Affinage

ANAPC2

Anaphase-promoting complex subunit 2 · UniProt Q9UJX6

Round 2 corrected
Length
822 aa
Mass
93.8 kDa
Annotated
2026-04-28
80 papers in source corpus 26 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANAPC2 encodes the cullin-homology subunit of the anaphase-promoting complex/cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase essential for cell-cycle progression through mitosis. ANAPC2 heterodimerizes with the RING subunit APC11 to form the minimal catalytic module sufficient for ubiquitin chain formation on substrates such as securin and cyclin B1, with its C-terminal cullin homology domain serving as the docking platform for E2 enzymes (UbcH10/Ubc4) (PMID:11739784, PMID:10230407). Coactivator (CDH1/CDC20) binding induces a conformational change in the ANAPC2-containing face of the APC/C that enables E2 engagement and substrate ubiquitination (PMID:16364912). Beyond cell-cycle control, ANAPC2 stabilizes microtubules along axons and dendrites, organizes cortical actin, and is required for neuronal migration downstream of NSD1; bi-allelic loss-of-function mutations cause a posterior-predominant lissencephaly in humans (PMID:19759310, PMID:25753423, PMID:31585108).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 High

    Identification of APC2 as an essential APC/C subunit resolved whether the complex contained a cullin-family member and established that APC2 is required for securin destruction and anaphase onset.

    Evidence Temperature-sensitive rsi1/apc2 yeast mutants arrest in metaphase with stabilized Clb2p; co-IP with Cdc23p confirms physical complex membership

    PMID:9430641

    Open questions at the time
    • Catalytic mechanism of APC2 within the complex not yet defined
    • Mammalian APC2 function not yet tested
  2. 1999 High

    Demonstrating that APC2–APC11 constitutes the catalytic core of the APC/C established the minimal ubiquitin ligase module and clarified how a cullin-RING architecture underpins APC/C activity.

    Evidence APC11 immunocomplexes catalyze E1/E2-dependent polyubiquitin chain formation; APC11 RING mutagenesis abolishes activity; APC11 binds specifically to APC2 among cullins

    PMID:10230407

    Open questions at the time
    • Substrate specificity mechanism unknown
    • How coactivators CDH1/CDC20 contribute to catalysis not resolved
  3. 1999 High

    Discovery that mammalian and Drosophila APC2 orthologs bind β-catenin/Armadillo and negatively regulate Wnt signaling revealed a major Wnt-pathway function independent of APC/C E3 ligase activity.

    Evidence SAMP-domain mapping shows APC2 binds Axin2/conductin; APC2 regulates β-catenin–TCF complexes in APC-null colon carcinoma cells; Drosophila APC2 colocalizes with actin and acts genetically upstream of Armadillo

    PMID:10021369 PMID:10491393

    Open questions at the time
    • Whether Wnt-regulatory and APC/C-ubiquitin-ligase functions are structurally separable in the same protein
    • Direct biochemical mechanism of β-catenin destruction by APC2 not resolved
  4. 2001 High

    Reconstitution of the human APC2–APC11 heterodimer showed it is sufficient for ubiquitin transfer to securin and cyclin B1 and mapped E2-binding to APC2's cullin homology domain, defining the catalytic architecture.

    Evidence Baculoviral co-expression of human APC2/APC11; in vitro ubiquitination of securin/cyclin B1 with Ubc4 or UbcH10; binding-domain mapping

    PMID:11739784

    Open questions at the time
    • No substrate specificity without coactivators — mechanism of substrate selection unresolved
    • Structural basis of E2 docking unknown
  5. 2002 High

    Double-mutant analyses in Drosophila demonstrated that APC1 and APC2 act redundantly to restrain β-catenin destruction-complex activity in all tissues, while also revealing a separable cytoskeletal function in neuroblasts.

