Affinage

CYLC2

Cylicin-2 · UniProt Q14093

Length
348 aa
Mass
39.1 kDa
Annotated
2026-04-28
9 papers in source corpus 2 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CYLC2 is a testis-specific, lysine-rich cytoskeletal protein that localizes to the acrosomal region of round spermatids and subsequently to the calyx of the perinuclear theca in mature spermatozoa (PMID:38013430). CYLC2 is essential for proper calyx assembly during spermiogenesis; its loss in mice causes decreased epididymal sperm counts, impaired cytoplasm shedding, severe structural sperm malformations, and male infertility, with partial functional redundancy provided by the paralog CYLC1 as demonstrated by additive defects in compound knockouts (PMID:38013430).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2008 Medium

    Proteomic detection of CYLC2 in mouse spermatozoa established it as a bona fide sperm protein, but its function and subcellular localization remained unknown.

    Evidence LC-MS/MS proteomic profiling of mouse spermatozoa

    PMID:18340633

    Open questions at the time
    • Identification was catalog-level; no functional or localization data provided
    • No validation by orthogonal methods such as immunofluorescence
  2. 2023 High

    CRISPR/Cas9 knockout and immunolocalization resolved CYLC2's precise subcellular trajectory during spermiogenesis and demonstrated its requirement for calyx assembly, cytoplasm shedding, sperm structural integrity, and male fertility, while compound mutants with CYLC1 revealed partial paralog compensation.

    Evidence CRISPR/Cas9 single and compound Cylc1/Cylc2 knockout mice with phenotypic characterization of sperm morphology, motility, fertility, and immunolocalization

    PMID:38013430

    Open questions at the time
    • Direct binding partners within the perinuclear theca have not been identified
    • No structural model for how lysine-rich repeats mediate calyx assembly
    • Whether CYLC2 loss causes male infertility in humans has not been tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular mechanism by which CYLC2 organizes the calyx — including its direct protein–protein interactions, higher-order assembly, and the basis for partial redundancy with CYLC1 — remains unresolved.
  • No interactome or co-immunoprecipitation data for CYLC2
  • No in vitro reconstitution of calyx-like structures with purified Cylicins
  • Human genetic evidence linking CYLC2 mutations to infertility is absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2
Localization
GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1
Pathway
R-HSA-1474165 Reproduction 2
Partners
CYLC1

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 CYLC2 (Cylicin 2) is a testis-specific cytoskeletal protein that localizes to the acrosomal region of round spermatids and then to the calyx within the perinuclear theca at the posterior part of mature sperm nuclei. CRISPR/Cas9-mediated Cylc2 knockout in mice demonstrated that CYLC2 is essential for proper calyx assembly during spermiogenesis; loss of CYLC2 results in decreased epididymal sperm counts, impaired shedding of excess cytoplasm, severe structural sperm malformations, and infertility. CRISPR/Cas9 gene knockout in mice, phenotypic characterization of sperm morphology and motility, immunolocalization eLife High 38013430
2023 CYLC2 contains lysine-rich repeats that confer an overall positive charge, consistent with its role as a structural cytoskeletal component of the calyx/perinuclear theca. Compound Cylc1/Cylc2 double-knockout males showed additive infertility compared to single knockouts, indicating the two Cylicins partially compensate for one another during calyx assembly. CRISPR/Cas9 compound mutant analysis, genetic epistasis, protein domain analysis eLife High 38013430
2008 CYLC2 protein was identified as a constituent of the mouse spermatozoon proteome, confirming its presence as a structural sperm protein. LC-MS/MS proteomic profiling of mouse spermatozoa after IPG strip prefractionation Proteomics Medium 18340633

Source papers

Stage 0 corpus · 9 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 The mouse sperm proteome characterized via IPG strip prefractionation and LC-MS/MS identification. Proteomics 126 18340633
2019 Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland. Translational psychiatry 93 30718454
2016 Optimizing a Male Reproductive Aging Mouse Model by D-Galactose Injection. International journal of molecular sciences 48 26771610
2019 Proteomic markers of low and high fertility bovine spermatozoa separated by Percoll gradient. Molecular reproduction and development 29 31134708
2023 Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human. eLife 16 38013430
2018 Typing tumors using pathways selected by somatic evolution. Nature communications 16 30297789
2020 Comparison of spermatozoal RNA extraction methods in goats. Analytical biochemistry 14 33285124
2021 Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first degree relatives of familial pancreatic cancer patients. Clinical genetics 10 34313325
2022 Mixed model-based eQTL analysis reveals lncRNAs associated with regulation of genes involved in sex determination and spermatogenesis: The key to understanding human gender imbalance. Computational biology and chemistry 0 35709667