Affinage

CPLANE2

Ciliogenesis and planar polarity effector 2 · UniProt Q9BU20

Length
258 aa
Mass
28.5 kDa
Annotated
2026-06-09
31 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CPLANE2 (RSG1) is a small GTPase that governs a late maturation step of ciliogenesis at the mother centriole, where it is required for axonemal microtubule elongation after the basal body has docked onto ciliary vesicles (PMID:29038301). It localizes to the mother centriole in a manner dependent on tau tubulin kinase 2 (TTBK2), the CPLANE complex protein Inturned (INTU), and its own GTPase activity, and its loss in mouse embryos produces lethality with diminished Hedgehog signaling despite proper recruitment of cilia initiation proteins and ciliary vesicle docking (PMID:29038301). A point mutation in the GTP-binding (G1) pocket disrupts Hedgehog signaling and cilia initiation without preventing basal body localization of RSG1 or IFT proteins, establishing that its GTPase activity acts downstream of basal body maturation to drive axonemal extension (PMID:38721990). CPLANE2 physically associates with the CPLANE complex and the transition zone protein FAM92 in a GTP-dependent manner, and its disease-associated variants disrupt basal body docking, intraflagellar transport protein recruitment, and transition zone architecture, causing ciliopathy in humans (PMID:40593758). Across multiciliated cells it additionally regulates axonemal IFT dynamics, cytoplasmic localization of the retrograde IFT-A protein IFT43, and apical positioning of basal bodies (PMID:24192041).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2013 Medium

    Established RSG1 as a multi-functional ciliogenesis regulator by showing it is needed for IFT dynamics, IFT43 localization, and basal body trafficking, moving it beyond a single discrete role.

    Evidence Morpholino loss-of-function in Xenopus multiciliated cells with live IFT imaging and marker immunofluorescence

    PMID:24192041

    Open questions at the time
    • Did not define the molecular activity linking RSG1 to IFT
    • Knockdown specificity not orthogonally validated
    • No direct partner identified
  2. 2017 High

    Placed RSG1 at a defined point in the ciliogenesis pathway by showing its mother-centriole localization depends on TTBK2, INTU, and GTPase activity, and that its loss blocks axonemal elongation after vesicle docking.

    Evidence Mouse knockout with localization imaging, genetic epistasis in TTBK2/INTU backgrounds, and GTPase activity assays

    PMID:29038301

    Open questions at the time
    • Direct molecular effectors of axonemal elongation not identified
    • How GTPase cycling is regulated at the centriole unknown
    • Mechanism connecting RSG1 to Hedgehog signaling not resolved
  3. 2024 Medium

    Separated RSG1's structural localization role from its catalytic role by showing a G1-domain point mutation blocks cilia initiation while leaving basal body localization of RSG1 and IFT proteins intact.

    Evidence Forward genetic screen and point mutation mapping with localization imaging in mutant vs wild-type mouse embryos

    PMID:38721990

    Open questions at the time
    • GTP-loaded effector engaged during elongation not identified
    • Single lab, single allele
    • Does not explain how GTP hydrolysis is coupled to axonemal extension
  4. 2025 High

    Identified the physical partners of RSG1 and tied human disease variants to specific ciliogenesis failures, defining how RSG1 operates within the CPLANE complex and at the transition zone.

    Evidence Affinity purification mass spectrometry with GTP-dependency, patient-variant functional ciliogenesis assays, and transition zone imaging (peer-reviewed; preceded by a confirming preprint)

    PMID:39386566 PMID:40593758

    Open questions at the time
    • Direct vs indirect nature of the FAM92 interaction not fully resolved
    • Structural basis of GTP-dependent binding undefined
    • Order of events linking docking, IFT recruitment, and transition zone assembly unclear
  5. 2025 Low

    Proposed that RSG1 GTPase activity is redox-sensitive, offering a mechanistic rationale for folic acid rescue of neural tube defects in mutant mice.

