FZR1

FZR1 (Fizzy And Cell Division Cycle 20 Related 1) is a Protein Coding gene. Among its related pathways are CDK-mediated phosphorylation and removal of Cdc6 and Innate Immune System. An important paralog of this gene is CDC20.

Fizzy And Cell Division Cycle 20 Related 1

Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. Acts as an adapter for APC/C to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, may play a role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:25349192).

Anaphase-promoting complex-dependent catabolic process Source: UniProtKB
Cell division Source: UniProtKB-KW
DNA repair Source: UniProtKB-KW
Lens fiber cell differentiation Source: Ensembl
Mitotic G2 DNA damage checkpoint signaling Source: UniProtKB
Negative regulation of cell aging Source: Ensembl
Positive regulation of anaphase-promoting complex-dependent catabolic process Source: GO_Central
Positive regulation of cell population proliferation Source: Ensembl
Positive regulation of protein catabolic process Source: UniProtKB
Positive regulation of ubiquitin protein ligase activity Source: UniProtKB
Protein K11-linked ubiquitination Source: UniProtKB
Regulation of meiotic nuclear division Source: Ensembl

Isoform 2: Nucleus
Isoform 3: Cytoplasm

Acetylated. Deacetylated by SIRT2 at Lys-69 and Lys-159; deacetylation enhances the interaction of FZR1 with CDC27, leading to activation of anaphase promoting complex/cyclosome (APC/C).
Phosphorylated during mitosis, probably by maturation promoting factor (MPF), leading to its dissociation of the APC/C. Following DNA damage, it is dephosphorylated by CDC14B in G2 phase, leading to its reassociation with the APC/C, and allowing an efficient G2 DNA damage checkpoint. Phosphorylated by MAK.
Ubiquitinated by the SCF(CCNF) E3 ubiquitin-protein ligase complex; leading to its degradation by the proteasome.