IFT122 (intraflagellar transport protein 122 homolog) is a WD40-repeat and TPR-containing subunit of the six-protein intraflagellar transport complex A (IFT-A; IFT144/WDR19, IFT140, IFT122, IFT121/WDR35, IFT139/TTC21B and IFT43). Within IFT-A it belongs to the core subcomplex (IFT122-IFT140-IFT144) and bridges the core to the peripheral subcomplex through the IFT43-IFT121 dimer, making it a structural linchpin of the complex. IFT-A is carried on anterograde IFT trains to the ciliary tip and mediates retrograde transport driven by cytoplasmic dynein-2; with the tubby-family adaptor TULP3, which docks on the core subcomplex, it also imports ciliary membrane proteins such as GPCRs (e.g. GPR161) into the cilium. IFT122 localizes to the cilium, the ciliary base (basal body and transition zone) and photoreceptor connecting cilium. Unlike most other IFT-A subunits, loss of IFT122 abolishes ciliogenesis in human RPE1 cells. Through these ciliary roles IFT-A restrains Hedgehog signalling and is required for embryonic patterning. Biallelic IFT122 variants cause cranioectodermal dysplasia (Sensenbrenner syndrome, CED1) and related short-rib thoracic dysplasias.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001843 neural tube closure | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: neural tube closure (ISS from mouse). Reason: Developmental process inferred by sequence similarity from mouse Ift122 mutants, whose embryos show ciliary and Hedgehog-pathway patterning defects. These are downstream consequences of the core ciliary transport function rather than a distinct activity of IFT122; retained as non-core. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Involved in cilia formation during neuronal patterning (By similarity). PMID:20889716 TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo |
| GO:0005515 protein binding | IPI PMID:22190034 Global landscape of HIV-human protein complexes. | REMOVE | Summary: High-throughput AP-MS interaction with an HIV-1 protein. Reason: Generic protein binding from a high-throughput interaction screen. 'Protein binding' is uninformative and no more specific molecular function is supported by this screen alone. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | REMOVE | Summary: Interaction of IFT122 with other IFT-A subunits (IFT144/WDR19, IFT140, IFT43, WDR35). 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 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 |
| GO:0005515 protein binding | IPI PMID:27932497 Intraflagellar transport-A complex mediates ciliary entry an... | REMOVE | Summary: Interaction of IFT122 with other IFT-A subunits (IFT144/WDR19, IFT140, IFT43, WDR35). 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 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 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Interaction of IFT122 with other IFT-A subunits (IFT144/WDR19, IFT140, IFT43, WDR35). 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 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 |
| GO:0005515 protein binding | IPI PMID:29220510 Ciliopathy-associated mutations of IFT122 impair ciliary pro... | REMOVE | Summary: Interaction of IFT122 with other IFT-A subunits (IFT144/WDR19, IFT140, IFT43, WDR35). 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 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 |
| GO:0005515 protein binding | IPI PMID:30476139 C11ORF74 interacts with the IFT-A complex and participates i... | REMOVE | Summary: Interaction of IFT122 with IFTAP/C11ORF74. 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. IFTAP associates with IFT-A via IFT122 but its function is limited. Supporting Evidence: PMID:30476139 C11ORF74, interacts with the IFT-A complex via the IFT122 subunit |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction of IFT122 with other IFT-A subunits (IFT144/WDR19, IFT140, IFT43, WDR35). 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 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 |
| GO:0005929 cilium | IDA PMID:29220510 Ciliopathy-associated mutations of IFT122 impair ciliary pro... | ACCEPT | Summary: IFT122 localizes to the cilium. Reason: Ciliary localization is established experimentally and is intrinsic to IFT-A function. Supporting Evidence: PMID:29220510 The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: IFT122 localizes to the cilium. Reason: Ciliary localization is established experimentally and is intrinsic to IFT-A function. Electronic annotation consistent with experimental and phylogenetic evidence. Supporting Evidence: PMID:29220510 The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| GO:0005929 cilium | ISS GO_REF:0000024 | ACCEPT | Summary: IFT122 localizes to the cilium. Reason: Ciliary localization is established experimentally and is intrinsic to IFT-A function. Electronic annotation consistent with experimental and phylogenetic evidence. Supporting Evidence: PMID:29220510 The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| GO:0005929 cilium | NAS PMID:27806291 Role for the IFT-A Complex in Selective Transport to the Pri... | ACCEPT | Summary: IFT122 localizes to the cilium. Reason: Ciliary localization is established experimentally and is intrinsic to IFT-A function. Electronic annotation consistent with experimental and phylogenetic evidence. Supporting Evidence: PMID:29220510 The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| 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: IFT122 is a ciliary protein; consistent with experimental data. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| 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: IFT122 is a ciliary protein; consistent with experimental data. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| 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: IFT122 is a ciliary protein; consistent with experimental data. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| 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: IFT122 is a ciliary protein; consistent with experimental data. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| 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: IFT122 is a ciliary protein; consistent with experimental data. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| 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: IFT122 is a ciliary protein; consistent with experimental data. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| 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: IFT122 is a ciliary protein; consistent with experimental data. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| GO:0010172 embryonic body morphogenesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Embryonic body morphogenesis (ISS from mouse). Reason: Very broad organismal phenotype term reflecting pleiotropic embryonic defects of Ift122 mutant mice; it adds little beyond the more specific patterning annotations and does not describe an activity of IFT122. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Involved in cilia formation during neuronal patterning (By similarity). |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Membrane, from an NK-cell membrane proteome (HDA). Reason: IFT122 is a soluble peripheral complex subunit that associates with ciliary membrane cargo via TULP3; detection in a bulk membrane proteome is uninformative and likely reflects co-purification. |
| GO:0021513 spinal cord dorsal/ventral patterning | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: spinal cord dorsal/ventral patterning (ISS from mouse). Reason: Developmental process inferred by sequence similarity from mouse Ift122 mutants, whose embryos show ciliary and Hedgehog-pathway patterning defects. These are downstream consequences of the core ciliary transport function rather than a distinct activity of IFT122; retained as non-core. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Involved in cilia formation during neuronal patterning (By similarity). PMID:20889716 TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo |
| GO:0030991 intraciliary transport particle A | IBA GO_REF:0000033 | ACCEPT | Summary: IFT122 is a core subunit of the IFT-A complex. Reason: Membership of IFT-A is the defining feature of IFT122, shown biochemically (VIP assays, interactome studies), structurally (cryo-EM of human IFT-A) and phylogenetically (IBA). 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:36775821 Here we report cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3 at overall resolutions of 3.0-3.9 Γ
. PMID:29220510 As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. |
| GO:0030991 intraciliary transport particle A | IDA PMID:20889716 TULP3 bridges the IFT-A complex and membrane phosphoinositid... | ACCEPT | Summary: IFT122 is a core subunit of the IFT-A complex. Reason: Membership of IFT-A is the defining feature of IFT122, shown biochemically (VIP assays, interactome studies), structurally (cryo-EM of human IFT-A) and phylogenetically (IBA). 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:36775821 Here we report cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3 at overall resolutions of 3.0-3.9 Γ
. PMID:29220510 As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. |
| GO:0030991 intraciliary transport particle A | IDA PMID:27932497 Intraflagellar transport-A complex mediates ciliary entry an... | ACCEPT | Summary: IFT122 is a core subunit of the IFT-A complex. Reason: Membership of IFT-A is the defining feature of IFT122, shown biochemically (VIP assays, interactome studies), structurally (cryo-EM of human IFT-A) and phylogenetically (IBA). 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:36775821 Here we report cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3 at overall resolutions of 3.0-3.9 Γ
. PMID:29220510 As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. |
| GO:0030991 intraciliary transport particle A | IDA PMID:29220510 Ciliopathy-associated mutations of IFT122 impair ciliary pro... | ACCEPT | Summary: IFT122 is a core subunit of the IFT-A complex. Reason: Membership of IFT-A is the defining feature of IFT122, shown biochemically (VIP assays, interactome studies), structurally (cryo-EM of human IFT-A) and phylogenetically (IBA). 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:36775821 Here we report cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3 at overall resolutions of 3.0-3.9 Γ
