IFT81 is a coiled-coil core (IFT-B1) subunit of the intraflagellar transport B complex. It forms an obligate heterodimer with IFT74 through their C-terminal coiled coils, and the IFT81/IFT74 pair constitutes the main tubulin-binding module of IFT-B: the N-terminal calponin-homology (CH) domain of IFT81 binds the globular body of alpha/beta-tubulin while the basic N-terminus of IFT74 binds the beta-tubulin acidic tail, together giving micromolar affinity suited to loading tubulin onto anterograde trains. Tubulin binding by IFT81 is required for ciliogenesis in human cells. The C-terminal parts of IFT81/IFT74 also bind GTP-RABL2B, which captures IFT-B at the ciliary base. IFT81 localizes to the ciliary base, along the axoneme and at the ciliary tip, and is required for sperm flagellum assembly in mice. Biallelic IFT81 variants cause short-rib thoracic dysplasia (SRTD19).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:26980730 Overall Architecture of the Intraflagellar Transport (IFT)-B... | REMOVE | Summary: Protein binding (IPI) from PMID:26980730. The partner is another IFT-B subunit identified in the visible immunoprecipitation (VIP) mapping of IFT-B architecture; this is captured more informatively by the IFT-B complex (GO:0030992) annotation. Reason: Generic 'protein binding' conveys no functional information. Removal does not dispute the reported interaction; the informative content (membership of the IFT complex, or a specific interaction partner) is better represented by complex membership or a specific binding term. Supporting Evidence: PMID:26980730 Using the visible immunoprecipitation assay, which we recently developed as a convenient protein-protein interaction assay, we determined the overall architecture of the IFT-B complex, which can be divided into core and peripheral subcomplexes composed of 10 and 6 subunits, respectively. |
| GO:0005515 protein binding | IPI PMID:28428259 RABL2 interacts with the intraflagellar transport-B complex ... | REMOVE | Summary: Protein binding (IPI) from PMID:28428259. Reason: Generic 'protein binding' conveys no functional information. Removal does not dispute the reported interaction; the informative content (membership of the IFT complex, or a specific interaction partner) is better represented by complex membership or a specific binding term. |
| GO:0005515 protein binding | IPI PMID:28428259 RABL2 interacts with the intraflagellar transport-B complex ... | MODIFY | Summary: IPI with RABL2B (Q9UNT1). GTP-bound RABL2B binds the IFT-B complex through the IFT74-IFT81 heterodimer, an interaction thought to capture IFT-B at the ciliary base and gate its ciliary entry. Reason: Generic 'protein binding' is uninformative. The cited work shows that GTP-bound RABL2B, a small Ras-like GTPase, binds the C-terminal regions of IFT74 and IFT81 (distinct from their tubulin-binding N-termini); 'small GTPase binding' captures the informative content. This is a recruitment/regulatory interaction rather than the core cargo-binding activity. Proposed replacements: small GTPase binding Supporting Evidence: PMID:28428259 We also show that RABL2 interacts, in its GTP-bound state, with the intraflagellar transport (IFT)-B complex via the IFT74-IFT81 heterodimer and that the interaction is disrupted by a mutation found in male infertile mice (Mot mice) with a sperm flagella motility defect. |
| GO:0005515 protein binding | IPI PMID:28625565 The CEP19-RABL2 GTPase Complex Binds IFT-B to Initiate Intra... | REMOVE | Summary: Protein binding (IPI) from PMID:28625565. Reason: Generic 'protein binding' conveys no functional information. Removal does not dispute the reported interaction; the informative content (membership of the IFT complex, or a specific interaction partner) is better represented by complex membership or a specific binding term. |
