Affinage

ARL2

ADP-ribosylation factor-like protein 2 · UniProt P36404

Length
184 aa
Mass
20.9 kDa
Annotated
2026-06-09
63 papers in source corpus 32 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARL2 is a small ADP-ribosylation factor-like GTPase that cycles between GDP- and GTP-bound states and coordinates microtubule biogenesis, mitochondrial function, and the trafficking of lipidated proteins across spatially distinct cellular pools (PMID:11980706, PMID:10831612, PMID:24911211). Its nucleotide cycle is governed by GAPs of the ELMO-domain family (ELMOD1, ELMOD2, ELMOD3) and by tubulin cofactor C orthologs, with continuous GDP/GTP cycling required for activity (PMID:17452337, PMID:24039609, PMID:23576550). In the cytosol, GDP-bound ARL2 binds tubulin-specific chaperone cofactor D (TBCD) and assembles into a TBCD·ARL2·β-tubulin trimer in which ARL2 is the GTP-exchanging subunit; through this complex ARL2 restrains TBCD's tubulin- and microtubule-destructive activity and drives the β-tubulin folding pathway, controlling microtubule density, centrosomal microtubule growth, and cell-cycle progression (PMID:10831612, PMID:12912990, PMID:28126905, PMID:28970104, PMID:20740604, PMID:39137170). Inside mitochondria, where ARL2 escapes N-myristoylation and is imported to the intermembrane space, ARL2·GTP promotes mitochondrial fusion through the ELMOD2 effector acting with the mitofusins and regulates ATP levels and mitochondrial morphology, in part via interaction with the adenine nucleotide transporter ANT1 (PMID:11809823, PMID:24911211, PMID:28944094, PMID:30865555). In lipidated-cargo trafficking, ARL2·GTP acts as a release factor that allosterically expels prenylated cargo from the carrier PDEδ and myristoylated cargo from UNC119, with ARL2 releasing low-affinity cargo while the paralog Arl3 handles high-affinity ciliary cargo, establishing a spatial sorting mechanism (PMID:11980706, PMID:27481943, PMID:28106325). The dedicated effector BART (BinderofArlTwo) binds ARL2·GTP specifically and modulates its activity, including at the leading edge of migrating cells where it antagonizes ARL2-dependent suppression of RhoA (PMID:10488091, PMID:21833473). A de novo ARL2 variant (p.R15L) that weakens binding to HRG4/UNC119 causes MRCS syndrome with retinal degeneration, microcornea, and cataract (PMID:30945270).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Establishing that ARL2 has dedicated GTP-state-specific effectors answered whether it functions as a genuine signaling GTPase rather than a structural ARF; BART was the first such effector identified.

    Evidence Affinity purification of BART from bovine brain with recombinant binding and GTPase assays

    PMID:10488091

    Open questions at the time
    • Cellular consequence of BART binding undefined at discovery
    • No structure of the ARL2-BART complex
  2. 2000 High

    Linking GDP-ARL2 to the tubulin chaperone cofactor D established its first concrete role: a negative regulator of cofactor-driven tubulin destruction and microtubule integrity.

    Evidence In vitro tubulin GTPase and binding-inhibition assays plus cofactor overexpression in cultured cells with ARL2 point mutants

    PMID:10831612

    Open questions at the time
    • Did not resolve whether ARL2 is part of a stable trimer with tubulin
    • Nucleotide-cycle requirement not directly tested
  3. 2002 High

    Solving the Arl2-GTP·PDEδ structure showed how ARL2 nucleotide state controls a prenyl-binding carrier, framing ARL2 as a regulator of prenylated-protein transport.

    Evidence X-ray crystallography of full-length Arl2-GTP·PDEδ in two crystal forms with binding assays

    PMID:11980706

    Open questions at the time
    • Release mechanism for cargo not directly demonstrated
    • In vivo trafficking consequences not tested
  4. 2002 High

    Demonstrating mitochondrial localization and ANT1 binding of the BART·ARL2·GTP complex revealed an unexpected second compartment for ARL2 beyond tubulin folding.

