ANAPC2 encodes anaphase-promoting complex subunit 2, the cullin-like scaffold of the APC/C catalytic module. In the APC/C E3 ubiquitin ligase, ANAPC2 works with the RING subunit ANAPC11 and ubiquitin-conjugating enzymes to ubiquitinate cell-cycle substrates, promoting ordered proteasomal degradation during mitotic progression and mitotic exit. Structural and biochemical studies place ANAPC2 in the APC/C catalytic platform, and APC/C activity is regulated by coactivators, phosphorylation, checkpoint inhibitors, and substrate adaptors in nuclear and cytosolic cell-cycle contexts.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007091 metaphase/anaphase transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: ANAPC2 is part of the APC/C module that controls mitotic chromosome segregation and mitotic exit, so the metaphase/anaphase transition annotation is supported. Reason: This captures a central APC/C cell-cycle role rather than a distant phenotype. The IBA transfer is consistent with structural and biochemical evidence that APC/C is a ubiquitin ligase essential for mitotic progression. Supporting Evidence: PMID:16364912 The anaphase-promoting complex/cyclosome (APC/C) is a ubiquitin ligase with essential functions in mitosis, meiosis, and G1 phase of the cell cycle. PMID:26083744 These structures define the architecture of all APC/C subunits, the position of the catalytic module |
| GO:0070979 protein K11-linked ubiquitination | IBA GO_REF:0000033 | ACCEPT | Summary: APC/C-dependent K11-linked ubiquitin-chain assembly is a well-supported output of the ANAPC2-containing APC/C catalytic module. Reason: K11-linked ubiquitination is a core APC/C activity, and ANAPC2 is part of the catalytic Apc2-Apc11 module that positions the E2 machinery for substrate ubiquitination. Supporting Evidence: PMID:18485873 We find that the APC/C triggers substrate degradation by assembling K11-linked ubiquitin chains PMID:29033132 engineered a bispecific antibody to detect K11/K48-linked chains and identified mitotic regulators, misfolded nascent polypeptides, and pathological Huntingtin variants as their endogenous substrates. PMID:16364912 bound substrates are ubiquitinated by E2 enzymes that interact with a hetero-dimer of the RING subunit Apc11 and the cullin Apc2 |
| GO:0005680 anaphase-promoting complex | IBA GO_REF:0000033 | ACCEPT | Summary: ANAPC2 is a core subunit of the anaphase-promoting complex/cyclosome. Reason: This is the most specific cellular-component annotation for ANAPC2. Structural studies place Apc2 in APC/C particles and in the catalytic platform with Apc11. Supporting Evidence: PMID:16364912 These proteins are located on the same side of the asymmetric APC/C, implying that this is where substrates are ubiquitinated. PMID:26083744 These structures define the architecture of all APC/C subunits, the position of the catalytic module |
| GO:0010498 proteasomal protein catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: APC/C ubiquitination of cell-cycle substrates leads to proteasome-mediated degradation. Reason: The term is broad but appropriate for ANAPC2 as an APC/C catalytic-module scaffold because APC/C controls ordered degradation of cell-cycle proteins through ubiquitin-dependent proteasomal proteolysis. Supporting Evidence: PMID:26083744 Two cullin-RING E3 ubiquitin ligases, the APC/C and SCF, catalyze the ubiquitination of multiple cell cycle proteins to regulate their proteasome-mediated proteolysis. PMID:27120157 In eukaryotes, the anaphase-promoting complex (APC/C, also known as the cyclosome) regulates the ubiquitin-dependent proteolysis of specific cell-cycle proteins to coordinate chromosome segregation in mitosis and entry into the G1 phase. |
| GO:0031461 cullin-RING ubiquitin ligase complex | IEA GO_REF:0000117 | MODIFY | Summary: ANAPC2 belongs to a cullin-like RING E3 module, but the specific complex is APC/C rather than a generic CRL complex. Reason: The broad cullin-RING ubiquitin ligase complex annotation is mechanistically related but less precise for ANAPC2. The more accurate cellular-component term is anaphase-promoting complex. Proposed replacements: anaphase-promoting complex Supporting Evidence: PMID:16364912 bound substrates are ubiquitinated by E2 enzymes that interact with a hetero-dimer of the RING subunit Apc11 and the cullin Apc2 PMID:26083744 the catalytic module comprising the RING subunit Apc11 and the C-terminal domain of Apc2 (Apc2CTD) file:human/ANAPC2/ANAPC2-uniprot.txt Belongs to the cullin family. |
| GO:0005515 protein binding | IPI PMID:23708001 Emi1 preferentially inhibits ubiquitin chain elongation by t... | MARK AS OVER ANNOTATED | Summary: This protein-binding record reflects APC/C interactions with Emi1/Ube2S regulatory machinery, but the generic term is not informative as a core ANAPC2 function. Reason: Protein binding is true but over-general. The same evidence is better interpreted in the context of ANAPC2's APC/C scaffold and E2-positioning role. Supporting Evidence: PMID:23708001 the carboxy-terminal tail of Emi1 antagonizes chain elongation by Ube2S, by competitively preventing its binding to the APC cullin subunit |
