Apc11 is the 94-residue RING-H2 zinc-finger subunit of the Schizosaccharomyces pombe anaphase-promoting complex/cyclosome (APC/C), the 13-subunit cullin-RING E3 ubiquitin ligase that drives the metaphase-to-anaphase transition and exit from mitosis. Anchored on the cullin-homology domain of Apc2, Apc11 forms the catalytic module of the complex: its RING domain, which coordinates zinc through conserved cysteine and histidine ligands, binds and activates ubiquitin-charged E2 enzymes (Ubc11 and Ubc4 in fission yeast) so that ubiquitin is transferred directly from the E2 thioester to lysine residues of APC/C-bound substrates, building polyubiquitin chains that are recognised by the 26S proteasome. Apc11 forms no ubiquitin thioester of its own and does not recognise substrates; D-box and KEN-box degrons are read by the coactivators Slp1/Cdc20 and Ste9/Cdh1 (Mfr1/Fzr1 in meiosis) together with the co-receptor Apc10, and the spindle assembly checkpoint restrains the complex until chromosomes are bioriented. Through the APC/C, Apc11 ubiquitinates the securin Cut2, whose destruction releases the separase Cut1 to cleave cohesin and permit sister-chromatid separation, and the B-type cyclin Cdc13, whose destruction lowers Cdc2 kinase activity and allows mitotic exit and the establishment of G1. Apc11 is present at one copy per APC/C particle and lies with Apc2 and Apc10 on the catalytic side of the complex, opposite the TPR scaffold; it is essential for viability, acts in the nucleus during the closed mitosis of fission yeast, and is the orthologue of human ANAPC11 and budding-yeast Apc11, belonging to the RING-box family alongside the SCF subunit Rbx1/Pip1 from which it differs by pairing exclusively with Apc2.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from the RING-box family node PTN000129805 (RBX1/RBX2/APC11 clade) that apc11 is active in the nucleus. Fission yeast undergoes a closed mitosis in which the APC/C substrates Cut2/securin and Cdc13 are nuclear and spindle-associated, and the pombe apc11 gene product is itself listed in the WITH/FROM as a descendant evidence. Reason: The IBD is placed at the family node whose experimental descendants (yeast Apc11/Rbx1, fly and mouse Rbx1, human RBX1/ANAPC11) act on nuclear substrates, and the target-specific biology agrees: securin Cut2 is nuclear and concentrated on the metaphase spindle and is destroyed there by the Cut9-containing APC/C, so the APC/C RING catalytic module must act in the nucleus during the closed mitosis of S. pombe. No apc11-specific imaging series exists (the deep-research survey found none), so the site is inferred from complex biology rather than from direct localisation of the subunit, which is a knowledge gap rather than a reason to doubt the term. PomBase:SPAC343.03 appearing in its own WITH/FROM is the expected marker that target-side evidence was used to place the node. Supporting Evidence: PMID:8632802 Cut2 is located in the nucleus, where it is concentrated along the short metaphase spindle. PMID:8632802 The rapid degradation of Cut2 at anaphase requires its amino-terminal region and the activity of Cut9 (ref. 14), a component of the 20S cyclosome/anaphase-promoting complex (APC), which is necessary for cyclin destruction. file:SCHPO/apc11/apc11-deep-research-falcon.md Structural labeling places Apc11 on the catalytic side of purified mitotic APC/C. APC/C activity acts on soluble/nuclear mitotic regulators associated with chromosome segregation and mitotic exit. file:SCHPO/apc11/apc11-deep-research-falcon.md However, the retrieved literature did not provide an Apc11-specific live-cell localization series establishing enrichment at nuclei, spindle-pole bodies, kinetochores, spindles, or chromosomes. PMID:10888670 Cdc16p/APC6, Cdc23p/APC8, Cdc27p/APC3, and APC7 were identified as tetratricopeptide repeat (TPR)- containing proteins, which function in the nucleus Knowledge gap: No direct imaging of tagged Apc11 in living or fixed S. pombe cells has been reported; the nuclear site of activity is inferred from the localisation of APC/C substrates and other APC/C subunits. OPEN BIOLOGY CC_DARK Resolve: Endogenous fluorescent tagging or immunofluorescence of Apc11 through the fission-yeast cell cycle. "However, the retrieved literature did not provide an Apc11-specific live-cell localization series establishing enrichment at nuclei, spindle-pole bodies, kinetochores, spindles, or chromosomes." — file:SCHPO/apc11/apc11-deep-research-falcon.md |