    Evidence Subcellular fractionation, protease protection, overlay assay, and ant1-/- mouse mitochondria analysis

    PMID:11809823

    Open questions at the time
    • Functional role of ANT1 interaction not established
    • Mechanism of mitochondrial import not defined
  5. 2003 High

    Defining the ~300 kDa cytosolic ARL2-TBCD-PP2A complex clarified that most cellular ARL2 is held in a GTP-incompetent, sequestered state, implying regulated release governs activity.

    Evidence Gel filtration, purification from bovine brain, mass spectrometry, GTP-binding and tubulin refolding assays

    PMID:12912990

    Open questions at the time
    • Signal that releases ARL2/TBCD from the complex unknown
    • Role of PP2A in the complex not mechanistically resolved
  6. 2003 Medium

    Identifying UNC119/HRG4 as an ARL2 partner extended the carrier-protein paradigm from prenylated to myristoylated cargo and connected ARL2 to retinal biology.

    Evidence Yeast two-hybrid, co-IP, direct binding, and retinal co-localization

    PMID:12527357

    Open questions at the time
    • Cargo release from UNC119 not yet shown
    • Functional retinal consequence not tested
  7. 2006 Medium

    Showing that constitutively active ARL2 destroys microtubules and arrests cells in M phase while distinguishing ARL2 from Arl3 separated the paralogs' roles in microtubule-dependent processes.

    Evidence siRNA knockdown, dominant-active mutant expression, immunofluorescence, and cell-cycle analysis in HeLa cells

    PMID:16525022

    Open questions at the time
    • Centrosomal function of ARL2 not mechanistically defined
    • Single-lab phenotype
  8. 2007 High

    Identifying ELMOD2 (and ELMOD1) as ARL2 GAPs provided the missing regulators that terminate ARL2 signaling, defining the off-switch of its cycle.

    Evidence Purification of GAP activity from bovine testis and in vitro GAP assays

    PMID:17452337

    Open questions at the time
    • Which ARL2 functions each GAP regulates not yet assigned
    • Cross-activity toward Arf raised specificity questions
  9. 2013 Medium

    Identifying ELMOD3 as a third ARL2 GAP whose activity is abolished by a disease mutation, and resolving RPGR scaffolding of cargo-loaded PDEδ, sharpened both the regulatory network and the ciliary-delivery model.

    Evidence In vitro GAP assays with mutagenesis (ELMOD3) and crystallography with binding assays (RPGR-PDEδ)

    PMID:23559067 PMID:24039609

    Open questions at the time
    • Direct role of ARL2 (vs Arl3) in RPGR-mediated release not pinned down
    • Tissue specificity of GAP usage unclear
  10. 2014 Medium

    Separating ARL2's mitochondrial phenotypes (morphology, motility, ATP) from its tubulin role, and placing ELMOD2 downstream, established a distinct mitochondrial pathway.

    Evidence siRNA knockdown, dominant-negative expression, live imaging, ATP assays, and ELMOD2 epistasis

    PMID:24911211

    Open questions at the time
    • Molecular target of ARL2 in mitochondria not identified
    • ATP defect not phenocopied by ELMOD2 loss
  11. 2016 High

    Demonstrating ARL2/Arl3 cargo release and its affinity-based selectivity, and dissecting ARL2's centrosomal microtubule control in Drosophila neuroblasts, unified the trafficking and microtubule arms mechanistically.

    Evidence Crystallography and fluorescence polarization (cargo release); RNAi, Co-IP with cofactors C/D/E, and imaging in Drosophila neuroblasts

    PMID:26953351 PMID:27481943

    Open questions at the time
    • How a single GTPase is partitioned among compartments unresolved
    • Quantitative cargo handoff to membranes in cells incomplete
  12. 2017 High

    Reconstituting the TBCD·ARL2·β-tubulin trimer with ARL2 as the GTP-exchanging subunit, and showing IMS-restricted ARL2 drives mitofusin-dependent fusion, gave direct biochemical mechanism for both the tubulin-folding and mitochondrial-fusion roles.

