Affinage

ACTR2

Actin-related protein 2 · UniProt P61160

Round 2 corrected
Length
394 aa
Mass
44.8 kDa
Annotated
2026-04-28
130 papers in source corpus 27 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACTR2 (Arp2) is an essential actin-related ATPase subunit of the heptameric Arp2/3 complex that nucleates branched actin filament networks to drive lamellipodia formation, endocytosis, and pathogen motility (PMID:9000076, PMID:9651243, PMID:8698808). Upon activation by WASP-family nucleation-promoting factors that deliver actin monomers to two binding sites on Arp2 and Arp3, Arp2 undergoes a ~30 Å conformational movement toward Arp3, and the first incorporated actin monomer triggers rapid ATP hydrolysis on Arp2; subsequent phosphate release converts branch junctions from a mechanically strong to a force-sensitive state that facilitates debranching (PMID:15094799, PMID:32917641, PMID:32461373, PMID:20959098). Phosphorylation of Arp2 at Thr237/Thr238 by kinases NIK/MAP4K4 and Plk4 is required for nucleation activity and growth-factor-stimulated membrane protrusion (PMID:18725535, PMID:25601402, PMID:27872092). Beyond cytoplasmic actin remodeling, nuclear Arp2/3 drives DNA double-strand break clustering for homology-directed repair, and loss of Arp2/3 function causes DNA damage, micronuclei, and cGAS-STING-dependent senescence (PMID:29925947, PMID:36706133).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    The question of whether Arp2 has a cellular function beyond sequence similarity to actin was answered: yeast Arp2 is essential for actin cytoskeleton organization, cell polarity, and endocytosis, establishing it as a functional cytoskeletal component.

    Evidence Temperature-sensitive arp2 mutants in S. cerevisiae showing actin, budding, and endocytosis defects

    PMID:8698808

    Open questions at the time
    • Molecular mechanism of Arp2 action unknown
    • Whether Arp2 acts alone or in a complex not yet established
  2. 1997 High

    Identification of the seven-subunit Arp2/3 complex and its sufficiency for actin nucleation at pathogen surfaces resolved how Arp2 functions—as a core subunit of a dedicated actin-nucleating machine localized to lamellipodia and Listeria actin tails.

    Evidence Purification of bovine Arp2/3 complex, immunolocalization, and in vitro actin polymerization reconstitution

    PMID:9000076 PMID:9230079

    Open questions at the time
    • Activation mechanism of the complex unknown
    • Structural basis for nucleation not determined
  3. 1998 High

    How the Arp2/3 complex is activated was elucidated: bacterial ActA and host WASP/Scar proteins engage the complex through its p21-Arc subunit, establishing the NPF-dependent activation paradigm.

    Evidence In vitro reconstitution with purified ActA and Arp2/3, domain mapping of WASP/Scar binding to p21-Arc, dominant-negative cellular assays

    PMID:9651243 PMID:9889097

    Open questions at the time
    • Stoichiometry of NPF binding unclear
    • How NPF binding triggers nucleation structurally unknown
  4. 2001 High

    The 2.0 Å crystal structure of the Arp2/3 complex revealed that Arp2 and Arp3 adopt actin-like folds in a splayed-apart inactive conformation, predicting that activation requires bringing Arp2 toward Arp3 to template a new filament; meanwhile, quantitative binding studies defined the WA domain's affinities for actin monomers and the complex, and cortactin was identified as an alternative NPF.

    Evidence X-ray crystallography of bovine Arp2/3 complex; fluorescence anisotropy binding assays; cortactin mutagenesis and nucleation assays

    PMID:11146629 PMID:11231575 PMID:11721045

    Open questions at the time
    • No structure of the activated conformation
    • ATP hydrolysis role in branch nucleation undefined
  5. 2004 High

    The timing and trigger of ATP hydrolysis on Arp2 were pinpointed: hydrolysis occurs rapidly upon nucleation and is triggered specifically by the first actin monomer delivered by VCA to the daughter filament pointed end, not by filaments or VCA alone.

    Evidence Radioactive ATP hydrolysis assay with purified Arp2/3 complex, VCA, and actin variants

    PMID:15094799

    Open questions at the time
    • Functional consequence of Arp2 ATP hydrolysis for branch stability unknown
    • Nucleotide state of Arp3 not resolved
  6. 2008 High

    The specific requirement for Arp2 in nucleation was dissected: a ΔArp2 complex retains overall structure and NPF/monomer binding but is completely inactive, demonstrating that Arp2 is dispensable for upstream docking but essential for the branch-forming step itself.

