GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000041

Gene Ontology annotation based on UniPathway vocabulary mapping

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:32296183

A reference map of the human binary protein interactome.

PMID:34052850

FBXO43 variants in patients with female infertility characterized by early embryonic arrest.

Homozygous FBXO43 variants cause female infertility with early embryonic arrest; FBXO43 inhibits the APC/C and mediates metaphase II arrest as a cytostatic-factor component, with the truncating variant failing to upregulate CCNB1 and failing to rescue the mouse oocyte phenotype.

PMID:34445249

The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.

Review of the 69 SCF E3 ubiquitin ligase complexes in which variable F-box proteins determine substrate specificity.

PMID:34595750

A homozygous loss-of-function mutation in FBXO43 causes human non-obstructive azoospermia.

FBXO43 is a direct inhibitor of the APC/C E3 ligase; a homozygous nonsense mutation causes non-obstructive azoospermia with meiotic arrest at early diplotene; FBXO43 interacts directly with multiple APC/C subunits and does not interact with SKP1.

file:human/FBXO43/FBXO43-deep-research-falcon.md

Falcon deep research report for human FBXO43

FBXO43/EMI2 is the meiotic APC/C inhibitor underlying cytostatic-factor (CSF) metaphase-II arrest in vertebrate oocytes, suppressing APC/C-mediated cyclin B destruction to sustain MPF/CDK1 until fertilization.

"FBXO43/EMI2 is best understood functionally as a **meiotic inhibitor of the anaphase-promoting complex/cyclosome (APC/C)**—a multi-subunit E3 ubiquitin ligase controlling anaphase onset and exit from M phase. In vertebrate oocytes, APC/C inhibition is the core biochemical requirement for maintaining **metaphase II arrest** (cytostatic factor/CSF arrest) until fertilization."
The EMI2 C-terminal zinc-binding region (ZBR) inhibits APC/C by both impairing CDC20 coactivator association with the APC/C core and inhibiting UBE2C-dependent ubiquitin chain formation, i.e. it directly perturbs APC/C catalytic activity rather than acting only as a stoichiometric/pseudosubstrate blocker.

"the ZBR can (i) **impair association of the APC/C coactivator CDC20 with the APC/C core**, and (ii) **inhibit APC/C catalytic activity**, including UBE2C-dependent ubiquitin chain formation/elongation steps—implying EMI2 is not merely a stoichiometric blocker but directly perturbs APC/C function."
EMI2 requires a short C-terminal RL tail for physical docking to the APC/C, and this docking is required for its inhibitory activity, enabling engagement of the D-box and ZBR inhibitory modules.

"EMI2 requires a short **C-terminal RL tail** for physical docking to the APC/C; this docking is required for inhibitory activity, facilitating the functional engagement of other inhibitory regions (including ZBR)."
At fertilization, Ca2+/CaMKII and Plx1/PLK1 phosphorylation generate a beta-TrCP-recognized phosphodegron driving EMI2 ubiquitination and degradation, releasing APC/C inhibition for meiotic exit.

"Ca2+-activated signaling (via **CaMKII**) and **Plx1/Plk1** phosphorylation leads to **β-TrCP recognition**, ubiquitination, and degradation of EMI2, thereby releasing APC/C inhibition and allowing meiotic exit."