    Evidence Trimer purification with HDX-MS and nucleotide assays; targeted localization constructs, fusion assays, SIM, and MFN1/2 KO epistasis

    PMID:28126905 PMID:28944094 PMID:28970104

    Open questions at the time
    • Structural basis of ARL2-induced β-tubulin conformational change not at atomic resolution
    • Effector linking ARL2 to mitofusins not yet identified in this study
  13. 2019 Medium

    Showing ELMOD2 acts as a GAP-independent effector for ARL2-driven mitochondrial fusion, alongside identifying an ARL2 disease variant, connected mechanism to human pathology.

    Evidence GAP-dead ELMOD2 mutant fusion assays and co-localization; Co-IP, mitochondrial function assays, and transgenic mouse for the p.R15L MRCS variant

    PMID:30865555 PMID:30945270

    Open questions at the time
    • How the same ELMOD2 serves both GAP and effector roles unclear
    • Whether MRCS pathology is primarily trafficking- or mitochondria-driven not resolved
  14. 2024 Medium

    Identifying Cdk5rap2 as an ARL2-associated centrosomal target whose overexpression rescues ARL2-loss neurogenesis defects extended ARL2's microtubule role into cortical development.

    Evidence Co-IP, proximity ligation, in utero electroporation knockdown, rescue, and live imaging in mouse neural progenitors

    PMID:39137170

    Open questions at the time
    • Whether ARL2 nucleotide state controls Cdk5rap2 localization unknown
    • Direct vs indirect interaction not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single GTPase is partitioned and selectively activated across its cytosolic tubulin-folding, mitochondrial, and membrane-trafficking pools, and how its sequestered cytosolic complex is mobilized, remains unresolved.
  • No mechanism for compartment-specific GEF/GAP targeting
  • Release mechanism from the inhibitory TBCD-PP2A complex unknown
  • ARL2 chromatin/HRR role (Low confidence) lacks direct mechanism

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005739 mitochondrion 4 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-9609507 Protein localization 2 R-HSA-1640170 Cell Cycle 1
Partners
ANT1BARTCDK5RAP2ELMOD2ELMOD3PDE6DTBCDUNC119
Complex memberships
ARL2-TBCD-PP2A ~300 kDa complexBART·ARL2·GTP complexTBCD·ARL2·β-tubulin trimer