    Evidence X-ray crystallography of ΔArp2 fission yeast complex and in vitro actin nucleation assays

    PMID:18640983

    Open questions at the time
    • Precise structural rearrangement of Arp2 during activation not experimentally captured
    • Whether Arp2 contributes a barbed or pointed end contact unknown
  7. 2008 High

    A regulatory phosphorylation switch on Arp2 was discovered: phosphorylation at Thr237/Thr238 is necessary for nucleation activity and growth-factor-stimulated protrusion, adding a signaling layer to Arp2/3 activation beyond NPF binding.

    Evidence Mass spectrometry phosphosite identification, alanine mutagenesis, in vitro nucleation and cell protrusion assays

    PMID:18725535

    Open questions at the time
    • Kinase(s) responsible not yet identified
    • Whether phosphorylation alters the conformational activation step unknown
  8. 2011 High

    The long-standing controversy over NPF binding stoichiometry was resolved: two VCA molecules bind simultaneously—one at Arp3 and one at Arp2/ARPC1—each delivering an actin monomer, explaining the cooperative activation mechanism.

    Evidence Fluorescence anisotropy, ITC, analytical ultracentrifugation, and site-specific mutagenesis

    PMID:21676863

    Open questions at the time
    • Whether both sites must be occupied simultaneously for nucleation in vivo not tested
    • Species-specific differences in dual-site requirement not assessed
  9. 2015 High

    The upstream kinases phosphorylating Arp2 were identified: NIK/MAP4K4 directly binds and phosphorylates Arp2 to increase nucleation, linking receptor tyrosine kinase signaling to Arp2/3 activation; Plk4 similarly phosphorylates Arp2 at T237/T238 to drive cancer cell invasion.

    Evidence In vitro kinase assays, co-immunoprecipitation, BioID, dominant-negative and phospho-mutant cellular assays

    PMID:25601402 PMID:27872092

    Open questions at the time
    • Full kinase repertoire targeting Arp2 likely incomplete
    • Structural basis of kinase–Arp2 interaction unresolved
  10. 2018 High

    A non-cytoplasmic function was uncovered: nuclear Arp2/3 is recruited to damaged chromatin and drives actin-dependent clustering of DNA double-strand breaks for homology-directed repair, establishing Arp2/3 as a genome integrity factor.

    Evidence Xenopus cell-free extracts and mammalian cells with CK666 inhibition, ChIP, and HDR/NHEJ repair assays

    PMID:29925947

    Open questions at the time
    • How Arp2/3 is imported into the nucleus upon DNA damage not defined
    • Which NPF activates nuclear Arp2/3 at break sites incompletely characterized
  11. 2020 High

    Two key structural and biophysical questions were answered simultaneously: cryo-EM showed that actin-NPF binding to Arp2 precedes Arp3 and that delivery to both subunits is required for activation; single-molecule force experiments revealed that ATP hydrolysis/phosphate release on Arp2 converts branches from a strong to a force-sensitive state, explaining how branch age is mechanically decoded.

    Evidence Cryo-EM of human Arp2/3–NPF complex with mutagenesis; TIRF-based microfluidic force assay on fission yeast branches

    PMID:32461373 PMID:32917641

    Open questions at the time
    • Whether phosphorylation at T237/T238 affects the conformational activation pathway seen by cryo-EM not tested
    • In vivo force magnitudes at branch junctions uncertain
  12. 2022 High

    The mechanism of Arp2/3 inhibition by Arpin was structurally defined: Arpin mimics NPFs at the Arp3 site only, leaving the Arp2-ARPC1 site unoccupied, thereby blocking activation; sequence differences in Arpin's C-helix encode the distinction between inhibition and activation.

    Evidence Cryo-EM at 3.24 Å, site-directed mutagenesis, in vitro nucleation and cell migration assays

    PMID:35110533

    Open questions at the time
    • Whether Arpin competes with NPFs at endogenous concentrations in vivo quantitatively unknown
    • Other endogenous inhibitors may use different binding modes
  13. 2023 High

    Permanent Arp2/3 loss was shown to cause genomic instability, micronuclei, and cGAS-STING-dependent senescence, linking the nuclear actin-repair function to a cell-autonomous innate immune response when the complex is absent.

