IFT74 (originally capillary morphogenesis gene 1, CMG-1) is a coiled-coil core (IFT-B1) subunit of the intraflagellar transport B complex that heterodimerizes with IFT81. Its highly basic, disordered N-terminus binds the acidic C-terminal tail of beta-tubulin, enhancing tubulin binding by the IFT81 CH domain about 18-fold, so that IFT74/IFT81 form the tubulin-transport module of anterograde IFT trains. The C-terminal coiled coils of IFT74/IFT81 also bind GTP-RABL2B at the ciliary base, and IFT74 is required for ciliogenesis. IFT74 localizes to the ciliary base/basal body, cilia and centriolar satellites, and is essential for sperm flagellum formation. Variants cause Bardet-Biedl syndrome 22, Joubert syndrome 40 and male infertility with multiple morphological abnormalities of the sperm flagellum.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001669 acrosomal vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Located in acrosomal vesicle (IEA, GO_REF:0000044); 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 IFT74 but are outside its core ciliary role. |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Enables chromatin binding (IEA, Ensembl Compara from mouse Ift74 IDA, PMID:20545763). Reason: No human evidence and no mechanistic link between IFT74 and chromatin; all functional data place IFT74 in the IFT-B complex in cilia. The mouse source paper was not reviewed here, so the claim is not removed outright, but projecting it as a molecular function of human IFT74 over-states the evidence. |
| 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: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:0005634 nucleus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Located in nucleus (IEA, Ensembl Compara from mouse Ift74). Reason: Nuclear IFT74 is not supported by human data (HPA localizes IFT74 to basal body, centriolar satellites and Golgi); likely reflects a minor or antibody-dependent signal in the mouse source studies. Not part of the characterized biology. |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Located in Golgi apparatus (IDA, HPA immunofluorescence). Reason: HPA v25 lists Golgi apparatus among IFT74's main locations. IFT-B subunits (notably IFT20) have a Golgi pool linked to ciliary membrane-protein delivery, so this is plausible, but no Golgi function of IFT74 is established. Non-core. Supporting Evidence: PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. |
| 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 IFT74 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 | IBA GO_REF:0000033 | ACCEPT | Summary: Located in cilium (IBA, GO_REF:0000033). IFT particles containing IFT74 move bidirectionally along the ciliary axoneme. Reason: IFT74 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 | IEA GO_REF:0000120 | ACCEPT | Summary: Located in cilium (IEA, GO_REF:0000120). IFT particles containing IFT74 move bidirectionally along the ciliary axoneme. Reason: IFT74 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 IFT74 move bidirectionally along the ciliary axoneme. Reason: IFT74 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 IFT74 move bidirectionally along the ciliary axoneme. Reason: IFT74 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 IFT74 move bidirectionally along the ciliary axoneme. Reason: IFT74 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 IFT74 move bidirectionally along the ciliary axoneme. Reason: IFT74 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 IFT74 move bidirectionally along the ciliary axoneme. Reason: IFT74 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: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. IFT74 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 IFT74 as a subunit of the IFT-B complex (and the same paper supports the GO:0030992 IFT-B annotation for IFT74); 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). IFT74 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT74 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). IFT74 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT74 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). IFT74 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT74 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). IFT74 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT74 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). IFT74 is a core (IFT-B1) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT74 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:0031410 cytoplasmic vesicle | EXP PMID:11683410 Differential gene expression during capillary morphogenesis ... | KEEP AS NON CORE | Summary: Located in cytoplasmic vesicle (EXP, PMID:11683410). IFT74 was first identified as capillary morphogenesis gene-1 (CMG-1), whose GFP fusion targeted to an intracellular vesicular compartment. Reason: The overexpression-based vesicular localization (and the rodent spermatid vesicle signal) are plausible minor pools; IFT74 function is in IFT-B trains at and within cilia. Non-core. Supporting Evidence: PMID:11683410 A CMG-1-green fluorescent protein (GFP) chimera was observed to target to an intracellular vesicular compartment. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Located in cytoplasmic vesicle (IEA, GO_REF:0000044). IFT74 was first identified as capillary morphogenesis gene-1 (CMG-1), whose GFP fusion targeted to an intracellular vesicular compartment. Reason: The overexpression-based vesicular localization (and the rodent spermatid vesicle signal) are plausible minor pools; IFT74 function is in IFT-B trains at and within cilia. Non-core. |