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Crystal structure of full-length Arl2-GTP in complex with its effector PDE delta solved at 1.8–2.3 Å resolution. Arl2 undergoes a dramatic conformational change from the GDP-bound form, suggesting reversible membrane association. PDE delta is structurally related to RhoGDI and contains a deep hydrophobic pocket that binds prenylated proteins including H-Ras, Rheb, Rho6, and Gαi1. Arl2-GTP was proposed to act as a regulator of PDE delta-mediated transport of prenylated proteins. X-ray crystallography (two crystal forms, PDB: 1KSG, 1KSH, 1KSJ); co-expression and copurification; binding assays The EMBO journal High 11980706
2000 Arl2 in its GDP-bound form interacts with tubulin-specific chaperone cofactor D (TBCD) and downregulates the tubulin GAP activity of cofactors C, D, and E, inhibiting binding of D to native tubulin in vitro. GDP-Arl2 specifically prevents tubulin and microtubule destruction caused by cofactor D overexpression in cultured cells, but not by cofactor E. Established using Ras-family-based Arl2 point mutants in vitro and in vivo. In vitro tubulin GTPase assays; in vitro binding inhibition assays; overexpression in cultured cells; site-directed mutagenesis of Arl2 The Journal of cell biology High 10831612
1999 BART (Binder of Arl Two), a 19 kDa novel protein, was purified from bovine brain and identified as the first ARL2-specific effector. BART binds specifically to ARL2·GTP with high affinity but does not interact with ARL2·GDP, activated ARF, or RHO proteins. BART lacks GTPase-activating protein activity toward ARL2. Affinity purification from bovine brain; recombinant protein binding assays; GTPase activity assays; Northern and Western blot The Journal of biological chemistry High 10488091
2002 ARL2 and BART both localize to mitochondria in a protease-resistant form. ARL2 lacks N-myristoylation (unlike other ARF family members), preserving its N-terminal amphipathic helix as a potential mitochondrial import sequence. The BART·ARL2·GTP complex specifically binds the adenine nucleotide transporter ANT1 (but not the homologous ANT2) in mitochondria. Mitochondria from ant1−/− mice showed increased ARL2 levels, indicating that ARL2 in mitochondria is regulated via an ANT1-sensitive pathway. Subcellular fractionation; protease protection assay; overlay assay; protein purification and microsequencing; ant1−/− knockout mouse mitochondria analysis Molecular biology of the cell High 11809823
2007 ELMOD2 was purified from bovine testis and identified as an ARL2 GTPase-activating protein (GAP). A second ELMO domain protein, ELMOD1, also has ARL2 GAP activity. Surprisingly, ELMOD2 also exhibits GAP activity against Arf proteins despite lacking the canonical Arf GAP sequence signature. Protein purification from bovine testis; in vitro GAP activity assays The Journal of biological chemistry High 17452337
2003 Cytosolic Arl2 exists predominantly (~90%) as part of a ~300 kDa complex containing cofactor D (TBCD) and at least two distinct protein phosphatase 2A (PP2A) trimers (all three PP2A subunits identified by mass spectrometry). Arl2 in this complex cannot bind GTP, and complexed cofactor D does not efficiently participate in tubulin refolding reactions. This suggests the complex sequesters both Arl2 and TBCD in inactive states. Gel filtration; ~500-fold purification from bovine brain soluble fraction; mass spectrometry protein identification; GTP-binding assays; tubulin refolding assays The Journal of biological chemistry High 12912990
2002 C. elegans evl-20, a functional homolog of human ARL2, is required for cytoskeletal dynamics during cytokinesis and morphogenesis. Loss of evl-20 causes microtubule cytoskeleton defects and developmental abnormalities. EVL-20 localizes to the cell cortex and astral microtubules. Loss-of-function genetics (C. elegans); immunofluorescence localization; phenotypic analysis Developmental cell Medium 12015966
2006 Expression of constitutively active [Q70L]Arl2 in HeLa cells caused loss of microtubules and cell cycle arrest in M phase, attributed to a defect in tubulin polymerization. Arl2 was found to localize to centrosomes. Arl3 knockdown (not Arl2 knockdown) caused cytokinesis failure and binucleation, distinguishing the two paralogs' roles in microtubule-dependent processes. siRNA knockdown; dominant-active mutant expression; immunofluorescence; cell cycle analysis Molecular biology of the cell Medium 16525022