. PMID:29220510 As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. |
| GO:0030991 intraciliary transport particle A | IDA PMID:30476139 C11ORF74 interacts with the IFT-A complex and participates i... | ACCEPT | Summary: IFT122 is a core subunit of the IFT-A complex. Reason: Membership of IFT-A is the defining feature of IFT122, shown biochemically (VIP assays, interactome studies), structurally (cryo-EM of human IFT-A) and phylogenetically (IBA). 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:36775821 Here we report cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3 at overall resolutions of 3.0-3.9 Γ
. PMID:29220510 As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. |
| GO:0030991 intraciliary transport particle A | IDA PMID:36775821 Human IFT-A complex structures provide molecular insights in... | ACCEPT | Summary: IFT122 is a core subunit of the IFT-A complex. Reason: Membership of IFT-A is the defining feature of IFT122, shown biochemically (VIP assays, interactome studies), structurally (cryo-EM of human IFT-A) and phylogenetically (IBA). 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:36775821 Here we report cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3 at overall resolutions of 3.0-3.9 Γ
. PMID:29220510 As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. |
| GO:0030991 intraciliary transport particle A | IEA GO_REF:0000117 | ACCEPT | Summary: IFT122 is a core subunit of the IFT-A complex. Reason: Membership of IFT-A is the defining feature of IFT122, shown biochemically (VIP assays, interactome studies), structurally (cryo-EM of human IFT-A) and phylogenetically (IBA). 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:36775821 Here we report cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3 at overall resolutions of 3.0-3.9 Γ
. PMID:29220510 As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. |
| GO:0030991 intraciliary transport particle A | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | ACCEPT | Summary: IFT122 is a core subunit of the IFT-A complex. Reason: Membership of IFT-A is the defining feature of IFT122, shown biochemically (VIP assays, interactome studies), structurally (cryo-EM of human IFT-A) and phylogenetically (IBA). 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:36775821 Here we report cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3 at overall resolutions of 3.0-3.9 Γ
. PMID:29220510 As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. |
| GO:0032391 photoreceptor connecting cilium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Photoreceptor connecting cilium (ISS from mouse). Reason: Localization in photoreceptor connecting cilia is reported for mouse IFT122; a cell-type specific instance of its ciliary localization. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Localizes to photoreceptor connecting cilia. |
| GO:0035050 embryonic heart tube development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: embryonic heart tube development (ISS from mouse). Reason: Developmental process inferred by sequence similarity from mouse Ift122 mutants, whose embryos show ciliary and Hedgehog-pathway patterning defects. These are downstream consequences of the core ciliary transport function rather than a distinct activity of IFT122; retained as non-core. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Involved in cilia formation during neuronal patterning (By similarity). PMID:20889716 TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo |
| GO:0035115 embryonic forelimb morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: embryonic forelimb morphogenesis (ISS from mouse). Reason: Developmental process inferred by sequence similarity from mouse Ift122 mutants, whose embryos show ciliary and Hedgehog-pathway patterning defects. These are downstream consequences of the core ciliary transport function rather than a distinct activity of IFT122; retained as non-core. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Involved in cilia formation during neuronal patterning (By similarity). PMID:20889716 TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo |
| GO:0035556 intracellular signal transduction | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Intracellular signal transduction (ISS from mouse). Reason: IFT122 is not a signal transducer; its effect on Hedgehog signalling is indirect, via ciliary trafficking of pathway components. The specific term negative regulation of smoothened signaling captures this better. Supporting Evidence: PMID:20889716 TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo |
| GO:0035720 intraciliary anterograde transport | IDA PMID:20889716 TULP3 bridges the IFT-A complex and membrane phosphoinositid... | ACCEPT | Summary: Intraciliary anterograde transport. Reason: IFT-A rides anterograde trains and, with TULP3, directs ciliary entry of membrane cargo (GPCRs); IFT-A loss (IFT144/IFT122 core) blocks ciliary entry of GPCRs. The 40472089 full text discusses TULP3-dependent GPR45 entry and cites IFT-A as the TULP3 partner; deferring to the curator, the term is biologically correct for IFT122. Supporting Evidence: PMID:20889716 IFT-A is linked to retrograde ciliary transport, but, surprisingly, we find that the IFT-A complex has a second role directing ciliary entry of TULP3. PMID:27932497 the IFT-A complex mediates not only retrograde trafficking but also entry into cilia of GPCRs PMID:36775821 Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. |
| GO:0035720 intraciliary anterograde transport | IDA PMID:40472089 GPR45 modulates GΞ±(s) at primary cilia of the paraventricula... | ACCEPT | Summary: Intraciliary anterograde transport. Reason: IFT-A rides anterograde trains and, with TULP3, directs ciliary entry of membrane cargo (GPCRs); IFT-A loss (IFT144/IFT122 core) blocks ciliary entry of GPCRs. The 40472089 full text discusses TULP3-dependent GPR45 entry and cites IFT-A as the TULP3 partner; deferring to the curator, the term is biologically correct for IFT122. Supporting Evidence: PMID:20889716 IFT-A is linked to retrograde ciliary transport, but, surprisingly, we find that the IFT-A complex has a second role directing ciliary entry of TULP3. PMID:27932497 the IFT-A complex mediates not only retrograde trafficking but also entry into cilia of GPCRs PMID:36775821 Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. |
| GO:0035720 intraciliary anterograde transport | IEA GO_REF:0000117 | ACCEPT | Summary: Intraciliary anterograde transport. Reason: IFT-A rides anterograde trains and, with TULP3, directs ciliary entry of membrane cargo (GPCRs); IFT-A loss (IFT144/IFT122 core) blocks ciliary entry of GPCRs. The 40472089 full text discusses TULP3-dependent GPR45 entry and cites IFT-A as the TULP3 partner; deferring to the curator, the term is biologically correct for IFT122. Supporting Evidence: PMID:20889716 IFT-A is linked to retrograde ciliary transport, but, surprisingly, we find that the IFT-A complex has a second role directing ciliary entry of TULP3. PMID:27932497 the IFT-A complex mediates not only retrograde trafficking but also entry into cilia of GPCRs PMID:36775821 Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. |
| GO:0035720 intraciliary anterograde transport | ISS GO_REF:0000024 | ACCEPT | Summary: Intraciliary anterograde transport. Reason: IFT-A rides anterograde trains and, with TULP3, directs ciliary entry of membrane cargo (GPCRs); IFT-A loss (IFT144/IFT122 core) blocks ciliary entry of GPCRs. The 40472089 full text discusses TULP3-dependent GPR45 entry and cites IFT-A as the TULP3 partner; deferring to the curator, the term is biologically correct for IFT122. Supporting Evidence: PMID:20889716 IFT-A is linked to retrograde ciliary transport, but, surprisingly, we find that the IFT-A complex has a second role directing ciliary entry of TULP3. PMID:27932497 the IFT-A complex mediates not only retrograde trafficking but also entry into cilia of GPCRs PMID:36775821 Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. |
| GO:0035721 intraciliary retrograde transport | IBA GO_REF:0000033 | ACCEPT | Summary: Intraciliary retrograde transport. Reason: IFT-A is the retrograde IFT complex; loss of IFT-A subunits causes accumulation of IFT and cargo at bulged ciliary tips. Supported by phylogeny (IBA) and experimental data. Supporting Evidence: PMID:27932497 Intraflagellar transport (IFT)-A and -B complexes mediate retrograde and anterograde ciliary protein trafficking, respectively. PMID:27932497 IFT139 is dispensable for IFT-A assembly but essential for retrograde trafficking of IFT-A, IFT-B, and GPCRs file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| GO:0035721 intraciliary retrograde transport | ISS GO_REF:0000024 | ACCEPT | Summary: Intraciliary retrograde transport. Reason: IFT-A is the retrograde IFT complex; loss of IFT-A subunits causes accumulation of IFT and cargo at bulged ciliary tips. Supported by phylogeny (IBA) and experimental data. Supporting Evidence: PMID:27932497 Intraflagellar transport (IFT)-A and -B complexes mediate retrograde and anterograde ciliary protein trafficking, respectively. PMID:27932497 IFT139 is dispensable for IFT-A assembly but essential for retrograde trafficking of IFT-A, IFT-B, and GPCRs file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| 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: IFT-A is the retrograde IFT complex; loss of IFT-A subunits causes accumulation of IFT and cargo at bulged ciliary tips. Supported by phylogeny (IBA) and experimental data. Supporting Evidence: PMID:27932497 Intraflagellar transport (IFT)-A and -B complexes mediate retrograde and anterograde ciliary protein trafficking, respectively. PMID:27932497 IFT139 is dispensable for IFT-A assembly but essential for retrograde trafficking of IFT-A, IFT-B, and GPCRs file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| GO:0035869 ciliary transition zone | IDA GO_REF:0000052 | ACCEPT | Summary: ciliary transition zone localization. Reason: IFT-A assembles with IFT trains at the ciliary base (basal body/transition fibres) before entry; IFT122 is detected at the basal body and, in the HPA cilium atlas, at the transition zone (Supported grade). Supporting Evidence: PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. |