    Evidence Simultaneous loss of Apc1 and Apc2 causes global nuclear Armadillo accumulation; neuroblast maintenance is affected without Wg misregulation

    PMID:11923210 PMID:12297097 PMID:12297098

    Open questions at the time
    • Molecular basis of the cytoskeletal function distinct from Wnt regulation not biochemically defined
    • Whether mammalian APC2 has similar tissue-specific dual roles unclear
  6. 2005 High

    Cryo-EM localization of APC2 and CDH1 to the same face of the APC/C, together with conformational changes induced by CDH1, established how coactivator binding physically repositions the catalytic module for substrate ubiquitination.

    Evidence Cryo-EM with antibody-based subunit mapping of vertebrate APC/C; angular reconstitution reveals conformational change upon CDH1 binding

    PMID:16364912

    Open questions at the time
    • Atomic-resolution structure of the APC2 catalytic module not yet available
    • Mechanism of E2 engagement upon conformational change not resolved
  7. 2009 High

    Establishing that APC2 localizes to axonal microtubules, stabilizes them, and is required for growth-cone responses to guidance cues revealed a cell-biological function in the nervous system independent of cell-cycle control.

    Evidence APC2 knockdown in chick retina reduces microtubule stability, impairs ephrin-A2 response, and disrupts retinotectal projections in vivo

    PMID:19759310

    Open questions at the time
    • Whether microtubule stabilization is direct or requires adaptor proteins unclear
    • Mechanism linking microtubule stabilization to ephrin receptor signaling not dissected
  8. 2011 High

    Domain dissection of Drosophila APC2 showed that cortical targeting via the Armadillo repeats and C30 domain is required for actin organization but dispensable for Wnt regulation, definitively separating these two functions at the domain level.

    Evidence Deletion/rescue experiments in S2 cells and APC mutant embryos; cortical localization assays and functional readouts for actin and Wnt signaling

    PMID:21486956

    Open questions at the time
    • Identity of cortical binding partner(s) for the C30 domain unknown
    • Whether this domain architecture is conserved in mammalian APC2 not tested
  9. 2015 High

    Human genetic and mouse knockout evidence placed APC2 downstream of NSD1 in neuronal migration and linked APC2 loss-of-function to Sotos-syndrome-like features, connecting cytoskeletal regulation to a neurodevelopmental disease.

    Evidence Whole-exome sequencing identifies APC2 mutations in Sotos-like patients; Apc2-/- mice show impaired learning/abnormal head shape; forced Apc2 expression rescues Nsd1-knockdown migration defects in mouse cortex

    PMID:25753423

    Open questions at the time
    • Transcriptional versus post-transcriptional regulation of APC2 by NSD1 not fully resolved
    • Downstream cytoskeletal targets of APC2 in migrating neurons not identified
  10. 2018 High

    Discovery that APC2 promotes minus-end-out microtubule dynamics in vertebrate dendrites via LC8-binding and microtubule-interacting domains, and is positioned at branch points by multiple upstream modules, established APC2 as a central microtubule organizer in neuronal polarity.

    Evidence shRNA knockdown in neurons with live TIRF/spinning-disk imaging of microtubule dynamics; RNAi screen in Drosophila identifying Arp2/3, Axin, mitochondrial, and Nrg/Ank2 modules upstream of APC2 positioning

    PMID:29602811 PMID:30018294

    Open questions at the time
    • Whether LC8-mediated clustering is regulated by phosphorylation or other modifications unknown
    • How APC2 steers microtubule growth direction at branch points mechanistically unclear
  11. 2019 Medium

    Identification of bi-allelic APC2 loss-of-function mutations as causal for a distinct posterior-predominant lissencephaly in humans provided definitive human genetic validation of APC2's essential role in cortical neuronal migration.

    Evidence Whole-exome sequencing in 12 individuals from 8 families; brain MRI characterization of posterior agyria/pachygyria and subcortical heterotopia

    PMID:31585108

    Open questions at the time
    • No functional rescue or patient-derived cellular model to confirm pathogenicity of each variant
    • Relative contribution of Wnt-regulatory versus cytoskeletal functions to lissencephaly not determined
  12. 2020 High

    Demonstrating that APC2–CDH1 ubiquitinates DOK7 at the neuromuscular junction in a MuSK-phosphorylation-dependent manner revealed a postmitotic APC/C function providing negative feedback on acetylcholine receptor clustering.

