8uy3

Structural highlights

Function

FEM1B_MOUSE Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (By similarity). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (By similarity). The CRL2(FEM1B) complex specifically recognizes proteins ending with -Gly-Leu-Asp-Arg, such as CDK5R1, leading to their ubiquitination and degradation (By similarity). Also acts as a regulator of the reductive stress response by mediating ubiquitination of reduced FNIP1: in response to reductive stress, the CRL2(FEM1B) complex specifically recognizes a conserved Cys degron in FNIP1 when this degron is reduced, leading to FNIP1 degradation and subsequent activation of mitochondria to recalibrate reactive oxygen species (ROS) (PubMed:32941802, PubMed:34562363). Mechanistically, recognizes and binds reduced FNIP1 through two interface zinc ions, which act as a molecular glue that recruit reduced FNIP1 to FEM1B (PubMed:34562363). Promotes ubiquitination of GLI1, suppressing GLI1 transcriptional activator activity (By similarity). Promotes ubiquitination and degradation of ANKRD37 (PubMed:21723927). Promotes ubiquitination and degradation of SLBP (By similarity). Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis (By similarity). Also involved in glucose homeostasis in pancreatic islet (PubMed:16024793). May also act as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1 (By similarity).[UniProtKB:Q9UK73]^{[1] [2] [3] [4]}

References

1. ↑ Lu D, Ventura-Holman T, Li J, McMurray RW, Subauste JS, Maher JF. Abnormal glucose homeostasis and pancreatic islet function in mice with inactivation of the Fem1b gene. Mol Cell Biol. 2005 Aug;25(15):6570-7. PMID:16024793 doi:10.1128/MCB.25.15.6570-6577.2005
2. ↑ Shi YQ, Liao SY, Zhuang XJ, Han CS. Mouse Fem1b interacts with and induces ubiquitin-mediated degradation of Ankrd37. Gene. 2011 Oct 10;485(2):153-9. PMID:21723927 doi:10.1016/j.gene.2011.06.025
3. ↑ Manford AG, Rodríguez-Pérez F, Shih KY, Shi Z, Berdan CA, Choe M, Titov DV, Nomura DK, Rape M. A Cellular Mechanism to Detect and Alleviate Reductive Stress. Cell. 2020 Oct 1;183(1):46-61.e21. PMID:32941802 doi:10.1016/j.cell.2020.08.034
4. ↑ Manford AG, Mena EL, Shih KY, Gee CL, McMinimy R, Martínez-González B, Sherriff R, Lew B, Zoltek M, Rodríguez-Pérez F, Woldesenbet M, Kuriyan J, Rape M. Structural basis and regulation of the reductive stress response. Cell. 2021 Oct 14;184(21):5375-5390.e16. PMID:34562363 doi:10.1016/j.cell.2021.09.002
5. ↑ McMinimy R, Manford AG, Gee CL, Chandrasekhar S, Mousa GA, Chuang J, Phu L, Shih KY, Rose CM, Kuriyan J, Bingol B, Rapé M. Reactive oxygen species control protein degradation at the mitochondrial import gate. Mol Cell. 2024 Dec 5;84(23):4612-4628.e13. PMID:39642856 doi:10.1016/j.molcel.2024.11.004