FZR1 Antibody – Rabbit Polyclonal

Function: 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. Ref.9 Ref.14 Ref.18

Pathway: Protein modification; protein ubiquitination.

Subunit structure: 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. Ref.9 Ref.11 Ref.12 Ref.13 Ref.18 Ref.19

Subcellular location: Isoform 2: Nucleus Ref.4. Isoform 3: Cytoplasm Ref.4.

Tissue specificity: 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. Ref.4

Post-translational modification: 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. Ref.10 Ref.14 Ref.19

Sequence similarities: Belongs to the WD repeat CDC20/Fizzy family.Contains 7 WD repeats.

Sequence caution: The sequence AAD26623.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the C-terminal part.The sequence AAD26624.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.The sequence BAA86556.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.