ID:FZR_HUMAN DESCRIPTION: RecName: Full=Fizzy-related protein homolog; Short=Fzr; AltName: Full=CDC20-like protein 1; AltName: Full=Cdh1/Hct1 homolog; Short=hCDH1; 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. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: 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. INTERACTION: P30260:CDC27; NbExp=8; IntAct=EBI-724997, EBI-994813; Q9HAW4:CLSPN; NbExp=4; IntAct=EBI-724997, EBI-1369377; Q9UI95:MAD2L2; NbExp=2; IntAct=EBI-724997, EBI-77889; P20794:MAK; NbExp=7; IntAct=EBI-724997, EBI-3911321; P31350:RRM2; NbExp=2; IntAct=EBI-724997, EBI-2339245; Q8IXJ6-2:SIRT2; NbExp=2; IntAct=EBI-724997, EBI-5240785; Q13309:SKP2; NbExp=2; IntAct=EBI-724997, EBI-456291; P40337:VHL; NbExp=2; IntAct=EBI-724997, EBI-301246; P40337-1:VHL; NbExp=2; IntAct=EBI-724997, EBI-3504450; P40337-3:VHL; NbExp=2; IntAct=EBI-724997, EBI-301270; SUBCELLULAR LOCATION: Isoform 2: Nucleus. SUBCELLULAR LOCATION: Isoform 3: Cytoplasm. 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. PTM: 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. SIMILARITY: Belongs to the WD repeat CDC20/Fizzy family. SIMILARITY: Contains 7 WD repeats. SEQUENCE CAUTION: Sequence=AAD26623.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part; Sequence=AAD26624.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part; Sequence=BAA86556.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): FZR1 CDC HuGE Published Literature: FZR1
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UM11
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.