| GO:0005515 protein binding | IPI PMID:28625565 The CEP19-RABL2 GTPase Complex Binds IFT-B to Initiate Intra... | MODIFY | Summary: IPI with RABL2B (Q9UNT1). GTP-bound RABL2B binds the IFT-B complex through the IFT74-IFT81 heterodimer, an interaction thought to capture IFT-B at the ciliary base and gate its ciliary entry. Reason: Generic 'protein binding' is uninformative. The cited work shows that GTP-bound RABL2B, a small Ras-like GTPase, binds the C-terminal regions of IFT74 and IFT81 (distinct from their tubulin-binding N-termini); 'small GTPase binding' captures the informative content. This is a recruitment/regulatory interaction rather than the core cargo-binding activity. Proposed replacements: small GTPase binding Supporting Evidence: PMID:28625565 GTP-bound RABL2 then binds to the IFT-B holocomplex via the IFT74/81 heterodimer to capture and trigger the entry of IFT-B into cilia, prior to classical motor-driven intraflagellar transport. PMID:28625565 The IFT-B complex in cells lacking IFT74 or IFT81, but not other components, failed to bind to RABL2B, suggesting that the IFT74/81 heterodimer is the interaction partner of RABL2B (Fig. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Located in cytoplasm (IEA, GO_REF:0000120). Reason: IFT complexes are assembled in the cytoplasm and a cytosolic pool of IFT81 exists before recruitment to the ciliary base; the location is correct but not where the core function is executed. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Located in cytoplasm (ISS, GO_REF:0000024). Reason: IFT complexes are assembled in the cytoplasm and a cytosolic pool of IFT81 exists before recruitment to the ciliary base; the location is correct but not where the core function is executed. |
| GO:0005813 centrosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Located in centrosome (IEA, GO_REF:0000107). Reason: The ciliary basal body is a modified mother centriole, so pericentriolar/centrosomal signal for IFT81 largely reflects its pool at the ciliary base; the more specific 'ciliary basal body' location is annotated separately. Retained as a correct but non-core location. |
| GO:0005814 centriole | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Located in centriole (IEA, GO_REF:0000107). Reason: The ciliary basal body is a modified mother centriole, so pericentriolar/centrosomal signal for IFT81 largely reflects its pool at the ciliary base; the more specific 'ciliary basal body' location is annotated separately. Retained as a correct but non-core location. |
| GO:0005815 microtubule organizing center | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Located in microtubule organizing center (IEA, GO_REF:0000117). Reason: The ciliary basal body is a modified mother centriole, so pericentriolar/centrosomal signal for IFT81 largely reflects its pool at the ciliary base; the more specific 'ciliary basal body' location is annotated separately. Retained as a correct but non-core location. |
| GO:0005929 cilium | IEA GO_REF:0000120 | ACCEPT | Summary: Located in cilium (IEA, GO_REF:0000120). IFT particles containing IFT81 move bidirectionally along the ciliary axoneme. Reason: IFT81 is an intrinsic component of the IFT machinery that operates inside cilia; cilium is a correct (if general) location. More specific locations (ciliary base/basal body, axoneme, ciliary tip) are also annotated. Supporting Evidence: PMID:24140113 Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. |
| GO:0005929 cilium | NAS PMID:26980730 Overall Architecture of the Intraflagellar Transport (IFT)-B... | ACCEPT | Summary: Located in cilium (NAS, PMID:26980730). IFT particles containing IFT81 move bidirectionally along the ciliary axoneme. Reason: IFT81 is an intrinsic component of the IFT machinery that operates inside cilia; cilium is a correct (if general) location. More specific locations (ciliary base/basal body, axoneme, ciliary tip) are also annotated. Supporting Evidence: PMID:24140113 Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. |
| GO:0005929 cilium | TAS Reactome:R-HSA-5624949 | ACCEPT | Summary: Located in cilium (TAS, Reactome:R-HSA-5624949). IFT particles containing IFT81 move bidirectionally along the ciliary axoneme. Reason: IFT81 is an intrinsic component of the IFT machinery that operates inside cilia; cilium is a correct (if general) location. More specific locations (ciliary base/basal body, axoneme, ciliary tip) are also annotated. Supporting Evidence: Reactome:R-HSA-5624949 Both the anterograde and retrograde trains are associated with the outer microtubule doublets and with the inner surface of the flagellar membrane |
