Affinage

ANAPC10

Anaphase-promoting complex subunit 10 · UniProt Q9UM13

Length
185 aa
Mass
21.3 kDa
Annotated
2026-06-09
17 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANAPC10 (APC10/DOC1) is a core, stoichiometric subunit of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase that is required for substrate degron recognition and the metaphase-to-anaphase transition (PMID:10318877, PMID:11247669). Its structure is a beta-sandwich jellyroll DOC domain, and its C-terminus directly binds the TPR-repeat APC subunit CDC27/APC3 to anchor it within the complex (PMID:11524682, PMID:11884135). Functionally, APC10 together with the co-activator Cdh1 forms a co-receptor for the destruction-box (D-box) degron: cryo-EM positions Cdh1 adjacent to Apc10 in the central APC/C cavity, and NMR demonstrates direct D-box–Apc10 contacts, explaining why APC10 is needed for processive substrate ubiquitylation rather than for complex assembly (PMID:21107322, PMID:31562243). Loss of APC10 inactivates APC/C ubiquitination activity without destabilizing the complex, causing cell-autonomous metaphase arrest and accumulation of the substrate cyclin B across yeast, fly, and mouse systems (PMID:10318877, PMID:9736616, PMID:18297794). Beyond its constitutive APC/C role, APC10 interacts with Smad3 to recruit the APC/C–CDH1 ligase for degradation of HEF1/NEDD9 (PMID:15144564), and during interphase binds NLRP3 to promote inflammasome activation, dissociating during mitosis—a cell-cycle-gated function in innate immune signaling (PMID:34407203).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1998 High

    Established that Apc10/Doc1 is essential for APC/C-mediated mitotic cyclin destruction, linking it directly to chromosome segregation control.

    Evidence Genetic loss-of-function, co-IP, and ubiquitination assays in fission yeast

    PMID:9736616

    Open questions at the time
    • Mechanism of D-box recognition not yet defined
    • Only a subpopulation co-IPs with APC, leaving stoichiometry ambiguous at the time
  2. 1999 High

    Resolved whether Apc10 is a regulatory factor or a true subunit by showing it is a stoichiometric, cell-cycle-invariant APC component whose mutation abolishes ubiquitination without disassembling the complex.

    Evidence Reciprocal co-IP, biochemical fractionation, mass spectrometry, and in vivo ubiquitination assays in yeast and vertebrates

    PMID:10318877

    Open questions at the time
    • Molecular basis of how a stable subunit contributes to catalysis unresolved
    • No structural model
  3. 1999 Medium

    Provided spatial context by mapping human APC10 to centrosomes, spindles, kinetochores, and the midbody through mitosis.

    Evidence Co-IP and immunofluorescence microscopy in human cells

    PMID:10498862

    Open questions at the time
    • Functional consequence of each localization not tested
    • Single lab
  4. 2001 High

    Defined the APC10 fold as a beta-sandwich jellyroll resembling ligand-binding domains and showed its C-terminus binds CDC27/APC3, explaining how it is tethered within the APC/C.

    Evidence 1.6 Å X-ray crystallography plus biochemical binding assay

    PMID:11524682

    Open questions at the time
    • Did not identify the ligand engaged by the jellyroll surface
    • D-box binding not yet demonstrated
  5. 2001 Medium

    Demonstrated in mammals that Apc10/Doc1 disruption causes a cell-autonomous metaphase-to-anaphase block, confirming in vivo requirement in a vertebrate.

    Evidence Genetic mapping and characterization of three mouse mutant alleles with cell cycle phenotyping

    PMID:11247669

    Open questions at the time
    • Substrate-level mechanism not directly assayed
    • Single study
  6. 2002 High

    Mapped functionally essential, invariant residues—including a temperature-sensitive arrest mutant—onto a beta-sheet surface, predicting the interaction face used for APC ubiquitination.

    Evidence 2.2 Å crystallography of yeast Doc1 with mutagenesis mapping

    PMID:11884135

    Open questions at the time
    • The predicted interaction partner of the beta-sheet face not yet identified structurally
  7. 2004 Medium

    Extended APC10 function beyond the core cell cycle by showing Smad3 directly binds APC10 to recruit the APC/C–CDH1 ligase for HEF1/NEDD9 degradation.

    Evidence Co-IP, domain mapping, and overexpression protein-level assays

    PMID:15144564

    Open questions at the time
    • No in vitro reconstitution of HEF1 ubiquitination
    • Single lab
  8. 2010 High

    Settled how APC10 contributes to specificity by showing it acts with Cdh1 as a bipartite D-box co-receptor, with direct Apc10–D-box contacts within the APC/C cavity.

