Affinage

ANAPC13

Anaphase-promoting complex subunit 13 · UniProt Q9BS18

Round 2 corrected
Length
74 aa
Mass
8.5 kDa
Annotated
2026-04-28
58 papers in source corpus 9 papers cited in narrative 9 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANAPC13 (Swm1/Apc13) is a small, evolutionarily conserved core subunit of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase that is essential for maintaining complex integrity and cell cycle progression. It resides in the Arc Lamp sub-structure of the APC/C alongside APC16 and CDC26, and promotes the stable association of the TPR-repeat subunits CDC16 (APC6) and CDC27 (APC3) with the complex; loss of ANAPC13 causes their dissociation and abolishes APC/C ubiquitin ligase activity (PMID:15060174, PMID:25043029, PMID:26083744). ANAPC13 expression is regulated post-transcriptionally by SF3B1-dependent splicing, and its reduction impairs regulatory T cell differentiation, while biallelic loss-of-function mutations cause human oocyte maturation arrest at metaphase I (PMID:39303038, PMID:41997520). Biallelic ANAPC13 mutations have been identified as a cause of female infertility due to oocyte maturation failure, with partial rescue by wild-type mRNA microinjection confirming a causal role (PMID:41997520, PMID:40238067).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2003 High

    The identity of Swm1/Apc13 as a constitutive APC/C core subunit was established, resolving whether it was a stoichiometric component or a transient interactor, and revealing its direct contacts with Cdc23 and Apc5.

    Evidence Mass spectrometry of purified yeast APC, in vitro co-translation interaction assay, and genetic deletion analysis in S. cerevisiae

    PMID:12609981

    Open questions at the time
    • No structural information on how Swm1 integrates into the APC/C architecture
    • No direct evidence for the human orthologue at this stage
  2. 2004 High

    The functional requirement for Swm1/Apc13 was defined: it stabilizes TPR subunits Cdc16 and Cdc27 within the APC/C, and its absence abolishes ubiquitin ligase activity, explaining the cell cycle delays seen in swm1Δ cells.

    Evidence Genetic deletion, in vitro ubiquitin ligase assay, co-immunoprecipitation, and cross-species complementation using human and fission yeast homologues in budding yeast

    PMID:15060174

    Open questions at the time
    • Molecular contacts mediating TPR subunit stabilization were undefined
    • Whether the human protein was an endogenous APC/C subunit in human cells remained unproven
  3. 2010 High

    APC13 was confirmed as a bona fide subunit of the human APC/C, closing the gap between yeast genetics and human cell biology and demonstrating its requirement for proper chromosome segregation.

    Evidence Tandem-affinity purification–mass spectrometry, fluorescence microscopy localization, and RNAi phenotypic screening in human cells

    PMID:20360068

    Open questions at the time
    • Precise position of APC13 within the ~1.2 MDa human APC/C structure was unknown
    • Mechanism by which APC13 supports chromosome segregation was not molecularly resolved
  4. 2014 High

    Structural studies placed APC13 within the Arc Lamp sub-complex of the human APC/C alongside APC16 and CDC26, defining its three-dimensional context and how it interfaces with the TPR lobe.

    Evidence Cryo-EM at 7.4 Å resolution and X-ray crystallography of APC3–APC16 complexes with biochemical mapping

    PMID:25043029 PMID:25490258

    Open questions at the time
    • Atomic-resolution contacts of APC13 with neighbouring subunits were not fully resolved
    • No disease-associated mutations had been linked to APC13
  5. 2015 High

    Atomic-resolution cryo-EM structures of APC/C–coactivator complexes confirmed and refined the Arc Lamp placement of APC13, completing the architectural picture of how the full APC/C is assembled and regulated.

    Evidence Near-atomic cryo-EM with mutagenesis-based functional validation

    PMID:26083744

    Open questions at the time
    • Physiological consequences of APC13 loss in mammalian tissues remained untested
    • Whether APC13 has tissue-specific roles was unknown
  6. 2024 High

    A new regulatory axis was revealed: the cancer-associated SF3B1-K700E splicing-factor mutation reduces ANAPC13 protein by aberrant 5′ UTR splicing, linking APC/C function to splicing fidelity and demonstrating that ANAPC13 deficiency impairs Treg differentiation and immune homeostasis.

