Affinage

IFT22

Intraflagellar transport protein 22 homolog · UniProt Q9H7X7

Round 2 corrected
Length
185 aa
Mass
20.8 kDa
Annotated
2026-04-28
34 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IFT22 (RABL5) is a Rab-like GTPase and peripheral subunit of the intraflagellar transport complex B (IFT-B) that regulates the cellular pool size and ciliary partitioning of IFT particles rather than serving as a structural scaffold for ciliogenesis (PMID:22076686, PMID:29654116). IFT22 possesses low intrinsic GTPase activity; in its GTP-bound state it binds and stabilizes the Arf-like GTPase BBS3/ARL6, and the two GTPases cooperatively recruit the BBSome to the basal body for coupling with the IFT-B1 subcomplex and ciliary entry (PMID:31953262). IFT22 is dispensable for IFT-B complex assembly and cilia formation in mammalian cells, consistent with a regulatory rather than core-structural role in IFT (PMID:29654116, PMID:20409822). The requirement for IFT22 in flagellum construction varies across organisms: it is essential in Trypanosoma brucei, where its depletion phenocopies retrograde IFT loss, but dispensable in mammalian RPE1 cells and C. elegans sensory cilia (PMID:19240117, PMID:29654116).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2009 High

    Establishing that IFT22 is a motile IFT-associated factor that is not required for cilium construction resolved whether it is a core structural IFT component or a regulatory accessory subunit.

    Evidence GFP-tagged IFTA-2/RABL5 tracked by live imaging in C. elegans sensory cilia; mutant analysis showed normal cilia structure (C. elegans) while RNAi in T. brucei produced short flagella phenocopying retrograde IFT loss

    PMID:19240117 PMID:20409822

    Open questions at the time
    • Organism-specific essentiality was unexplained mechanistically
    • GTPase activity of IFT22 had not been measured
    • Mammalian function was untested
  2. 2010 High

    Biochemical placement of IFT22 within the ~500 kDa IFT-B core in Chlamydomonas established it as a bona fide complex subunit rather than a transient IFT cargo.

    Evidence Biochemical fractionation, yeast two-hybrid, bacterial coexpression, and chemical cross-linking in Chlamydomonas reinhardtii

    PMID:20435895

    Open questions at the time
    • Precise position within IFT-B subcomplex hierarchy was unresolved
    • Interaction topology in human IFT-B was unknown
  3. 2012 High

    Bidirectional genetic manipulation in Chlamydomonas demonstrated that IFT22 controls the total cellular pool of IFT particles and governs their partitioning between cell body and flagella, defining a unique regulatory function.

    Evidence RNAi knockdown and overexpression with quantitative immunofluorescence and Western blotting in Chlamydomonas

    PMID:22076686

    Open questions at the time
    • Whether pool-size regulation depends on GTPase cycling was unknown
    • Downstream effectors of IFT22-mediated partitioning were unidentified
  4. 2016 High

    Systematic pairwise mapping of all 16 IFT-B subunits reclassified IFT22 as a peripheral rather than core subunit, refining its architectural position within IFT-B and explaining its dispensability for complex integrity.

    Evidence Visible immunoprecipitation (VIP) assay and affinity proteomics of human ciliary proteins

    PMID:26980730 PMID:27173435

    Open questions at the time
    • Direct binding partner within the peripheral subcomplex was not narrowed to a single subunit
    • Structural basis for peripheral attachment was lacking
  5. 2018 High

    CRISPR knockout of IFT22 in mammalian RPE1 cells showed no ciliogenesis or ciliary trafficking defects, definitively demonstrating dispensability in mammals and focusing its role on regulatory rather than structural IFT functions.

    Evidence CRISPR/Cas9 knockout in human RPE1 cells with ciliogenesis and ciliary protein trafficking assays

    PMID:29654116

    Open questions at the time
    • BBSome recruitment and signaling-dependent phenotypes were not assessed in these knockout cells
    • Possible redundancy with IFT27 was not tested
  6. 2020 High

    Demonstration that GTP-bound IFT22 binds and stabilizes GTP-bound BBS3/ARL6 to cooperatively recruit the BBSome to the basal body provided the first mechanistic explanation for IFT22's regulatory role, linking its GTPase cycle to BBSome-IFT coupling.

