| 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
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