    Evidence Conditional SF3B1-K700E knock-in mouse model, RNA splicing analysis, adoptive transfer colitis assay, and forced ANAPC13 re-expression rescue

    PMID:39303038

    Open questions at the time
    • Whether ANAPC13 reduction affects APC/C substrate repertoire in T cells is unresolved
    • Other SF3B1-dependent APC/C subunit transcripts have not been examined
  7. 2025 Medium

    Compound heterozygous ANAPC13 mutations were linked to female infertility, with in vitro evidence of aberrant protein localization, providing the first patient-level genetic evidence that APC13 integrity is required for human oocyte function.

    Evidence Whole-exome sequencing, structural modelling, and in vitro localization assay in cell lines

    PMID:40238067

    Open questions at the time
    • Structural modelling is computational and awaits experimental confirmation of disrupted contacts
    • Single patient study without independent replication cohort
    • No direct APC/C activity measurement in patient-derived cells
  8. 2026 High

    Biallelic ANAPC13 mutations were causally linked to oocyte metaphase I arrest through a knock-in mouse model and proteomic analysis, establishing that APC13 is required for the metaphase I–anaphase I transition via APC/C-dependent substrate degradation rather than spindle assembly checkpoint regulation.

    Evidence Knock-in mouse model, in vitro maturation, oocyte proteomics, co-IP subunit interaction assay, and mRNA microinjection rescue (49% polar body extrusion recovery)

    PMID:41997520

    Open questions at the time
    • Incomplete rescue (~49%) suggests additional factors or irreversible damage from early APC/C disruption
    • Identity of the specific APC/C substrates whose failed degradation causes metaphase I arrest was not determined
    • Whether ANAPC13 mutations affect male meiosis is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The specific APC/C substrates whose degradation is impaired by ANAPC13 loss in oocytes and T cells remain unidentified, and whether ANAPC13 has APC/C-independent functions has not been addressed.
  • No substrate-level resolution of APC/C targets affected by ANAPC13 deficiency
  • No study has tested APC/C-independent roles for ANAPC13
  • Tissue-specific essentiality beyond oocytes and T cells is unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1474165 Reproduction 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-168256 Immune System 1
Partners
APC16APC5APC7CDC16CDC23CDC26CDC27
Complex memberships
APC/C