2009 miR-15b targets the 3'-UTR of Arl2 mRNA and suppresses Arl2 mRNA and protein expression. Knockdown of Arl2 by siRNA decreases cellular ATP levels and causes mitochondrial degeneration, phenocopying miR-15b overexpression. Restoration of Arl2 expression rescues the miR-15b-induced reduction in ATP levels. Luciferase reporter assay (3'-UTR); siRNA knockdown; miRNA overexpression; ATP assay; electron microscopy of mitochondria The Journal of biological chemistry Medium 20007690
2013 Crystal structure of the RPGR propeller domain in complex with PDEδ was solved, revealing that RPGR binds cargo-loaded PDEδ via a conserved surface patch while exposing the Arl2/Arl3-binding site on PDEδ. Biochemical experiments showed RPGR can bind with high affinity to cargo-loaded PDEδ, suggesting RPGR acts as a scaffold recruiting cargo-loaded PDEδ and Arl3 to release lipidated cargo into cilia. X-ray crystallography; biochemical binding assays EMBO reports High 23559067
2003 HRG4 (UNC119) interacts with ARL2 as identified by yeast two-hybrid; confirmed by co-immunoprecipitation and direct binding assay. ARL2 co-localizes with HRG4 in the retina. Conserved amino acid residues in HRG4 homologous to those in PDEδ that mediate ARL2 binding and form the hydrophobic pocket suggest a similar binding mechanism. Yeast two-hybrid; co-immunoprecipitation; direct binding assay; Western blot; immunofluorescence FEBS letters Medium 12527357
2014 ARL2 depletion by siRNA impairs mitochondrial morphology (fragmentation), motility, and ATP levels in cultured cells. These mitochondrial roles are distinct from ARL2's roles in tubulin folding. Knockdown of the ARL2 GAP ELMOD2 phenocopies two of three mitochondrial phenotypes of ARL2 siRNA (morphology and motility but not ATP), placing ELMOD2 as a likely effector downstream of ARL2 for mitochondrial functions. siRNA knockdown; dominant-negative mutant expression; live-cell imaging of mitochondrial morphology and motility; ATP assays; genetic epistasis PloS one Medium 24911211
2017 ARL2 is present in and required for mitochondrial fusion from the intermembrane space (IMS). Increased ARL2 activity promotes mitochondrial elongation/fusion, while loss of ARL2 decreases fusion rate. Activated ARL2 can partially rescue loss of MFN1 or MFN2 individually but not both together, placing ARL2 upstream of/parallel to mitofusins. IMS-restricted ARL2 constructs were active, while matrix or excluded constructs were inactive. By SIM microscopy, ARL2 and mitofusin immunoreactivities co-localize as puncta along mitochondria. Dominant-active/dominant-negative mutant expression; mitochondrial fusion assay; targeted subcellular localization constructs; structured illumination microscopy (SIM); MFN1/MFN2 knockout cell epistasis Cellular logistics Medium 28944094
2019 ELMOD2 is required for ARL2-dependent mitochondrial elongation and fusion. Loss of ELMOD2 causes mitochondrial fragmentation and decreased fusion rate; ELMOD2 overexpression promotes tubulation and fusion in a mitofusin-dependent manner. A GAP-dead ELMOD2 mutant retains the ability to promote fusion, indicating ELMOD2 acts as an effector (not purely via GAP activity) downstream of ARL2 and upstream of mitofusins. ELMOD2, ARL2, MFN1/2, Miro1/2, and mitoPLD co-localize at discrete puncta along mitochondria. siRNA knockdown; ELMOD2 overexpression; GAP-dead mutant expression; mitochondrial fusion assay; confocal microscopy co-localization Molecular biology of the cell Medium 30865555
2017 A trimeric complex of TBCD·ARL2·β-tubulin was purified from mammalian cells and tissues. ARL2 (not β-tubulin) is the GTP-exchanging subunit in the trimer. ARL2 binds GTP with higher affinity in the trimer than as a monomer. ARL2 point mutants that disrupt TBCD binding impair microtubule density in cells. The trimer represents a functional intermediate in the β-tubulin folding pathway regulated by ARL2 nucleotide cycling. Native PAGE and immunoblotting; purification of trimer from HEK293 cells; hydrogen/deuterium exchange-mass spectrometry; nucleotide-binding assays; ARL2 point mutants; cell-based microtubule density assay The Journal of biological chemistry; Journal of molecular biology High 28126905 28970104