| GO:0005515 protein binding | IPI PMID:26083744 Atomic structure of the APC/C and its mechanism of protein u... | MARK AS OVER ANNOTATED | Summary: The structural study supports APC/C subunit and E2/regulator interactions, but generic protein binding is not a useful core molecular-function annotation. Reason: Protein binding does not describe ANAPC2's specific activity; the informative function is cullin-like APC/C scaffold activity and contribution to ubiquitin ligase activity. Supporting Evidence: PMID:26083744 These structures define the architecture of all APC/C subunits, the position of the catalytic module |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: This high-throughput binary interactome record is useful interaction context but not a core ANAPC2 function. Reason: The HuRI-style protein-binding annotation records physical interaction data without establishing a specific ANAPC2 molecular activity or pathway role. Supporting Evidence: PMID:32296183 HuRI provides an unbiased genome-scale scaffold with which to coordinate this information as it emerges. |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of gene expression is an indirect orthology-transferred process annotation, likely reflecting downstream APC/C substrate degradation rather than a direct ANAPC2 function. Reason: ANAPC2's core role is APC/C scaffold-dependent ubiquitination. A broad gene-expression regulation term loses the mechanistic APC/C context and should not be treated as a core annotation for human ANAPC2. Supporting Evidence: file:human/ANAPC2/ANAPC2-uniprot.txt Together with the RING-H2 protein ANAPC11, constitutes the catalytic component of the anaphase promoting complex/cyclosome |
| GO:0031915 positive regulation of synaptic plasticity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Synaptic plasticity is a broad orthology-derived neuronal process annotation and overstates the local ANAPC2 evidence; the cited UniProt text more directly supports presynaptic differentiation context. Reason: APC/C-CDC20 has neuronal roles by similarity, but the record does not establish human ANAPC2 as a direct synaptic-plasticity regulator. In PN context this should not be treated as core proteostasis evidence. Supporting Evidence: file:human/ANAPC2/ANAPC2-uniprot.txt CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation |
| GO:0045773 positive regulation of axon extension | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of axon extension is an over-specific orthology-transferred neuronal process annotation for ANAPC2. Reason: The local UniProt text supports CDC20-APC/C presynaptic vesicle clustering and differentiation context by similarity, not axon extension specifically. ANAPC2's conserved core function is the APC/C scaffold/catalytic module. Supporting Evidence: file:human/ANAPC2/ANAPC2-uniprot.txt CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons |
| GO:0050775 positive regulation of dendrite morphogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of dendrite morphogenesis is an over-specific orthology-transferred neuronal process annotation for ANAPC2. Reason: The local UniProt text supports CDC20-APC/C presynaptic vesicle clustering and differentiation context by similarity, not dendrite morphogenesis specifically. ANAPC2's conserved core function is the APC/C scaffold/catalytic module. Supporting Evidence: file:human/ANAPC2/ANAPC2-uniprot.txt CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons |
| GO:0090129 positive regulation of synapse maturation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synapse maturation is retained as non-core orthology-derived context for CDC20-APC/C neuronal roles, not as ANAPC2's defining molecular function. Reason: UniProt records CDC20-APC/C neuronal effects by similarity, but ANAPC2's conserved core function is the APC/C scaffold/catalytic module. These process terms should not drive PN proteostasis projection for ANAPC2. Supporting Evidence: file:human/ANAPC2/ANAPC2-uniprot.txt CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000041 | ACCEPT | Summary: Protein ubiquitination is a broad but correct process annotation for ANAPC2-containing APC/C. Reason: ANAPC2 is part of the APC/C E3 ubiquitin ligase catalytic module, and APC/C catalyzes substrate ubiquitination through E2 enzymes. Supporting Evidence: PMID:16364912 bound substrates are ubiquitinated by E2 enzymes that interact with a hetero-dimer of the RING subunit Apc11 and the cullin Apc2 PMID:26083744 the catalytic module comprising the RING subunit Apc11 and the C-terminal domain of Apc2 (Apc2CTD) PMID:26083744 Two cullin-RING E3 ubiquitin ligases, the APC/C and SCF, catalyze the ubiquitination of multiple cell cycle proteins to regulate their proteasome-mediated proteolysis. |