| GO:0005680 anaphase-promoting complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from the APC11-specific subclade node PTN000129916 (seeded by human ANAPC11, fly APC11, budding-yeast Apc11 and pombe apc11) that apc11 is part of the anaphase-promoting complex. Directly confirmed in S. pombe by TAP/mass-spectrometry purifications of the APC/C. Reason: Membership of the APC/C is the defining property of the APC11 subclade of the RING-box family, and the target itself carries IDA evidence (Yoon et al. 2002 identified SPAC343.03 peptides in Lid1-TAP and Apc13-TAP purifications; Schwickart et al. 2004 recovered the same subunit set with Cut9-TAP). PomBase:SPAC343.03 in the WITH/FROM reflects that experimental grounding on the target. Core, defining complex for the gene. Supporting Evidence: PMID:12477395 Here, we have applied a tandem affinity purification approach coupled with direct analysis of the purified complexes by mass spectrometry (DALPC) to reveal additional subunits of both the S. pombe and S. cerevisiae APCs. PMID:12477395 Our data increase the total number of identified APC subunits to 13 in both yeasts and indicate that previous approaches were biased against the identification of small subunits. file:SCHPO/apc11/apc11-uniprot.txt The APC/C is composed of at least 13 subunits: apc1, apc2, file:SCHPO/apc11/apc11-deep-research-falcon.md These data directly connect the exact fission-yeast ORF to the APC/C and support the supplied Q9UT86 annotation. |
| GO:0005680 anaphase-promoting complex | IDA PMID:12477395 Proteomics analysis identifies new components of the fission... | ACCEPT | Summary: Yoon et al. 2002 applied tandem affinity purification with direct analysis by tandem mass spectrometry (DALPC) to the S. pombe APC/C and raised the subunit count to 13; the small RING subunit apc11 (SPAC343.03) was among the components recovered, the founding demonstration that this ORF encodes an APC/C subunit. Reason: Direct, exact-organism evidence of complex membership from a purification designed to capture small subunits that earlier approaches missed. The cached record is abstract-only and the abstract does not name individual subunits, but UniProt cites this paper for the 13-subunit composition including apc11 and the deep-research synthesis records the peptide counts for SPAC343.03 in the Lid1-TAP and Apc13-TAP preparations. Defining, core annotation. Supporting Evidence: PMID:12477395 Here, we have applied a tandem affinity purification approach coupled with direct analysis of the purified complexes by mass spectrometry (DALPC) to reveal additional subunits of both the S. pombe and S. cerevisiae APCs. PMID:12477395 Our data increase the total number of identified APC subunits to 13 in both yeasts and indicate that previous approaches were biased against the identification of small subunits. file:SCHPO/apc11/apc11-uniprot.txt The APC/C is composed of at least 13 subunits: apc1, apc2, file:SCHPO/apc11/apc11-deep-research-falcon.md These data directly connect the exact fission-yeast ORF to the APC/C and support the supplied Q9UT86 annotation. |
| GO:0005680 anaphase-promoting complex | IDA PMID:15060174 Swm1/Apc13 is an evolutionarily conserved subunit of the ana... | ACCEPT | Summary: Schwickart et al. 2004 purified TAP-tagged Cut9 and TAP-tagged Apc13 from fission yeast and identified by mass spectrometry the full set of known and predicted APC/C subunits (including apc11) plus the small subunits Apc13, Apc14 and Apc15; the paper also introduces Apc11 as the RING subunit that by itself has minimal ubiquitin ligase properties. Reason: Independent, exact-organism co-purification of apc11 with two different tagged APC/C subunits in a study whose control (Set1C) shows the association is specific. Full text is cached; the subunit list is in Fig. 2C, and the introduction correctly positions Apc11 as the RING finger anchored to the complex through the cullin-like Apc2. Core annotation. Supporting Evidence: PMID:15060174 Mass spectrometric analysis of the Cut9-TAP purification identified 10 proteins known or predicted to be APC/C subunits ( 48 ). PMID:15060174 Accordingly, purification of a TAP-tagged version of Apc13 yielded the same set of APC/C subunits as Cut9-TAP (Fig. 2C ), demonstrating that apc13 + encodes a subunit of the fission yeast APC/C. PMID:15060174 APC/C's RING finger is located within the small subunit Apc11, which by itself has the properties of a minimal ubiquitin ligase ( 13 , 22 ). PMID:15060174 Apc11 is anchored to the complex through Apc2, a subunit distantly related to cullins ( 50 , 54 ). |
