Affinage

EFCAB5

EF-hand calcium-binding domain-containing protein 5 · UniProt A4FU69

Round 2 corrected
Length
1503 aa
Mass
173.4 kDa
Annotated
2026-04-28
20 papers in source corpus 1 papers cited in narrative 1 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EFCAB5 is a sperm-specific axonemal protein that localizes in proximity to the radial spoke scaffold protein CFAP91 in mature spermatozoa (PMID:40931011). Loss of EFCAB5 in knockout mice reduces sperm motility and male fertility, establishing it as a structural or regulatory component required for normal flagellar beating (PMID:40931011).

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 2025 Medium

    The identity and functional requirement of EFCAB5 in sperm were unknown; BioID2 proximity labeling of CFAP91 in transgenic mouse spermatozoa identified EFCAB5 as a sperm-specific axonemal factor, and knockout of Efcab5 revealed that it is required for normal sperm motility and male fertility.

    Evidence BioID2 proximity labeling in CFAP91-tagged transgenic mouse spermatozoa; Efcab5 knockout mouse model with motility and fertility phenotyping

    PMID:40931011

    Open questions at the time
    • Single study from one laboratory; independent replication is lacking
    • Direct physical interaction with CFAP91 or other radial spoke subunits has not been confirmed by reciprocal pull-down or structural methods
    • Whether EFCAB5 calcium-binding EF-hand domains are functionally required for motility regulation is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown whether EFCAB5 acts as a calcium sensor within the radial spoke complex to modulate flagellar waveform, and whether its function is conserved beyond mice.
  • No calcium-binding assays or EF-hand mutagenesis studies have been reported
  • No structural or cryo-EM data positioning EFCAB5 within the axoneme
  • Relevance to human male infertility has not been investigated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005929 cilium 1
Pathway
R-HSA-1474165 Reproduction 1
Partners
CFAP91

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 EFCAB5 was identified as a sperm-specific component in proximity to the radial spoke protein CFAP91 via BioID2-based proximity labeling in mature spermatozoa, establishing it as a sperm-specialized axonemal factor. Efcab5 knockout male mice exhibit reduced sperm motility and fertility, demonstrating that EFCAB5 is required for normal sperm flagellar movement. BioID2 proximity labeling in transgenic mice expressing FLAG/BioID2-tagged CFAP91 in mature spermatozoa; Efcab5 knockout mouse model with sperm motility and fertility assays Nature communications Medium 40931011

Source papers

Stage 0 corpus · 20 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 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2014 Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Molecular psychiatry 205 25288136
2000 Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. Proceedings of the National Academy of Sciences of the United States of America 135 10737800
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2017 Genetic architecture of epigenetic and neuronal ageing rates in human brain regions. Nature communications 84 28516910
2021 Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy. Acta pharmaceutica Sinica. B 66 35256949
2022 In-Depth In Vivo Crosslinking in Minutes by a Compact, Membrane-Permeable, and Alkynyl-Enrichable Crosslinker. Analytical chemistry 38 35575683
2022 USP7 targets XIAP for cancer progression: Establishment of a p53-independent therapeutic avenue for glioma. Oncogene 28 36243803
2023 SERBP1 Promotes Stress Granule Clearance by Regulating 26S Proteasome Activity and G3BP1 Ubiquitination and Protects Male Germ Cells from Thermostimuli Damage. Research (Washington, D.C.) 21 37223481
2020 Wnt regulation: exploring Axin-Disheveled interactions and defining mechanisms by which the SCF E3 ubiquitin ligase is recruited to the destruction complex. Molecular biology of the cell 19 32129710
2011 Differential expression of a set of genes in follicular and classic variants of papillary thyroid carcinoma. Endocrine pathology 19 21509594
2023 TRIM21 ameliorates hepatic glucose and lipid metabolic disorders in type 2 diabetes mellitus by ubiquitination of PEPCK1 and FASN. Cellular and molecular life sciences : CMLS 17 37249651
2019 Regulation of ETAA1-mediated ATR activation couples DNA replication fidelity and genome stability. The Journal of cell biology 17 31615875
2024 Whole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary sclerosing cholangitis. Hepatology communications 4 38967597
2022 Gene-Set Enrichment Analysis for Identifying Genes and Biological Activities Associated with Growth Traits in Dromedaries. Animals : an open access journal from MDPI 3 35049806
2025 Human protein interaction networks of ancestral and variant SARS-CoV-2 in organ-specific cells and bodily fluids. Nature communications 2 40593736
2025 Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility. Nature communications 1 40931011
2025 Clinical implications and molecular mechanism of long noncoding RNA LINC00518 and protein-coding genes in skin cutaneous melanoma by genome‑wide investigation. Archives of dermatological research 0 39987414