    Evidence Inducible ArpC2 knockout in mouse fibroblasts with live-cell imaging, DNA damage markers, and cGAS-STING pathway analysis

    PMID:36706133

    Open questions at the time
    • Whether Arp2 specifically (versus other subunits) is rate-limiting for the nuclear repair function unknown
    • Relevance to human disease or tumor suppression not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Arp2 phosphorylation at T237/T238 integrates with the conformational activation pathway resolved by cryo-EM, and how nuclear import and NPF selection for Arp2/3 at DNA damage sites are regulated, remain open mechanistic questions.
  • No structure of phosphorylated Arp2/3 complex in the activated state
  • Mechanism of Arp2/3 nuclear import upon DNA damage undefined
  • Whether phosphate release kinetics on Arp2 differ in nuclear vs. cytoplasmic contexts untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0140657 ATP-dependent activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-1500931 Cell-Cell communication 2 R-HSA-73894 DNA Repair 2 R-HSA-1640170 Cell Cycle 1 R-HSA-5653656 Vesicle-mediated transport 1
Partners
ACTR3ARPC1ARPC2CTTNMAP4K4PLK4WASF1WASL
Complex memberships
Arp2/3 complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 The human Arp2/3 complex is a seven-subunit complex containing Arp2 and Arp3 as actin-related proteins plus five novel subunits (p41-Arc, p34-Arc, p21-Arc, p20-Arc, p16-Arc). The complex localizes to lamellipodia of fibroblasts and to Listeria actin tails, and is sufficient to initiate ActA-dependent actin polymerization at the bacterial surface, establishing Arp2 as a core nucleating subunit. Protein purification from bovine brain, immunolocalization in fibroblasts and infected cells, in vitro actin polymerization assay with purified complex Nature High 9000076 9230079
1998 Purified Arp2/3 complex accelerates nucleation of actin polymerization in vitro; the bacterial protein ActA and host Arp2/3 complex synergistically stimulate actin filament nucleation, establishing that ActA activates the Arp2/3 complex to drive Listeria motility. In vitro actin polymerization assay with purified human Arp2/3 complex and recombinant ActA protein Science High 9651243
1998 WASP and Scar1 interact with the p21-Arc subunit of the Arp2/3 complex through their C-terminal domains; overexpression of these C-terminal fragments disrupts Arp2/3 localization and abolishes lamellipodia, establishing WASP-family proteins as upstream regulators of Arp2/3-dependent actin assembly. Deletion analysis, co-immunoprecipitation, dominant-negative overexpression in cells Current biology High 9889097
1999 Actin-based motility of Listeria and Shigella was reconstituted in vitro using purified actin, activated Arp2/3 complex, ADF/cofilin, and capping protein, demonstrating that Arp2/3-mediated actin nucleation drives bacterial propulsion and that ATP hydrolysis linked to actin polymerization provides the force. In vitro reconstitution of actin-based motility with pure proteins including purified Arp2/3 complex Nature High 10524632
2000 N-WASP integrates Cdc42 and PIP2 signals cooperatively to activate the Arp2/3 complex; in the inactive state, regulatory domains hold the VCA-Arp2/3 interaction in a closed conformation, and binding of either Cdc42 or PIP2 destabilizes this closed state and enhances binding of the other input, yielding potent Arp2/3-dependent actin polymerization. In vitro actin polymerization assay, domain deletion analysis, fluorescence anisotropy binding assays Science High 11052943
2001 Crystal structure of bovine Arp2/3 complex at 2.0 Å resolution revealed that Arp2 and Arp3 are folded like actin with distinctive surface features; ARPC2/p34 and ARPC4/p20 form the core through long C-terminal alpha helices; the structure predicted that WASp/Scar proteins activate the complex by bringing Arp2 into proximity with Arp3 for nucleation of a branch on the side of a preexisting filament. X-ray crystallography at 2.0 Å resolution Science High 11721045
2001 The WA domain of WASP binds a single actin monomer (Kd ~0.6 µM) and the Arp2/3 complex (Kd ~0.9 µM); both WH-2 and CA sequences contribute to actin binding, and actin filaments produce a fivefold increase in the affinity of WASP-WA for the Arp2/3 complex, indicating positive feedback in filament nucleation. Fluorescence anisotropy binding assays with purified components Nature cell biology High 11146629
2001 Cortactin directly binds the Arp2/3 complex via its N-terminal acidic domain (DDW motif) and activates it to promote actin filament nucleation; this activation depends on cortactin's F-actin binding activity, which enhances the interaction between Arp2/3 and actin filaments. Co-localization, direct binding assays, mutagenesis of DDW motif, in vitro actin nucleation assay Nature cell biology High 11231575