| GO:0005929 cilium | TAS Reactome:R-HSA-5625416 | ACCEPT | Summary: Located in cilium (TAS, Reactome:R-HSA-5625416). IFT particles containing IFT81 move bidirectionally along the ciliary axoneme. Reason: IFT81 is an intrinsic component of the IFT machinery that operates inside cilia; cilium is a correct (if general) location. More specific locations (ciliary base/basal body, axoneme, ciliary tip) are also annotated. Supporting Evidence: Reactome:R-HSA-5625416 Anterograde trains travel along the axoneme of the cilium at an estimated rate of 2 micrometers per second in an ATP- and kinesin-2-dependent fashion |
| GO:0005929 cilium | TAS Reactome:R-HSA-5625424 | ACCEPT | Summary: Located in cilium (TAS, Reactome:R-HSA-5625424). IFT particles containing IFT81 move bidirectionally along the ciliary axoneme. Reason: IFT81 is an intrinsic component of the IFT machinery that operates inside cilia; cilium is a correct (if general) location. More specific locations (ciliary base/basal body, axoneme, ciliary tip) are also annotated. Supporting Evidence: Reactome:R-HSA-5625424 At the base of the cilium, retrograde trains are believed to disassemble and recycle for a subsequent round of IFT transport |
| GO:0005929 cilium | TAS Reactome:R-HSA-5625426 | ACCEPT | Summary: Located in cilium (TAS, Reactome:R-HSA-5625426). IFT particles containing IFT81 move bidirectionally along the ciliary axoneme. Reason: IFT81 is an intrinsic component of the IFT machinery that operates inside cilia; cilium is a correct (if general) location. More specific locations (ciliary base/basal body, axoneme, ciliary tip) are also annotated. Supporting Evidence: Reactome:R-HSA-5625426 Retrograde trains are shorter than anterograde particles and travel along the cilliary axoneme at an estimated rate of 3 micrometers per second |
| GO:0007018 microtubule-based movement | IEA GO_REF:0000117 | ACCEPT | Summary: Involved in microtubule-based movement (IEA). Reason: IFT81 is not a motor, but IFT trains are moved along axonemal microtubules by kinesin-2 and dynein-2; intraciliary transport is a form of microtubule-based transport. Broad but not incorrect for an ARBA electronic annotation; intraciliary transport is the informative term. Supporting Evidence: PMID:15955805 Anterograde movement of particles away from the cell body is mediated by kinesin-2, whereas retrograde movement away from the flagellar tip is powered by cytoplasmic dynein 1b/2. |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Involved in spermatogenesis (IEA, GO_REF:0000107). Reason: Ift81 is required for sperm flagellum formation in mice (and IFT74 variants cause male infertility with flagellar defects in humans). Sperm flagellum assembly is a tissue-specific instance of IFT-dependent cilium assembly; spermatogenesis is a broader downstream process. Non-core. |
| GO:0007283 spermatogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Involved in spermatogenesis (ISS, GO_REF:0000024). Reason: Ift81 is required for sperm flagellum formation in mice (and IFT74 variants cause male infertility with flagellar defects in humans). Sperm flagellum assembly is a tissue-specific instance of IFT-dependent cilium assembly; spermatogenesis is a broader downstream process. Non-core. |
| GO:0008589 regulation of smoothened signaling pathway | IMP PMID:27666822 Destabilization of the IFT-B cilia core complex due to mutat... | KEEP AS NON CORE | Summary: Involved in regulation of smoothened signaling pathway (IMP, PMID:27666822). Reason: IFT81 mutant chondrocytes have altered Hedgehog signalling, but mammalian Hh signalling depends on cilia generally; this is an indirect consequence of disturbed IFT/cilium structure rather than a regulatory activity of IFT81. Kept as non-core. Supporting Evidence: PMID:27666822 In mutant chondrocytes, the mutations led to low levels of IFT81 and mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components. |