| GO:0031514 motile cilium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Located in motile cilium (IEA). 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: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:0034451 centriolar satellite | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Located in centriolar satellite (IDA, HPA immunofluorescence). Reason: HPA reports IFT74 at centriolar satellites (Supported). Satellites traffic many ciliogenesis proteins toward the basal body, so a satellite pool is plausible; not the site of the core IFT function. Supporting Evidence: PMID:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. |
| 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). IFT74 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; IFT74 is an integral subunit of these trains. Supporting Evidence: PMID:33689014 IFT74 encodes for a core component of the IFT machinery that is essential for the anterograde transport of tubulin. 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 | IBA GO_REF:0000033 | ACCEPT | Summary: Involved in intraciliary transport involved in cilium assembly (IBA). Reason: IFT74 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: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: IFT74 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 | IDA GO_REF:0000052 | ACCEPT | Summary: Located at ciliary basal body (IDA, GO_REF:0000052). 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 IFT74 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:41005307 We employed antibody-based spatial proteomics to expand the Human Protein Atlas to primary cilia. |
| GO:0042073 intraciliary transport | IEA GO_REF:0000002 | ACCEPT | Summary: Involved in intraciliary transport (IEA). IFT74 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:0048487 beta-tubulin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Enables beta-tubulin binding (IBA, GO_REF:0000033). IFT74's highly basic N-terminus binds the acidic C-terminal tail (E-hook) of beta-tubulin, raising the affinity of the IFT74/81 module about 18-fold. 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 IFT74. 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 Thus, IFT81N appears to bind the globular domain of tubulin to provide specificity, and IFT74N recognizes the Ξ²-tubulin tail to increase affinity (Fig. 1H). |
| GO:0048487 beta-tubulin binding | IDA PMID:23990561 Molecular basis of tubulin transport within the cilium by IF... | ACCEPT | Summary: Enables beta-tubulin binding (IDA, PMID:23990561). IFT74's highly basic N-terminus binds the acidic C-terminal tail (E-hook) of beta-tubulin, raising the affinity of the IFT74/81 module about 18-fold. 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 IFT74. 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 Thus, IFT81N appears to bind the globular domain of tubulin to provide specificity, and IFT74N recognizes the Ξ²-tubulin tail to increase affinity (Fig. 1H). |
| GO:0048487 beta-tubulin binding | IEA GO_REF:0000002 | ACCEPT | Summary: Enables beta-tubulin binding (IEA, GO_REF:0000002). IFT74's highly basic N-terminus binds the acidic C-terminal tail (E-hook) of beta-tubulin, raising the affinity of the IFT74/81 module about 18-fold. 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 IFT74. 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 Thus, IFT81N appears to bind the globular domain of tubulin to provide specificity, and IFT74N recognizes the Ξ²-tubulin tail to increase affinity (Fig. 1H). |
| GO:0060271 cilium assembly | IEA GO_REF:0000002 | ACCEPT | Summary: Involved in cilium assembly (IEA, GO_REF:0000002). Reason: IFT is required to build cilia; loss of IFT74 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT74 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. 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: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 IFT74 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT74 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. 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: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 IFT74 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT74 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. 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: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 |
| 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 |
| 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. |
| 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 |
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Download this section (compressed HTML)Q: Does the IFT74 basic N-terminus have cargo specificity beyond beta-tubulin, and how do BBS22/JBTS40 variants that spare the N-terminus impair IFT?
Q: Is the electronically transferred mouse 'chromatin binding'/nuclear localization of IFT74 reproducible for human IFT74?
Experiment: Rescue of IFT74-knockout cells with N-terminal basic-region deletions to separate tubulin-binding from IFT-B assembly roles, combined with tubulin-transport imaging.
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