UniProt functional annotation for Q9UM11



	UniProt functional annotation for Q9UM11

UniProt code: Q9UM11.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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). {ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:9734353}.

Pathway: Protein modification; protein ubiquitination.

Subunit: The unphosphorylated form interacts with APC/C during mitosis (PubMed:26083744, PubMed:9734353). Interacts with NINL (PubMed:17403670). Interacts (in complex with the anaphase promoting complex APC) with MAD2L2; inhibits FZR1-mediated APC/C activation (PubMed:11459825, PubMed:11459826). Interacts with SIRT2 and USP37 (PubMed:21596315, PubMed:22014574). Interacts (via WD repeats) with MAK (PubMed:21986944). Interacts with RBBP8/CtIP; this interaction leads to RBBP8 proteasomal degradation (PubMed:25349192). Interacts with HECW2 (PubMed:24163370). Interacts with SASS6; the interaction is regulated by CENATAC and leads to SASS6 proteasomal degradation (PubMed:31722219). {ECO:0000269|PubMed:11459825, ECO:0000269|PubMed:11459826, ECO:0000269|PubMed:17403670, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:21986944, ECO:0000269|PubMed:22014574, ECO:0000269|PubMed:24163370, ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:26083744, ECO:0000269|PubMed:31722219, ECO:0000269|PubMed:9734353}.

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. {ECO:0000269|PubMed:12797865}.

Ptm: 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). {ECO:0000269|PubMed:22014574}.

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. {ECO:0000269|PubMed:10459014, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:21986944}.

Miscellaneous: [Isoform 2]: Major. {ECO:0000305}.

Miscellaneous: [Isoform 3]: Minor. {ECO:0000305}.

Similarity: Belongs to the WD repeat CDC20/Fizzy family. {ECO:0000305}.

Sequence caution: Sequence=AAD26623.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305}; Sequence=AAD26624.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=BAA86556.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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). {ECO:0000269\|PubMed:18662541, ECO:0000269\|PubMed:21596315, ECO:0000269\|PubMed:25349192, ECO:0000269\|PubMed:9734353}.


Pathway:		Protein modification; protein ubiquitination.
Subunit:		The unphosphorylated form interacts with APC/C during mitosis (PubMed:26083744, PubMed:9734353). Interacts with NINL (PubMed:17403670). Interacts (in complex with the anaphase promoting complex APC) with MAD2L2; inhibits FZR1-mediated APC/C activation (PubMed:11459825, PubMed:11459826). Interacts with SIRT2 and USP37 (PubMed:21596315, PubMed:22014574). Interacts (via WD repeats) with MAK (PubMed:21986944). Interacts with RBBP8/CtIP; this interaction leads to RBBP8 proteasomal degradation (PubMed:25349192). Interacts with HECW2 (PubMed:24163370). Interacts with SASS6; the interaction is regulated by CENATAC and leads to SASS6 proteasomal degradation (PubMed:31722219). {ECO:0000269\|PubMed:11459825, ECO:0000269\|PubMed:11459826, ECO:0000269\|PubMed:17403670, ECO:0000269\|PubMed:21596315, ECO:0000269\|PubMed:21986944, ECO:0000269\|PubMed:22014574, ECO:0000269\|PubMed:24163370, ECO:0000269\|PubMed:25349192, ECO:0000269\|PubMed:26083744, ECO:0000269\|PubMed:31722219, ECO:0000269\|PubMed:9734353}.
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. {ECO:0000269\|PubMed:12797865}.
Ptm:		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). {ECO:0000269\|PubMed:22014574}.
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. {ECO:0000269\|PubMed:10459014, ECO:0000269\|PubMed:18662541, ECO:0000269\|PubMed:21986944}.
Miscellaneous:		[Isoform 2]: Major. {ECO:0000305}.
Miscellaneous:		[Isoform 3]: Minor. {ECO:0000305}.
Similarity:		Belongs to the WD repeat CDC20/Fizzy family. {ECO:0000305}.
Sequence caution:		Sequence=AAD26623.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305}; Sequence=AAD26624.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=BAA86556.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};