| GO:0015631 tubulin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Enables tubulin binding (IBA, GO_REF:0000033). IFT81's N-terminal calponin-homology domain binds the globular body of alpha/beta-tubulin. Reason: IFT81 and IFT74 form the tubulin-binding module of IFT-B; tubulin is the principal axonemal cargo carried by anterograde trains. This is the best-defined cargo-binding activity of any IFT-B subunit and a core molecular function of IFT81. Supporting Evidence: PMID:23990561 Here, we found that the two core IFT proteins IFT74 and IFT81 form a tubulin-binding module and mapped the interaction to a calponin homology domain of IFT81 and a highly basic domain in IFT74. PMID:23990561 HsIFT81N bound tubulin with a dissociation constant (Kd) of 16 ΞΌM via a highly conserved, positively charged surface patch, which was enhanced 18-fold by IFT74N (Fig. 1G and fig. S3). |
| GO:0015631 tubulin binding | IDA PMID:23990561 Molecular basis of tubulin transport within the cilium by IF... | ACCEPT | Summary: Enables tubulin binding (IDA, PMID:23990561). IFT81's N-terminal calponin-homology domain binds the globular body of alpha/beta-tubulin. Reason: IFT81 and IFT74 form the tubulin-binding module of IFT-B; tubulin is the principal axonemal cargo carried by anterograde trains. This is the best-defined cargo-binding activity of any IFT-B subunit and a core molecular function of IFT81. Supporting Evidence: PMID:23990561 Here, we found that the two core IFT proteins IFT74 and IFT81 form a tubulin-binding module and mapped the interaction to a calponin homology domain of IFT81 and a highly basic domain in IFT74. PMID:23990561 HsIFT81N bound tubulin with a dissociation constant (Kd) of 16 ΞΌM via a highly conserved, positively charged surface patch, which was enhanced 18-fold by IFT74N (Fig. 1G and fig. S3). |
| GO:0015631 tubulin binding | IEA GO_REF:0000002 | ACCEPT | Summary: Enables tubulin binding (IEA, GO_REF:0000002). IFT81's N-terminal calponin-homology domain binds the globular body of alpha/beta-tubulin. Reason: IFT81 and IFT74 form the tubulin-binding module of IFT-B; tubulin is the principal axonemal cargo carried by anterograde trains. This is the best-defined cargo-binding activity of any IFT-B subunit and a core molecular function of IFT81. Supporting Evidence: PMID:23990561 Here, we found that the two core IFT proteins IFT74 and IFT81 form a tubulin-binding module and mapped the interaction to a calponin homology domain of IFT81 and a highly basic domain in IFT74. PMID:23990561 HsIFT81N bound tubulin with a dissociation constant (Kd) of 16 ΞΌM via a highly conserved, positively charged surface patch, which was enhanced 18-fold by IFT74N (Fig. 1G and fig. S3). |
| GO:0030991 intraciliary transport particle A | IDA PMID:26980730 Overall Architecture of the Intraflagellar Transport (IFT)-B... | REMOVE | Summary: Part of intraciliary transport particle A (IFT-A), IDA from the Katoh et al. 2016 VIP study of IFT-B architecture. IFT81 is a core (IFT-B1) subunit of the IFT-B complex, not of IFT-A. Reason: IFT-A and IFT-B are biochemically distinct subcomplexes (IFT-A: IFT144/WDR19, IFT140, IFT122, IFT139/TTC21B, IFT121/WDR35, IFT43). The cited paper itself mapped IFT81 as a subunit of the IFT-B complex (and the same paper supports the GO:0030992 IFT-B annotation for IFT81); the IFT-A term is contradicted by decades of biochemistry and structural work, and the same IDA appears on every IFT-B subunit annotated from this paper, consistent with a batch term-selection error. IFT-B does associate with IFT-A within IFT trains, but train co-assembly is not complex membership. This is a genuinely contradicted claim, not a judgment based on an abstract foregrounding a different gene. Supporting Evidence: PMID:15955805 revealing a 500-kDa core that contains IFT88, IFT81, IFT74/72, IFT52, IFT46, and IFT27. PMID:26980730 Using the visible immunoprecipitation assay, which we recently developed as a convenient protein-protein interaction assay, we determined the overall architecture of the IFT-B complex, which can be divided into core and peripheral subcomplexes composed of 10 and 6 subunits, respectively. PMID:15955805 IFT particles contain multiple copies of two distinct protein complexes, A and B, which contain at least 6 and 11 protein subunits, respectively. PMID:27932497 Intraflagellar transport (IFT)-A and -B complexes mediate retrograde and anterograde ciliary protein trafficking, respectively. |