    Evidence In vitro GTPase activity assay, co-immunoprecipitation, single-particle in vivo fluorescence imaging, and functional rescue experiments in Chlamydomonas

    PMID:31953262

    Open questions at the time
    • GTPase-activating protein (GAP) and guanine-nucleotide exchange factor (GEF) for IFT22 are unidentified
    • Structural basis of the IFT22–BBS3 interaction is unresolved
    • Whether IFT22 GTPase cycling explains the IFT particle pool-size regulation phenotype remains untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the identity of IFT22's GAP and GEF, the structural basis for IFT22–BBS3 cooperative BBSome recruitment, and whether IFT22 GTPase cycling underlies the organism-specific differences in its essentiality for ciliogenesis.
  • No GAP or GEF identified for IFT22
  • No high-resolution structure of IFT22 in complex with BBS3 or the BBSome
  • Mechanism underlying organism-specific essentiality (T. brucei vs mammals) is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0003924 GTPase activity 1
Localization
GO:0005929 cilium 4 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 4
Partners
BBS3IFT25IFT27IFT46IFT52IFT81IFT88
Complex memberships
IFT-B complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 IFT22 was identified as a component of the ~500 kDa core of IFT complex B in Chlamydomonas reinhardtii, alongside IFT88, IFT81, IFT74/72, IFT52, IFT46, IFT27, and IFT25. Chemical cross-linking provided evidence of an association between IFT27 and IFT81, placing IFT22 within a defined subunit architecture of the IFT-B core. Biochemical fractionation, yeast two-hybrid, bacterial coexpression, chemical cross-linking The Journal of biological chemistry High 20435895
2009 In Caenorhabditis elegans, the IFT22 ortholog IFTA-2/RABL5 moves in an IFT-like manner within sensory cilia and participates in signaling processes but is not required for cilia construction, establishing it as a potential regulatory rather than structural IFT component. GFP-tagging, in vivo time-lapse microscopy, IFT velocity measurements, mutant analysis Methods in cell biology Medium 20409822
2009 In Trypanosoma brucei, the RABL5/IFT22 ortholog colocalizes with IFT proteins at the basal body and in the flagellum matrix, moves anterogradely, accumulates in short flagella of retrograde IFT mutants, and is restricted to the basal body in anterograde IFT mutants. RNAi knockdown of RABL5 is essential for flagellum construction, producing a phenotype similar to retrograde IFT inactivation with short flagella filled with IFT proteins. GFP fusion live imaging, RNAi knockdown, analysis of IFT mutant backgrounds Journal of cell science High 19240117
2012 In Chlamydomonas reinhardtii, IFT22 (RABL5 homolog) is confirmed as an IFT-B subunit. Depletion of IFT22 reduces the cellular pool of both IFT complex A and B proteins, yet paradoxically increases the amount of IFT particles in flagella. Overexpression of IFT22 also causes accumulation of IFT particles in flagella. These data establish that IFT22 controls the cellular availability of IFT particles and regulates partitioning of IFT particles between the cell body and flagellar compartments. RNAi knockdown, overexpression, quantitative immunofluorescence, Western blotting Cytoskeleton (Hoboken, N.J.) High 22076686
2016 Affinity proteomics of 217 human ciliary proteins placed IFT22 within the IFT-B complex network, revealing sub-complex interactions consistent with IFT-B core architecture and linking IFT22 to vesicle transport and ubiquitination pathways at cilia. Affinity proteomics, AP-MS, biochemical validation of sub-complexes Nature communications Medium 27173435
2016 Using the visible immunoprecipitation (VIP) assay, IFT22 was mapped as a peripheral subunit of the IFT-B complex, associated with the peripheral subcomplex (rather than the core) alongside IFT57, IFT38, IFT54, IFT20, and IFT172. Visible immunoprecipitation (VIP) assay, systematic pairwise protein-protein interaction mapping The Journal of biological chemistry High 26980730
2018 IFT22 knockout cells generated by CRISPR/Cas9 in RPE1 cells showed no defects in ciliogenesis or ciliary protein trafficking, demonstrating that IFT22 is dispensable for IFT-B complex assembly at the ciliary base and for cilia formation in mammalian cells. CRISPR/Cas9 knockout, ciliogenesis assay, ciliary protein trafficking analysis Biology open High 29654116
2020 IFT22 (RABL5) is an active GTPase with low intrinsic GTPase activity. In Chlamydomonas, IFT22 is part of the IFT-B1 subcomplex but, independently of IFT-B1 association, binds and stabilizes the Arf-like GTPase BBS3 (ARL6). When both IFT22 and BBS3 are in their GTP-bound states, they cooperatively recruit the BBSome to the basal body for coupling with the IFT-B1 subcomplex and ciliary entry. IFT22 is not required for BBSome transport within cilia, indicating that the BBSome is transferred from IFT22 to IFT trains at the ciliary base. GTPase activity assay, co-immunoprecipitation, single-particle in vivo fluorescence imaging, biochemical fractionation, functional rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 31953262
2014 In zebrafish, knockdown of ift22 (anterograde IFT component) suppresses the bbs7-related retrograde intracellular melanosome transport delay, functionally placing IFT22-mediated anterograde transport as a modulator of retrograde transport balance. This epistatic relationship reveals a role for IFT22 in directional intracellular transport. Morpholino knockdown in zebrafish, melanosome transport assay, genetic epistasis Developmental biology Medium 24938409
2015 High-throughput affinity-purification mass spectrometry (BioPlex) in HEK293T cells identified IFT22 as part of a human protein interaction network, placing it in co-complex with other IFT-B subunits in human cells. Affinity purification–mass spectrometry (AP-MS), BioPlex network analysis Cell Low 26186194