    Evidence Single-particle cryo-EM with difference mapping and NMR of D-box–Apc10 binding

    PMID:21107322

    Open questions at the time
    • Atomic-resolution contacts limited by ~10 Å EM
    • Generality across diverse D-box substrates not exhaustively tested
  9. 2019 Medium

    Reinforced the processivity role by showing the inhibitor Acm1 uses a D-box extension to specifically disrupt the Doc1/Apc10 interaction, confirming Apc10–degron engagement drives processive ubiquitylation.

    Evidence In vivo mutant analysis, biochemical APC/C activity assays, and site-directed mutagenesis in budding yeast

    PMID:31562243

    Open questions at the time
    • Quantitative kinetics of processivity loss not fully resolved
    • Single lab
  10. 2021 Medium

    Identified a moonlighting role in which APC10 binds NLRP3 in interphase to promote inflammasome activation and dissociates in mitosis, coupling cell cycle phase to innate immune output.

    Evidence Co-IP and cell-cycle stage-specific inflammasome activation assays

    PMID:34407203

    Open questions at the time
    • Whether this requires APC/C catalytic activity or is APC/C-independent unresolved
    • Single lab, no reciprocal in vivo validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How APC10's non-canonical interactions (Smad3/HEF1, NLRP3) are mechanistically integrated with—or separated from—its constitutive APC/C role remains unresolved.
  • No reconstituted system distinguishing APC/C-dependent from APC/C-independent APC10 activities
  • Physiological significance of testis-restricted expression uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-392499 Metabolism of proteins 3
Complex memberships
APC/C (anaphase-promoting complex/cyclosome)

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Cryo-EM structure of APC/C(Cdh1) bound to a D-box peptide at ~10 Å resolution revealed that Cdh1 and Apc10 together form a co-receptor for the D-box degron motif. Cdh1 repositions toward Apc10 within the central cavity of the APC/C, and NMR spectroscopy demonstrated direct D-box–Apc10 interactions, establishing that Apc10 directly contributes to D-box recognition alongside the co-activator. Single-particle cryo-EM, difference mapping, NMR spectroscopy Nature High 21107322
2001 Crystal structure of human APC10/DOC1 at 1.6 Å resolution revealed a beta-sandwich jellyroll fold homologous to ligand-binding domains of galactose oxidase and coagulation factor Va. Biochemical experiments further demonstrated that the C-terminus of APC10 directly binds CDC27/APC3, a TPR-repeat-containing APC subunit. X-ray crystallography (1.6 Å); biochemical binding assay (C-terminus of APC10 binding to CDC27/APC3) Nature structural biology High 11524682
2002 Crystal structure of S. cerevisiae Doc1/Apc10 at 2.2 Å resolution showed a beta-sandwich homologous to the galactose-binding domain of galactose oxidase, the C2 domain of coagulation factor, and XRCC1. Residues invariant across Doc1/Apc10 sequences, including a temperature-sensitive mitotic arrest mutant, map to a beta-sheet region proposed to mediate biomolecular interactions and APC ubiquitination function. X-ray crystallography (2.2 Å); comparative structural analysis with mutagenesis data mapping Journal of molecular biology High 11884135
1999 Doc1/Apc10 was shown to be a stoichiometric subunit of the yeast APC throughout the cell cycle. Mutation of Doc1/Apc10 inactivates APC ubiquitination activity without destabilizing the complex. The orthologous human APC10 protein is also a genuine APC subunit in vertebrates (human and frog), and its cellular levels and APC association are not cell-cycle-regulated, as determined by biochemical fractionation and mass spectrometric analysis. Immunoprecipitation, biochemical fractionation, mass spectrometry, in vivo ubiquitination assays The Journal of biological chemistry High 10318877
1998 In fission yeast, apc10+ is essential for viability and required for ubiquitination and degradation of mitotic B-type cyclins. apc10 mutants show temperature-sensitive growth with defects in chromosome segregation and fail to arrest at G1 upon nitrogen starvation. A subpopulation of Apc10 co-immunoprecipitates with the APC, though it does not co-sediment with the 20S complex, suggesting a regulatory association. Genetic mutant analysis, co-immunoprecipitation, cell cycle analysis, ubiquitination assay The EMBO journal High 9736616
1999 Human APC10/Doc1 binds APC core subunits throughout the cell cycle and localizes to centrosomes and mitotic spindles during mitosis, to kinetochores from prophase to anaphase, and to the midbody during telophase/cytokinesis, as determined by co-immunoprecipitation and immunofluorescence localization studies. Co-immunoprecipitation; immunofluorescence microscopy (subcellular localization) Oncogene Medium 10498862
2004 ANAPC10 physically interacts with Smad3 (via the MH2 domain), and together with CDH1 forms a complex with HEF1 (NEDD9). Domain mapping showed distinct Smad3 MH2 subdomains bind APC10 and HEF1. Overexpression of APC10 and CDH1 regulated HEF1 protein levels, suggesting Smad3 recruits the APC/C to HEF1 for ubiquitination and proteasomal degradation via direct Smad3–APC10 interaction. Co-immunoprecipitation, domain mapping, overexpression/protein level assay BMC cell biology Medium 15144564
2019 The pseudosubstrate APC/C inhibitor Acm1 from budding yeast suppresses APC/C activity by combining high-affinity Cdh1 binding with a C-terminal D-box extension that specifically disrupts the normal interaction with Doc1/Apc10, thereby perturbing reaction processivity in ubiquitylation. Mutation of the conserved D-box converted Acm1 into an ABBA-motif-dependent APC/CCdh1 substrate, and biochemical analysis confirmed the extension's role in inhibiting processivity via Doc1/Apc10. In vivo mutant analysis, biochemical APC/C activity assays, site-directed mutagenesis The Journal of biological chemistry Medium 31562243
2001 Disruption of the mouse Apc10/Doc1 gene underlies the oligosyndactylism (Os) radiation-induced mutation and two transgene-induced alleles (94-A and 94-K), all exhibiting a cell-autonomous block in metaphase-to-anaphase transition, establishing that Apc10/Doc1 is required for this cell cycle transition in vivo. Genetic mapping, molecular characterization of three mutant alleles, cell cycle phenotype analysis Genomics Medium 11247669
2007 In Drosophila, loss-of-function mutations in Apc10/Doc1 cause metaphase-like arrest, chromosome overcondensation, high mitotic index, and accumulation of cyclin B (an APC/C substrate) in larval neuroblasts, establishing that Apc10/Doc1 is essential for APC/C E3 ubiquitin ligase activity and cyclin B ubiquitination in vivo. Genetic loss-of-function (mutant alleles), immunostaining for cyclin B, mitotic index quantification Acta biologica Hungarica Medium 18297794
2021 During interphase, APC10 interacts with NLRP3 and promotes NLRP3 inflammasome activation; during mitosis, APC10 dissociates from NLRP3 to repress inflammatory responses, establishing a cell-cycle-dependent switch role for APC10 in innate immune signaling. Co-immunoprecipitation, cell cycle stage-specific analysis, inflammasome activation assays FEBS letters Medium 34407203
2012 ANAPC10 protein is mainly expressed in the cytoplasm of spermatogonia and leptotene/pachytene spermatocytes in the developing mouse testis, as established by immunofluorescence and in situ hybridization. In situ hybridization, immunofluorescence microscopy Biology of reproduction Low 22190705