    Evidence Co-IP, ubiquitination assay with K243 mutagenesis, MuSK kinase-dead controls, AChR clustering assay in myotubes

    PMID:32687671

    Open questions at the time
    • Whether other APC/C subunits are present at the NMJ or APC2–CDH1 acts as a minimal module unknown
    • In vivo physiological consequences at the NMJ not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the cell-cycle E3 ligase and Wnt-regulatory/cytoskeletal functions of APC2 are coordinated at the protein level — including whether distinct APC2 pools or post-translational modifications partition these roles — remains unresolved.
  • No structural model of full-length mammalian APC2 showing how APC/C-binding, β-catenin-destruction, and microtubule-binding surfaces are arranged
  • Whether PARylation by tankyrase regulates APC2 function in vivo not confirmed
  • Relative contribution of cytoskeletal versus Wnt-signaling defects to human lissencephaly undetermined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0016874 ligase activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005856 cytoskeleton 5 GO:0005886 plasma membrane 3 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1640170 Cell Cycle 6 R-HSA-112316 Neuronal System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1266738 Developmental Biology 2
Complex memberships
APC/C

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 A heterodimeric complex of APC2 (the cullin subunit) and APC11 (the RING subunit) constitutes the minimal ubiquitin ligase module of the human APC/C; in combination with Ubc4 or UbcH10 this module is sufficient to catalyze ubiquitination of securin and cyclin B1, though without substrate specificity. APC11 and UbcH10 both bind the C-terminal cullin homology domain of APC2, while Ubc4 interacts with APC11 directly. Baculoviral reconstitution of human APC2/APC11 complex, in vitro ubiquitination assay with securin and cyclin B1, mutagenesis of APC11 RING finger Zn2+-binding residues, binding domain mapping Molecular biology of the cell High 11739784
1998 Budding yeast RSI1/APC2 is an essential subunit of the APC/C; temperature-sensitive rsi1/apc2 mutants arrest in metaphase, fail to degrade Clb2p, and this arrest is relieved by deletion of PDS1 (securin). Rsi1p/Apc2p co-immunoprecipitates with the known APC subunit Cdc23p, demonstrating its physical association with the complex. Genetic screen (SIC1 synthetic lethality), temperature-sensitive mutant analysis, cyclin B degradation assay, co-immunoprecipitation with Cdc23p, PDS1 epistasis rescue The EMBO journal High 9430641
1999 Mammalian APC2 contains two SAMP domains both required for binding to conductin (Axin2), and functions like APC to regulate the formation of active β-catenin–TCF complexes, as demonstrated in APC−/− colon carcinoma cells. Human APC2 maps to chromosome 19p13.3. Domain deletion analysis, transient transcriptional activation (TOP-FLASH) assays in APC-null colon carcinoma cells, SAMP-domain mutagenesis, chromosomal mapping Current biology : CB High 10021369
1999 Drosophila APC2 (dAPC2) binds Armadillo (β-catenin homolog) and negatively regulates Wingless signaling in the embryonic epidermis; it colocalizes with actin in many cellular contexts and shows striking asymmetric distribution in neuroblasts. Genetically, the dAPC2 allele acts downstream of wg and upstream of arm, dTCF, and dishevelled, suggesting a role as a mediator of Wg effects on the cytoskeleton. Genetic epistasis analysis, loss-of-function mutation characterization, immunolocalization (colocalization with actin/microtubules), protein–protein binding assay (Armadillo binding) The Journal of cell biology High 10491393
2001 Drosophila APC2 and Armadillo (β-catenin) both localize to sites of cortical spindle attachment during syncytial mitoses and play roles in spindle anchoring. APC2–Armadillo complexes often co-localize with interphase microtubules. Zeste-white 3 kinase (GSK-3β homolog), which phosphorylates Armadillo and APC, is required for spindle positioning and regulates the localization of APC2–Armadillo complexes. Live imaging and immunofluorescence in Drosophila embryos, genetic loss-of-function analysis, epistasis with zw3 kinase, co-localization with α-catenin and cortical actin markers Nature cell biology High 11584277