2004 ATP hydrolysis on the Arp2 subunit occurs rapidly upon nucleation of a new actin filament; neither filamentous actin nor VCA alone stimulates ATP hydrolysis, but a single actin monomer delivered by VCA to the pointed end of the daughter filament triggers this hydrolysis, identifying the first actin monomer as the key activating signal for Arp2 ATPase activity. Radioactive ATP hydrolysis assay with purified Arp2/3 complex, VCA, actin variants including Latrunculin B-bound monomers, and phalloidin-stabilized filaments PLoS biology High 15094799
2005 Phosphorylation of Arp2 at Thr237 and Thr238 (identified by mass spectrometry) is necessary for Arp2/3 complex to nucleate actin filaments; phosphorylation is not required for NPF or filament-side binding but is critical for pointed-end binding and nucleation. In cells, phosphorylation of Arp2 increases in response to growth factors, and Ala substitutions at T237/T238 or Y202 inhibit membrane protrusion. Mass spectrometry phosphosite identification, alanine mutagenesis, in vitro actin nucleation assay, cell protrusion assay The Journal of cell biology High 18725535
2007 Kinetic analyses of fission yeast Arp2/3 complex showed that the complex binds to and dissociates from actin filaments extremely slowly; VCA binds both Arp2/3 and actin monomers with high affinity; mathematical modeling constrained the pathway to a single main route: ternary complex (Arp2/3-VCA-actin monomer) binds filament side, followed by an activation step with rate constant ≥0.15 s⁻¹. Spectroscopic pyrene assay, fluorescence anisotropy, mathematical modeling of actin polymerization kinetics The Journal of biological chemistry High 18165685
2008 Fission yeast Arp2/3 complex lacking the Arp2 subunit retains its overall structure (confirmed by X-ray crystallography) but is completely inactive in actin nucleation assays; Arp2 does not contribute to VCA binding affinity or to VCA-mediated actin monomer recruitment, establishing Arp2 as specifically essential for branch formation rather than for NPF or actin monomer docking. X-ray crystallography of ΔArp2 complex, in vitro actin nucleation assay, fluorescence anisotropy, FRET The Journal of biological chemistry High 18640983
2010 Molecular dynamics simulations starting from the inactive crystal structure showed that activation involves a ~30 Å movement of Arp2 toward Arp3; one structural block (Arp2, ARPC1, globular domain of ARPC4, ARPC5) rotates ~30° counterclockwise around a pivot point in an ARPC4 alpha-helix (Glu81-Asn100) to align Arp2 next to Arp3, burying additional surface area in the active conformation. Atomistic molecular dynamics simulations based on crystal structure Biophysical journal Medium 20959098
2011 Activation of Arp2/3 complex most likely involves engagement of two distinct VCA-binding sites simultaneously: one on Arp3 and one on ARPC1/Arp2; each site binds one VCA molecule delivering one actin monomer, reconciling conflicting models of activation. Fluorescence anisotropy, isothermal titration calorimetry, analytical ultracentrifugation, mutagenesis of binding sites Proceedings of the National Academy of Sciences High 21676863
2015 Nck-interacting kinase (NIK/MAP4K4) directly binds and phosphorylates the Arp2 subunit, increasing the nucleating activity of the Arp2/3 complex; NIK kinase activity is required for EGF-stimulated Arp2 phosphorylation and plasma membrane protrusion in mammary carcinoma cells; phosphorylation-deficient Arp2 dominantly suppresses actin filament assembly. Co-immunoprecipitation, in vitro kinase assay with purified NIK and Arp2/3 complex, dominant-negative mutagenesis, cell protrusion assay The Journal of cell biology High 25601402
2016 Plk4 physically interacts with Arp2 (identified by BioID screen and confirmed by co-IP) through its Polo-box 1/2 domain, and phosphorylates Arp2 at the T237/T238 activation site; this phosphorylation is required for Plk4-driven cancer cell movement and invasion. BioID proximity labeling screen, co-immunoprecipitation, in vitro phosphorylation assay, cell migration/invasion assays with phospho-mutants Cancer research High 27872092
2016 Actin-related protein 2 (ARP2) was identified as a host factor required for RSV spread; ARP2 knockdown did not reduce RSV entry but decreased viral gene expression after 24 hr and caused a 10-fold reduction in infectious progeny at 72 hr. RSV infection induced ARP2-dependent filopodia formation that shuttled virus to neighboring cells; RSV F protein alone was sufficient to induce filopodia in an ARP2-dependent manner. Genome-wide siRNA screen, targeted ARP2 siRNA knockdown, viral titer assay, live-cell imaging of filopodia, plasmid/viral vector expression of RSV F protein PLoS pathogens High 27926942