| GO:0005680 anaphase-promoting complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from IPR024991 (RING-H2 zinc finger, APC11) to anaphase-promoting complex; the domain is diagnostic of APC11 orthologues. Reason: The APC11 RING-H2 family signature is found only in APC/C RING subunits, and the mapping is confirmed for apc11 by the IDA/IPI rows from TAP purifications. Redundant with experimental evidence but correct. Supporting Evidence: file:SCHPO/apc11/apc11-uniprot.txt The APC/C is composed of at least 13 subunits: apc1, apc2, PMID:12477395 Our data increase the total number of identified APC subunits to 13 in both yeasts and indicate that previous approaches were biased against the identification of small subunits. |
| GO:0005680 anaphase-promoting complex | IPI PMID:12477395 Proteomics analysis identifies new components of the fission... | ACCEPT | Summary: Complex Portal curation (CPX-763, S. pombe anaphase-promoting complex, with the Slp1, Srw1/Ste9 and Mfr1 coactivator variants CPX-764/765/766) based on the Yoon et al. 2002 TAP/DALPC proteomics; apc11 is listed as a core subunit. Reason: Same underlying experiment as the PomBase IDA row, propagated through Complex Portal; apc11 is a constitutive one-copy subunit of the core complex present in all coactivator-bound forms. Core annotation. Supporting Evidence: PMID:12477395 Here, we have applied a tandem affinity purification approach coupled with direct analysis of the purified complexes by mass spectrometry (DALPC) to reveal additional subunits of both the S. pombe and S. cerevisiae APCs. PMID:12477395 Our data increase the total number of identified APC subunits to 13 in both yeasts and indicate that previous approaches were biased against the identification of small subunits. file:SCHPO/apc11/apc11-deep-research-falcon.md Apc11, Apc2, and Apc10 occupy the catalytic side of the assembly, spatially separated from much of the TPR scaffold. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from the RING-box family node PTN000129805 that apc11 is involved in ubiquitin-dependent protein catabolism. In S. pombe the APC/C polyubiquitinates Cut2/securin and the cyclin Cdc13 for proteasomal destruction at anaphase. Reason: Targeting proteins for proteasomal destruction is the ancestral function of the whole RING-box family (Rbx1 in cullin-RING ligases, Apc11 in the APC/C), so the node placement is sound, and it is documented for the fission-yeast complex: Cut2 is polyubiquitinated in a destruction-box-dependent manner and degraded through the Cut9-containing cyclosome. The term is broad, but the specific child (anaphase-promoting complex-dependent catabolic process, GO:0031145) is annotated separately, so the two are complementary. Supporting Evidence: PMID:10651900 Securin, like mitotic cyclins, is the target of the anaphase promoting complex (APC)/cyclosome and is polyubiquitinated before destruction in a manner dependent upon the destruction sequence. PMID:8632802 The rapid degradation of Cut2 at anaphase requires its amino-terminal region and the activity of Cut9 (ref. 14), a component of the 20S cyclosome/anaphase-promoting complex (APC), which is necessary for cyclin destruction. PMID:12477395 The anaphase-promoting complex (APC) is a conserved multisubunit ubiquitin ligase required for the degradation of key cell cycle regulators. PMID:10888670 His-Apc11p mediated the polyubiquitination of Clb2p in the presence of Ubc4p, but not Cdc34p (Figure 5 D, compare lanes 2 and 4). |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from IPR024991 (RING-H2 finger of APC11) to zinc ion binding. The 94-residue apc11 is essentially a RING-H2 zinc finger (UniProt ZN_FING 35-78) with the conserved cysteine/histidine ligand pattern of the APC11/RBX1 family. Reason: Zinc coordination is intrinsic to the RING-H2 fold and required for function: mutating the zinc-ligand cysteines of budding-yeast Apc11 abolishes E3 activity and viability, and human APC11 binds three Zn2+ ions. The pombe sequence retains the ligand residues, so the mapping is correct, though this is a structural property that supports rather than defines the gene's function. Supporting Evidence: PMID:11739784 Zn(2+)-binding and mutagenesis experiments indicate that APC11 binds Zn(2+) at a 1:3 M ratio. PMID:10888670 However, Apc11p bearing mutations in putative metal-binding cysteines (C41, C44, or C91) showed little or no activity in this assay (Figure 5 A, lanes 3, 4, and 9), demonstrating that the RING-H2 finger is absolutely required for its E3 activity. file:SCHPO/apc11/apc11-deep-research-falcon.md In budding yeast, mutation of zinc-coordinating Apc11 residues disrupted complementation, showing that RING integrity is essential for function file:SCHPO/apc11/apc11-uniprot.txt RING-type |