2002 Simultaneous loss of both Drosophila Apc1 and Apc2 causes global nuclear accumulation of Armadillo (β-catenin) and constitutive activation of Wg/Wnt transduction throughout all tissues, revealing that Apc1 and Apc2 act redundantly to maintain tight regulation of β-catenin–mediated transcriptional activation in all cells. Double-mutant genetic analysis, immunolocalization of β-catenin/Armadillo, Wingless target gene expression assays Development (Cambridge, England) High 11923210
2002 Drosophila APC2 and APC1 play overlapping roles in regulating Wingless signaling in the embryonic epidermis and imaginal discs, with APC1 functioning even at very low expression levels; the two paralogs differ dramatically in intracellular localization yet still exhibit functional redundancy. Single and double loss-of-function mutant analysis, Wingless target gene expression assays, immunolocalization Developmental biology High 12297098
2002 In the Drosophila larval brain, APC2 localizes dynamically and asymmetrically to the cell cortex of neuroblasts through the cell cycle, while APC1 localizes to centrosomes and microtubules. Despite different localizations, both proteins redundantly maintain neuroblast numbers without misregulating Wg signaling, suggesting a cytoskeletal or adhesive rather than Wnt-signaling role in this tissue. Immunolocalization, single and double mutant analysis, neuroblast quantification, Wg target gene expression assays Developmental biology Medium 12297097
2002 Inversin interacts with the APC/C subunit APC2; this interaction is mediated by destruction-box (D-box) motifs in inversin, and site-directed mutagenesis of conserved D-box residues abolishes inversin–APC2 interaction, identifying inversin as an APC2-interacting protein regulated in a cell-cycle-dependent manner. Co-immunoprecipitation, site-directed mutagenesis of D-box residues, cell-cycle expression analysis with inversin-specific antibody Human molecular genetics Medium 12471060
2005 Cryo-EM analysis of vertebrate APC/C localized Cdh1 (coactivator) and Apc2 (cullin subunit) to the same side of the asymmetric complex, implying that substrate ubiquitination occurs on this face. Cdh1 binding induces a conformational change in a large flexible domain of APC/C, suggesting Cdh1 activates APC/C both by recruiting substrates and by inducing structural rearrangements. Cryo-EM with angular reconstitution and random conical tilt, STEM mass measurement, antibody-based subunit mapping of Cdh1 and Apc2 positions Molecular cell High 16364912
2009 APC2 is expressed preferentially in the nervous system and is distributed along microtubules in growth cones and axon shafts of retinal axons. Overexpression of APC2 stabilizes microtubules in cultured cells, while shRNA knockdown in chick retinas reduces microtubule stability, impairs growth cone responses to ephrin-A2, and causes drastic alterations in retinotectal topographic projections in vivo. Immunohistochemistry, shRNA knockdown in chick retina, microtubule stability assay, in vitro ephrin-A2 response assay, in vivo retinotectal projection analysis The Journal of neuroscience High 19759310
2011 In Drosophila S2 cells and the embryo, the Armadillo repeats and a novel C-terminal 30 amino acid (C30) domain of APC2 are both necessary and together sufficient for cortical localization; neither domain alone is sufficient. The Armadillo repeats mediate self-association of APC2. Cortical localization is required for APC2's role in actin organization but dispensable for its role in Wnt/Wg signaling. Domain deletion analysis, rescue experiments in APC mutant embryos, S2 cell localization assays, actin organization phenotypic assay, Wnt reporter assay Journal of cell science High 21486956
2013 In Drosophila embryos, APC2 loss leads to increased chromosome segregation errors through a cascade beginning with incomplete centrosome separation, which triggers ectopic cleavage furrow formation, mitotic defects, and DNA damage. APC2 functions at the embryonic cortex together with Axin to promote mitotic fidelity through cytoskeletal regulation. Loss-of-function genetics, live imaging of mitosis, centrosome separation assays, DNA damage marker analysis, epistasis with Axin Development (Cambridge, England) High 24026117