2016 The Arp2/3 complex can form 'hybrid complexes' containing actin-nucleating Arp2/Arp3 core subunits together with vinculin or vinculin/α-actinin instead of the full seven-subunit assembly; suppression of p41-ARC (ARPC1), which is absent from hybrid complexes, increases Arp2/3 core at focal adhesion sites and stimulates FA growth and dynamics. Biochemical fractionation from smooth muscle tissue, mass spectrometry, immunoprecipitation, siRNA knockdown with FA dynamics imaging Nature communications Medium 24781749
2018 Nuclear actin, WASP, and the Arp2/3 complex are recruited to damaged chromatin undergoing homology-directed repair (HDR) in Xenopus cell-free extracts and mammalian cells; nuclear actin polymerization driven by Arp2/3 is required for migration of DNA double-strand breaks into sub-nuclear clusters specifically during HDR in G2; Arp2/3 inhibition impairs DNA end-processing and HDR but does not affect non-homologous end joining. Xenopus cell-free extracts, mammalian cell imaging, Arp2/3 inhibition (CK666), ChIP, HDR/NHEJ repair assays Nature High 29925947
2020 Cryo-EM structure of human Arp2/3 complex bound to two WASP-family NPFs revealed that actin-NPF binding to Arp2 precedes binding to Arp3 and is sufficient to promote the filament-like conformation but not activation; NPF-mediated actin delivery at the barbed end of both Arp2 and Arp3 is required for activation of human Arp2/3 complex, contrasting with budding yeast. Cryo-EM structure determination, cross-linking assay to capture Arp activation, structure-guided mutagenesis validated in vitro and in cells Science advances High 32917641
2020 Force applied to actin filament branches containing Arp2/3 complex accelerates debranching more than 100-fold (from hours to <1 min); Arp2/3 complex at branch junctions adopts two mechanical states: 'young/strong' (ADP-Pi bound) and 'old/weak' (ADP bound after phosphate release); the ADP state is 20× more sensitive to force and more susceptible to GMF-mediated debranching. Microfluidics to apply defined force, real-time TIRF microscopy of debranching, purified fission yeast Arp2/3 complex and actin Proceedings of the National Academy of Sciences High 32461373
2022 Cryo-EM structure of Arpin bound to Arp2/3 complex at 3.24 Å revealed that Arpin binds similarly to WASP-family NPFs but only occupies the Arp3 site (not the Arp2-ArpC1 site); Arpin's C-helix binds at the barbed end of Arp3 like activating NPFs, but sequence differences in the C-helix define the molecular basis for inhibition vs. activation; mutagenesis validated these distinct roles in vitro and in cells. Cryo-EM structure determination, site-directed mutagenesis, in vitro actin nucleation assays, cell migration assays Nature communications High 35110533
2023 Permanent Arp2/3 complex ablation (ArpC2 iKO in mouse fibroblasts) causes DNA damage, cytosolic micronuclei, and cellular senescence; micronuclei arise from chromatin segregation defects during mitosis due to damaged DNA fragments failing to attach to the mitotic spindle, abnormal actin assembly during metaphase, and asymmetric microtubule architecture; micronuclei activate cGAS-STING-IRF3 interferon response. Inducible knockout of ArpC2 in mouse fibroblasts, live-cell imaging, micronuclei quantification, DNA damage markers, flow cytometry, immunofluorescence of spindle architecture PLoS genetics High 36706133
1996 Yeast Arp2p (ortholog of human ACTR2) is an essential actin cytoskeleton component; temperature-sensitive arp2-H330L mutants show altered actin cytoskeleton, random budding patterns, severely reduced endocytosis, and genetic interaction with CDC10 (neck filament protein), establishing Arp2 as involved in membrane growth, polarity, and endocytosis. Gene disruption, temperature-sensitive allele generation by PCR mutagenesis, indirect immunofluorescence, Lucifer yellow endocytosis assay, genetic interaction analysis The Journal of cell biology High 8698808
2014 In C. elegans, Musashi (MSI-1) binds mRNAs of three Arp2/3 complex subunits including ARX-2 (arx-2 encodes the Arp2 ortholog) in vivo and downregulates their translation upon associative learning; reduced Arp2/3 complex activity mediates time-dependent memory loss, placing Arp2/3-dependent actin branching in neurons downstream of a forgetting pathway. RNA-binding protein immunoprecipitation, translational reporter assays, genetic epistasis in C. elegans learning/forgetting assays Cell High 24630719
2016 miR-24-1* targets ARP2 mRNA in Hirschsprung disease samples; downregulation of ARP2 (and ARP3) suppresses migration and proliferation in 293T and SH-SY5Y cells via inhibition of RAC1 and RAC2; co-immunoprecipitation showed that reduction of ARP2 weakens Arp2/3 complex function. qRT-PCR, siRNA knockdown, co-immunoprecipitation, migration/proliferation assays Journal of cellular and molecular medicine Medium 26991540

