| Aspect | Key findings | Evidence type (review/primary; organism) | Representative source(s) with year and URL | Citation ID(s) |
|---|---|---|---|---|
| Identity/domains | Human FBXO43 is the same protein as EMI2/Erp1/XERP1; it is an FBXO-class F-box protein and contains a C-terminal zinc-binding region (ZBR/IBR-like region) central to APC/C inhibition. Structural work maps distinct inhibitory surfaces within the ZBR and a post-ZBR segment that contacts APC/C. | Primary biochemical/structural; vertebrate/human protein context | Shoji et al., 2014, FEBS Open Bio, https://doi.org/10.1016/j.fob.2014.06.010; Vadhan et al., 2020, Kaohsiung J Med Sci, https://doi.org/10.1002/kjm2.12208 | (pqac-00000001, pqac-00000007, pqac-00000006) |
| Mechanism | FBXO43/EMI2 is the key APC/C inhibitor underlying cytostatic factor arrest in mature oocytes. The ZBR impairs Cdc20 association with the APC/C core and inhibits APC/C-mediated ubiquitylation, including UBE2C/Ube2S-dependent steps; Emi2 can act catalytically/substoichiometrically rather than as a simple pseudosubstrate. | Primary mechanistic biochemistry; Xenopus/vertebrate oocyte systems | Shoji et al., 2014, https://doi.org/10.1016/j.fob.2014.06.010; Sako et al., 2014, https://doi.org/10.1038/ncomms4667; Tang, 2010 review of primary literature | (pqac-00000001, pqac-00000007, pqac-00000000, pqac-00000003, pqac-00000010) |
| Regulation | Emi2 activity/stability is controlled by multisite phosphorylation. Cdc2/Cdk1 phosphorylation destabilizes Emi2 around MI; CaMKII and Plx1 phosphorylation at fertilization promotes β-TrCP recognition, ubiquitination, and degradation, relieving APC/C inhibition for meiotic exit. PP2A antagonizes destabilizing phosphorylation and helps restabilize APC/C binding. | Primary + synthesis/review; Xenopus/vertebrate oocyte systems | Ohe et al., 2010, Mol Biol Cell, https://doi.org/10.1091/mbc.e09-11-0974; Tang, 2010; Vadhan et al., 2020, https://doi.org/10.1002/kjm2.12208 | (pqac-00000004, pqac-00000009, pqac-00000010, pqac-00000006) |
| Localization | Function is executed in the oocyte cytoplasm on/with the APC/C during meiotic metaphase II; docking requires a short C-terminal RL tail that mediates Emi2 association with APC/C, enabling D-box and ZBR inhibitory actions. | Primary cell-cycle biochemistry; vertebrate oocyte systems | Ohe et al., 2010, https://doi.org/10.1091/mbc.e09-11-0974 | (pqac-00000004) |
| Biological processes | Canonical role is maintenance of metaphase II arrest and prevention of premature cyclin B destruction in oocytes, thereby preserving MPF/Cdk1 activity until fertilization-triggered Ca2+ signaling. Additional meiosis-related roles are reported in spermatogenesis, where loss causes meiotic failure and male infertility in mice. | Review + primary genetics; vertebrates/mouse | Madgwick & Jones, 2007, https://doi.org/10.1186/1747-1028-2-4; Gopinathan et al., 2017, https://doi.org/10.1016/j.celrep.2017.06.033; Xuan et al., 2024, https://doi.org/10.1186/s13619-024-00196-9 | (pqac-00000011, pqac-00000008) |
| Human genetics | In a consanguineous Chinese family, a homozygous FBXO43 missense variant p.G664D segregated with male infertility/teratozoospermia; the variant was absent from 1000 Genomes and ExAC. Among 124 sporadic teratozoospermia cases, 4 additional heterozygous FBXO43 variants were found, versus none in 200 fertile controls; IVF/ICSI outcomes in affected brothers showed poor embryo quality and no live birth. A 2024 review also cites homozygous p.Q583X and p.G664D variants associated with male infertility. | Primary human genetics + review; human | Ma et al., 2019, Fertil Steril, https://doi.org/10.1016/j.fertnstert.2019.01.007; Xuan et al., 2024, https://doi.org/10.1186/s13619-024-00196-9 | (pqac-00000008, pqac-00000011) |
| Cancer associations | FBXO43/EMI2 is emerging as a cancer-associated marker, but evidence is less mature than for reproductive biology. In breast cancer IHC, 105/192 tumors (54.7%) had high EMI2; high expression associated with higher grade, larger tumor size, lymph-node metastasis, and worse survival, with reported HR 3.93. Recent HCC transcriptomic models also include FBXO43 as part of poor-risk/diagnostic signatures, though these are primarily bioinformatic rather than mechanistic. | Primary clinical association + bioinformatics; human | Vadhan et al., 2020, https://doi.org/10.1002/kjm2.12208; Gao et al., 2024, https://doi.org/10.31083/j.fbl2905202; Sucularlı, 2025, https://doi.org/10.1371/journal.pone.0331118 | (pqac-00000006, pqac-00000014) |
| Other roles | Beyond meiosis, emi2/fbxo43 is up-regulated in multiciliated cell progenitors and transiently inhibits APC/C^Cdh1 after cell-cycle exit, enabling Plk1 activation and centriole amplification/basal-body formation during ciliogenesis. This supports a broader APC/C-modulatory role outside gametogenesis. | Primary developmental cell biology; Xenopus | Kim et al., 2022, Science Advances, https://doi.org/10.1126/sciadv.abm7538 | (pqac-00000013) |
| Structural/mechanistic visual evidence | Figure-level evidence shows the Emi2 ZBR structure, sequence conservation, and a model in which the ZBR/post-ZBR region both disrupts APC/C-Cdc20 association and inhibits the APC/C catalytic module. Useful for mapping UniProt domain annotations to experimentally defined inhibitory functions. | Image/structure from primary paper; vertebrate protein | Shoji et al., 2014, Figure 7, https://doi.org/10.1016/j.fob.2014.06.010 | (pqac-00000012) |


*Table: This table condenses the main experimentally supported functions, mechanisms, regulation, localization, and disease links for human FBXO43/EMI2. It is useful as a source-mapped annotation summary that distinguishes well-established meiotic APC/C inhibition from newer infertility and cancer associations.*