2014 The spliceosome subunit SNW1 is required for proper splicing of APC2 pre-mRNA; SNW1 depletion reduces APC2 protein levels, decreases APC/C activity, and indirectly contributes to sister chromatid cohesion defects by delaying mitosis and causing cohesion fatigue. Simultaneous expression of sororin and APC2 from intron-less cDNAs rescues cohesion in SNW1-depleted cells. RNAi depletion, transcriptome-wide splicing analysis, APC/C activity assay, sister chromatid cohesion assay, intron-less cDNA rescue experiment The EMBO journal High 25257309
2015 Loss-of-function mutation in APC2 causes Sotos syndrome features in humans; Apc2-deficient mice show impaired learning/memory and abnormal head shape. Endogenous Apc2 expression is downregulated by Nsd1 knockdown, placing APC2 downstream of NSD1. Nsd1 knockdown impairs cortical neuron migration and laminar positioning similarly to Apc2-/- mice, and forced Apc2 expression rescues this defect, establishing APC2 as an NSD1 downstream effector in neuronal cytoskeletal regulation. Whole-exome sequencing (human patients), Apc2-/- mouse generation, behavioral testing, Nsd1 knockdown with cortical neuron migration assay, Apc2 rescue by forced expression in embryonic mouse brain Cell reports High 25753423
2016 Tankyrase (TNKS) binds a C-terminal RPQPSG motif in Drosophila APC2 (conserved in human APC2 but absent from human APC1), can be recruited by APC2 into the β-catenin destruction complex, and directly PARylates both Drosophila Axin and APC2. PARylation does not globally regulate APC2 protein levels as it does for Axin, yet TNKS inhibition in colon cancer cells decreases β-catenin signaling beyond what can be explained by Axin stabilization alone, implicating APC2 PARylation as an additional regulatory point. Yeast two-hybrid screen, motif mapping, co-immunoprecipitation, in vitro PARylation assay, TNKS inhibitor treatment in colon cancer cells, β-catenin signaling reporter The Journal of biological chemistry High 27068743
2018 APC2 promotes dynamics of minus-end-out microtubules in vertebrate dendrites. APC2 localizes as distinct clusters along microtubule bundles in dendrites via LC8-binding and two separate microtubule-interacting domains. APC2 depletion reduces plus-end dynamics of minus-end-out microtubules, increases microtubule sliding, and causes defects in dendritic morphology. shRNA knockdown in neurons, live TIRF/spinning-disk microscopy of microtubule dynamics, domain deletion analysis (LC8-binding and MT-interacting domains), dendritic morphology analysis Nature communications High 30018294
2018 In Drosophila neurons, APC2 is positioned at dendrite branch points through four independent modules: mitochondrial energy production (via spastin-regulated mitochondria), Nrg/Ank2 membrane scaffold, branched actin generated by Arp2/3, and Frizzled/G protein/Axin Wnt signaling. At branch points, APC2 recruits APC1 to steer growing microtubules, maintaining minus-end-out polarity. RNAi screen, secondary candidate RNAi screens, live imaging of APC2-GFP localization, epistasis analysis with Axin, G proteins, Arp2/3, Miro and spastin G3 (Bethesda, Md.) Medium 29602811
2018 In Drosophila, Brain Tumor (Brat) regulates the expression and localization of APC2 at microtubule plus ends in commissural axons to promote midline crossing; this function is independent of Wnt/β-catenin transcriptional regulation and instead requires the microtubule-stabilizing role of APC2. Genetic analysis (brat and apc2 mutants), epistasis with Netrin/Fra pathway, cell-autonomy assay, localization of APC2 at microtubule plus ends, Wnt reporter assay PLoS genetics Medium 29617376
2018 APC2 cortical localization in Drosophila follicular epithelium and nurse cells requires self-association through an N-terminal APC Self-Association Domain (ASAD) and a conserved coiled-coil within the C-terminal C30 domain. APC2 regulates cortical actin dynamics and the distribution of cortical actin at the apical side of follicular epithelium. Domain deletion and mutagenesis in S2 cells, immunofluorescence in Drosophila ovary, cortical actin dynamics assay (live imaging), self-association biochemical assay Cytoskeleton (Hoboken, N.J.) Medium 30019417
