FZR1: Key regulator of ligase activity of the anaphase promoting complex/cyclosome (APC/C), which confers substrate specificity upon the 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. The unphosphorylated form interacts with APC/C during mitosis. Interacts with NINL. Interacts (in complex with the anaphase promoting complex APC) with MAD2L2; inhibits FZR1- mediated APC/C activation. Interacts with USP37. Interacts (via WD repeats) with MAK. Isoform 2 is expressed at high levels in heart, liver, spleen and some cancer cell lines whereas isoform 3 is expressed only at low levels in these tissues. Belongs to the WD repeat CDC20/Fizzy family. 3 isoforms of the human protein are produced by alternative splicing.
Protein type: Ubiquitin conjugating system
Chromosomal Location of Human Ortholog: 19p13.3
Cellular Component: anaphase-promoting complex; cytosol; nuclear membrane; nucleoplasm
Molecular Function: protein binding
Biological Process: anaphase-promoting complex activation; anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; cell division; DNA repair; G2/M transition DNA damage checkpoint; mitosis; mitotic cell cycle; negative regulation of ubiquitin-protein ligase activity during mitotic cell cycle; positive regulation of cell proliferation; positive regulation of protein catabolic process; positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle; regulation of meiosis; regulation of ubiquitin-protein ligase activity during mitotic cell cycle
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