FEM1B

Description

The FEM1B (fem-1 homolog B) is a protein-coding gene located on chromosome 15.

FEM1B is a substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex, specifically within the DesCEND pathway, which targets proteins for ubiquitination and degradation based on their C-terminal sequence. This pathway identifies a 'C-degron', a short motif of less than 10 residues, located at the extreme C-terminus of target proteins. The CRL2(FEM1B) complex preferentially binds proteins with a C-terminal sequence of -Gly-Leu-Asp-Arg, like CDK5R1, leading to their ubiquitination and degradation. FEM1B also plays a role in regulating the reductive stress response by targeting reduced FNIP1 for ubiquitination. During reductive stress, the CRL2(FEM1B) complex recognizes a reduced cysteine degron within FNIP1, triggering its degradation and subsequent activation of mitochondria to adjust reactive oxygen species levels. Mechanistically, FEM1B interacts with reduced FNIP1 through zinc ions, which act as a molecular bridge. Additionally, FEM1B promotes the ubiquitination of GLI1, suppressing its transcriptional activator function. FEM1B also promotes the ubiquitination and degradation of ANKRD37 and SLBP. It plays a role in apoptosis as a death receptor-associated protein that mediates the apoptotic process. Furthermore, it is involved in glucose homeostasis in pancreatic islets and may act as an adapter/mediator in replication stress-induced signaling leading to the activation of CHEK1. {ECO:0000250|UniProtKB:Q9Z2G0, ECO:0000269|PubMed:10542291, ECO:0000269|PubMed:19330022, ECO:0000269|PubMed:24076122, ECO:0000269|PubMed:28118078, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:33398168, ECO:0000269|PubMed:33398170}

FEM1B is also known as F1A-ALPHA, F1AA, FEM1-beta.

Associated Diseases

WES Whole Exome Sequencing