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2017 The human cytoplasmic dynein interactome reveals novel activators of motility. eLife 118 28718761
2016 Overall Architecture of the Intraflagellar Transport (IFT)-B Complex Containing Cluap1/IFT38 as an Essential Component of the IFT-B Peripheral Subcomplex. The Journal of biological chemistry 100 26980730
2017 Cell cycle-dependent phosphorylation regulates RECQL4 pathway choice and ubiquitination in DNA double-strand break repair. Nature communications 89 29229926
2015 Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis. Nature cell biology 81 26389662
2016 Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways. Cell reports 77 26972000
2002 Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants. Molecular vision 71 12107410
2010 Direct interactions of intraflagellar transport complex B proteins IFT88, IFT52, and IFT46. The Journal of biological chemistry 68 20435895
2009 A novel function for the atypical small G protein Rab-like 5 in the assembly of the trypanosome flagellum. Journal of cell science 52 19240117
2018 Robust interaction of IFT70 with IFT52-IFT88 in the IFT-B complex is required for ciliogenesis. Biology open 39 29654116
2020 Intraflagellar transport protein RABL5/IFT22 recruits the BBSome to the basal body through the GTPase ARL6/BBS3. Proceedings of the National Academy of Sciences of the United States of America 35 31953262
2012 The RABL5 homolog IFT22 regulates the cellular pool size and the amount of IFT particles partitioned to the flagellar compartment in Chlamydomonas reinhardtii. Cytoskeleton (Hoboken, N.J.) 24 22076686
2018 CRISPR/Cas9-mediated Genomic Editing of Cluap1/IFT38 Reveals a New Role in Actin Arrangement. Molecular & cellular proteomics : MCP 20 29615496
2025 Multimodal cell maps as a foundation for structural and functional genomics. Nature 18 40205054
2023 CRISPR-based screening identifies XPO7 as a positive regulator of senescence. Protein & cell 18 36897256
2021 Genetic basis of chicken plumage color in artificial population of complex epistasis. Animal genetics 16 34224160
2009 Functional genomics of intraflagellar transport-associated proteins in C. elegans. Methods in cell biology 13 20409822
2014 Functional characterization of Prickle2 and BBS7 identify overlapping phenotypes yet distinct mechanisms. Developmental biology 7 24938409
2024 Identification of the principal neuropeptide MIP and its action pathway in larval settlement of the echiuran worm Urechis unicinctus. BMC genomics 3 38641568
2024 Autism Spectrum Disorder and Atypical Brain Connectivity: Novel Insights from Brain Connectivity-Associated Genes by Combining Random Forest and Support Vector Machine Algorithm. Omics : a journal of integrative biology 2 39417279
2025 Design of a Pan-Tumor Fluorescence Imaging Cocktail for Fluorescence-Guided Surgery. Bioconjugate chemistry 0 41412973