UniProt functional annotation for Q12834



	UniProt functional annotation for Q12834

UniProt code: Q12834.

Organism: Homo sapiens (Human).

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

Function: Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation. {ECO:0000269|PubMed:9637688, ECO:0000269|PubMed:9734353, ECO:0000269|PubMed:9811605}.

Pathway: Protein modification; protein ubiquitination.

Subunit: Component of a complex with CDC20, CDC27, SPATC1 and TUBG1 (By similarity). Interacts with NEUROD2 (By similarity). Interacts with dimeric MAD2L1 in its closed conformation form (PubMed:9811605, PubMed:9637688, PubMed:15525512, PubMed:19098431, PubMed:29162720). Interacts with BUB1B (PubMed:15525512, PubMed:18997788, PubMed:19098431). The phosphorylated form interacts with APC/C (PubMed:9811605, PubMed:9734353, PubMed:9637688). Interacts with NINL (PubMed:17403670). May interact with MAD2L2 (PubMed:11459826). Interacts with CDK5RAP2 (PubMed:19282672). Interacts with SIRT2 (PubMed:22014574). Interacts with isoform 1 of NEK2 (PubMed:20034488). Interacts with HSF1 (via phosphorylated form); this interaction occurs in mitosis in a MAD2L1-dependent manner and prevents PLK1-stimulated degradation of HSF1 by blocking the recruitment of the SCF(BTRC) ubiquitin ligase complex (PubMed:18794143). Interacts (via the N- terminal substrate-binding domain) with FBXO5 (By similarity). {ECO:0000250|UniProtKB:Q9JJ66, ECO:0000269|PubMed:11459826, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:17403670, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:18997788, ECO:0000269|PubMed:19098431, ECO:0000269|PubMed:19282672, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:22014574, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:9637688, ECO:0000269|PubMed:9734353, ECO:0000269|PubMed:9811605}.

Subcellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:20034488}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:20034488}.

Developmental stage: Synthesis is initiated at G1/S, protein level peaks in M phase and protein is abruptly degraded at M/G1 transition.

Ptm: Acetylated. Deacetylated at Lys-66 by SIRT2; deacetylation enhances the interaction of CDC20 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). Phosphorylated by BUB1 at Ser-41; Ser-72; Ser-92; Ser- 153; Thr-157 and Ser-161. Phosphorylated by NEK2. {ECO:0000269|PubMed:10459014, ECO:0000269|PubMed:14657031, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:20034488}.

Ptm: Dephosphorylated by CTDP1.

Ptm: Ubiquitinated and degraded by the proteasome during spindle assembly checkpoint. Deubiquitinated by USP44, leading to stabilize the MAD2L1-CDC20-APC/C ternary complex, thereby preventing premature activation of the APC/C. Ubiquitinated at Lys-490 during prometaphase. Ubiquitination at Lys-485 and Lys-490 has no effect on its ability to bind the APC/C complex. {ECO:0000269|PubMed:17443180, ECO:0000269|PubMed:18997788, ECO:0000269|PubMed:19098431, ECO:0000269|PubMed:21926987}.

Similarity: Belongs to the WD repeat CDC20/Fizzy family. {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:		Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation. {ECO:0000269\|PubMed:9637688, ECO:0000269\|PubMed:9734353, ECO:0000269\|PubMed:9811605}.


Pathway:		Protein modification; protein ubiquitination.
Subunit:		Component of a complex with CDC20, CDC27, SPATC1 and TUBG1 (By similarity). Interacts with NEUROD2 (By similarity). Interacts with dimeric MAD2L1 in its closed conformation form (PubMed:9811605, PubMed:9637688, PubMed:15525512, PubMed:19098431, PubMed:29162720). Interacts with BUB1B (PubMed:15525512, PubMed:18997788, PubMed:19098431). The phosphorylated form interacts with APC/C (PubMed:9811605, PubMed:9734353, PubMed:9637688). Interacts with NINL (PubMed:17403670). May interact with MAD2L2 (PubMed:11459826). Interacts with CDK5RAP2 (PubMed:19282672). Interacts with SIRT2 (PubMed:22014574). Interacts with isoform 1 of NEK2 (PubMed:20034488). Interacts with HSF1 (via phosphorylated form); this interaction occurs in mitosis in a MAD2L1-dependent manner and prevents PLK1-stimulated degradation of HSF1 by blocking the recruitment of the SCF(BTRC) ubiquitin ligase complex (PubMed:18794143). Interacts (via the N- terminal substrate-binding domain) with FBXO5 (By similarity). {ECO:0000250\|UniProtKB:Q9JJ66, ECO:0000269\|PubMed:11459826, ECO:0000269\|PubMed:15525512, ECO:0000269\|PubMed:17403670, ECO:0000269\|PubMed:18794143, ECO:0000269\|PubMed:18997788, ECO:0000269\|PubMed:19098431, ECO:0000269\|PubMed:19282672, ECO:0000269\|PubMed:20034488, ECO:0000269\|PubMed:22014574, ECO:0000269\|PubMed:29162720, ECO:0000269\|PubMed:9637688, ECO:0000269\|PubMed:9734353, ECO:0000269\|PubMed:9811605}.
Subcellular location:		Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:20034488}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269\|PubMed:20034488}.
Developmental stage:		Synthesis is initiated at G1/S, protein level peaks in M phase and protein is abruptly degraded at M/G1 transition.
Ptm:		Acetylated. Deacetylated at Lys-66 by SIRT2; deacetylation enhances the interaction of CDC20 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). Phosphorylated by BUB1 at Ser-41; Ser-72; Ser-92; Ser- 153; Thr-157 and Ser-161. Phosphorylated by NEK2. {ECO:0000269\|PubMed:10459014, ECO:0000269\|PubMed:14657031, ECO:0000269\|PubMed:15525512, ECO:0000269\|PubMed:20034488}.
Ptm:		Dephosphorylated by CTDP1.
Ptm:		Ubiquitinated and degraded by the proteasome during spindle assembly checkpoint. Deubiquitinated by USP44, leading to stabilize the MAD2L1-CDC20-APC/C ternary complex, thereby preventing premature activation of the APC/C. Ubiquitinated at Lys-490 during prometaphase. Ubiquitination at Lys-485 and Lys-490 has no effect on its ability to bind the APC/C complex. {ECO:0000269\|PubMed:17443180, ECO:0000269\|PubMed:18997788, ECO:0000269\|PubMed:19098431, ECO:0000269\|PubMed:21926987}.
Similarity:		Belongs to the WD repeat CDC20/Fizzy family. {ECO:0000305}.