| GO:0030992 intraciliary transport particle B | IBA GO_REF:0000033 | ACCEPT | Summary: Part of intraciliary transport particle B (IBA). IFT81 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT81 and is established biochemically (Chlamydomonas IFT-B core/peripheral fractionation; human VIP mapping) and structurally. Supporting Evidence: PMID:15955805 revealing a 500-kDa core that contains IFT88, IFT81, IFT74/72, IFT52, IFT46, and IFT27. PMID:26980730 Using the visible immunoprecipitation assay, which we recently developed as a convenient protein-protein interaction assay, we determined the overall architecture of the IFT-B complex, which can be divided into core and peripheral subcomplexes composed of 10 and 6 subunits, respectively. |
| GO:0030992 intraciliary transport particle B | IEA GO_REF:0000120 | ACCEPT | Summary: Part of intraciliary transport particle B (IEA). IFT81 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT81 and is established biochemically (Chlamydomonas IFT-B core/peripheral fractionation; human VIP mapping) and structurally. Supporting Evidence: PMID:15955805 revealing a 500-kDa core that contains IFT88, IFT81, IFT74/72, IFT52, IFT46, and IFT27. PMID:26980730 Using the visible immunoprecipitation assay, which we recently developed as a convenient protein-protein interaction assay, we determined the overall architecture of the IFT-B complex, which can be divided into core and peripheral subcomplexes composed of 10 and 6 subunits, respectively. |
| GO:0030992 intraciliary transport particle B | IPI PMID:26980730 Overall Architecture of the Intraflagellar Transport (IFT)-B... | ACCEPT | Summary: Part of intraciliary transport particle B (IPI). IFT81 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT81 and is established biochemically (Chlamydomonas IFT-B core/peripheral fractionation; human VIP mapping) and structurally. Supporting Evidence: PMID:15955805 revealing a 500-kDa core that contains IFT88, IFT81, IFT74/72, IFT52, IFT46, and IFT27. PMID:26980730 Using the visible immunoprecipitation assay, which we recently developed as a convenient protein-protein interaction assay, we determined the overall architecture of the IFT-B complex, which can be divided into core and peripheral subcomplexes composed of 10 and 6 subunits, respectively. |
| GO:0030992 intraciliary transport particle B | ISS GO_REF:0000024 | ACCEPT | Summary: Part of intraciliary transport particle B (ISS). IFT81 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT81 and is established biochemically (Chlamydomonas IFT-B core/peripheral fractionation; human VIP mapping) and structurally. Supporting Evidence: PMID:15955805 revealing a 500-kDa core that contains IFT88, IFT81, IFT74/72, IFT52, IFT46, and IFT27. PMID:26980730 Using the visible immunoprecipitation assay, which we recently developed as a convenient protein-protein interaction assay, we determined the overall architecture of the IFT-B complex, which can be divided into core and peripheral subcomplexes composed of 10 and 6 subunits, respectively. |
| GO:0030992 intraciliary transport particle B | ISS GO_REF:0000024 | ACCEPT | Summary: Part of intraciliary transport particle B (ISS). IFT81 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT81 and is established biochemically (Chlamydomonas IFT-B core/peripheral fractionation; human VIP mapping) and structurally. Supporting Evidence: PMID:15955805 revealing a 500-kDa core that contains IFT88, IFT81, IFT74/72, IFT52, IFT46, and IFT27. PMID:26980730 Using the visible immunoprecipitation assay, which we recently developed as a convenient protein-protein interaction assay, we determined the overall architecture of the IFT-B complex, which can be divided into core and peripheral subcomplexes composed of 10 and 6 subunits, respectively. |
| GO:0031514 motile cilium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Located in motile cilium (ISS). IFT is also required to assemble motile cilia and flagella. Reason: IFT is conserved in motile cilia and flagella (it was discovered in Chlamydomonas flagella), so the location is correct; it is kept as non-core because the core role reviewed here is assembly of cilia in general, with most human data from primary cilia. Supporting Evidence: PMID:11062270 Intraflagellar transport (IFT) is a rapid movement of multi-subunit protein particles along flagellar microtubules and is required for assembly and maintenance of eukaryotic flagella. |