| GO:0005680 anaphase-promoting complex | IPI PMID:27120157 Molecular mechanism of APC/C activation by mitotic phosphory... | ACCEPT | Summary: ANAPC2 is a core subunit of the anaphase-promoting complex/cyclosome. Reason: This is the most specific cellular-component annotation for ANAPC2. Structural studies place Apc2 in APC/C particles and in the catalytic platform with Apc11. Supporting Evidence: PMID:16364912 These proteins are located on the same side of the asymmetric APC/C, implying that this is where substrates are ubiquitinated. PMID:26083744 These structures define the architecture of all APC/C subunits, the position of the catalytic module |
| GO:0007346 regulation of mitotic cell cycle | NAS PMID:15678131 The anaphase-promoting complex: a key factor in the regulati... | ACCEPT | Summary: ANAPC2 supports mitotic cell-cycle regulation through APC/C-mediated ubiquitination and degradation of cell-cycle regulators. Reason: This is a central biological process for APC/C rather than a secondary phenotype. The review article and structural work both support APC/C as a key cell-cycle ubiquitin ligase. Supporting Evidence: PMID:15678131 Two different ubiquitin ligases play an important role in the cell cycle: the SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC). PMID:26083744 Two cullin-RING E3 ubiquitin ligases, the APC/C and SCF, catalyze the ubiquitination of multiple cell cycle proteins to regulate their proteasome-mediated proteolysis. |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | NAS PMID:15678131 The anaphase-promoting complex: a key factor in the regulati... | ACCEPT | Summary: APC/C-dependent catabolic process is directly aligned with ANAPC2's role in APC/C substrate ubiquitination and proteasomal degradation. Reason: ANAPC2 is part of the APC/C catalytic module, and APC/C-dependent ubiquitination of cell-cycle substrates is a core output of the complex. Supporting Evidence: PMID:26083744 Two cullin-RING E3 ubiquitin ligases, the APC/C and SCF, catalyze the ubiquitination of multiple cell cycle proteins to regulate their proteasome-mediated proteolysis. PMID:27120157 In eukaryotes, the anaphase-promoting complex (APC/C, also known as the cyclosome) regulates the ubiquitin-dependent proteolysis of specific cell-cycle proteins to coordinate chromosome segregation in mitosis and entry into the G1 phase. PMID:18485873 The anaphase-promoting complex (APC/C) orchestrates progression through mitosis by decorating cell-cycle regulators with ubiquitin chains. |
| GO:0051445 regulation of meiotic cell cycle | NAS PMID:15678131 The anaphase-promoting complex: a key factor in the regulati... | KEEP AS NON CORE | Summary: Regulation of meiotic cell cycle is plausible APC/C biology but is not the main context for this human ANAPC2 review. Reason: APC/C has essential meiotic functions, but the strongest ANAPC2 evidence here centers on the APC/C catalytic module and mitotic cell-cycle proteolysis. Retain as non-core. Supporting Evidence: PMID:16364912 The anaphase-promoting complex/cyclosome (APC/C) is a ubiquitin ligase with essential functions in mitosis, meiosis, and G1 phase of the cell cycle. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: PMID:26083744 These structures define the architecture of all APC/C subunits, the position of the catalytic module |
| GO:0005680 anaphase-promoting complex | NAS PMID:27120157 Molecular mechanism of APC/C activation by mitotic phosphory... | ACCEPT | Summary: ANAPC2 is a core subunit of the anaphase-promoting complex/cyclosome. Reason: This is the most specific cellular-component annotation for ANAPC2. Structural studies place Apc2 in APC/C particles and in the catalytic platform with Apc11. Supporting Evidence: PMID:16364912 These proteins are located on the same side of the asymmetric APC/C, implying that this is where substrates are ubiquitinated. PMID:26083744 These structures define the architecture of all APC/C subunits, the position of the catalytic module |
| GO:0141198 protein branched polyubiquitination | IDA PMID:29033132 Assembly and Function of Heterotypic Ubiquitin Chains in Cel... | ACCEPT | Summary: Branched ubiquitin-chain assembly is supported for APC/C-dependent cell-cycle and protein-quality-control substrates. Reason: The K11/K48 branched-chain paper supports APC/C-linked heterotypic ubiquitin chains, and ANAPC2 is part of the APC/C catalytic module that enables this output. Supporting Evidence: PMID:29033132 engineered a bispecific antibody to detect K11/K48-linked chains and identified mitotic regulators, misfolded nascent polypeptides, and pathological Huntingtin variants as their endogenous substrates. PMID:29033132 these conjugates promote rapid proteasomal clearance of aggregation-prone proteins. PMID:16364912 bound substrates are ubiquitinated by E2 enzymes that interact with a hetero-dimer of the RING subunit Apc11 and the cullin Apc2 |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | IDA