2019 Bi-allelic loss-of-function mutations in APC2 cause a distinct form of lissencephaly with posterior-predominant agyria/pachygyria, subcortical heterotopia, and global developmental delay in humans, linking APC2's established role in integrating actin and microtubule cytoskeletons to neuronal migration defects shared with other lissencephaly proteins (LIS1, CTNNA2). Whole-exome sequencing in 12 individuals from 8 families, brain MRI characterization, genotype-phenotype correlation American journal of human genetics Medium 31585108
2020 APC2 (functioning as APC2-CDH1) is enriched at the post-synapse of neuromuscular junctions in postmitotic myotubes and negatively regulates AChR clustering by promoting ubiquitination of the adaptor protein DOK7 at lysine 243, leading to its proteolytic degradation. This requires MuSK kinase activity and phosphorylation of tyrosine 106 in DOK7, revealing a mechanism of negative feedback in agrin-LRP4-MuSK signaling. Co-immunoprecipitation, immunofluorescence localization at NMJs, ubiquitination assay, site-directed mutagenesis (K243 and Y106), AChR clustering assay, MuSK kinase-dead controls FASEB journal High 32687671
2010 FBG1, an F-box protein, directly interacts with APC2 through a D-box motif within its F-box domain; co-expression with FBG1 increases total APC2 levels but reduces free APC2 by sequestration, inhibiting cell proliferation and inducing S-phase arrest. Co-immunoprecipitation, D-box mutagenesis, FACS cell-cycle analysis, protein level quantification by western blot Cell cycle (Georgetown, Tex.) Medium 21135578
1999 ROC1 (APC11 homolog) specifically interacts with APC2 (a cullin-related APC subunit), and APC11 immunocomplexes can catalyze ubiquitin isopeptide ligation (polyubiquitin chain formation) in an E1- and E2-dependent manner, establishing the APC2–APC11 pair as the catalytic core of the APC/C. Co-immunoprecipitation showing specificity of APC11 for APC2 vs. other cullins, in vitro ubiquitin ligase assay with APC11 immunocomplexes, RING-finger mutagenesis abolishing ligase activity Molecular cell High 10230407
2012 In Drosophila, the APC11 subunit (LmgA/Lemming) interacts with Morula/Apc2 and together they form a ternary complex with the E2-C type ubiquitin-conjugating enzyme Vihar, establishing that Lmg/Apc11 recruits the E2 enzyme to the APC/C via Apc2. Genetic rescue assays (Drosophila null and yeast ts mutant complementation), protein–protein interaction assays, immunolocalization, mutant phenotype analysis (cyclin accumulation, metaphase arrest) Cell division Medium 22417125
2021 FOXO4 functions as a transcription factor that binds the APC2 promoter and upregulates APC2 expression, which in turn increases phosphorylated degradation of β-catenin and suppresses CRC cell migration and metastasis; APC2 knockdown reverses the anti-metastatic effects of FOXO4 overexpression. Chromatin immunoprecipitation (ChIP), luciferase reporter for APC2 promoter, FOXO4 overexpression/APC2 knockdown rescue, β-catenin phosphorylation western blot, in vivo xenograft metastasis assay Frontiers in cell and developmental biology Medium 34631691
2024 Comparative cryo-EM structures of S. cerevisiae and human APC/C reveal that in human APC/C, coactivator (CDH1) binding induces a conformational change of the catalytic module APC2:APC11 to allow E2 binding, whereas in S. cerevisiae apo-APC/C the catalytic module (Apc2:Apc11) is already pre-positioned to bind E2 without requiring coactivator-induced conformational change—demonstrating a species-specific regulatory difference in how APC2 engages E2 enzymes. Cryo-EM structure determination of multiple APC/C states (apo, CDH1-bound, phosphorylated), comparative structural analysis between yeast and human APC/C bioRxivpreprint Medium
2025 The BubR1 TPR domain interacts with Apc2 within the MCC–APC/C complex, as identified by cryo-EM structural guidance; this interaction, together with TPR domain contacts with Mad2 and Cdc20-APC/C, promotes MCC assembly and MCC–APC/C binding to enable rapid spindle assembly checkpoint activation. cryo-EM structure-guided mutagenesis, biochemical MCC assembly assay, MCC–APC/C binding assay, functional SAC signaling assay bioRxivpreprint Medium