2010 siRNA-mediated suppression of ARL2 in HeLa cells overcomes the inability of human TBCD (which normally does not disrupt microtubules upon overexpression) to destroy microtubule integrity in vivo, confirming that Arl2 negatively regulates TBCD's microtubule-destructive activity in cells. siRNA knockdown of Arl2; TBCD overexpression; immunofluorescence of microtubules Cytoskeleton Medium 20740604
2016 Drosophila Arl2 controls microtubule growth and asymmetric division of neural stem cells (neuroblasts) by localizing Msps (XMAP215 ortholog) to centrosomes via regulation of dynein function and centrosomal D-TACC/Msps localization. Arl2 physically associates with tubulin cofactors C, D, and E, and functions together with cofactor D (TBCD) to control microtubule growth. Arl2 loss-of-function causes microtubule abnormalities and asymmetric division defects; Arl2 overactivation causes microtubule overgrowth and NB depletion. RNAi knockdown; dominant-negative and activated mutant expression; co-immunoprecipitation with TBCC/D/E; immunofluorescence; genetic epistasis in Drosophila NBs The Journal of cell biology High 26953351
2016 Arl2 and Arl3 both release prenylated and myristoylated cargo from carrier proteins (PDEδ for prenylated cargo; Unc119a/b for myristoylated cargo), but differ in selectivity: Arl3·GTP exclusively releases high-affinity ciliary cargo from Unc119, while both Arl2·GppNHp and Arl3·GppNHp can release low-affinity cargo. Crystal structure of myristoylated NPHP3 peptide in complex with Unc119a revealed molecular determinants of high-affinity binding; swapping residues at +2/+3 positions reversed cargo affinities and caused partial mislocalization. X-ray crystallography; fluorescence polarization binding assays; mutagenesis; cell localization studies The Journal of biological chemistry High 27481943
2011 BART interacts with GTP-bound ARL2 at the leading edges of migrating pancreatic cancer cells. GTP-bound ARL2 inactivates RhoA, and BART prevents ARL2 from regulating RhoA activity by binding GTP-ARL2, thereby increasing active RhoA levels. BART functions as an inhibitor of ARL2 at leading edges, and BART knockdown reduces active RhoA, increases actin-cytoskeleton rearrangements, and promotes cell invasion. Co-immunoprecipitation; RhoA activation assay; siRNA knockdown of BART; Rho inhibitor (C3 exoenzyme) treatment; invasion assay; immunofluorescence International journal of oncology Medium 21833473
2007 In polarized epithelial MDCK cells, ARL2 and TBCD (beta-tubulin cofactor D) participate in apical junctional complex (AJC) disassembly and cell dissociation from the epithelial monolayer independently of microtubule depolymerization. TBCD partially localizes to the lateral plasma membrane via its 15 C-terminal amino acids and requires intact microtubules for this. ARL2 inhibits TBCD-dependent cell dissociation and AJC disassembly. Overexpression in MDCK cells; immunofluorescence; dominant-active/inactive ARL2 constructs; microtubule depolymerization assays FASEB journal Medium 17704193
2013 ELMOD3, a second ELMO domain-containing protein, exhibits GAP activity against Arl2 GTPase; this activity is completely abolished by the disease-causing p.Leu265Ser mutation in the ELMO domain. ELMOD3 co-localizes with the actin cytoskeleton in epithelial cells and is expressed in cochlear hair cell stereocilia. Recombinant GST-ELMOD3 in vitro GAP assay; site-directed mutagenesis; immunofluorescence; exome sequencing/co-segregation for human genetics PLoS genetics Medium 24039609
2008 The solution structure of BART was solved by NMR, revealing a novel fold of six alpha-helices forming three interlocking 'L' shapes. Mapping of ARL2-binding regions onto the surface showed they localize to dynamic loop regions between central helices. NMR structure determination; backbone dynamics analysis The Journal of biological chemistry Medium 18981177
2010 In Trypanosoma brucei, TbARL2 RNAi causes inhibition of cleavage furrow formation, cytokinesis defects, multinucleation, and loss of acetylated alpha-tubulin (but not total tubulin) from microtubules. Overexpression of myc-tagged (but not untagged) TbARL2 also causes cytokinesis defects, demonstrating importance of the C-terminus for correct function. RNAi in bloodstream T. brucei; overexpression; immunofluorescence; Western blot Molecular and biochemical parasitology Medium 20653091