| GO:0035869 ciliary transition zone | IEA GO_REF:0000117 | ACCEPT | Summary: ciliary transition zone localization. Reason: IFT-A assembles with IFT trains at the ciliary base (basal body/transition fibres) before entry; IFT122 is detected at the basal body and, in the HPA cilium atlas, at the transition zone (Supported grade). Supporting Evidence: PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. |
| GO:0036064 ciliary basal body | IDA PMID:29220510 Ciliopathy-associated mutations of IFT122 impair ciliary pro... | ACCEPT | Summary: ciliary basal body localization. Reason: IFT-A assembles with IFT trains at the ciliary base (basal body/transition fibres) before entry; IFT122 is detected at the basal body and, in the HPA cilium atlas, at the transition zone (Supported grade). Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Cytoplasm, cytoskeleton, cilium basal body PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. |
| GO:0036064 ciliary basal body | IEA GO_REF:0000117 | ACCEPT | Summary: ciliary basal body localization. Reason: IFT-A assembles with IFT trains at the ciliary base (basal body/transition fibres) before entry; IFT122 is detected at the basal body and, in the HPA cilium atlas, at the transition zone (Supported grade). Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Cytoplasm, cytoskeleton, cilium basal body PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. |
| GO:0042073 intraciliary transport | IMP PMID:29220510 Ciliopathy-associated mutations of IFT122 impair ciliary pro... | ACCEPT | Summary: Intraciliary transport (IMP). Reason: IFT122 knockout and disease mutants disrupt ciliary protein trafficking. Supporting Evidence: PMID:29220510 IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation 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 |
| GO:0045879 negative regulation of smoothened signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of smoothened signaling (ISS from mouse). Reason: IFT-A loss causes ligand-independent Hedgehog pathway activation in mouse embryos; IFT-A restrains Hh signalling by trafficking GPR161 and other components into cilia. A real but downstream, context-specific role. Supporting Evidence: PMID:20889716 TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo PMID:29220510 IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation |
| GO:0048593 camera-type eye morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: camera-type eye morphogenesis (ISS from mouse). Reason: Developmental process inferred by sequence similarity from mouse Ift122 mutants, whose embryos show ciliary and Hedgehog-pathway patterning defects. These are downstream consequences of the core ciliary transport function rather than a distinct activity of IFT122; retained as non-core. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Involved in cilia formation during neuronal patterning (By similarity). PMID:20889716 TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo |
| GO:0060173 limb development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: limb development (ISS from mouse). Reason: Developmental process inferred by sequence similarity from mouse Ift122 mutants, whose embryos show ciliary and Hedgehog-pathway patterning defects. These are downstream consequences of the core ciliary transport function rather than a distinct activity of IFT122; retained as non-core. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Involved in cilia formation during neuronal patterning (By similarity). PMID:20889716 TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo |
| GO:0060271 cilium assembly | IEA GO_REF:0000120 | ACCEPT | Summary: Cilium assembly. Reason: IFT122 KO in RPE1 cells causes a severe ciliogenesis defect, more severe than other IFT-A subunits, consistent with its pivotal structural role; IFT trains build the axoneme. 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:36775821 Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. |
| GO:0060271 cilium assembly | IMP PMID:29220510 Ciliopathy-associated mutations of IFT122 impair ciliary pro... | ACCEPT | Summary: Cilium assembly. Reason: IFT122 KO in RPE1 cells causes a severe ciliogenesis defect, more severe than other IFT-A subunits, consistent with its pivotal structural role; IFT trains build the axoneme. 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:36775821 Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Cilium assembly. Reason: IFT122 KO in RPE1 cells causes a severe ciliogenesis defect, more severe than other IFT-A subunits, consistent with its pivotal structural role; IFT trains build the axoneme. 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:36775821 Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. |
