Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G [protein-coupled receptors]
GO:0005515 protein binding	IPI PMID:29220510 Ciliopathy-associated mutations of IFT122 impair ciliary pro...	REMOVE	Summary: Interaction of TTC21B with an IFT122 isoform. Reason: Generic protein binding derived from an interaction with another IFT-A subunit or partner. The interaction itself is real and well documented, but 'protein binding' conveys no functional information; the informative content (stable membership of the IFT-A complex) is already captured by the part_of intraciliary transport particle A annotations. Removal does not mean the interaction is false. Supporting Evidence: PMID:27932497 IFT122 interacted robustly with the IFT43–IFT121 dimer (lane 5), through which it indirectly interacted with IFT139 (lane 8).
GO:0005929 cilium	NAS PMID:27806291 Role for the IFT-A Complex in Selective Transport to the Pri...	ACCEPT	Summary: cilium localization. Reason: TTC21B is a ciliary IFT-A subunit moving along the axoneme; HPA detects it in the primary cilium (Approved). Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G [protein-coupled receptors] PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia.
GO:0005929 cilium	TAS Reactome:R-HSA-5610725	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: TTC21B is a ciliary IFT-A subunit moving along the axoneme; HPA detects it in the primary cilium (Approved). Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G [protein-coupled receptors] PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia.
GO:0005929 cilium	TAS Reactome:R-HSA-5610726	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: TTC21B is a ciliary IFT-A subunit moving along the axoneme; HPA detects it in the primary cilium (Approved). Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G [protein-coupled receptors] PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia.
GO:0005929 cilium	TAS Reactome:R-HSA-5617829	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: TTC21B is a ciliary IFT-A subunit moving along the axoneme; HPA detects it in the primary cilium (Approved). Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G [protein-coupled receptors] PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia.
GO:0005929 cilium	TAS Reactome:R-HSA-5624949	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: TTC21B is a ciliary IFT-A subunit moving along the axoneme; HPA detects it in the primary cilium (Approved). Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G [protein-coupled receptors] PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia.
GO:0005929 cilium	TAS Reactome:R-HSA-5625416	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: TTC21B is a ciliary IFT-A subunit moving along the axoneme; HPA detects it in the primary cilium (Approved). Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G [protein-coupled receptors] PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia.
GO:0005929 cilium	TAS Reactome:R-HSA-5625424	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: TTC21B is a ciliary IFT-A subunit moving along the axoneme; HPA detects it in the primary cilium (Approved). Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G [protein-coupled receptors] PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia.
GO:0005929 cilium	TAS Reactome:R-HSA-5625426	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: TTC21B is a ciliary IFT-A subunit moving along the axoneme; HPA detects it in the primary cilium (Approved). Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G [protein-coupled receptors] PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia.
GO:0005930 axoneme	IEA GO_REF:0000044	ACCEPT	Summary: axoneme localization. Reason: TTC21B is a ciliary IFT-A subunit moving along the axoneme; HPA detects it in the primary cilium (Approved). Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Cytoplasm, cytoskeleton, cilium axoneme PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia.
GO:0006357 regulation of transcription by RNA polymerase II	IMP PMID:22302990 Direct role of Bardet-Biedl syndrome proteins in transcripti...	UNDECIDED	Summary: Regulation of transcription by RNA polymerase II (IMP, acts upstream of or within), from a study of BBS proteins and the polycomb protein RNF2. Reason: The cached record is abstract-only and centres on BBS7; how TTC21B was assayed cannot be checked. Even if TTC21B depletion altered RNF2 target expression, this would reflect an indirect consequence rather than a transcription-regulatory activity of an IFT-A subunit. Left undecided pending full-text review. Supporting Evidence: PMID:22302990 loss of BBS proteins leads to the aberrant expression of endogenous RNF2 targets in vivo