2013 Fission yeast cofactor C ortholog Tbc1 acts as a GAP for Alp41/Arl2 (S. pombe Arl2). Continuous cycling between GDP- and GTP-bound Alp41 is required for microtubule function (both constitutive GDP and GTP forms cause microtubule loss). GDP-bound Alp41 interacts with Alp1D (cofactor D ortholog), and Alp1D co-overproduction with GDP-Alp41 prevents Alp1D-induced microtubule depolymerization. In vitro GAP assay; genetic analysis of GDP/GTP mutants in S. pombe; co-immunoprecipitation; fluorescence microscopy Molecular biology of the cell Medium 23576550
2017 Novel PDE6δ inhibitors with picomolar affinity (up to 7 hydrogen bonds to PDE6δ) are poorly released from PDE6δ by Arl2, unlike earlier lower-affinity inhibitors that are rapidly displaced. This demonstrates that Arl2 functions as a release factor for PDE6δ-bound cargo/inhibitors and that inhibitor affinity determines the efficiency of Arl2-mediated displacement. Biophysical binding assays (SPR/ITC); cellular KRas signaling assays; cell viability assays; structure-activity relationship chemistry Angewandte Chemie Medium 28106325
2015 Arl2 binds to membranes in a nucleotide-independent manner (unlike Arl3 and other Arfs that require GTP for membrane interaction). Arl2 and Arl3 both preferentially localize to liquid-disordered membrane domains. In contrast to Arl3, the N-terminal helix of Arl2 does not increase binding affinity to UNC119a, and UNC119a does not impede Arl2 membrane binding. Biophysical membrane-binding assays (fluorescence spectroscopy with phase-separated vesicles); nucleotide loading comparisons Biophysical journal Medium 26488653
2018 Molecular dynamics simulations revealed that Arl2·GTP binding to PDE6δ allosterically compresses the hydrophobic pocket via changes in β6 of PDEδ and additional residues, pushing the KRas4B farnesylated HVR out. Mutating PDEδ residues mediating these allosteric changes abolishes the release process. All-atom molecular dynamics simulation; mutational analysis of PDEδ allosteric residues The journal of physical chemistry B Low 29961325
2024 Mouse Arl2 physically associates with the centrosomal protein Cdk5rap2, validated by co-immunoprecipitation and proximity ligation assay (PLA). Arl2 knockdown in mouse neural progenitor cells reduces centrosomal microtubule growth and delocalizes centrosomal proteins Cdk5rap2 and γ-tubulin. Overexpression of Cdk5rap2 rescues the neurogenesis defects caused by Arl2 knockdown, placing Cdk5rap2 downstream of Arl2 in cortical development. Co-immunoprecipitation; proximity ligation assay; in utero electroporation knockdown; rescue by Cdk5rap2 overexpression; live imaging of centrosomal microtubule growth PLoS biology Medium 39137170
2022 Conditional deletion of ARL2 in the mouse retina early in development (retArl2−/−) disrupts the microtubule cytoskeleton as early as postnatal day 6, prevents rod and cone outer segment formation, and reduces cytoplasmic dynein levels in inner segments, suggesting dynein stability depends on a functional microtubule cytoskeleton organized by ARL2. Rod-specific late deletion was stable, indicating ARL2 is specifically required during early photoreceptor development for microtubule neogenesis. Conditional knockout mouse; immunofluorescence; Western blot; ERG functional assay Cells Medium 36611941
2019 A de novo variant in ARL2 (p.R15L) causes MRCS syndrome. Co-immunoprecipitation showed the mutant ARL2 protein has 62% lower binding affinity for HRG4 but only 18% lower binding affinity for ARL2BP. ARL2 and HRG4 co-localize with cytochrome c in HeLa cells, indicating mitochondrial co-localization. Mutant ARL2 causes abnormalities in mitochondrial respiratory chain function and ATP production. Transgenic mice expressing the mutant develop retinal degeneration, microcornea, and cataract. Co-immunoprecipitation; immunofluorescence; mitochondrial function assays; ATP production assay; site-directed mutagenesis; transgenic mouse model Clinical genetics Medium 30945270
2022 ARL2 is required for homologous recombination repair (HRR) in colon cancer stem cells (CSCs). ARL2 depletion leads to DNA double-strand break accumulation and apoptosis specifically in CSCs. ARL2 is detected within chromatin compartments and its expression correlates with RAD51 family gene expression. siRNA depletion; DNA damage assays; subcellular fractionation (chromatin compartment); flow cytometry (apoptosis, cell cycle) FEBS open bio Low 35567502