Source papers

Stage 0 corpus · 80 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
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
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2008 Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 787 18854154
2001 Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. The Journal of cell biology 726 11535616
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
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-scale RNAi screen for host factors required for HIV replication. Cell host & microbe 627 18976975
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
1998 The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes & development 507 9637688
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
1999 ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Molecular cell 410 10230407
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2001 Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. The Journal of cell biology 372 11285280
2000 Mitotic regulation of the APC activator proteins CDC20 and CDH1. Molecular biology of the cell 363 10793135
2000 Characterization of vertebrate cohesin complexes and their regulation in prophase. The Journal of cell biology 358 11076961
2003 Mitotic regulation of the human anaphase-promoting complex by phosphorylation. The EMBO journal 341 14657031
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2007 Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation. Nature 301 17443186
2002 Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1. The Journal of cell biology 274 12070128
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
1999 Drosophila APC2 is a cytoskeletally-associated protein that regulates wingless signaling in the embryonic epidermis. The Journal of cell biology 162 10491393
2001 APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. Molecular biology of the cell 156 11739784
2001 Drosophila APC2 and Armadillo participate in tethering mitotic spindles to cortical actin. Nature cell biology 141 11584277
2002 Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle. Human molecular genetics 123 12471060
1999 Identification of APC2, a homologue of the adenomatous polyposis coli tumour suppressor. Current biology : CB 106 10021369
2003 The Arabidopsis anaphase-promoting complex or cyclosome: molecular and genetic characterization of the APC2 subunit. The Plant cell 99 14508008
2019 Hsa_circ_0009361 acts as the sponge of miR-582 to suppress colorectal cancer progression by regulating APC2 expression. Clinical science (London, England : 1979) 97 31109967
2018 Overexpressing circular RNA hsa_circ_0002052 impairs osteosarcoma progression via inhibiting Wnt/β-catenin pathway by regulating miR-1205/APC2 axis. Biochemical and biophysical research communications 84 29852168
2002 Drosophila Apc1 and Apc2 regulate Wingless transduction throughout development. Development (Cambridge, England) 84 11923210
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
2002 Drosophila APC2 and APC1 have overlapping roles in the larval brain despite their distinct intracellular localizations. Developmental biology 57 12297097
2002 Drosophila APC2 and APC1 play overlapping roles in wingless signaling in the embryo and imaginal discs. Developmental biology 57 12297098
2015 MiR-939 promotes the proliferation of human ovarian cancer cells by repressing APC2 expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 55 25960217
1998 Budding yeast RSI1/APC2, a novel gene necessary for initiation of anaphase, encodes an APC subunit. The EMBO journal 51 9430641
2019 circ-PKD2 inhibits carcinogenesis via the miR-204-3p/APC2 axis in oral squamous cell carcinoma. Molecular carcinogenesis 49 31206208
2014 SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs. The EMBO journal 49 25257309
2015 Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Features. Cell reports 37 25753423
2009 APC2 plays an essential role in axonal projections through the regulation of microtubule stability. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 19759310
2016 The Poly(ADP-ribose) Polymerase Enzyme Tankyrase Antagonizes Activity of the β-Catenin Destruction Complex through ADP-ribosylation of Axin and APC2. The Journal of biological chemistry 34 27068743
2020 SMYD2 suppresses APC2 expression to activate the Wnt/β-catenin pathway and promotes epithelial-mesenchymal transition in colorectal cancer. American journal of cancer research 30 32266106
