FEM1B

This gene encodes an ankyrin repeat protein that belongs to the death receptor-associated family of proteins and plays a role in mediating apoptosis. The encoded protein is also thought to function in the replication stress-induced checkpoint signaling pathway via interaction with checkpoint kinase 1.

Full Name

fem-1 homolog b (C. elegans)

Research Area

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 (PubMed:29779948, PubMed:33398170, PubMed:33398168).

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 (PubMed:29779948, PubMed:33398170, PubMed:33398168).

The CRL2(FEM1B) complex specifically recognizes proteins ending with -Gly-Leu-Asp-Arg, such as CDK5R1, leading to their ubiquitination and degradation (PubMed:33398170, PubMed:33398168).

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) (By similarity).

Promotes ubiquitination of GLI1, suppressing GLI1 transcriptional activator activity (PubMed:24076122).

Promotes ubiquitination and degradation of ANKRD37 (By similarity).

Promotes ubiquitination and degradation of SLBP (PubMed:28118078).

Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis (PubMed:10542291).

Also involved in glucose homeostasis in pancreatic islet (By similarity).

May also act as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1 (PubMed:19330022).

Biological Process

Apoptotic process Source: UniProtKB
Branching involved in prostate gland morphogenesis Source: Ensembl
Epithelial cell maturation involved in prostate gland development Source: Ensembl
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
Regulation of DNA damage checkpoint Source: UniProtKB
Regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
Regulation of ubiquitin-protein transferase activity Source: UniProtKB
Ubiquitin-dependent protein catabolic process via the C-end degron rule pathway Source: UniProtKB

Cellular Location

Nucleus; Cytoplasm. In the nucleus, the protein level increased slightly after camptothecin (CPT) treatment (PubMed:19330022). Associated with chromatin (PubMed:19330022).