Affinage

IFT52

Intraflagellar transport protein 52 homolog · UniProt Q9Y366

Length
437 aa
Mass
49.7 kDa
Annotated
2026-04-28
14 papers in source corpus 9 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IFT52 is a central scaffold subunit of the intraflagellar transport complex B (IFT-B) that bridges the IFT-B1 and IFT-B2 subcomplexes and is essential for ciliogenesis, anterograde ciliary trafficking, and Hedgehog signal transduction. Structurally, IFT52 directly contacts IFT88 (residues 281–329), IFT70 (residues 330–370 buried in the IFT70 TPR superhelix), and IFT46 (via its C-terminal domain), and these interfaces are required for IFT-B holocomplex integrity, interaction with kinesin-II, and ciliary delivery of cargoes including ICK/CILK1 and KIF17 (PMID:25349261, PMID:35704471). IFT52 localizes to basal body transitional fibers—the docking site for IFT particles—and pre-assembles with IFT46 in the cytoplasm before basal body targeting (PMID:11676918, PMID:28302912). Beyond its ciliary role, IFT52 interacts with centrin at the distal centriole to maintain centrosome cohesion, and compound-heterozygous IFT52 mutations cause short-rib polydactyly syndrome (SRPS) through impaired IFT-B assembly and anterograde trafficking (PMID:31042281, PMID:27466190).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2001 High

    Identification of IFT52 as the product of the Chlamydomonas bld1 locus and its localization to basal body transitional fibers established these fibers as the IFT particle docking site and linked IFT52 loss to complete aflagellia.

    Evidence Immunofluorescence, immunoelectron microscopy, and genetic analysis of the bld1 mutant in Chlamydomonas

    PMID:11676918

    Open questions at the time
    • Direct binding partners within the IFT-B complex were unknown
    • Mammalian function not yet tested
  2. 2010 High

    Demonstration that IFT52 forms a direct ternary complex with IFT88 and IFT46 defined the minimal IFT-B core architecture.

    Evidence Yeast two-hybrid, bacterial coexpression, and chemical cross-linking

    PMID:20435895

    Open questions at the time
    • Atomic-resolution interfaces not yet determined
    • How IFT52 bridges the two IFT-B subcomplexes was unclear
  3. 2014 High

    Crystal structures of IFT70/52 and IFT52/46 subcomplexes revealed the precise binding interfaces and showed that IFT52's C-terminal domain bridges the IFT88/70/52/46 and IFT81/74/27/25/22 modules, explaining why its disruption collapses the IFT-B holocomplex.

    Evidence X-ray crystallography (2.3–2.5 Å), biochemical reconstitution, and dominant-negative overexpression in MDCK cells

    PMID:25349261

    Open questions at the time
    • Full-length IFT-B holocomplex structure not yet available
    • Structure-function relationship in disease mutations not tested
  4. 2016 Medium

    Compound heterozygous IFT52 mutations in a short-rib polydactyly syndrome (SRPS) patient demonstrated that reduced IFT52 destabilizes multiple IFT-B subunits, impairs ciliogenesis, and causes a human skeletal ciliopathy.

    Evidence Patient-derived cell lines with immunoblotting and ciliogenesis assays

    PMID:27466190

    Open questions at the time
    • Single family; allelic series not established
    • Downstream signaling consequences not assessed
  5. 2017 High

    Showing that IFT52 recruits IFT46 to basal bodies via specific leucine residues and that the two proteins preassemble in the cytoplasm revealed the order of IFT-B assembly prior to ciliary entry.

    Evidence Truncation constructs in Chlamydomonas ift46-1 mutant, co-IP, and nuclear mis-targeting assay

    PMID:28302912

    Open questions at the time
    • Whether other IFT-B subunits join the pre-assembled complex in the cytoplasm was untested
    • Temporal regulation of the assembly pathway unknown
  6. 2018 High

    Functional analysis of IFT70 TPR domain deletions confirmed that IFT70's interaction with the IFT52–IFT88 dimer is essential for ciliogenesis, validating the structural model in a cellular context.

    Evidence CRISPR IFT70-KO cells with rescue by deletion mutants, co-IP, ciliogenesis assays

    PMID:29654116

    Open questions at the time
    • Contribution of each TPR repeat to binding affinity not quantified
    • Whether IFT70 stabilizes IFT52 protein levels or just complex formation was unclear
  7. 2019 Medium

    Discovery that IFT52 interacts with centrin at centriole distal ends and that its loss causes centriole splitting established an extra-ciliary role for IFT52 in centrosome cohesion.