| GO:0060271 cilium assembly | NAS PMID:27806291 Role for the IFT-A Complex in Selective Transport to the Pri... | ACCEPT | Summary: Cilium assembly. Reason: IFT122 KO in RPE1 cells causes a severe ciliogenesis defect, more severe than other IFT-A subunits, consistent with its pivotal structural role; IFT trains build the axoneme. 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:36775821 Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. |
| GO:0060971 embryonic heart tube left/right pattern formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: embryonic heart tube left/right pattern formation (ISS from mouse). Reason: Developmental process inferred by sequence similarity from mouse Ift122 mutants, whose embryos show ciliary and Hedgehog-pathway patterning defects. These are downstream consequences of the core ciliary transport function rather than a distinct activity of IFT122; retained as non-core. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt Involved in cilia formation during neuronal patterning (By similarity). PMID:20889716 TULP3 and IFT-A proteins both negatively regulate Hedgehog signaling in the mouse embryo |
| GO:0061512 protein localization to cilium | IBA GO_REF:0000033 | ACCEPT | Summary: protein localization to cilium. Reason: IFT-A with TULP3 imports membrane proteins (GPCRs, Smoothened in IFT122 mutants) into the (non-motile) primary cilium. The 40472089 rows rest on TULP3-dependent ciliary entry of GPR45, with IFT-A as the TULP3 partner. Supporting Evidence: PMID:20889716 TULP3 and IFT-A, in turn, promote trafficking of a subset of G protein-coupled receptors (GPCRs), but not Smoothened, to cilia. PMID:29220510 IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation PMID:36775821 TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. |
| GO:0061512 protein localization to cilium | IEA GO_REF:0000117 | ACCEPT | Summary: protein localization to cilium. Reason: IFT-A with TULP3 imports membrane proteins (GPCRs, Smoothened in IFT122 mutants) into the (non-motile) primary cilium. The 40472089 rows rest on TULP3-dependent ciliary entry of GPR45, with IFT-A as the TULP3 partner. Supporting Evidence: PMID:20889716 TULP3 and IFT-A, in turn, promote trafficking of a subset of G protein-coupled receptors (GPCRs), but not Smoothened, to cilia. PMID:29220510 IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation PMID:36775821 TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. |
| 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 with TULP3 imports membrane proteins (GPCRs, Smoothened in IFT122 mutants) into the (non-motile) primary cilium. The 40472089 rows rest on TULP3-dependent ciliary entry of GPR45, with IFT-A as the TULP3 partner. Supporting Evidence: PMID:20889716 TULP3 and IFT-A, in turn, promote trafficking of a subset of G protein-coupled receptors (GPCRs), but not Smoothened, to cilia. PMID:29220510 IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation PMID:36775821 TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. |
| GO:0061512 protein localization to cilium | IMP PMID:29220510 Ciliopathy-associated mutations of IFT122 impair ciliary pro... | ACCEPT | Summary: protein localization to cilium. Reason: IFT-A with TULP3 imports membrane proteins (GPCRs, Smoothened in IFT122 mutants) into the (non-motile) primary cilium. The 40472089 rows rest on TULP3-dependent ciliary entry of GPR45, with IFT-A as the TULP3 partner. Supporting Evidence: PMID:20889716 TULP3 and IFT-A, in turn, promote trafficking of a subset of G protein-coupled receptors (GPCRs), but not Smoothened, to cilia. PMID:29220510 IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation PMID:36775821 TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. |
| GO:0072594 establishment of protein localization to organelle | ISS GO_REF:0000024 | ACCEPT | Summary: establishment of protein localization to organelle. Reason: IFT-A with TULP3 imports membrane proteins (GPCRs, Smoothened in IFT122 mutants) into the (non-motile) primary cilium. The 40472089 rows rest on TULP3-dependent ciliary entry of GPR45, with IFT-A as the TULP3 partner. Supporting Evidence: PMID:20889716 TULP3 and IFT-A, in turn, promote trafficking of a subset of G protein-coupled receptors (GPCRs), but not Smoothened, to cilia. PMID:29220510 IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation PMID:36775821 TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. |
| GO:0097499 protein localization to non-motile cilium | IDA PMID:20889716 TULP3 bridges the IFT-A complex and membrane phosphoinositid... | ACCEPT | Summary: protein localization to non-motile cilium. Reason: IFT-A with TULP3 imports membrane proteins (GPCRs, Smoothened in IFT122 mutants) into the (non-motile) primary cilium. The 40472089 rows rest on TULP3-dependent ciliary entry of GPR45, with IFT-A as the TULP3 partner. Supporting Evidence: PMID:20889716 TULP3 and IFT-A, in turn, promote trafficking of a subset of G protein-coupled receptors (GPCRs), but not Smoothened, to cilia. PMID:29220510 IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation PMID:36775821 TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. |