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Swm1/Apc13 is an evolutionarily conserved subunit of the APC/C that promotes the stable association of the essential TPR subunits Cdc16 and Cdc27 with the complex; without Swm1/Apc13, Cdc16 and Cdc27 dissociate from the APC/C, abolishing ubiquitin ligase activity in vitro and causing delayed execution of APC/C-dependent cell cycle events in vivo. Human and fission yeast homologues associate with APC/C subunits and complement the yeast swm1Δ deletion phenotype. Genetic deletion, in vitro ubiquitin ligase assay, co-immunoprecipitation, cross-species complementation Molecular and cellular biology High 15060174
2003 Swm1 (Apc13) was identified as a constitutive core subunit of the yeast APC by mass spectrometry of highly purified APC preparations; it is present throughout the cell cycle (G1, S, M) and in meiotic cells. In vitro transcription/translation showed Swm1 interacts directly with Cdc23 and Apc5. Deletion of SWM1 causes slow growth and accumulation of G2/M cells, consistent with an APC defect. Mass spectrometry of purified APC, co-immunoprecipitation with epitope-tagged subunits, in vitro co-translation interaction assay, genetic analysis of deletion strains The Journal of biological chemistry High 12609981
2014 Cryo-EM reconstruction of the human APC/C at 7.4 Å resolution placed APC13 within the 'Arc Lamp' subcomplex alongside APC16 and CDC26, defining its position within the overall 1.2 MDa assembly alongside all 20 APC/C subunits. Cryo-electron microscopy reconstruction Nature High 25043029
2015 Atomic-resolution cryo-EM structures of APC/C-coactivator complexes confirm APC13 as part of the Arc Lamp sub-structure; the structures define the architecture of all APC/C subunits and explain how Emi1 mediates inhibition. Cryo-electron microscopy at near-atomic resolution, biochemical validation Nature High 26083744
2014 Crystal structures of human APC3 alone and in complex with the C-terminal domain of APC16 revealed that APC13 is part of the Arc Lamp alongside APC16 and APC7; the data show that APC16 bridges APC13 context within the TPR sub-complex and recruits APC7 to APC3. X-ray crystallography, biochemical mapping, in vitro ubiquitination assay Journal of molecular biology High 25490258
2010 Tandem-affinity purification-mass spectrometry and localization studies in human cells identified APC13 as a previously unknown, evolutionarily conserved subunit of the human anaphase-promoting complex essential for chromosome segregation. TAP-MS, protein localization by fluorescence microscopy, RNAi phenotypic screening Science High 20360068
2024 The cancer-associated SF3B1-K700E mutation causes aberrant splicing of ANAPC13 pre-mRNA, inserting a 231-bp fragment into the 5′ UTR and reducing ANAPC13 protein expression. Reduced ANAPC13 impairs regulatory T cell (Treg) differentiation and inhibitory function; forced re-expression of ANAPC13 restores Treg function and prevents adoptive transfer colitis. Conditional knock-in mouse model, RNA splicing analysis, adoptive transfer colitis assay, rescue by forced ANAPC13 expression Science advances High 39303038
2025 Compound heterozygous missense mutations in APC13 (c.C6A and c.116_126del) were identified in an infertile female patient; structural modelling predicted disrupted chemical bonds with other APC/C subunits, and in vitro experiments demonstrated aberrant cellular localization of the mutant APC13 protein, implicating correct APC13 localization as necessary for APC/C-dependent female fertility. Whole-exome sequencing, structural modelling, in vitro localization assay in cell lines Journal of assisted reproduction and genetics Medium 40238067
2026 Biallelic ANAPC13 mutations (p.D2E and p.L24R) cause oocyte maturation arrest at metaphase I in humans and in a knock-in mouse model. Mutant ANAPC13 disrupts APC/C subunit interactions, impairs APC/C ubiquitin ligase function (without altering spindle assembly checkpoint dynamics), and leads to abnormal protein composition during the metaphase I-to-anaphase I transition. Microinjection of wild-type Anapc13 mRNA partially rescues polar body extrusion (49%). Whole-exome sequencing, knock-in mouse model, in vitro maturation assay, proteomic analysis of oocytes, co-IP/subunit interaction assay, mRNA microinjection rescue American journal of obstetrics and gynecology High 41997520