    Evidence Co-IP, co-localization, Ift52−/− cells, and zebrafish in vivo studies

    PMID:31042281

    Open questions at the time
    • Molecular basis of centrin–IFT52 interaction not mapped structurally
    • Whether centrosome cohesion function is independent of other IFT-B subunits is unknown
    • Single lab; not independently confirmed
  8. 2022 Medium

    Reconstitution of SRPS-associated IFT52 variants in KO cells showed that these mutations specifically impair IFT-B holocomplex assembly, kinesin-II interaction, and ciliary tip delivery of ICK/CILK1 and KIF17, defining the cargo trafficking defects underlying the disease.

    Evidence IFT52-KO cell rescue with variant proteins, co-IP, ciliary cargo localization assays

    PMID:35704471

    Open questions at the time
    • Full cargo spectrum affected by IFT52 loss not catalogued
    • Whether kinesin-II interaction is direct or mediated through other IFT-B subunits not resolved
  9. 2022 Medium

    IFT52 knockdown in mesenchymal stem cells demonstrated that IFT52-dependent ciliogenesis is required upstream of Hedgehog signaling during osteogenic differentiation, linking IFT52 to developmental signaling.

    Evidence shRNA knockdown, Hedgehog pathway reporter, and osteogenic differentiation assay in C3H10T1/2 cells with SAG rescue

    PMID:35839863

    Open questions at the time
    • Whether IFT52 has Hh-independent roles in osteogenesis not fully excluded
    • In vivo skeletal phenotype of conditional Ift52 knockout not reported
  10. 2025 Medium

    In vitro reconstitution showed that the IFT52/IFT70 subcomplex directly binds and oligomerizes the mitotic kinesin HSET, enhancing its processivity and microtubule-sliding activity, providing a molecular mechanism for IFT-B-promoted centrosome clustering.

    Evidence Purified protein reconstitution, TIRF microscopy, microtubule sliding assays (preprint)

    Open questions at the time
    • Preprint; not yet peer-reviewed
    • Whether HSET oligomerization by IFT52/70 occurs in cells during mitosis not demonstrated
    • Relationship between centrin-mediated cohesion and HSET-mediated clustering roles not clarified

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete understanding of how IFT52 coordinates its ciliary scaffold function with extra-ciliary roles at centrosomes, and a full structural model of IFT52 within the intact IFT-B train, remain unresolved.
  • Full cryo-EM structure of intact IFT-B train with IFT52 in context not published
  • Mechanism by which IFT52 is partitioned between ciliary and centrosomal pools unknown
  • Complete set of IFT52-dependent ciliary cargoes not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005929 cilium 3 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1640170 Cell Cycle 2 R-HSA-162582 Signal Transduction 1
Partners
CETN2IFT46IFT70IFT88KIFC1
Complex memberships
IFT-B complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 IFT52 localizes to transitional fibers at the distal portion of the basal body (by immunofluorescence and immunoelectron microscopy), identifying these fibers as the docking site for IFT particles destined for the flagellum. The flagellaless mutant bld1 carries a deletion in the IFT52 gene and completely lacks IFT52 protein. Immunofluorescence, immunoelectron microscopy, genetic analysis of bld1 mutant (Chlamydomonas reinhardtii) Current biology : CB High 11676918
2010 IFT88, IFT52, and IFT46 directly interact with each other and form a ternary complex within the IFT-B core, as shown by yeast two-hybrid, bacterial coexpression, and chemical cross-linking. Yeast two-hybrid, bacterial coexpression, chemical cross-linking The Journal of biological chemistry High 20435895
2014 Crystal structures of IFT70/52 (2.5 Å) and IFT52/46 (2.3 Å) subcomplexes reveal that IFT52 residues 330–370 are buried in the IFT70 TPR superhelix, and IFT52 residues 281–329 bind IFT88. The IFT52C/IFT46C interface is essential for IFT-B core integrity by bridging the IFT88/70/52/46 and IFT81/74/27/25/22 subcomplexes. Overexpression of mammalian IFT52C in MDCK cells acts dominantly negative, causing IFT protein mislocalization and disrupted ciliogenesis. X-ray crystallography, biochemical reconstitution, dominant-negative overexpression in MDCK cells The Journal of cell biology High 25349261
2016 IFT52 mutations (compound heterozygous) in SRPS patient cells reduce IFT52 protein levels, leading to reduced levels of IFT74, IFT81, IFT88, and ARL13B, demonstrating IFT52 is required for anterograde IFT-B complex integrity and stability. Mutant cells show 60% reduction in cilia presence and loss of cilia length regulation. Patient-derived cell lines, immunoblotting, ciliogenesis assay (loss-of-function) Human molecular genetics Medium 27466190
2017 IFT52 directly recruits IFT46 to the basal body via interaction with IFT46 residues L285 and L286. Ectopic nuclear expression of IFT52 C-terminal domain sequesters IFT46 to the nucleus, demonstrating that IFT52 and IFT46 preassemble as a complex in the cytoplasm before targeting to basal bodies. Truncation/deletion constructs in Chlamydomonas ift46-1 mutant, co-immunoprecipitation, subcellular localization by live imaging, IFT and motor mutant analysis Journal of cell science High 28302912
2018 IFT70 is required for ciliogenesis through robust interaction with the IFT52–IFT88 dimer; deletion of the first TPR or the terminal helix α36 of IFT70A reduces its interaction with the IFT52–IFT88 dimer and abolishes its ability to rescue ciliogenesis in IFT70-KO cells. CRISPR knockout, rescue experiments with deletion mutants, co-immunoprecipitation, ciliogenesis assay Biology open High 29654116
2019 IFT52 interacts with centrin at the distal end of centrioles and is involved in centrin recruitment and/or maintenance there; loss of IFT52 leads to centriole splitting, revealing an extra-ciliary role for IFT52 in microtubule network regulation and centrosome cohesion. SRTD-associated IFT52 missense mutation impairs IFT-B complex assembly and IFT-B2 ciliary localization, reducing cilia length. Co-immunoprecipitation, co-localization, Ift52-/- cells, zebrafish in vivo studies, exon-skipping analysis Human molecular genetics Medium 31042281
2022 IFT52 variants found in SRPS patients are impaired in IFT-B holocomplex assembly from two subcomplexes and in interaction with heterotrimeric kinesin-II. IFT52-KO cells expressing SRPS variants show decreased ciliary IFT-B levels and significantly impaired ciliary tip localization of ICK/CILK1 and KIF17, demonstrating that anterograde trafficking defects underlie the ciliary phenotypes of SRPS-associated IFT52 mutations. IFT52-KO cells, co-immunoprecipitation, ciliogenesis assay, ciliary cargo localization assays Molecular biology of the cell Medium 35704471
2022 IFT52 depletion in mouse mesenchymal stem cells disrupts IFT-B anterograde trafficking, impairs primary ciliogenesis, attenuates Hedgehog pathway upregulation during osteogenesis, and blocks osteogenic differentiation; Hh pathway agonist (SAG) only partially restores differentiation, placing IFT52 upstream of Hh signaling in osteoblast differentiation. shRNA knockdown, ciliogenesis assay, Hedgehog pathway reporter, osteogenic differentiation assay in C3H10T1/2 cells Experimental cell research Medium 35839863
2025 In a reconstituted in vitro system, IFT52/IFT70 form a minimal subcomplex that directly binds the mitotic kinesin HSET, inducing HSET oligomerization and promoting formation of processive HSET complexes with increased microtubule-sliding activity, providing a mechanistic basis for IFT-promoted centrosome clustering. In vitro reconstitution with purified proteins, TIRF microscopy, microtubule sliding assay bioRxivpreprint Medium