| GO:0016567 protein ubiquitination | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from the RING-box family node PTN000129805 that apc11 is involved in protein ubiquitination. Apc11 is the RING subunit through which the APC/C recruits ubiquitin-charged E2s (Ubc11 and Ubc4 in fission yeast) and transfers ubiquitin to substrates. Reason: Mediating E2-dependent ubiquitin transfer is the shared function of all RING-box proteins and is demonstrated directly for the orthologous budding-yeast and human APC11 with purified components; purified S. pombe APC/C ubiquitylates Cdc13 and Cut2 with fission-yeast E1 and E2s. This is the process that apc11 itself executes, so the row is core. Supporting Evidence: PMID:10888670 Here, we provide evidence that the Saccharomyces cerevisiae RING-H2 finger protein Apc11 defines the minimal ubiquitin ligase activity of the APC. PMID:10888670 His-Apc11p mediated the polyubiquitination of Clb2p in the presence of Ubc4p, but not Cdc34p (Figure 5 D, compare lanes 2 and 4). PMID:11739784 In combination with Ubc4 or UbcH10, a heterodimeric complex of APC2 and APC11 is sufficient to catalyze the ubiquitination of human securin and cyclin B1. file:SCHPO/apc11/apc11-deep-research-falcon.md APC/C ubiquitylated a Cdc2–Cdc13 substrate in an E1-, E2-, and ATP-dependent assay, while cellular APC/C activity generated ubiquitylated Cut2. file:SCHPO/apc11/apc11-deep-research-falcon.md Ubc11 can generate short ubiquitin chains in the absence of Ubc4, whereas Ubc4 cannot ubiquitylate APC/C substrates without Ubc11, supporting a model in which Ubc11 participates in initial substrate modification and Ubc4 supports chain extension. |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from IPR024991 to anaphase-promoting complex-dependent catabolic process; the APC11 RING-H2 signature is specific to the catalytic RING subunit of the APC/C. Reason: Correct and specific: the APC11 domain family exists only in APC/C RING subunits, whose function is to catalyse the ubiquitination that initiates APC/C-dependent proteolysis of securin and cyclins. Consistent with the NAS row and with the experimental complex-membership rows. Supporting Evidence: PMID:15060174 The anaphase-promoting complex (APC/C) is a large ubiquitin-protein ligase which controls progression through anaphase by triggering the degradation of cell cycle regulators such as securin and B-type cyclins. PMID:15060174 APC/C's RING finger is located within the small subunit Apc11, which by itself has the properties of a minimal ubiquitin ligase ( 13 , 22 ). PMID:8632802 The rapid degradation of Cut2 at anaphase requires its amino-terminal region and the activity of Cut9 (ref. 14), a component of the 20S cyclosome/anaphase-promoting complex (APC), which is necessary for cyclin destruction. |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | NAS PMID:12477395 Proteomics analysis identifies new components of the fission... | ACCEPT | Summary: Complex Portal statement (from the Yoon et al. 2002 proteomics paper) that the S. pombe APC/C, of which apc11 is a subunit, carries out APC/C-dependent proteolysis of cell-cycle regulators. Reason: The abstract states that the APC is a conserved ubiquitin ligase required for degradation of key cell-cycle regulators, and apc11 is the catalytic RING subunit that performs the ubiquitination step, so it does the work of this process rather than merely being required for it. Fission-yeast-specific outputs (Cut2 and Cdc13 ubiquitylation) are documented. Core process. Supporting Evidence: PMID:12477395 The anaphase-promoting complex (APC) is a conserved multisubunit ubiquitin ligase required for the degradation of key cell cycle regulators. file:SCHPO/apc11/apc11-deep-research-falcon.md APC/C ubiquitylated a Cdc2–Cdc13 substrate in an E1-, E2-, and ATP-dependent assay, while cellular APC/C activity generated ubiquitylated Cut2. PMID:10651900 Securin, like mitotic cyclins, is the target of the anaphase promoting complex (APC)/cyclosome and is polyubiquitinated before destruction in a manner dependent upon the destruction sequence. PMID:15060174 APC/C's RING finger is located within the small subunit Apc11, which by itself has the properties of a minimal ubiquitin ligase ( 13 , 22 ). |