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Genome-wide association analysis identifies 20 loci that influence adult height. Nature genetics 621 18391952
2008 Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 442 18485873
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2001 Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver. Proceedings of the National Academy of Sciences of the United States of America 300 11752456
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2017 Assembly and Function of Heterotypic Ubiquitin Chains in Cell-Cycle and Protein Quality Control. Cell 255 29033132
2018 Mapping the Genetic Landscape of Human Cells. Cell 225 30033366
2005 The anaphase-promoting complex: a key factor in the regulation of cell cycle. Oncogene 211 15678131
2015 Atomic structure of the APC/C and its mechanism of protein ubiquitination. Nature 187 26083744
2014 Molecular architecture and mechanism of the anaphase-promoting complex. Nature 175 25043029
2016 Molecular mechanism of APC/C activation by mitotic phosphorylation. Nature 154 27120157
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
2022 EZH2 depletion potentiates MYC degradation inhibiting neuroblastoma and small cell carcinoma tumor formation. Nature communications 99 35013218
2005 Localization of the coactivator Cdh1 and the cullin subunit Apc2 in a cryo-electron microscopy model of vertebrate APC/C. Molecular cell 81 16364912
2020 Gene expression and cell identity controlled by anaphase-promoting complex. Nature 79 32076268
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
2011 The anaphase-promoting complex is a dual integrator that regulates both MicroRNA-mediated transcriptional regulation of cyclin B1 and degradation of Cyclin B1 during Arabidopsis male gametophyte development. The Plant cell 72 21441434
1996 An abundant cell-surface polypeptide is required for swimming by the nonflagellated marine cyanobacterium Synechococcus. Proceedings of the National Academy of Sciences of the United States of America 72 8692845
2009 Mutations in two independent pathways are sufficient to create hermaphroditic nematodes. Science (New York, N.Y.) 67 19965511
2006 Regulation of sperm activation by SWM-1 is required for reproductive success of C. elegans males. Current biology : CB 65 16461278
2004 Swm1/Apc13 is an evolutionarily conserved subunit of the anaphase-promoting complex stabilizing the association of Cdc16 and Cdc27. Molecular and cellular biology 62 15060174
2010 The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature. BMC medical genetics 54 20546612
2003 Mnd2 and Swm1 are core subunits of the Saccharomyces cerevisiae anaphase-promoting complex. The Journal of biological chemistry 51 12609981
2021 Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children. Pediatric pulmonology 33 33751861
2007 Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1. PloS one 32 17440621
2014 Structure of an APC3-APC16 complex: insights into assembly of the anaphase-promoting complex/cyclosome. Journal of molecular biology 31 25490258
2013 The Arabidopsis anaphase-promoting complex/cyclosome subunit 1 is critical for both female gametogenesis and embryogenesis(F). Journal of integrative plant biology 29 23206231
2017 Identifying miRNA-mRNA regulation network of chronic pancreatitis based on the significant functional expression. Medicine 27 28538367
2020 Male reproductive toxicity involved in spermatogenesis induced by perfluorooctane sulfonate and perfluorooctanoic acid in Caenorhabditis elegans. Environmental science and pollution research international 26 32839910
1999 SWM1, a developmentally regulated gene, is required for spore wall assembly in Saccharomyces cerevisiae. Molecular and cellular biology 26 10022899
1999 Identification of human APC10/Doc1 as a subunit of anaphase promoting complex. Oncogene 22 10498862
2012 Down-regulation of ANAPC13 and CLTCL1: Early Events in the Progression of Preinvasive Ductal Carcinoma of the Breast. Translational oncology 16 22496928
2022 Dietary Inclusion of Defatted Silkworm (Bombyx mori L.) Pupa Meal for Broiler Chickens at Different Ages: Growth Performance, Carcass and Meat Quality Traits. Animals : an open access journal from MDPI 12 36611728
2024 Cancer-associated SF3B1-K700E mutation controls immune responses by regulating Treg function via aberrant Anapc13 splicing. Science advances 9 39303038
2018 Soma-germ line interactions and a role for muscle in the regulation of C. elegans sperm motility. Development (Cambridge, England) 9 30470702
2024 A reverse vaccinology approach identified novel recombinant tick proteins with protective efficacy against Rhipicephalus microplus infestation. Ticks and tick-borne diseases 8 39427604
2020 Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children. medRxiv : the preprint server for health sciences 5 33173928
2004 Swm1p, a subunit of the APC/cyclosome, is required to maintain cell wall integrity during growth at high temperature in Saccharomyces cerevisiae. FEMS microbiology letters 4 15135545
2024 MicroRNAome profiling of breast cancer unveils hsa-miR-5683 as a tumor suppressor microRNA predicting favorable clinical outcome. Cancer cell international 3 39538254
2012 Identification of ANAPC13 gene polymorphisms associated with body measurement traits in Bos taurus. Genetics and molecular research : GMR 3 22782628
2021 A non-coding cancer mutation disrupting an HNF4α binding motif affects an enhancer regulating genes associated to the progression of liver cancer. Experimental oncology 2 33785712
2020 Exploring the Protective Effect of ShenQi Compound on Skeletal Muscle in Diabetic Macrovasculopathy Mice. Endocrine, metabolic & immune disorders drug targets 2 32096754
2025 Infertile females with biallelic mutations in APC/C genes are characterized by oocyte or early embryo defects. Journal of assisted reproduction and genetics 1 40238067
2026 Biallelic mutations in ANAPC13 cause female infertility characterized by oocyte maturation arrest both in humans and mice. American journal of obstetrics and gynecology 0 41997520
2025 Identifying genes associated with Sorafenib resistance in hepatocellular carcinoma to develop risk model. Discover oncology 0 40835789