PMID:29033132 Assembly and Function of Heterotypic Ubiquitin Chains in Cel... | ACCEPT | Summary: APC/C-dependent catabolic process is directly aligned with ANAPC2's role in APC/C substrate ubiquitination and proteasomal degradation. Reason: ANAPC2 is part of the APC/C catalytic module, and APC/C-dependent ubiquitination of cell-cycle substrates is a core output of the complex. Supporting Evidence: PMID:26083744 Two cullin-RING E3 ubiquitin ligases, the APC/C and SCF, catalyze the ubiquitination of multiple cell cycle proteins to regulate their proteasome-mediated proteolysis. PMID:27120157 In eukaryotes, the anaphase-promoting complex (APC/C, also known as the cyclosome) regulates the ubiquitin-dependent proteolysis of specific cell-cycle proteins to coordinate chromosome segregation in mitosis and entry into the G1 phase. PMID:18485873 The anaphase-promoting complex (APC/C) orchestrates progression through mitosis by decorating cell-cycle regulators with ubiquitin chains. |
| GO:0070936 protein K48-linked ubiquitination | IDA PMID:29033132 Assembly and Function of Heterotypic Ubiquitin Chains in Cel... | ACCEPT | Summary: K48-linked ubiquitination is supported as part of APC/C-generated K11/K48 heterotypic chains and proteasomal clearance outputs. Reason: Although APC/C is especially associated with K11-linked chains, the cited evidence supports K11/K48 branched conjugates that promote proteasomal clearance. Supporting Evidence: PMID:29033132 engineered a bispecific antibody to detect K11/K48-linked chains and identified mitotic regulators, misfolded nascent polypeptides, and pathological Huntingtin variants as their endogenous substrates. PMID:29033132 these conjugates promote rapid proteasomal clearance of aggregation-prone proteins. |
| GO:0070979 protein K11-linked ubiquitination | IDA PMID:29033132 Assembly and Function of Heterotypic Ubiquitin Chains in Cel... | ACCEPT | Summary: APC/C-dependent K11-linked ubiquitin-chain assembly is a well-supported output of the ANAPC2-containing APC/C catalytic module. Reason: K11-linked ubiquitination is a core APC/C activity, and ANAPC2 is part of the catalytic Apc2-Apc11 module that positions the E2 machinery for substrate ubiquitination. Supporting Evidence: PMID:18485873 We find that the APC/C triggers substrate degradation by assembling K11-linked ubiquitin chains PMID:29033132 engineered a bispecific antibody to detect K11/K48-linked chains and identified mitotic regulators, misfolded nascent polypeptides, and pathological Huntingtin variants as their endogenous substrates. PMID:16364912 bound substrates are ubiquitinated by E2 enzymes that interact with a hetero-dimer of the RING subunit Apc11 and the cullin Apc2 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-174057 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-174057 Cdh1 is multiubiquitinated by the APC/C:Cdh1 complex prior to degradation by the 26S proteasome. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-174058 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-174058 At the beginning of this reaction, 1 molecule of 'multiubiquitinated Cdh1 associated with APC/C' is present. At the end of this reaction, 1 molecule of 'phosphorylated anaphase promoting complex (APC/C)', and 3 molecules of 'ubiquitin' are present.<br><br> This reaction takes place in the 'nucleoplasm' and is mediated by the 'endopeptidase activity' of '26S proteasome'.<br> |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-174079 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-174079 At the G1/S transition, the Cdh1 subunit of the APC:Cdh1 complex is phosphorylated by Cyclin A:Cdk2 and dissociates from APC/C. This inactivates APC/C and permits the accumulation of cell cycle proteins required for DNA synthesis and entry into mitosis. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-174119 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-174119 Phosphorylation of the APC/C is believed to be required for its activation. While the identity of the essential phosphorylation sites and the kinase(s) responsible are not known with certainty, in vitro studies have shown that the Apc1 and the tetratricopeptide repeat (TPR) subunits Cdc27, Cdc16, Cdc23 and Apc7 are phosphorylated and that the Cdk1 and Plk1 kinases may play a role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-174132 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-174132 Phosphorylation of the APC/C is believed to be required for its activation. While the identity of the essential phosphorylation sites and the kinase(s) responsible are not known with certainty, in vitro studies have shown that the Apc1 and the tetratricopeptide repeat (TPR) subunits Cdc27, Cdc16, Cdc23 and Apc7 are phosphorylated and that the Cdk1 and Plk1 kinases may play a role. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-174139 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-174139 Following its phosphorylation, Cdh1 dissociates from the APC/C, rendering the APC/C inactive. This allows the stabilization of proteins required for subsequent cell cycle progression. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-188191 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-188191 SKP2 is degraded by the anaphase promoting complex/Cyclosome and its activator FZR1 (Cdh1) [APC/C(Cdh1)] (Bashir et al, 2004; Wei et al, 2004). The tight regulation of APC/C(Cdh1) activity ensures the timely elimination SKP2 and, thus, plays a critical role in controlling the M/G1 transition (mitotic exit). APC/C:Cdh1-mediated degradation of SKP2 depends on RB1, as RB1 recruits SKP2 to the APC/C:Cdh1 complex, by simultaneously interacting with SKP2 and FZR1. RB1 does not undergo APC/C:Cdh1-mediated ubiquitination (Binne et al. 2007). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-188371 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-188371 Cyclin A-Cdk2 prevents unscheduled APC reactivation during S phase by binding and subsequently phosphorylating Cdh1. Phosphorylation-dependent dissociation of the Cdh1-activating subunit inhibits the APC/C. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3788705 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-3788705 At the G1/S transition, the Cdh1 (FZR1) subunit of the APC/C:Cdh1 complex is phosphorylated by Cyclin A:Cdk2 (CCNA:CDK2) and dissociates from APC/C. This inactivates APC/C and permits the accumulation of cell cycle proteins required for DNA synthesis and entry into mitosis (Lukas et al. 1999). Activation of the ATM kinase by DNA damage in the form of double strand breaks results in TP53-mediated induction of CDKN1A (p21) expression. CDKN1A binds CCNA:CDK2 complex and prevents it from phosphorylating Cdh1 (Takahashi et al. 2012). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3788708 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-3788708 Cyclin A-Cdk2 (CCNA:CDK2) prevents unscheduled APC reactivation during S phase by binding and subsequently phosphorylating FZR1 (Cdh1). Phosphorylation-dependent dissociation of the Cdh1-activating subunit inhibits the APC/C (Sorensen et al. 2001). DNA damage activates ATM kinase, resulting in TP53-mediated induction of CDKN1A (p21) expression. CDKN1A binds CCNA:CDK2 complex and prevents its association with Cdh1 (Takahashi et al. 2012). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3788724 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-3788724 Cdh1:APC/C complex, stabilized by the DNA damage-induced ATM-TP53-CDKN1A axis, ubiquitinates EHMT1 (GLP) and EHMT2 (G9a) histone methyltransferases, targeting them for degradation (Takahashi et al. 2012). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3788725 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-3788725 Cdh1 (FZR1) is able to bind both G9a (EHMT2) and GLP (EHMT1) (Takahashi et al. 2012). EHMT1 and EHMT2 histone methyltransferases were shown to function as a heterodimer in vivo (Tachibana et al. 2005). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-68712 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-68712 From the end of anaphase and throughout G1, the Cdh1 (FZR1) containing anaphase-promoting complex (APC/C:Cdh1) ubiquitinates geminin (GMNN), targeting it for degradation and enabling release of CDT1 and the subsequent association of CDT1 with the replication origins.The presence of an APC destruction box in geminin and its APC/C-mediated ubiquitination and degradation was first demonstrated in Xenopus egg extracts (McGarry and Kirschner 1998) and was later confirmed in human cells, where it was shown to largely depend on Cdh1 and not Cdc20 component of the APC/C (Pfleger et al. 2001; Di Fiore and Pines 2007; Machida and Dutta 2007). Emi1 (FBXO5) mediated inhibition of the APC/C:Cdh1 complex in S and G2 phases is needed for stabilization of geminin and prevention of re-replication (Di Fiore and Pines 2007; Machida and Dutta 2007). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9686969 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-9686969 RB1-dependent polyubiquitination of SKP2 by the APC/C:Cdh1 complex is an important mechanism of RB1-mediated cell cycle exit, which contributes to the RB1 tumor suppressive role. ABC/C:Cdh1-mediated polyubiquitination targets SKP2 for proteasome-mediated degradation. RB1 and APC/C:Cdh1-dependent degradation of SKP2 allows accumulation of CDKN1B (p27Kip1) in the cell, as CDKN1B is a target of the SKP2-containing SCF ubiquitin ligase complex. CDKN1B acts as a CDK inhibitor, enabling mitotic exit (Ji et al. 2004, Binne et al. 2007). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9686980 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-9686980 The pocket domain of the RB1 tumor suppressor protein binds to the N-terminal domain of SKP2, a component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex, whose targets include the cyclin-dependent kinase (CDK) inhibitor p27Kip1 (CDKN1B) (Ji et al. 2004, Binne et al. 2007). RB1 is able to simultanously interact with SKP2 and with FZR1 (Cdh1). FZR1 is a substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C). The interaction with FZR1 involves a different subregion of the pocket domain than the interaction with SKP2, and is partially dependent on the LxCxE binding cleft (Binne et al. 2007). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9687377 | KEEP AS NON CORE | Summary: Nucleoplasm is retained as APC/C reaction/localization context rather than a core molecular function. Reason: ANAPC2 participates in APC/C reactions assigned to nuclear cell-cycle contexts, but localization terms are supportive context and not the gene product's core function. Supporting Evidence: Reactome:R-HSA-9687377 A tripartite complex formed between RB1, SKP2 and FZR1 (Cdh1) targets SKP2 for the anaphase promoting complex/cyclosome (APC/C:Cdh1)-mediated ubiquitination and subsequent proteasome-mediated degradation. Both SKP2 and FZR1 interact with the pocket domain of RB1, with amino acid residues 637–738 and 772–824 involved in SKP2 binding and the cleft region (amino acids 753–761), containing the LxCxE motif, involved in FZR1 binding (Binne et al. 2007). RB1 T738_R775del (RB1 Ex22del) cancer mutant, which lacks exon 22, is able to associate with SKP2 but unable to bind FZR1. This mutant is defective in inducing accumulation of CDKN1B (p27Kip1) and promoting mitotic exit as it cannot prevent SKP2-mediated ubiquitination and degradation of CDKN1B (Ji et al. 2004, Binne et al. 2007). RB1 T738_R775del mutant is also defective in E2F binding (Ji et al. 2004). RB1 missense mutant, RB1 R661W, which causes low penetrance familial retinoblastoma, is unable to bind to E2Fs but retains the ability to bind to SKP2 and FZR2 and to induce CDKN1B accumulation (Ji et al. 2004, Binne et al. 2007). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141423 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-141423 In the direct inhibition model, association of the MCC with APCC results in the inactivation of APC/C. However, the affinity between MCC and APC/C is not high, so that the inhibition is readily reversible. The role of unattached kinetochores is to sensitize the APC/C to prolonged inhibition by the MCC. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174070 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174070 Following its dephosphorylation in late mitosis, Cdh1 replaces Cdc20 as the APC/C activator. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174088 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174088 The APC/C:Cdh1 complex recognizes substrates containing a D box, a KEN box (Pfleger and Kirschner, 2000) or a D box activated (DAD) domain (Castro et al., 2002). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174104 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174104 Rape et al. have recently demonstrated that the order in which APC/C targeted proteins are degraded is determined by the processivity of multiubiquitination of these substrates. Processive substrates acquire a polyubiquitin chain upon binding to the APC/C once and are degraded. Distributive substrates bind, dissociate and reassociate with the APC/C multiple times before acquiring an ubiquitin chain of sufficient length to insure degradation. In addition, distributive substrates that dissociate from the APC/C with short ubiquitin chains are targeted for deubiquitination (Rape et al., 2006). Paradoxically, although the multiubiquitination of cyclin A is distributive and later substrates of APC-Cdc20 such as Securin are processive (Rape et al., 2006), Cyclin A is degraded prior to Securin and Cyclin B. The mechanisms insuring this order have not yet be determined. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174105 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174105 Cell cycle proteins mulitubiquitinated by the APC/C are targeted for degradation by the 26S proteasome. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174120 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174120 Cyclin B is believed to be recognized by the APC/C:Cdc20 complex through its D-box sequence. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174121 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174121 Securin is thought to be recognized by the APC/C:Cdc20 complex through its conserved D-box sequence. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174144 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174144 Securin is ubiquitinated by APC/C:Cdc20 (Hagting et al., 2002; Jin et al. 2008). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174157 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174157 Mulitubiquitinated Cyclin B is targeted for degradation by the 26S proteasome. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174171 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174171 Cyclin A is believed to be recognized by the APC/C:Cdc20 complex through its D-box sequence, which is 10-20 residues longer than the D-box of cyclin B (Geley et al., 2001). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174195 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174195 At the beginning of this reaction, 3 molecules of 'ubiquitin', and 1 molecule of 'cell cycle proteins:phospho-APC/C:Cdh1 complex' are present. At the end of this reaction, 1 molecule of 'multiubiquitinated cell cycle protein:APC/C:Cdh1 complex' is present.<br><br> This reaction takes place in the 'cytosol' and is mediated by the 'ubiquitin-protein ligase activity' of 'cell cycle proteins:phospho-APC/C:Cdh1 complex' (Rape et al.1996).<br> |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174202 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174202 Following ubiquitination, securin is degraded by the 26S proteasome. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174224 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174224 In late mitosis, Cdc20 dissociates from the APC/C and is replaced by the activator Cdh1 (Ballabeni et al. 2011). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174227 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174227 At the beginning of this reaction, 1 molecule of 'Cdc20:phospho-APC/C:Cyclin B:Cdc2 complex', and 3 molecules of 'ubiquitin' are present. At the end of this reaction, 1 molecule of 'multiubiquitinated Cyclin B:Cdc2:Cdc20:phospho-APC/C complex' is present.<br><br> This reaction takes place in the 'cytosol' and is mediated by the 'ubiquitin-protein ligase activity' of 'Cdc20:Phospho-APC/C'.<br> |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174238 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174238 One model ( the direct inhibition model) describing the inhibition of the APC/C during the mitotic spindle checkpoint suggests that the association of the hBUBR1:hBUB3:MAD2*:CDC20 mitotic checkpoint complex (MCC) with APC/C results in the inactivation of APC/C. The affinity between MCC and APC/C is not high, thus inhibition is readily reversible when the mitotic spindle checkpoint has been satisfied. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-174255 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-174255 Following multiubiquitination, Cyclin A is targeted for destruction by the 26S proteasome. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-179410 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-179410 Nek2A does not appear to be recruited to the APC/C by Cdc20 but rather binds directly to the APC/C in an interaction involving the NEK2A C-terminal methionine–arginine (MR) dipeptide tail (Hayes et al., 2006). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-179417 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-179417 Nek2A is ubiquitinated by the APC/C-Cdc20 ubiquitin ligase. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-179421 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-179421 Nek2A is degraded by the 26S proteasome following ubiquitylation by the E3 ubiquitin ligase APC/C: Cdc20. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-69015 | KEEP AS NON CORE | Summary: Cytosol is retained as APC/C reaction/localization context rather than a core molecular function. Reason: Reactome places some APC/C reactions in cytosolic contexts. This supports localization context for ANAPC2-containing APC/C but not a defining activity. Supporting Evidence: Reactome:R-HSA-69015 At the beginning of this reaction, 1 molecule of 'phosphorylated Cdc6', 1 molecule of 'ubiquitin', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'ubiquitinated Cdc6' is present.<br><br> This reaction takes place in the 'cytosol' and is mediated by the 'endopeptidase activity' of 'anaphase-promoting complex (APC)'.<br> |
| GO:0031915 positive regulation of synaptic plasticity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Synaptic plasticity is a broad orthology-derived neuronal process annotation and overstates the local ANAPC2 evidence; the cited UniProt text more directly supports presynaptic differentiation context. Reason: APC/C-CDC20 has neuronal roles by similarity, but the record does not establish human ANAPC2 as a direct synaptic-plasticity regulator. In PN context this should not be treated as core proteostasis evidence. Supporting Evidence: file:human/ANAPC2/ANAPC2-uniprot.txt CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation |
| GO:0090129 positive regulation of synapse maturation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Synapse maturation is retained as non-core orthology-derived context for CDC20-APC/C neuronal roles, not as ANAPC2's defining molecular function. Reason: UniProt records CDC20-APC/C neuronal effects by similarity, but ANAPC2's conserved core function is the APC/C scaffold/catalytic module. These process terms should not drive PN proteostasis projection for ANAPC2. Supporting Evidence: file:human/ANAPC2/ANAPC2-uniprot.txt CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation |
| GO:0005680 anaphase-promoting complex | IDA PMID:16364912 Localization of the coactivator Cdh1 and the cullin subunit ... | ACCEPT | Summary: ANAPC2 is a core subunit of the anaphase-promoting complex/cyclosome. Reason: This is the most specific cellular-component annotation for ANAPC2. Structural studies place Apc2 in APC/C particles and in the catalytic platform with Apc11. Supporting Evidence: PMID:16364912 These proteins are located on the same side of the asymmetric APC/C, implying that this is where substrates are ubiquitinated. PMID:26083744 These structures define the architecture of all APC/C subunits, the position of the catalytic module |
| GO:0070979 protein K11-linked ubiquitination | IDA PMID:18485873 Mechanism of ubiquitin-chain formation by the human anaphase... | ACCEPT | Summary: APC/C-dependent K11-linked ubiquitin-chain assembly is a well-supported output of the ANAPC2-containing APC/C catalytic module. Reason: K11-linked ubiquitination is a core APC/C activity, and ANAPC2 is part of the catalytic Apc2-Apc11 module that positions the E2 machinery for substrate ubiquitination. Supporting Evidence: PMID:18485873 We find that the APC/C triggers substrate degradation by assembling K11-linked ubiquitin chains PMID:29033132 engineered a bispecific antibody to detect K11/K48-linked chains and identified mitotic regulators, misfolded nascent polypeptides, and pathological Huntingtin variants as their endogenous substrates. PMID:16364912 bound substrates are ubiquitinated by E2 enzymes that interact with a hetero-dimer of the RING subunit Apc11 and the cullin Apc2 |
| GO:0160072 ubiquitin ligase complex scaffold activity | IC PMID:26083744 Atomic structure of the APC/C and its mechanism of protein u... | NEW | Summary: PN projects ubiquitin ligase complex scaffold activity for ANAPC2. Gene-level review supports this as a conservative NEW annotation because ANAPC2 is the cullin-like APC/C scaffold subunit that forms the Apc2-Apc11 catalytic module. Reason: The PN candidate is not accepted solely from taxonomy. It is supported by UniProt cullin-family annotation and structural literature describing Apc2 with Apc11 as the APC/C catalytic module. This is more specific than generic protein binding and complements existing APC/C component annotations. Supporting Evidence: PMID:16364912 bound substrates are ubiquitinated by E2 enzymes that interact with a hetero-dimer of the RING subunit Apc11 and the cullin Apc2 PMID:11739784 a heterodimeric complex of APC2 and APC11 is sufficient to catalyze the ubiquitination of human securin and cyclin B1 PMID:26083744 the catalytic module comprising the RING subunit Apc11 and the C-terminal domain of Apc2 (Apc2CTD) file:human/ANAPC2/ANAPC2-uniprot.txt Belongs to the cullin family. file:human/ANAPC2/ANAPC2-notes.md Conservative decision: ANAPC2 is not a canonical cullin like CUL1-CUL5, but the cached literature supports a cullin-like APC/C scaffold role. |
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Download this section (compressed HTML)Q: Should GO model ANAPC2/APC2 as a cullin-like scaffold activity for APC/C separately from canonical cullin-RING ligase scaffolds, or is GO:0160072 sufficiently broad for degenerate APC/C cullin subunits?
Q: Which human contexts justify retaining neuronal CDC20-APC/C process annotations on ANAPC2 versus restricting them to experimentally studied mammalian orthologs or pathway-level APC/C annotations?
Q: Should the newly described ANAPC2 E2-docking surfaces (the WHB region that clasps UBE2C and the ANAPC2-ANAPC4 groove that binds the UBE2S C-terminal peptide) and the APC2 zinc-binding module be captured by more specific molecular-function or domain annotations beyond GO:0160072?
Experiment: Use rescue of ANAPC2-depleted human cells with interface mutants in the Apc2CTD/Apc11 region, then measure APC/C substrate ubiquitination, K11/K48 chain formation, and mitotic exit timing.
Hypothesis: ANAPC2 scaffold surfaces that contact ANAPC11 and APC/C E2 enzymes are required for APC/C ubiquitin-chain initiation and elongation in human cells.
Type: mutational rescue and ubiquitination assay
Experiment: Reconstitute human APC/C with structure-guided point mutations in the ANAPC2 WHB and the ANAPC2-ANAPC4 groove and assay UBE2C priming versus UBE2S elongation in vitro, testing whether UBE2S titration rescues UBE2C recruitment and processive polyubiquitination on a model substrate.
Hypothesis: The ANAPC2 WHB region and the ANAPC2-ANAPC4 groove are required, respectively, for UBE2C-mediated ubiquitin priming and UBE2S-mediated K11 chain elongation, and UBE2S allosterically promotes UBE2C engagement via stabilization of the "CRL up" state.
Type: structure-guided mutagenesis with in vitro ubiquitination kinetics
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