Source papers

Stage 0 corpus · 130 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
2011 Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 1334 21906983
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
2009 A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 843 19490893
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1999 Reconstitution of actin-based motility of Listeria and Shigella using pure proteins. Nature 781 10524632
1998 Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Current biology : CB 761 9889097
2011 A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Molecular & cellular proteomics : MCP 749 21890473
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
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 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2005 Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. The Journal of cell biology 559 15684033
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
1997 Actin polymerization is induced by Arp2/3 protein complex at the surface of Listeria monocytogenes. Nature 494 9000076
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2001 Activation of Arp2/3 complex-mediated actin polymerization by cortactin. Nature cell biology 481 11231575
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1997 The human Arp2/3 complex is composed of evolutionarily conserved subunits and is localized to cellular regions of dynamic actin filament assembly. The Journal of cell biology 430 9230079
2000 Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex. Science (New York, N.Y.) 419 11052943
1998 Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein in actin filament nucleation. Science (New York, N.Y.) 414 9651243
2001 Crystal structure of Arp2/3 complex. Science (New York, N.Y.) 413 11721045
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2012 New insights into the regulation and cellular functions of the ARP2/3 complex. Nature reviews. Molecular cell biology 391 23212475
2000 Cortactin localization to sites of actin assembly in lamellipodia requires interactions with F-actin and the Arp2/3 complex. The Journal of cell biology 355 11018051
2011 Global identification of modular cullin-RING ligase substrates. Cell 354 21963094
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2002 Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. The Journal of cell biology 339 12473693
2011 Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chemistry & biology 326 22118674
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2018 Nuclear ARP2/3 drives DNA break clustering for homology-directed repair. Nature 312 29925947
2012 The Arp2/3 complex is required for lamellipodia extension and directional fibroblast cell migration. The Journal of cell biology 281 22492726
2001 Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex. Nature cell biology 277 11146629
2008 Arp2/3 complex interactions and actin network turnover in lamellipodia. The EMBO journal 242 18309290
2005 Protein complexes regulating Arp2/3-mediated actin assembly. Current opinion in cell biology 209 16343889
2007 Coronin 1B coordinates Arp2/3 complex and cofilin activities at the leading edge. Cell 207 17350576
2006 Filopodia formation in the absence of functional WAVE- and Arp2/3-complexes. Molecular biology of the cell 187 16597702
2008 N-wasp and the arp2/3 complex are critical regulators of actin in the development of dendritic spines and synapses. The Journal of biological chemistry 184 18430734
2003 A dynamin-cortactin-Arp2/3 complex mediates actin reorganization in growth factor-stimulated cells. Molecular biology of the cell 178 12631725
2011 Arp2/3 complex is bound and activated by two WASP proteins. Proceedings of the National Academy of Sciences of the United States of America 173 21676863
2017 Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease. Nature communications 162 28368018
2018 The Arp2/3 Regulatory System and Its Deregulation in Cancer. Physiological reviews 157 29212790