| GO:0035720 intraciliary anterograde transport | NAS PMID:26980730 Overall Architecture of the Intraflagellar Transport (IFT)-B... | ACCEPT | Summary: Involved in intraciliary anterograde transport (NAS, PMID:26980730). IFT81 is a core (IFT-B1) subunit of the IFT-B complex. Reason: IFT-B forms the backbone of anterograde IFT trains that are moved from the ciliary base to the tip by heterotrimeric kinesin-2; IFT81 is an integral subunit of these trains. Supporting Evidence: PMID:27666822 Herein we describe a new spectrum of SRPS caused by mutations in the gene IFT81, a key component of the IFT-B complex essential for anterograde transport. PMID:36354106 The IFT-B complex constitutes the backbone of polymeric IFT trains carrying cargo between the cilium and the cell body. |
| GO:0035735 intraciliary transport involved in cilium assembly | IMP PMID:23990561 Molecular basis of tubulin transport within the cilium by IF... | ACCEPT | Summary: Involved in intraciliary transport involved in cilium assembly (IMP). Reason: IFT81 is required for IFT-dependent ciliogenesis; this term precisely combines the transport activity with its biological purpose. Supporting Evidence: PMID:23990561 Here, we have shown that the two core IFT proteins IFT74 and IFT81 form a tubulin-binding module required for ciliogenesis, which suggests a role of IFT74/81 in the transport of tubulin within cilia. |
| GO:0036064 ciliary basal body | IBA GO_REF:0000033 | ACCEPT | Summary: Located at ciliary basal body (IBA, GO_REF:0000033). IFT complexes assemble into trains and are loaded at the ciliary base (basal body / transition fibres) before entering the cilium. Reason: A large pool of IFT81 resides at the ciliary base, where IFT trains are assembled and where RABL2-mediated capture of IFT-B occurs; this is a well-documented location for IFT subunits. Supporting Evidence: PMID:28625565 GTP-bound RABL2 then binds to the IFT-B holocomplex via the IFT74/81 heterodimer to capture and trigger the entry of IFT-B into cilia, prior to classical motor-driven intraflagellar transport. |
| GO:0036064 ciliary basal body | IDA PMID:23990561 Molecular basis of tubulin transport within the cilium by IF... | ACCEPT | Summary: Located at ciliary basal body (IDA, PMID:23990561). IFT complexes assemble into trains and are loaded at the ciliary base (basal body / transition fibres) before entering the cilium. Reason: A large pool of IFT81 resides at the ciliary base, where IFT trains are assembled and where RABL2-mediated capture of IFT-B occurs; this is a well-documented location for IFT subunits. Supporting Evidence: PMID:28625565 GTP-bound RABL2 then binds to the IFT-B holocomplex via the IFT74/81 heterodimer to capture and trigger the entry of IFT-B into cilia, prior to classical motor-driven intraflagellar transport. |
| GO:0036064 ciliary basal body | IDA PMID:36606424 CCDC66 regulates primary cilium length and signaling via int... | ACCEPT | Summary: Located at ciliary basal body (IDA, PMID:36606424). IFT complexes assemble into trains and are loaded at the ciliary base (basal body / transition fibres) before entering the cilium. Reason: A large pool of IFT81 resides at the ciliary base, where IFT trains are assembled and where RABL2-mediated capture of IFT-B occurs; this is a well-documented location for IFT subunits. Supporting Evidence: PMID:36606424 Moreover, CCDC66 is required for the basal body recruitment of transition zone proteins and intraflagellar transport B (IFT-B) machinery. |
| GO:0042073 intraciliary transport | IBA GO_REF:0000033 | ACCEPT | Summary: Involved in intraciliary transport (IBA). IFT81 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Intraciliary transport is the defining process of IFT complex subunits. The PAINT/IBA node placement is consistent with the conserved IFT machinery. Supporting Evidence: PMID:11062270 Intraflagellar transport (IFT) is a rapid movement of multi-subunit protein particles along flagellar microtubules and is required for assembly and maintenance of eukaryotic flagella. PMID:15955805 Anterograde movement of particles away from the cell body is mediated by kinesin-2, whereas retrograde movement away from the flagellar tip is powered by cytoplasmic dynein 1b/2. |