    Evidence Rsg1 mutant mouse NTD models with folic acid dosing, ROS measurement, and cilia formation assays

    PMID:39755226

    Open questions at the time
    • ROS-sensitivity of RSG1 GTPase activity not directly validated for the protein
    • Single lab
    • Mechanism is proposed, not biochemically demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The downstream GTP-dependent effector through which RSG1 drives axonemal microtubule elongation, and the structural basis of its CPLANE/FAM92 engagement, remain undefined.
  • No identified effector executing axonemal extension
  • No experimental structure of the RSG1-CPLANE-FAM92 assembly
  • Regulator of RSG1 GTP/GDP cycling at the centriole unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 2
Localization
GO:0005815 microtubule organizing center 2 GO:0005929 cilium 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-1266738 Developmental Biology 1
Partners
FAM92FUZINTUTTBK2
Complex memberships
CPLANE complex

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 RSG1 (CPLANE2) localizes to the mother centriole in a process that depends on tau tubulin kinase 2 (TTBK2), the CPLANE complex protein Inturned (INTU), and its own GTPase activity. Mouse embryos lacking RSG1 die at E12.5 with decreased Hedgehog signaling; mutant mother centrioles recruit cilia initiation proteins and dock onto ciliary vesicles, but axonemal microtubules fail to elongate, indicating RSG1 acts at a final maturation step of the mother centriole/ciliary vesicle to allow axonemal extension. Mouse knockout (loss-of-function), live imaging/immunofluorescence localization, genetic dependency analysis (TTBK2/INTU mutant backgrounds), GTPase activity assays The Journal of cell biology High 29038301
2013 Rsg1 (CPLANE2) is required for normal axonemal IFT dynamics in multiciliated cells, for cytoplasmic localization of the retrograde IFT-A protein IFT43, and for apical localization of basal bodies. Loss of Rsg1 in Xenopus impairs all three processes, placing RSG1 as a regulator of multiple aspects of ciliogenesis including basal body trafficking and IFT protein localization. Morpholino-based loss-of-function in Xenopus multiciliated cells, live imaging of IFT dynamics, immunofluorescence localization of IFT43 and basal body markers Cilia Medium 24192041
2024 A point mutation in the GTP-binding pocket (G1 domain) of RSG1 in the mouse L3P mutant disrupts Sonic hedgehog signaling and cilia initiation. The mutant RSG1 protein and other centrosomal/IFT proteins still localize to the basal body, indicating that RSG1 GTPase activity is not required for basal body maturation but is needed for a downstream step in axonemal elongation. Forward genetic screen, point mutation mapping, immunofluorescence localization of RSG1 and IFT proteins in mutant vs. wild-type mouse embryos Genesis (New York, N.Y. : 2000) Medium 38721990
2025 Affinity purification mass spectrometry (APMS) shows that RSG1 (CPLANE2) binds the CPLANE complex and the transition zone protein FAM92 in a GTP-dependent manner. Disease-associated variants in CPLANE2/RSG1 disrupt two vital steps of ciliogenesis: basal body docking and recruitment of intraflagellar transport proteins. CPLANE is required for normal transition zone architecture. Affinity purification mass spectrometry (APMS), patient-derived variant analysis, ciliogenesis assays (basal body docking, IFT recruitment), transition zone architecture imaging Nature communications High 40593758
2024 RSG1 (CPLANE2) binds the CPLANE complex and the transition zone protein FAM92 in a GTP-dependent manner (preprint version of the same finding, independently confirming the peer-reviewed result). Affinity purification mass spectrometry (APMS), GTP-dependency assay, ciliogenesis functional assays bioRxivpreprint Medium 39386566
2025 Folic acid at moderate levels benefits cilia-based neural tube defects in RSG1 mutant mice. The proposed mechanism is that fortified FA levels reduce basal reactive oxygen species (ROS), which in turn reduces ROS-sensitive GTPase activity required for ciliogenesis, suggesting RSG1 GTPase activity is ROS-sensitive. Mouse NTD models with Rsg1 mutation, folic acid dosage experiments, ROS measurement, cilia formation assays Developmental biology Low 39755226
2020 Bioinformatic analysis identifies INTU and FUZ (CPLANE complex partners of RSG1) as novel members of homologous HerMon complexes containing tripled Longin domains, suggesting INTU/FUZ may act as GEFs for Rab GTPases during ciliogenesis, providing structural context for how RSG1 operates within the CPLANE complex. Evolutionary coevolution-based contact prediction and sequence conservation analysis (computational) Bioinformatics (Oxford, England) Low 31562761
2030 In silico three-dimensional structural analysis predicts that a pathogenic FUZ variant alters interactions between FUZ and CPLANE2 (RSG1), potentially disrupting ciliogenesis. This supports a direct physical interaction between FUZ and RSG1 within the CPLANE complex. In silico 3D structural analysis of variant effect on FUZ–RSG1 interaction Clinical genetics Low 41952398