2003 Integration of signals to the Arp2/3 complex. Current opinion in cell biology 157 12517700
2010 WASH, WHAMM and JMY: regulation of Arp2/3 complex and beyond. Trends in cell biology 150 20888769
2003 The putative Arabidopsis arp2/3 complex controls leaf cell morphogenesis. Plant physiology 148 12913159
2010 WASH and the Arp2/3 complex regulate endosome shape and trafficking. Cytoskeleton (Hoboken, N.J.) 147 20175130
2006 Exo70 interacts with the Arp2/3 complex and regulates cell migration. Nature cell biology 147 17086175
2011 Arp2/3 complex regulates asymmetric division and cytokinesis in mouse oocytes. PloS one 143 21494665
2011 Filopodia initiation: focus on the Arp2/3 complex and formins. Cell adhesion & migration 141 21975549
2000 How WASP-family proteins and the Arp2/3 complex convert intracellular signals into cytoskeletal structures. Current opinion in cell biology 141 10679362
2008 Distinct roles for Arp2/3 regulators in actin assembly and endocytosis. PLoS biology 136 18177206
1999 The world according to Arp: regulation of actin nucleation by the Arp2/3 complex. Trends in cell biology 135 10511705
2006 IQGAP1 stimulates actin assembly through the N-WASP-Arp2/3 pathway. The Journal of biological chemistry 125 17085436
2016 Plk4 Promotes Cancer Invasion and Metastasis through Arp2/3 Complex Regulation of the Actin Cytoskeleton. Cancer research 121 27872092
2004 A Rickettsia WASP-like protein activates the Arp2/3 complex and mediates actin-based motility. Cellular microbiology 119 15236643
2008 A SPIKE1 signaling complex controls actin-dependent cell morphogenesis through the heteromeric WAVE and ARP2/3 complexes. Proceedings of the National Academy of Sciences of the United States of America 118 18308939
1996 The Saccharomyces cerevisiae actin-related protein Arp2 is involved in the actin cytoskeleton. The Journal of cell biology 113 8698808
2000 Actin-based motility of pathogens: the Arp2/3 complex is a central player. Cellular microbiology 110 11207576
2017 Kindlin-2 recruits paxillin and Arp2/3 to promote membrane protrusions during initial cell spreading. The Journal of cell biology 98 28912124
2016 The Diverse Family of Arp2/3 Complexes. Trends in cell biology 90 27595492
2005 Phosphoregulation of Arp2/3-dependent actin assembly during receptor-mediated endocytosis. Nature cell biology 90 15711538
2008 WAVE and Arp2/3 jointly inhibit filopodium formation by entering into a complex with mDia2. Nature cell biology 89 18516090
2006 BRICK1/HSPC300 functions with SCAR and the ARP2/3 complex to regulate epidermal cell shape in Arabidopsis. Development (Cambridge, England) 87 16481352
2020 The cell pushes back: The Arp2/3 complex is a key orchestrator of cellular responses to environmental forces. Current opinion in cell biology 86 32977244
2016 Function and regulation of the Arp2/3 complex during cell migration in diverse environments. Current opinion in cell biology 83 27164504
2014 Regulation of focal adhesion formation by a vinculin-Arp2/3 hybrid complex. Nature communications 83 24781749
2014 Forgetting is regulated via Musashi-mediated translational control of the Arp2/3 complex. Cell 81 24630719
2007 Pathway of actin filament branch formation by Arp2/3 complex. The Journal of biological chemistry 81 18165685
2007 Regulation of N-WASP and the Arp2/3 complex by Abp1 controls neuronal morphology. PloS one 80 17476322
2007 Src, cortactin and Arp2/3 complex are required for E-cadherin-mediated internalization of Listeria into cells. Cellular microbiology 78 17627624
2004 The WASP-Arp2/3 pathway: genetic insights. Current opinion in cell biology 77 15196561
2004 Association of Cdc42/N-WASP/Arp2/3 signaling pathway with Golgi membranes. Traffic (Copenhagen, Denmark) 76 15479449
2015 Initiation of lamellipodia and ruffles involves cooperation between mDia1 and the Arp2/3 complex. Journal of cell science 70 26349808
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