| GO:0042073 intraciliary transport | IEA GO_REF:0000002 | ACCEPT | Summary: Involved in intraciliary transport (IEA). IFT81 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Intraciliary transport is the defining process of IFT complex subunits. The PAINT/IBA node placement is consistent with the conserved IFT machinery. Supporting Evidence: PMID:11062270 Intraflagellar transport (IFT) is a rapid movement of multi-subunit protein particles along flagellar microtubules and is required for assembly and maintenance of eukaryotic flagella. PMID:15955805 Anterograde movement of particles away from the cell body is mediated by kinesin-2, whereas retrograde movement away from the flagellar tip is powered by cytoplasmic dynein 1b/2. |
| GO:0060271 cilium assembly | IEA GO_REF:0000120 | ACCEPT | Summary: Involved in cilium assembly (IEA, GO_REF:0000120). Reason: IFT is required to build cilia; loss of IFT81 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT81 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. Supporting Evidence: PMID:23990561 siRNA-mediated depletion of IFT81 (fig. S6E) strongly reduced the percentage of ciliated cells (Fig. 2), which could be rescued by coexpression of an siRNA-resistant full-length IFT81, as expected. |
| GO:0060271 cilium assembly | IMP PMID:23990561 Molecular basis of tubulin transport within the cilium by IF... | ACCEPT | Summary: Involved in cilium assembly (IMP, PMID:23990561). Reason: IFT is required to build cilia; loss of IFT81 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT81 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. Supporting Evidence: PMID:23990561 Knockdown of IFT81 and rescue experiments with point mutants showed that tubulin binding by IFT81 was required for ciliogenesis in human cells. |
| GO:0060271 cilium assembly | IMP PMID:27666822 Destabilization of the IFT-B cilia core complex due to mutat... | ACCEPT | Summary: Involved in cilium assembly (IMP, PMID:27666822). Reason: IFT is required to build cilia; loss of IFT81 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT81 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. Supporting Evidence: PMID:27666822 In mutant chondrocytes, the mutations led to low levels of IFT81 and mutant cells produced elongated cilia, had altered hedgehog signaling, had increased post-translation modification of tubulin, and showed evidence of destabilization of additional anterograde transport complex components. |
| GO:0060271 cilium assembly | NAS PMID:26980730 Overall Architecture of the Intraflagellar Transport (IFT)-B... | ACCEPT | Summary: Involved in cilium assembly (NAS, PMID:26980730). Reason: IFT is required to build cilia; loss of IFT81 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT81 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. Supporting Evidence: PMID:23990561 siRNA-mediated depletion of IFT81 (fig. S6E) strongly reduced the percentage of ciliated cells (Fig. 2), which could be rescued by coexpression of an siRNA-resistant full-length IFT81, as expected. |
| GO:0097225 sperm midpiece | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Located in sperm midpiece (IEA, GO_REF:0000107); transferred from rodent spermatogenesis studies. Reason: IFT is required for sperm flagellum assembly and IFT proteins are detected in spermatid structures (manchette, acrosome region, flagellum). These are plausible cell-type-specific locations for IFT81 but are outside its core ciliary role. |
