MYCBPAP

MYCBPAP is a testis-enriched protein that functions as a structural component of the C2a projection of the motile ciliary/flagellar central apparatus, where it forms a complex with CFAP65, CFAP70, and the Chlamydomonas-specific subunit FAP174, contributing to axonemal architecture (PMID:33988244, PMID:39092789, PMID:41724729). In spermiogenesis, MYCBPAP is required for centrosome–nuclear envelope docking, acrosome biogenesis, manchette organization, and sperm tail assembly, interacting with the centrosomal protein CCP110 and the ribosome elimination-associated protein ARMC3 (PMID:39092789, PMID:39704931). Loss-of-function mutations in MYCBPAP cause asthenoteratozoospermia and male infertility in both mice and humans (PMID:39092789, PMID:39704931).

1. 2002 Medium

   Identification of MYCBPAP as a testis-specific, post-meiotically expressed protein that binds the c-Myc-binding protein AMY-1 established it as a candidate spermatogenesis factor of unknown function.

   Evidence Yeast two-hybrid screen of human testis cDNA library with co-localization in 293T/HeLa cells

   PMID:12151104

   Open questions at the time

   • Interaction validated only by yeast two-hybrid and co-localization, not by endogenous co-IP or reconstitution
   • No functional consequence of interaction tested
   • Molecular activity of MYCBPAP undefined
2. 2020 Medium

   Localization of MYCBPAP mRNA and protein to motile ciliated cells extended its expression context beyond the testis and linked it to the motile cilia program.

   Evidence mRNA and protein localization in human motile ciliated cell populations

   PMID:32616903

   Open questions at the time

   • No functional consequence of ciliary localization demonstrated
   • Whether MYCBPAP contributes to airway cilia function is untested
3. 2021 High

   Structural and biochemical placement of the MYCBPAP ortholog FAP147 within the C2a projection of the Chlamydomonas central apparatus, in a complex with FAP65/CFAP65 and FAP70/CFAP70, defined its axonemal substructure and immediate molecular neighbors.

   Evidence Cryo-EM of wild-type and fap70-1 mutant axonemes, mass spectrometry, co-IP with HA-tagged FAP70

   PMID:33988244

   Open questions at the time

   • C2a projection function in motility regulation not directly tested
   • Whether MYCBPAP is an enzymatic or purely structural component is unknown
4. 2024 High

   Knockout studies in mice and identification of human loss-of-function variants established that MYCBPAP is essential for centrosome–nuclear envelope docking, acrosome biogenesis, manchette organization, and sperm tail assembly, with loss causing asthenoteratozoospermia and male infertility; interactome analysis confirmed the conserved CFAP65/CFAP70 complex and identified new partners CCP110 and ARMC3.

   Evidence Mycbpap-knockout mouse with fertility and cellular phenotyping, transgenic rescue, whole-exome sequencing of infertile patients, endogenous co-IP/mass spectrometry, testis proteomics

   PMID:39092789 PMID:39704931

   Open questions at the time

   • Enzymatic activity versus scaffolding role undetermined
   • How MYCBPAP coordinates centrosome–nuclear envelope docking mechanistically (e.g., via CCP110) is not resolved
   • Whether MYCBPAP loss causes primary ciliary dyskinesia phenotypes beyond infertility is untested
5. 2026 Medium

   Mapping the interaction interface between the MYCBPAP domain and FAP174 in Chlamydomonas revealed a distributed binding surface rather than discrete hotspot residues, refining the structural basis of C2a projection assembly.

   Evidence Overlay binding assay, CABS-Dock in silico docking, molecular dynamics simulation, alanine scanning mutagenesis

   PMID:41724729

   Open questions at the time

   • No high-resolution co-structure available
   • In vitro reconstitution of the full C2a subcomplex not performed
   • Whether FAP174/MYCBP-1 interaction is conserved in mammalian sperm flagella is untested

• Whether MYCBPAP possesses intrinsic catalytic activity or acts solely as a structural scaffold within the C2a projection and during spermiogenesis remains unresolved, and its potential role in motile cilia outside the testis (e.g., airway, ependymal) has not been functionally assessed.
• No enzymatic activity tested
• No structural model of mammalian MYCBPAP
• Role in non-testicular motile cilia undefined