| GO:0045842 positive regulation of mitotic metaphase/anaphase transition | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from the APC11 subclade node PTN000129916 (seeded by human ANAPC11 and fly APC11) that apc11 positively regulates the mitotic metaphase/anaphase transition. In S. pombe, APC/C ubiquitination of Cut2/securin releases the separase Cut1 and triggers sister-chromatid separation. Reason: The node is the APC11-specific clade, all of whose members are the RING subunit of the APC/C, and the function is ancestral to that clade. GO defines the metaphase/anaphase transition as triggered by activation of the APC/C and degradation of securin, so the catalytic subunit that ubiquitinates securin drives the transition; non-degradable Cut2 blocks sister-chromatid separation in fission yeast. Whether this is best expressed as positive regulation (this row) or as direct participation in GO:0007091 is a representation question raised under suggested questions; the biology is not in doubt. Core process. Supporting Evidence: PMID:10651900 Securin, like mitotic cyclins, is the target of the anaphase promoting complex (APC)/cyclosome and is polyubiquitinated before destruction in a manner dependent upon the destruction sequence. PMID:10651900 The anaphase never occurs properly in the absence of securin destruction. PMID:8632802 demonstrating that the regulated proteolysis of Cut2 is essential for sister-chromatid separation. PMID:10888670 Targets of APC/C include securin proteins (Pds1p in budding yeast and Cut2p in fission yeast), whose destruction is required for the separation of sister chromatids at anaphase PMID:16950791 The APC/C becomes active at the metaphase/anaphase transition and remains active during G(1) phase. |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from the RING-box family node PTN000129805 that apc11 enables ubiquitin protein ligase activity. The RING-H2 finger binds the E2~ubiquitin conjugate and catalyses direct transfer of ubiquitin from the E2 thioester to substrate lysines without forming a thioester itself. Reason: Ubiquitin ligase activity is the ancestral function of the RING-box family and is demonstrated with purified proteins for both the budding-yeast and human orthologues (Apc11 alone, or the APC2-APC11 heterodimer, suffices to ubiquitinate Clb2, securin and cyclin B1 with Ubc4/UbcH10). The pombe protein retains the RING-H2 fold, and the PomBase GO-CAM for spindle checkpoint signalling models the S. pombe APC/C as the entity enabling GO:0061630. The enables qualifier is appropriate because the RING subunit is the catalytic element. Core molecular function. Supporting Evidence: PMID:10888670 Here, we provide evidence that the Saccharomyces cerevisiae RING-H2 finger protein Apc11 defines the minimal ubiquitin ligase activity of the APC. PMID:10888670 However, Apc11p bearing mutations in putative metal-binding cysteines (C41, C44, or C91) showed little or no activity in this assay (Figure 5 A, lanes 3, 4, and 9), demonstrating that the RING-H2 finger is absolutely required for its E3 activity. PMID:11739784 In combination with Ubc4 or UbcH10, a heterodimeric complex of APC2 and APC11 is sufficient to catalyze the ubiquitination of human securin and cyclin B1. PMID:10888670 Our work, and that of others, indicates that RING-based E3s do not act as ubiquitin carriers that form thioester intermediates, but instead act as bridges between E2s and substrates that provide a favorable environment for the transfer of ubiquitin. file:SCHPO/apc11/apc11-deep-research-falcon.md The RING domain binds and positions an E2~ubiquitin conjugate in a transfer-competent state, while APC/C-associated recognition machinery positions the substrate lysine. |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from IPR024991 (RING-H2 finger, APC11) to ubiquitin protein ligase activity. Reason: The APC11 RING-H2 domain is the catalytic module of the APC/C; the mapping is confirmed by the biochemical evidence for the orthologues and by the IBA and TAS rows. Correct, if redundant. Supporting Evidence: PMID:15060174 APC/C's RING finger is located within the small subunit Apc11, which by itself has the properties of a minimal ubiquitin ligase ( 13 , 22 ). PMID:11739784 In combination with Ubc4 or UbcH10, a heterodimeric complex of APC2 and APC11 is sufficient to catalyze the ubiquitination of human securin and cyclin B1. |