GO:0010468 regulation of gene expression	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Regulation of gene expression (ARBA). Reason: Machine-learned annotation with no direct basis; any effect of TTC21B on gene expression is indirect, downstream of ciliary Hedgehog-pathway trafficking. Supporting Evidence: file:human/TTC21B/TTC21B-uniprot.txt Negatively modulates the SHH signal transduction (By similarity).
GO:0030991 intraciliary transport particle A	IBA GO_REF:0000033	ACCEPT	Summary: TTC21B/IFT139 is a subunit of the IFT-A complex. Reason: IFT139 is the most distal subunit of the IFT-A peripheral subcomplex, shown biochemically and supported by phylogeny. Supporting Evidence: PMID:27932497 the IFT-A complex is divided into a core subcomplex, composed of IFT122/IFT140/IFT144, which is associated with TULP3, and a peripheral subcomplex, composed of IFT43/IFT121/IFT139, where IFT139 is most distally located PMID:27932497 IFT122 interacted robustly with the IFT43–IFT121 dimer (lane 5), through which it indirectly interacted with IFT139 (lane 8).
GO:0030991 intraciliary transport particle A	IDA PMID:20889716 TULP3 bridges the IFT-A complex and membrane phosphoinositid...	ACCEPT	Summary: TTC21B/IFT139 is a subunit of the IFT-A complex. Reason: IFT139 is the most distal subunit of the IFT-A peripheral subcomplex, shown biochemically and supported by phylogeny. Supporting Evidence: PMID:27932497 the IFT-A complex is divided into a core subcomplex, composed of IFT122/IFT140/IFT144, which is associated with TULP3, and a peripheral subcomplex, composed of IFT43/IFT121/IFT139, where IFT139 is most distally located PMID:27932497 IFT122 interacted robustly with the IFT43–IFT121 dimer (lane 5), through which it indirectly interacted with IFT139 (lane 8).
GO:0030991 intraciliary transport particle A	IDA PMID:27932497 Intraflagellar transport-A complex mediates ciliary entry an...	ACCEPT	Summary: TTC21B/IFT139 is a subunit of the IFT-A complex. Reason: IFT139 is the most distal subunit of the IFT-A peripheral subcomplex, shown biochemically and supported by phylogeny. Supporting Evidence: PMID:27932497 the IFT-A complex is divided into a core subcomplex, composed of IFT122/IFT140/IFT144, which is associated with TULP3, and a peripheral subcomplex, composed of IFT43/IFT121/IFT139, where IFT139 is most distally located PMID:27932497 IFT122 interacted robustly with the IFT43–IFT121 dimer (lane 5), through which it indirectly interacted with IFT139 (lane 8).
GO:0030991 intraciliary transport particle A	IEA GO_REF:0000120	ACCEPT	Summary: TTC21B/IFT139 is a subunit of the IFT-A complex. Reason: IFT139 is the most distal subunit of the IFT-A peripheral subcomplex, shown biochemically and supported by phylogeny. Supporting Evidence: PMID:27932497 the IFT-A complex is divided into a core subcomplex, composed of IFT122/IFT140/IFT144, which is associated with TULP3, and a peripheral subcomplex, composed of IFT43/IFT121/IFT139, where IFT139 is most distally located PMID:27932497 IFT122 interacted robustly with the IFT43–IFT121 dimer (lane 5), through which it indirectly interacted with IFT139 (lane 8).
GO:0030991 intraciliary transport particle A	IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis...	ACCEPT	Summary: TTC21B/IFT139 is a subunit of the IFT-A complex. Reason: IFT139 is the most distal subunit of the IFT-A peripheral subcomplex, shown biochemically and supported by phylogeny. Supporting Evidence: PMID:27932497 the IFT-A complex is divided into a core subcomplex, composed of IFT122/IFT140/IFT144, which is associated with TULP3, and a peripheral subcomplex, composed of IFT43/IFT121/IFT139, where IFT139 is most distally located PMID:27932497 IFT122 interacted robustly with the IFT43–IFT121 dimer (lane 5), through which it indirectly interacted with IFT139 (lane 8).
GO:0035721 intraciliary retrograde transport	IBA GO_REF:0000033	ACCEPT	Summary: Intraciliary retrograde transport. Reason: IFT139-KO cells accumulate IFT-A, IFT-B and GPCRs at bulged ciliary tips: IFT139 is essential for retrograde trafficking. Supporting Evidence: PMID:27932497 IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips PMID:27932497 IFT139 is dispensable for IFT-A assembly but essential for retrograde trafficking of IFT-A, IFT-B, and GPCRs
GO:0035721 intraciliary retrograde transport	NAS PMID:27806291 Role for the IFT-A Complex in Selective Transport to the Pri...	ACCEPT	Summary: Intraciliary retrograde transport. Reason: IFT139-KO cells accumulate IFT-A, IFT-B and GPCRs at bulged ciliary tips: IFT139 is essential for retrograde trafficking. Supporting Evidence: PMID:27932497 IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips PMID:27932497 IFT139 is dispensable for IFT-A assembly but essential for retrograde trafficking of IFT-A, IFT-B, and GPCRs