Source papers

Stage 0 corpus · 14 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Localization of intraflagellar transport protein IFT52 identifies basal body transitional fibers as the docking site for IFT particles. Current biology : CB 313 11676918
2014 Crystal structures of IFT70/52 and IFT52/46 provide insight into intraflagellar transport B core complex assembly. The Journal of cell biology 102 25349261
2010 Direct interactions of intraflagellar transport complex B proteins IFT88, IFT52, and IFT46. The Journal of biological chemistry 68 20435895
2016 A homozygous nonsense variant in IFT52 is associated with a human skeletal ciliopathy. Clinical genetics 58 26880018
2018 Robust interaction of IFT70 with IFT52-IFT88 in the IFT-B complex is required for ciliogenesis. Biology open 39 29654116
2016 IFT52 mutations destabilize anterograde complex assembly, disrupt ciliogenesis and result in short rib polydactyly syndrome. Human molecular genetics 39 27466190
2017 Intraflagellar transport protein IFT52 recruits IFT46 to the basal body and flagella. Journal of cell science 31 28302912
2019 Human IFT52 mutations uncover a novel role for the protein in microtubule dynamics and centrosome cohesion. Human molecular genetics 23 31042281
2022 Molecular basis underlying the ciliary defects caused by IFT52 variations found in skeletal ciliopathies. Molecular biology of the cell 10 35704471
2018 IFT52 as a Novel Candidate for Ciliopathies Involving Retinal Degeneration. Investigative ophthalmology & visual science 9 30242358
2022 The intraflagellar transport protein IFT52 associated with short-rib thoracic dysplasia is essential for ciliary function in osteogenic differentiation in vitro and for sensory perception in Drosophila. Experimental cell research 5 35839863
2022 IFT52 plays an essential role in sensory cilia formation and neuronal sensory function in Drosophila. Insect science 3 36326027
2025 Complement Factor H and its C. elegans homolog regulate IFT52/OSM-6 and CNG channel localization in sensory neurons. bioRxiv : the preprint server for biology 1 41278837
2004 C20orf9-003 (ACI-1), a gene localized on chromosome 20q13.12 encoding for a 49 kD cytoplasmic protein with a putative nucleotide binding site. DNA sequence : the journal of DNA sequencing and mapping 0 15354348