| GO:0061630 ubiquitin protein ligase activity | TAS PMID:10651900 Cell cycle mechanisms of sister chromatid separation; roles ... | ACCEPT | Summary: Traceable author statement from a Yanagida 2000 review of sister-chromatid separation in fission yeast, which states that securin, like mitotic cyclins, is polyubiquitinated by the APC/cyclosome in a destruction-sequence-dependent manner before destruction. PomBase attached the ligase activity to apc11 as the RING catalytic subunit of that complex. Reason: The review is about Cut1/Cut2 and does not name apc11 in the cached abstract, but the statement it supports (the APC/C is the ubiquitin ligase that polyubiquitinates Cut2) is correct, and assigning the ligase activity to the RING subunit is the right subunit-level reading: Apc11 by itself has minimal ubiquitin ligase properties and the RING is absolutely required for E3 activity. The reference is weak for a subunit-specific claim, so reference relevance is recorded as medium, but the annotation is retained because the function is clearly correct for the gene. Supporting Evidence: PMID:10651900 Securin, like mitotic cyclins, is the target of the anaphase promoting complex (APC)/cyclosome and is polyubiquitinated before destruction in a manner dependent upon the destruction sequence. PMID:15060174 APC/C's RING finger is located within the small subunit Apc11, which by itself has the properties of a minimal ubiquitin ligase ( 13 , 22 ). PMID:10888670 However, Apc11p bearing mutations in putative metal-binding cysteines (C41, C44, or C91) showed little or no activity in this assay (Figure 5 A, lanes 3, 4, and 9), demonstrating that the RING-H2 finger is absolutely required for its E3 activity. |
| GO:0097602 cullin family protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from the RING-box family node PTN000129805 that apc11 binds a cullin family protein. The apc11 partner is the cullin-homology subunit Apc2 (SPBP23A10.04), which anchors the RING to the APC/C; in the pombe APC/C-Slp1 structure Apc11, Apc2 and Apc10 sit together on the catalytic side. Reason: Cullin binding is the defining shared property of the RING-box family (Rbx1/Pip1 binds Pcu1/Pcu3/Pcu4, Apc11 binds the cullin-like Apc2), so the node placement is correct. For the human orthologue APC11 binds the C-terminal cullin homology domain of APC2 directly, and in S. pombe the antibody labelling of the APC/C-Slp1 particle places Apc11 with Apc2 in the catalytic region. This is the informative binding activity for apc11. Supporting Evidence: PMID:11739784 Both APC11 and UbcH10 bind to the C-terminal cullin homology domain of APC2, whereas Ubc4 interacts with APC11 directly. PMID:15060174 Apc11 is anchored to the complex through Apc2, a subunit distantly related to cullins ( 50 , 54 ). file:SCHPO/apc11/apc11-deep-research-falcon.md Apc11, Apc2, and Apc10 occupy the catalytic side of the assembly, spatially separated from much of the TPR scaffold. PMID:10888670 The RING finger family is quite diverse, ranging from small proteins like Roc1/Rbx1/Hrt1 and Apc11, which consist almost solely of the RING domain, to large, modular proteins like c-Cbl, which bear several recognizable protein motifs in addition to the RING finger. |
| GO:0097602 cullin family protein binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from IPR024991 to cullin family protein binding; APC11-type RING-H2 fingers are the cullin-binding RING-box subunits of the APC/C. Reason: Correct: the partner is the cullin-homology subunit Apc2 that anchors Apc11 to the complex. Redundant with the IBA row but consistent with it. Supporting Evidence: PMID:15060174 Apc11 is anchored to the complex through Apc2, a subunit distantly related to cullins ( 50 , 54 ). PMID:11739784 Both APC11 and UbcH10 bind to the C-terminal cullin homology domain of APC2, whereas Ubc4 interacts with APC11 directly. |
