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;
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.
Biological Process: GO:0006281 DNA repair GO:0006974 cellular response to DNA damage stimulus GO:0007049 cell cycle GO:0008284 positive regulation of cell proliferation GO:0016567 protein ubiquitination GO:0031145 anaphase-promoting complex-dependent catabolic process GO:0040020 regulation of meiotic nuclear division GO:0045732 positive regulation of protein catabolic process GO:0051301 cell division GO:0070306 lens fiber cell differentiation GO:0070979 protein K11-linked ubiquitination GO:0072425 signal transduction involved in G2 DNA damage checkpoint GO:0090344 negative regulation of cell aging GO:1904668 positive regulation of ubiquitin protein ligase activity
Protein Q9UM11 (Reactome details) participates in the following event(s):
R-HSA-174251 Phosphorylation of Cdh1 by Cyclin B1:Cdc2 R-HSA-174124 Dephosphorylation of phospho-Cdh1 R-HSA-174070 Association of Cdh1 with the APC/C R-HSA-174139 Dissociation of phospho-Cdh1 from the APC/C complex R-HSA-188371 Association of Cyclin A:Cdk2 with Cdh1 R-HSA-3788708 CDKN1A (p21) prevents association of Cyclin A:Cdk2 with Cdh1 R-HSA-3788725 Cdh1:APC/C complex binds EHMT1:EHMT2 R-HSA-174097 Association of Emi1 with Cdh1 R-HSA-187948 Phosphorylation of proteins involved in the G1/S transition by Cyclin A:Cdk2 R-HSA-174088 Association of cell cycle proteins with the APC/C:Cdh1 complex R-HSA-174057 Multiubiquitination of APC/C-associated Cdh1 R-HSA-174079 Phosphorylation of Cdh1 by Cyclin A:Cdk2 R-HSA-3788705 CDKN1A (p21) prevents phosphorylation of Cdh1 by Cyclin A:Cdk2 R-HSA-3788724 Cdh1:APC/C ubiquitinates EHMT1 and EHMT2 R-HSA-174174 Phosphorylation of the Emi1 DSGxxS degron by Plk1 R-HSA-174122 Phosphorylation of the Emi1 DSGxxS degron by Cyclin B:Cdc2 R-HSA-174195 Ubiquitination of cell cycle proteins targeted by the APC/C:Cdh1complex R-HSA-69015 Cytoplasmic phosphorylated Cdc6 is ubiquitinated by the anaphase-promoting complex R-HSA-174209 Phosphorylated Emi1 binds the beta-TrCP in the SCF complex R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex R-HSA-983147 Release of E3 from polyubiquitinated substrate R-HSA-174159 Ubiquitination of Emi1 by SCF-beta-TrCP R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2 R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase R-HSA-176407 Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry R-HSA-174143 APC/C-mediated degradation of cell cycle proteins R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1 R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C R-HSA-2559583 Cellular Senescence R-HSA-176417 Phosphorylation of Emi1 R-HSA-69242 S Phase R-HSA-453276 Regulation of mitotic cell cycle R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 R-HSA-2262752 Cellular responses to stress R-HSA-69278 Cell Cycle (Mitotic) R-HSA-69052 Switching of origins to a post-replicative state R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation R-HSA-8953897 Cellular responses to external stimuli R-HSA-1640170 Cell Cycle R-HSA-69239 Synthesis of DNA R-HSA-983169 Class I MHC mediated antigen processing & presentation R-HSA-69306 DNA Replication R-HSA-1280218 Adaptive Immune System R-HSA-168256 Immune System
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