| GO:0097228 sperm principal piece | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Located in sperm principal piece (IEA, GO_REF:0000107); transferred from rodent spermatogenesis studies. Reason: IFT is required for sperm flagellum assembly and IFT proteins are detected in spermatid structures (manchette, acrosome region, flagellum). These are plausible cell-type-specific locations for IFT81 but are outside its core ciliary role. |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5624952 | ACCEPT | Summary: Located in ciliary tip (TAS). IFT trains are remodelled at the ciliary tip, where anterograde trains disassemble and retrograde trains assemble. Reason: The ciliary tip is the turnaround compartment of IFT; IFT subunits transiently concentrate there. Correct location reflecting the IFT cycle. Supporting Evidence: Reactome:R-HSA-5624952 Remodelling of IFT trains is thought to occur at the ciliary tip PMID:23990561 We detected both Flag-HsIFT81 and Flag-HsIFT81ΞN at the tip of the primary cilium and, to a minor extent, also along the axoneme (fig. S6A) |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5625416 | ACCEPT | Summary: Located in ciliary tip (TAS). IFT trains are remodelled at the ciliary tip, where anterograde trains disassemble and retrograde trains assemble. Reason: The ciliary tip is the turnaround compartment of IFT; IFT subunits transiently concentrate there. Correct location reflecting the IFT cycle. Supporting Evidence: Reactome:R-HSA-5625416 Anterograde trains travel along the axoneme of the cilium at an estimated rate of 2 micrometers per second in an ATP- and kinesin-2-dependent fashion PMID:23990561 We detected both Flag-HsIFT81 and Flag-HsIFT81ΞN at the tip of the primary cilium and, to a minor extent, also along the axoneme (fig. S6A) |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5625421 | ACCEPT | Summary: Located in ciliary tip (TAS). IFT trains are remodelled at the ciliary tip, where anterograde trains disassemble and retrograde trains assemble. Reason: The ciliary tip is the turnaround compartment of IFT; IFT subunits transiently concentrate there. Correct location reflecting the IFT cycle. Supporting Evidence: Reactome:R-HSA-5625421 anterograde IFT trains are believed to disassemble at the ciliary tip, releasing cargo and the IFT motors. PMID:23990561 We detected both Flag-HsIFT81 and Flag-HsIFT81ΞN at the tip of the primary cilium and, to a minor extent, also along the axoneme (fig. S6A) |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5625426 | ACCEPT | Summary: Located in ciliary tip (TAS). IFT trains are remodelled at the ciliary tip, where anterograde trains disassemble and retrograde trains assemble. Reason: The ciliary tip is the turnaround compartment of IFT; IFT subunits transiently concentrate there. Correct location reflecting the IFT cycle. Supporting Evidence: Reactome:R-HSA-5625426 Retrograde trains are shorter than anterograde particles and travel along the cilliary axoneme at an estimated rate of 3 micrometers per second PMID:23990561 We detected both Flag-HsIFT81 and Flag-HsIFT81ΞN at the tip of the primary cilium and, to a minor extent, also along the axoneme (fig. S6A) |
| GO:0120316 sperm flagellum assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Involved in sperm flagellum assembly (IEA, GO_REF:0000107). Reason: Ift81 is required for sperm flagellum formation in mice (and IFT74 variants cause male infertility with flagellar defects in humans). Sperm flagellum assembly is a tissue-specific instance of IFT-dependent cilium assembly; spermatogenesis is a broader downstream process. Non-core. |
| GO:0120316 sperm flagellum assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Involved in sperm flagellum assembly (ISS, GO_REF:0000024). Reason: Ift81 is required for sperm flagellum formation in mice (and IFT74 variants cause male infertility with flagellar defects in humans). Sperm flagellum assembly is a tissue-specific instance of IFT-dependent cilium assembly; spermatogenesis is a broader downstream process. Non-core. |
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Download this section (compressed HTML)Q: Does the IFT81-IFT74 coiled-coil act as a GTPase-activating module for human RABL2B (reported for Chlamydomonas RabL2 by Boegholm et al. 2023), which would justify a 'GTPase activator activity' annotation contributed by IFT81/IFT74?
Q: Is IFT81/IFT74 tubulin binding regulated (for example by RABL2B occupancy of their C-termini or by phosphorylation) to couple tubulin loading to cilium length?
Experiment: Live imaging of fluorescent tubulin transport in IFT81-knockout cells rescued with wild-type or tubulin-binding-deficient IFT81 to quantify tubulin cargo loading per train.
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