Source papers

Stage 0 corpus · 31 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Placental cell expression of HLA-G2 isoforms is limited to the invasive trophoblast phenotype. Journal of immunology (Baltimore, Md. : 1950) 90 14634138
1997 Molding a peptide into an RNA site by in vivo peptide evolution. Proceedings of the National Academy of Sciences of the United States of America 53 9342332
2017 The small GTPase RSG1 controls a final step in primary cilia initiation. The Journal of cell biology 29 29038301
2001 Structural characterization of the complex of the Rev response element RNA with a selected peptide. Chemistry & biology 26 11358697
1988 A new family of repetitive, retroposon-like sequences in the genome of the rainbow trout. European journal of biochemistry 26 2843369
2005 Evolvability of the mode of peptide binding by an RNA. RNA (New York, N.Y.) 24 16043495
2013 The Small GTPase Rsg1 is important for the cytoplasmic localization and axonemal dynamics of intraflagellar transport proteins. Cilia 19 24192041
2022 CPLANE Complex and Ciliopathies. Biomolecules 15 35740972
2020 Hexa-Longin domain scaffolds for inter-Rab signalling. Bioinformatics (Oxford, England) 13 31562761
2011 Specificity of RSG-1.2 peptide binding to RRE-IIB RNA element of HIV-1 over Rev peptide is mainly enthalpic in origin. PloS one 11 21853108
2020 Improved Detection of Potentially Pleiotropic Genes in Coronary Artery Disease and Chronic Kidney Disease Using GWAS Summary Statistics. Frontiers in genetics 8 33343632
2023 Integrated Microbiota and Metabolome Analysis to Assess the Effects of the Solid-State Fermentation of Corn-Soybean Meal Feed Using Compound Strains. Microorganisms 7 37317292
2022 Role of Mutations in Differential Recognition of Viral RNA Molecules by Peptides. Journal of chemical information and modeling 7 35833626
2002 Displacement of Mn2+ from RNA by K+, Mg2+, neomycin B, and an arginine-rich peptide: indirect detection of nucleic acid/ligand interactions using phosphorus relaxation enhancement. Journal of the American Chemical Society 7 12475335
1980 Necator americanus in infant rabbits: complete development, humoral antibody, leukocyte response and serum protein changes following infection. Journal of helminthology 7 7410812
2022 Characterization of Rsg3, a novel greenbug resistance gene from the Chinese barley landrace PI 565676. The plant genome 6 36479942
2025 The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture. Nature communications 4 40593758
2024 RSG1 is required for cilia-dependent neural tube closure. Genesis (New York, N.Y. : 2000) 3 38721990
2023 Genetic Diversity of Barley Accessions from East Asia for Greenbug Resistance. Plants (Basel, Switzerland) 3 38005694
2020 Probing the mechanism of peptide binding to REV response element RNA of HIV-1; MD simulations and free energy calculations. Journal of biomolecular structure & dynamics 3 33323039
2008 Tailoring the peptide-binding specificity of an RNA by combinations of specificity-altering mutations. Nucleosides, nucleotides & nucleic acids 3 18569791
1998 Inheritance of Complete Resistance to Pearl Millet Downy Mildew. Plant disease 3 30856952
1987 Physical map of the Rhodobacter sphaeroides bacteriophage phi RsG1 genome and location of the prophage on the host chromosome. Journal of bacteriology 3 3040695
2025 Moderate levels of folic acid benefit outcomes for cilia based neural tube defects. Developmental biology 2 39755226
2024 Characterization of a new barley greenbug resistance gene Rsg4 in the Chinese landrace CI 2458. The plant genome 2 39510979
2023 Identification of a new Rsg1 allele conferring resistance to multiple greenbug biotypes from barley accessions PI 499276 and PI 566459. The plant genome 2 38093595
2008 Manipulation of the peptide-binding specificity of an RNA in a rational manner by combinations of specificity-altering mutations. Nucleic acids symposium series (2004) 2 18776229
2003 The variability of the peptide-binding specificity of RNA. Nucleic acids research. Supplement (2001) 2 14510450
2024 The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture. bioRxiv : the preprint server for biology 1 39386566
2026 Phenotypic Expansion and Molecular Implications in Recessive FUZ-Related Ciliopathy. Clinical genetics 0 41952398
1999 In vivo selection of RNA-binding peptides from combinatorial libraries. Nucleic acids symposium series 0 10780455

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