| GO:1901970 positive regulation of mitotic sister chromatid separation | IC PMID:12477395 Proteomics analysis identifies new components of the fission... | ACCEPT | Summary: PomBase curator inference from APC/C membership (GO:0005680) that apc11 positively regulates mitotic sister chromatid separation: the APC/C polyubiquitinates the securin Cut2, whose destruction liberates the separase Cut1 to cleave cohesin. Reason: The inference is sound and is the pombe-specific formulation of what the IBA row GO:0045842 asserts: regulated proteolysis of Cut2 by the Cut9-containing APC/C is essential for sister-chromatid separation, and Apc11 is the RING subunit that catalyses that ubiquitination. The PomBase GO-CAM for spindle-checkpoint signalling models the APC/C ligase activity (with apc11 as a part) as directly negatively regulating the securin and Cdc13 activities upstream of mitotic sister chromatid separation, which is exactly the causal chain this term summarises. The APC/C does not perform the separation step itself (separase does), so a positive-regulation term rather than GO:0051306 is appropriate here. Core process. Supporting Evidence: PMID:8632802 The rapid degradation of Cut2 at anaphase requires its amino-terminal region and the activity of Cut9 (ref. 14), a component of the 20S cyclosome/anaphase-promoting complex (APC), which is necessary for cyclin destruction. PMID:8632802 demonstrating that the regulated proteolysis of Cut2 is essential for sister-chromatid separation. PMID:10651900 The anaphase never occurs properly in the absence of securin destruction. PMID:11739784 In mitosis, the anaphase-promoting complex (APC) regulates the onset of sister-chromatid separation and exit from mitosis by mediating the ubiquitination and degradation of the securin protein and mitotic cyclins. |
Loading supporting content…
Download this section (compressed HTML)Q: The APC/C RING subunit carries both positive regulation of mitotic metaphase/anaphase transition (GO:0045842, IBA) and positive regulation of mitotic sister chromatid separation (GO:1901970, IC), while the PomBase GO-CAM and the pathway module place the APC/C ligase activity as a direct part of metaphase/anaphase transition of mitotic cell cycle (GO:0007091), whose definition names APC/C activation and securin degradation. Should the catalytic subunit be annotated to the transition itself rather than, or in addition to, its regulation?
Q: Direct Apc11-E2 binding is demonstrated for the budding-yeast and human orthologues, yet no APC11 orthologue carries GO:0031624 ubiquitin conjugating enzyme binding (comparator check: human ANAPC11, RBX1, yeast Apc11, pombe apc11). Is E2 engagement considered part of ubiquitin protein ligase activity for RING E3s, and which fission-yeast E2 (Ubc11 or Ubc4) contacts the apc11 RING directly?
Q: Is apc11 present in the meiosis-specific Mfr1/Fzr1-activated APC/C (Complex Portal CPX-766) at the same one-copy stoichiometry, and does the RING module contribute to the Mes1-regulated meiosis I to II transition?
Experiment: Replace endogenous apc11 with alleles mutating the RING zinc ligands or the E2-contacting helix (equivalent to yeast W81) under a regulatable promoter; score viability, metaphase arrest and Cut2/Cdc13 stability, and assay purified APC/C-Slp1 from each strain for Cut2 ubiquitylation with Ubc11 alone, Ubc4 alone, or both.
Hypothesis: The zinc-ligand cysteines of the S. pombe apc11 RING-H2 finger are required for APC/C ubiquitin ligase activity and for viability, as for budding-yeast Apc11, and the Ubc11-dependent priming and Ubc4-dependent elongation steps use separable surfaces of the RING.
Type: structure-guided mutagenesis with in vivo phenotyping and in vitro ubiquitination assays
Experiment: Tag apc11 at its endogenous locus with a fluorescent protein (checking that the tagged strain grows normally, as reported for the double-tag stoichiometry strains), image through the cell cycle alongside Cut2-GFP or a tagged TPR subunit, and confirm with anti-Apc11 immunofluorescence.
Hypothesis: Apc11 is nuclear throughout the closed mitosis of fission yeast and co-localises with the APC/C on the metaphase spindle where Cut2 is destroyed.
Type: endogenous tagging and live-cell imaging
Experiment: Perform in vitro ubiquitylation of Cut2 and Cdc13 with purified S. pombe APC/C-Slp1, Uba1, Ubc11 and Ubc4 using lysine-to-arginine ubiquitin mutants and linkage-specific mass spectrometry, and compare with chains formed by the apc11 RING mutants.
Hypothesis: The S. pombe APC/C assembles K48-linked rather than K11-linked ubiquitin chains on Cut2 and Cdc13.
Type: in vitro reconstitution with ubiquitin linkage analysis
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)