IFT172 is the largest IFT protein (~198 kDa), composed of N-terminal WD40 beta-propellers and an extended C-terminal TPR-like domain, and is a peripheral (IFT-B2) subunit of the intraflagellar transport B complex; it dissociates from the IFT-B core at high salt. As part of IFT-B, IFT172 travels on anterograde IFT trains and is required for cilium formation and maintenance; work in model organisms implicates it in IFT turnaround at the ciliary tip and membrane association of trains. IFT172 localizes to the axoneme and around the ciliary base. Biallelic IFT172 variants cause short-rib thoracic dysplasia 10 (Jeune and Mainzer-Saldino syndromes), Bardet-Biedl syndrome 20 and isolated retinitis pigmentosa 71; patient fibroblasts show disturbed ciliary composition, and Ift172 mouse mutants lack cilia and Hedgehog signalling.
| 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: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:0005929 cilium | IEA GO_REF:0000120 | ACCEPT | Summary: Located in cilium (IEA, GO_REF:0000120). IFT particles containing IFT172 move bidirectionally along the ciliary axoneme. Reason: IFT172 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 | ISS GO_REF:0000024 | ACCEPT | Summary: Located in cilium (ISS, GO_REF:0000024). IFT particles containing IFT172 move bidirectionally along the ciliary axoneme. Reason: IFT172 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 IFT172 move bidirectionally along the ciliary axoneme. Reason: IFT172 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 IFT172 move bidirectionally along the ciliary axoneme. Reason: IFT172 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 IFT172 move bidirectionally along the ciliary axoneme. Reason: IFT172 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 IFT172 move bidirectionally along the ciliary axoneme. Reason: IFT172 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 IFT172 move bidirectionally along the ciliary axoneme. Reason: IFT172 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:0005930 axoneme | IBA GO_REF:0000033 | ACCEPT | Summary: Located in axoneme (IBA). IFT trains travel along the outer doublet microtubules of the axoneme. Reason: IFT trains are bound to axonemal outer-doublet microtubules during transport, so axoneme is an appropriate location for an IFT subunit. 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:0007224 smoothened signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Involved in smoothened signaling pathway (IEA, Ensembl Compara from mouse). Reason: Ift172 (wimple) mouse mutants were among the first to link IFT to Hedgehog signalling, but the role is indirect: cilia are required for Hh pathway activity. Non-core. Supporting Evidence: PMID:24140113 Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. |
| GO:0030990 intraciliary transport particle | IEA GO_REF:0000117 | ACCEPT | Summary: Part of intraciliary transport particle (IEA). IFT172 is a peripheral (IFT-B2) subunit of the IFT-B complex. Reason: Correct but general parent of the IFT-B complex term; acceptable for an electronic annotation. Supporting Evidence: PMID:15955805 This result demonstrates that the complex B subunits, IFT172, IFT80, IFT57, and IFT20 are not required for the core subunits to stay associated. 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: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. IFT172 is a peripheral (IFT-B2) 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 IFT172 as a subunit of the IFT-B complex (and the same paper supports the GO:0030992 IFT-B annotation for IFT172); 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 This result demonstrates that the complex B subunits, IFT172, IFT80, IFT57, and IFT20 are not required for the core subunits to stay associated. 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). IFT172 is a peripheral (IFT-B2) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT172 and is established biochemically (Chlamydomonas IFT-B core/peripheral fractionation; human VIP mapping) and structurally. Supporting Evidence: PMID:15955805 This result demonstrates that the complex B subunits, IFT172, IFT80, IFT57, and IFT20 are not required for the core subunits to stay associated. 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:0000107 | ACCEPT | Summary: Part of intraciliary transport particle B (IEA). IFT172 is a peripheral (IFT-B2) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT172 and is established biochemically (Chlamydomonas IFT-B core/peripheral fractionation; human VIP mapping) and structurally. Supporting Evidence: PMID:15955805 This result demonstrates that the complex B subunits, IFT172, IFT80, IFT57, and IFT20 are not required for the core subunits to stay associated. 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). IFT172 is a peripheral (IFT-B2) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT172 and is established biochemically (Chlamydomonas IFT-B core/peripheral fractionation; human VIP mapping) and structurally. Supporting Evidence: PMID:15955805 This result demonstrates that the complex B subunits, IFT172, IFT80, IFT57, and IFT20 are not required for the core subunits to stay associated. 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). IFT172 is a peripheral (IFT-B2) subunit of the IFT-B complex. Reason: Membership of the IFT-B complex is the defining feature of IFT172 and is established biochemically (Chlamydomonas IFT-B core/peripheral fractionation; human VIP mapping) and structurally. Supporting Evidence: PMID:15955805 This result demonstrates that the complex B subunits, IFT172, IFT80, IFT57, and IFT20 are not required for the core subunits to stay associated. 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: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). IFT172 is a peripheral (IFT-B2) 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; IFT172 is an integral subunit of these trains. Supporting Evidence: PMID:36354106 The IFT-B complex constitutes the backbone of polymeric IFT trains carrying cargo between the cilium and the cell body. 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: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 IFT172 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:0042073 intraciliary transport | IBA GO_REF:0000033 | ACCEPT | Summary: Involved in intraciliary transport (IBA). IFT172 is a peripheral (IFT-B2) 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:0044782 cilium organization | IEA GO_REF:0000117 | ACCEPT | Summary: Involved in cilium organization (IEA). Reason: Correct general parent of cilium assembly; acceptable electronic annotation. 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:0060271 cilium assembly | IDA PMID:24140113 Defects in the IFT-B component IFT172 cause Jeune and Mainze... | ACCEPT | Summary: Involved in cilium assembly (IDA, PMID:24140113). Reason: IFT is required to build cilia; loss of IFT172 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT172 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. Supporting Evidence: PMID:24140113 Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Involved in cilium assembly (IEA, GO_REF:0000107). Reason: IFT is required to build cilia; loss of IFT172 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT172 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. 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:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Involved in cilium assembly (ISS, GO_REF:0000024). Reason: IFT is required to build cilia; loss of IFT172 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT172 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. 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: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 IFT172 function impairs ciliogenesis or cilium structure in model organisms and/or patient cells. IFT172 participates directly as a component of the IFT machinery that delivers axonemal precursors, not merely as an upstream requirement. 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: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 IFT172 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 IFT172 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 |
| 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 |
| GO:0097598 sperm cytoplasmic droplet | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Located in sperm cytoplasmic droplet (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 IFT172 but are outside its core ciliary role. |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | MARK AS OVER ANNOTATED | Summary: Located in extracellular vesicle (HDA, CSF extracellular vesicle proteomics). Reason: Detection in a large-scale proteomic inventory of cerebrospinal-fluid EVs (1315 proteins) does not establish a functional extracellular-vesicle localization for IFT172; it may reflect ciliary ectosome shedding or contamination. Not part of its characterized biology. Supporting Evidence: PMID:24769233 We report an extensive catalog of 1315 proteins identified in EVs isolated from two different CSF pools by ultracentrifugation, including 230 novel EV proteins. |
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Download this section (compressed HTML)Q: Does human IFT172 act at the ciliary tip in remodelling anterograde into retrograde trains, as proposed from Chlamydomonas fla11 mutants?
Q: Is the in vitro phospholipid-membrane binding and remodelling activity of IFT172 (Wang et al. 2018) used in cilia, and would it warrant a lipid-binding molecular-function annotation?
Experiment: Acute degradation (degron) of IFT172 in ciliated human cells with live IFT imaging to distinguish roles in ciliary entry, tip turnaround and retrograde return of IFT-B.
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