| GO:0097499 protein localization to non-motile cilium | IDA PMID:36775821 Human IFT-A complex structures provide molecular insights in... | ACCEPT | Summary: protein localization to non-motile cilium. Reason: IFT-A with TULP3 imports membrane proteins (GPCRs, Smoothened in IFT122 mutants) into the (non-motile) primary cilium. The 40472089 rows rest on TULP3-dependent ciliary entry of GPR45, with IFT-A as the TULP3 partner. Supporting Evidence: PMID:20889716 TULP3 and IFT-A, in turn, promote trafficking of a subset of G protein-coupled receptors (GPCRs), but not Smoothened, to cilia. PMID:29220510 IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation PMID:36775821 TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. |
| GO:0097499 protein localization to non-motile cilium | IDA PMID:40472089 GPR45 modulates GΞ±(s) at primary cilia of the paraventricula... | ACCEPT | Summary: protein localization to non-motile cilium. Reason: IFT-A with TULP3 imports membrane proteins (GPCRs, Smoothened in IFT122 mutants) into the (non-motile) primary cilium. The 40472089 rows rest on TULP3-dependent ciliary entry of GPR45, with IFT-A as the TULP3 partner. Supporting Evidence: PMID:20889716 TULP3 and IFT-A, in turn, promote trafficking of a subset of G protein-coupled receptors (GPCRs), but not Smoothened, to cilia. PMID:29220510 IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog signaling activation PMID:36775821 TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. |
| 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 trains carrying IFT-A reach the ciliary tip where they remodel before retrograde return; IFT-A accumulates at tips when retrograde transport fails. 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 trains carrying IFT-A reach the ciliary tip where they remodel before retrograde return; IFT-A accumulates at tips when retrograde transport fails. 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 trains carrying IFT-A reach the ciliary tip where they remodel before retrograde return; IFT-A accumulates at tips when retrograde transport fails. 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 trains carrying IFT-A reach the ciliary tip where they remodel before retrograde return; IFT-A accumulates at tips when retrograde transport fails. 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:0097730 non-motile cilium | IBA GO_REF:0000033 | ACCEPT | Summary: Non-motile cilium (IBA). Reason: IFT122 functions in primary (non-motile) cilia; phylogenetically supported. Supporting Evidence: file:human/IFT122/IFT122-uniprot.txt As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking |
| GO:0140597 protein carrier activity | IDA PMID:20889716 TULP3 bridges the IFT-A complex and membrane phosphoinositid... | ACCEPT | Summary: Contributes to protein carrier activity (IDA). Reason: IFT-A, together with the TULP3 adaptor that binds the IFT122-containing core, carries membrane proteins into cilia; the contributes_to qualifier correctly reflects a complex-level activity. Supporting Evidence: PMID:36775821 TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. PMID:20889716 IFT-A is linked to retrograde ciliary transport, but, surprisingly, we find that the IFT-A complex has a second role directing ciliary entry of TULP3. |
| GO:0140597 protein carrier activity | IDA PMID:36775821 Human IFT-A complex structures provide molecular insights in... | ACCEPT | Summary: Contributes to protein carrier activity (IDA). Reason: IFT-A, together with the TULP3 adaptor that binds the IFT122-containing core, carries membrane proteins into cilia; the contributes_to qualifier correctly reflects a complex-level activity. Supporting Evidence: PMID:36775821 TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. PMID:20889716 IFT-A is linked to retrograde ciliary transport, but, surprisingly, we find that the IFT-A complex has a second role directing ciliary entry of TULP3. |
| GO:1905515 non-motile cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Cilium assembly. Reason: IFT122 KO in RPE1 cells causes a severe ciliogenesis defect, more severe than other IFT-A subunits, consistent with its pivotal structural role; IFT trains build the axoneme. 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:36775821 Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. |
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Download this section (compressed HTML)Q: Why does IFT122 loss abolish ciliogenesis in RPE1 cells whereas loss of other IFT-A subunits (IFT144, IFT139) mainly impairs ciliary protein trafficking? Does IFT122 have an IFT-A-independent role, or does it stabilise IFT-B train assembly?
Suggested experts: Nakayama K, Mukhopadhyay S
Q: Should IFT-A subunits carry intraciliary anterograde transport, given that IFT-A rides anterograde trains and mediates membrane-protein entry but is dispensable for anterograde IFT-B movement?
Experiment: Reconstitute wild-type and CED-variant IFT-A for cryo-EM and test variant rescue of IFT122-KO RPE1 cells using live imaging of IFT train velocities and ciliary GPCR import.
Hypothesis: CED-associated IFT122 missense variants selectively disrupt core-peripheral IFT-A coupling without affecting train assembly.
Type: structural biology and live-cell imaging
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