Source papers

Stage 0 corpus · 17 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Structures of APC/C(Cdh1) with substrates identify Cdh1 and Apc10 as the D-box co-receptor. Nature 172 21107322
1998 Apc10 and Ste9/Srw1, two regulators of the APC-cyclosome, as well as the CDK inhibitor Rum1 are required for G1 cell-cycle arrest in fission yeast. The EMBO journal 88 9736616
1999 Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex. The Journal of biological chemistry 78 10318877
2001 Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting complex. Nature structural biology 77 11524682
2002 Implications for the ubiquitination reaction of the anaphase-promoting complex from the crystal structure of the Doc1/Apc10 subunit. Journal of molecular biology 42 11884135
2004 Direct interaction between Smad3, APC10, CDH1 and HEF1 in proteasomal degradation of HEF1. BMC cell biology 38 15144564
1999 Identification of human APC10/Doc1 as a subunit of anaphase promoting complex. Oncogene 22 10498862
2020 Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ. iScience 21 32674056
2001 Disruption of Apc10/Doc1 in three alleles of oligosyndactylism. Genomics 18 11247669
2004 Apc10.1: an ApcMin/+ intestinal cell line with retention of heterozygosity. International journal of cancer 17 14750170
2009 APC10.1 cells as a model for assessing the efficacy of potential chemopreventive agents in the Apc(Min) mouse model in vivo. European journal of cancer (Oxford, England : 1990) 8 19695862
2021 Docking and ADMET studies for investigating the anticancer potency of Moscatilin on APC10/DOC1 and PKM2 against five clinical drugs. Journal, genetic engineering & biotechnology 7 34665359
2019 The pseudosubstrate inhibitor Acm1 inhibits the anaphase-promoting complex/cyclosome by combining high-affinity activator binding with disruption of Doc1/Apc10 function. The Journal of biological chemistry 7 31562243
2012 Experimental validation of Ankrd17 and Anapc10, two novel meiotic genes predicted by computational models in mice. Biology of reproduction 6 22190705
2021 The APC10 subunit of the anaphase-promoting complex/cyclosome orchestrates NLRP3 inflammasome activation during the cell cycle. FEBS letters 5 34407203
2007 Characterization of the Apc10/Doc1 subunit of the anaphase promoting complex in Drosophila melanogaster. Acta biologica Hungarica 4 18297794
2010 Sequence characterization and promoter identification of porcine APC10 gene. Molecular biology reports 0 20232159

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