GO:0060271 cilium assembly	NAS PMID:27806291 Role for the IFT-A Complex in Selective Transport to the Pri...	KEEP AS NON CORE	Summary: Cilium assembly (NAS). Reason: IFT139 is dispensable for ciliogenesis per se in RPE1 cells (cilia form but have bulged tips), so its role in cilium assembly is limited to maintaining normal ciliary architecture via retrograde IFT. Supporting Evidence: PMID:29220510 knockout (KO) of the IFT122 gene in hTERT-RPE1 cells using the CRISPR/Cas9 system led to a severe ciliogenesis defect, whereas KO of other IFT-A genes had minor effects on ciliogenesis but impaired ciliary protein trafficking PMID:27932497 IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips
GO:0061512 protein localization to cilium	IBA GO_REF:0000033	ACCEPT	Summary: Protein localization to cilium. Reason: IFT-A mediates ciliary entry of GPCRs and IFT139 is required for their retrograde trafficking; IFT139 loss disturbs ciliary GPCR distribution. Supporting Evidence: PMID:27932497 the IFT-A complex mediates not only retrograde trafficking but also entry into cilia of GPCRs PMID:27932497 IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips
GO:0061512 protein localization to cilium	IEA GO_REF:0000117	ACCEPT	Summary: Protein localization to cilium. Reason: IFT-A mediates ciliary entry of GPCRs and IFT139 is required for their retrograde trafficking; IFT139 loss disturbs ciliary GPCR distribution. Supporting Evidence: PMID:27932497 the IFT-A complex mediates not only retrograde trafficking but also entry into cilia of GPCRs PMID:27932497 IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips
GO:0061512 protein localization to cilium	IMP PMID:20889716 TULP3 bridges the IFT-A complex and membrane phosphoinositid...	ACCEPT	Summary: Protein localization to cilium. Reason: IFT-A mediates ciliary entry of GPCRs and IFT139 is required for their retrograde trafficking; IFT139 loss disturbs ciliary GPCR distribution. Supporting Evidence: PMID:27932497 the IFT-A complex mediates not only retrograde trafficking but also entry into cilia of GPCRs PMID:27932497 IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips
GO:0097542 ciliary tip	TAS Reactome:R-HSA-5624952	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: IFT-A trains reach the ciliary tip; IFT139 loss traps IFT components at the tip. Supporting Evidence: PMID:27932497 IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips
GO:0097542 ciliary tip	TAS Reactome:R-HSA-5625416	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: IFT-A trains reach the ciliary tip; IFT139 loss traps IFT components at the tip. Supporting Evidence: PMID:27932497 IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips
GO:0097542 ciliary tip	TAS Reactome:R-HSA-5625421	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: IFT-A trains reach the ciliary tip; IFT139 loss traps IFT components at the tip. Supporting Evidence: PMID:27932497 IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips
GO:0097542 ciliary tip	TAS Reactome:R-HSA-5625426	ACCEPT	Summary: Reactome pathway-level traceable author statement placing the protein in the cilium as part of the intraflagellar transport / ciliary cargo trafficking reactions. Reason: IFT-A trains reach the ciliary tip; IFT139 loss traps IFT components at the tip. Supporting Evidence: PMID:27932497 IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips
GO:1905799 regulation of intraciliary retrograde transport	IMP PMID:27932497 Intraflagellar transport-A complex mediates ciliary entry an...	MODIFY	Summary: Regulation of intraciliary retrograde transport (IMP). Reason: IFT139-KO data show that IFT139 is an essential component of the retrograde IFT machinery rather than a regulator of it; intraciliary retrograde transport (GO:0035721) better describes its participation. Proposed replacements: intraciliary retrograde transport Supporting Evidence: PMID:27932497 IFT139 is dispensable for IFT-A assembly but essential for retrograde trafficking of IFT-A, IFT-B, and GPCRs

Gene Description

Existing Annotations Review

Core Functions

As the distal subunit of the IFT-A peripheral subcomplex, TTC21B is required for retrograde intraflagellar transport, returning IFT-A, IFT-B and ciliary GPCRs from the ciliary tip.

Through IFT-A-mediated trafficking, TTC21B contributes to correct ciliary localization of membrane proteins such as Smoothened and GPR161.

References

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Notes

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