2001 Human APC2 localization and allelic imbalance. Cancer research 30 11691822
2018 APC2 controls dendrite development by promoting microtubule dynamics. Nature communications 25 30018294
2016 Functional redundancy between Apc and Apc2 regulates tissue homeostasis and prevents tumorigenesis in murine mammary epithelium. Oncogene 25 27694902
2011 Cortical localization of APC2 plays a role in actin organization but not in Wnt signaling in Drosophila. Journal of cell science 24 21486956
2017 miR-4326 promotes lung cancer cell proliferation through targeting tumor suppressor APC2. Molecular and cellular biochemistry 23 29101731
2019 APC2 is critical for ovarian WNT signalling control, fertility and tumour suppression. BMC cancer 22 31291912
2019 microRNA-1205 promotes cell growth by targeting APC2 in lung adenocarcinoma. European review for medical and pharmacological sciences 20 30779081
2019 Bi-allelic Loss of Human APC2, Encoding Adenomatous Polyposis Coli Protein 2, Leads to Lissencephaly, Subcortical Heterotopia, and Global Developmental Delay. American journal of human genetics 20 31585108
2021 FOXO4 Inhibits the Migration and Metastasis of Colorectal Cancer by Regulating the APC2/β-Catenin Axis. Frontiers in cell and developmental biology 18 34631691
2013 APC2 and Axin promote mitotic fidelity by facilitating centrosome separation and cytoskeletal regulation. Development (Cambridge, England) 16 24026117
2015 Overexpression of lipocalins and pro-inflammatory chemokines and altered methylation of PTGS2 and APC2 in oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide. PloS one 15 25635769
2015 The expression pattern of APC2 and APC7 in various cancer cell lines and AML patients. Advances in medical sciences 15 26046517
2017 Subtle Deregulation of the Wnt-Signaling Pathway Through Loss of Apc2 Reduces the Fitness of Intestinal Stem Cells. Stem cells (Dayton, Ohio) 14 29027285
2023 Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders. Seizure 10 37657306
2018 Identification of Proteins Required for Precise Positioning of Apc2 in Dendrites. G3 (Bethesda, Md.) 10 29602811
2017 Hsa-miR-11181 regulates Wnt signaling pathway through targeting of APC2 transcripts in SW480 cell line. Gene 10 29111205
2002 Expression of Apc2 during mouse development. Brain research. Gene expression patterns 10 15018807
2020 APC2CDH1 negatively regulates agrin signaling by promoting the ubiquitination and proteolytic degradation of DOK7. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 32687671
2018 Brain Tumor promotes axon growth across the midline through interactions with the microtubule stabilizing protein Apc2. PLoS genetics 9 29617376
2022 LncRNA-ANAPC2 and lncRNA-NEFM positively regulates the inflammatory response via the miR-451/npr2/ hdac8 axis in grass carp. Fish & shellfish immunology 8 35843524
2020 An LCI-like protein APC2 protects ginseng root from Fusarium solani infection. Journal of applied microbiology 8 32639629
2018 Hypermethylation of APC2 Is a Predictive Epigenetic Biomarker for Chinese Colorectal Cancer. Disease markers 8 30510602
2012 lemmingA encodes the Apc11 subunit of the APC/C in Drosophila melanogaster that forms a ternary complex with the E2-C type ubiquitin conjugating enzyme, Vihar and Morula/Apc2. Cell division 8 22417125
2016 APC2 and CYP1B1 methylation changes in the bone marrow of acute myeloid leukemia patients during chemotherapy. Experimental and therapeutic medicine 7 27882114
2010 FBG1 is a promiscuous ubiquitin ligase that sequesters APC2 and causes S-phase arrest. Cell cycle (Georgetown, Tex.) 7 21135578
2018 APC2 associates with the actin cortex through a multipart mechanism to regulate cortical actin organization and dynamics in the Drosophila ovary. Cytoskeleton (Hoboken, N.J.) 5 30019417
2024 Reprint of: Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders. Seizure 4 38523034
2022 Methylation of APC2, NR3C1, and DRD2 gene promoters in turkish patients with tobacco use disorder. Nigerian journal of clinical practice 2 35170441
2021 High miR-3648 expression and low APC2 expression are associated with shorter survival and tumor progression in NSCLC. Histology and histopathology 1 34927228
2026 Human papillomavirus16 E7 enhances cell stemness by regulating the APC2/SPIN4/β-catenin axis in cervical cancer. Oncogenesis 0 41730837