Affinage

PPIL6

Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 · UniProt Q8IXY8

Round 2 corrected
Length
311 aa
Mass
35.2 kDa
Annotated
2026-04-28
14 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPIL6 is a cyclophilin-family protein whose isomerase domain has been structurally characterized alongside other human cyclophilins, with regions outside the proline-binding surface conferring isoform specificity (PMID:20676357). PPIL6 assembles into the radial spoke 1 (RS1) head-neck complex of sperm flagella together with DYDC1, NME5, and DNAJB13, and its abundance depends on the RS1 scaffold protein IQUB, establishing it as a structural component of the axonemal radial spoke machinery (PMID:39849482).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2010 Medium

    Establishing PPIL6 as a cyclophilin-family member resolved whether its isomerase domain possesses PPIase activity and cyclosporin-binding capacity, placing it within the broader functional landscape of human peptidyl-prolyl isomerases.

    Evidence Enzymatic PPIase activity assay, crystal structure determination, and cyclosporin-binding assay across 17 human cyclophilin domains

    PMID:20676357

    Open questions at the time
    • PPIL6-specific catalytic activity was not elaborated in detail beyond the family-wide survey
    • No physiological substrate or binding partner was identified
    • Cellular context of PPIL6 function was not addressed
  2. 2025 Medium

    Identification of PPIL6 as a component of the RS1 head-neck complex in sperm flagella answered where in the cell and in what macromolecular assembly PPIL6 operates, linking a cyclophilin-family protein to axonemal radial spoke architecture.

    Evidence Mass spectrometry, western blotting, and structural modeling in IQUB-deficient patient sperm and Iqub-knockout mice

    PMID:39849482

    Open questions at the time
    • Single study; independent replication in a separate cohort or model system is lacking
    • Whether PPIL6 contributes catalytic isomerase activity or serves a purely structural role within RS1 is unknown
    • Role of PPIL6 in motile cilia outside of sperm (e.g., airway cilia) has not been directly tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether PPIL6 functions catalytically within the RS1 complex, what its specific substrates are, and whether its loss alone causes ciliary or flagellar motility defects remain unresolved.
  • No PPIL6-specific knockout or knockdown study exists
  • No direct enzymatic substrate has been identified in vivo
  • Structural position of PPIL6 within the RS1 complex has not been resolved at atomic resolution

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005929 cilium 1
Partners
DNAJB13DYDC1IQUBNME5

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 PPIL6 was identified as a critical component of the radial spoke 1 (RS1) head-neck complex in human and mouse sperm flagella. Specifically, PPIL6 was shown to assemble into the RS1 head-neck complex together with DYDC1, NME5, and DNAJB13. Loss of IQUB caused deficiency of RS1 (but not RS2 or RS3) and was accompanied by down-regulation of PPIL6 among other RS1 components, establishing PPIL6's position within the RS1 macromolecular architecture. Protein mass spectrometry, western blotting, and bioinformatic structural modeling of RS1 components in IQUB-deficient patient sperm and Iqub-/- mice Cell communication and signaling : CCS Medium 39849482
2010 PPIL6 was characterized as a member of the human cyclophilin family of peptidyl-prolyl isomerases. Enzymatic activity assays across 15 of 17 human cyclophilin isomerase domains were performed; PPIL6's isomerase domain was assessed for PPIase activity and cyclosporin-binding competence. Structural analysis revealed that regions outside the proline-binding surface impart isoform specificity, and a substrate-binding S2 position was identified as a site of diversity across the family. Enzymatic activity assay (PPIase activity), crystallographic structure determination, cyclosporin-binding assay, computational substrate-docking simulations PLoS biology Medium 20676357

Source papers

Stage 0 corpus · 14 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
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Many sequence variants affecting diversity of adult human height. Nature genetics 520 18391951
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2003 The DNA sequence and analysis of human chromosome 6. Nature 242 14574404
2010 Structural and biochemical characterization of the human cyclophilin family of peptidyl-prolyl isomerases. PLoS biology 238 20676357
2018 Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy. Proceedings of the National Academy of Sciences of the United States of America 59 29987050
2018 E3 ubiquitin ligase RNF123 targets lamin B1 and lamin-binding proteins. The FEBS journal 33 29676528
2021 Basic pH reversed-phase liquid chromatography (bRPLC) in combination with tip-based strong cation exchange (SCX-Tip), ReST, an efficient approach for large-scale cross-linked peptide analysis. Analytica chimica acta 11 34535262
2024 Obesity impairs ciliary function and mucociliary clearance in the murine airway epithelium. American journal of physiology. Lung cellular and molecular physiology 7 39104315
2025 IQUB mutation induces radial spoke 1 deficiency causing asthenozoospermia with normal sperm morphology in humans and mice. Cell communication and signaling : CCS 5 39849482
2026 Single-cell full-length transcriptome of human lung reveals genetic effects on isoform regulation beyond gene-level expression. bioRxiv : the preprint server for biology 0 42039472