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The complex of Arl2-GTP and PDE delta: from structure to function. The EMBO journal 192 11980706
2000 ADP ribosylation factor-like protein 2 (Arl2) regulates the interaction of tubulin-folding cofactor D with native tubulin. The Journal of cell biology 184 10831612
2006 Arl2 and Arl3 regulate different microtubule-dependent processes. Molecular biology of the cell 135 16525022
2007 ARL2, ARG1 and PIN3 define a gravity signal transduction pathway in root statocytes. The Plant journal : for cell and molecular biology 132 18047472
2009 MicroRNA-15b modulates cellular ATP levels and degenerates mitochondria via Arl2 in neonatal rat cardiac myocytes. The Journal of biological chemistry 129 20007690
2017 LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer via the MiR-195/ARL2 Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 99 29130995
2002 ARL2 and BART enter mitochondria and bind the adenine nucleotide transporter. Molecular biology of the cell 76 11809823
2017 A PDE6δ-KRas Inhibitor Chemotype with up to Seven H-Bonds and Picomolar Affinity that Prevents Efficient Inhibitor Release by Arl2. Angewandte Chemie (International ed. in English) 75 28106325
2007 ELMOD2 is an Arl2 GTPase-activating protein that also acts on Arfs. The Journal of biological chemistry 74 17452337
2013 The interplay between RPGR, PDEδ and Arl2/3 regulate the ciliary targeting of farnesylated cargo. EMBO reports 64 23559067
2002 The C. elegans evl-20 gene is a homolog of the small GTPase ARL2 and regulates cytoskeleton dynamics during cytokinesis and morphogenesis. Developmental cell 56 12015966
1999 The ARF-like 2 (ARL2)-binding protein, BART. Purification, cloning, and initial characterization. The Journal of biological chemistry 54 10488091
2003 Cytosolic Arl2 is complexed with cofactor D and protein phosphatase 2A. The Journal of biological chemistry 50 12912990
2017 miR-214 down-regulates ARL2 and suppresses growth and invasion of cervical cancer cells. Biochemical and biophysical research communications 49 28137590
2021 LncRNA XIST shuttled by adipose tissue-derived mesenchymal stem cell-derived extracellular vesicles suppresses myocardial pyroptosis in atrial fibrillation by disrupting miR-214-3p-mediated Arl2 inhibition. Laboratory investigation; a journal of technical methods and pathology 45 34389797
2003 Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain. FEBS letters 44 12527357
2016 Novel Biochemical and Structural Insights into the Interaction of Myristoylated Cargo with Unc119 Protein and Their Release by Arl2/3. The Journal of biological chemistry 41 27481943
2010 Effect of TBCD and its regulatory interactor Arl2 on tubulin and microtubule integrity. Cytoskeleton (Hoboken, N.J.) 41 20740604
2017 A Trimer Consisting of the Tubulin-specific Chaperone D (TBCD), Regulatory GTPase ARL2, and β-Tubulin Is Required for Maintaining the Microtubule Network. The Journal of biological chemistry 40 28126905
2016 Sorting of lipidated cargo by the Arl2/Arl3 system. Small GTPases 40 27806215
2014 The ARL2 GTPase is required for mitochondrial morphology, motility, and maintenance of ATP levels. PloS one 40 24911211
2013 An alteration in ELMOD3, an Arl2 GTPase-activating protein, is associated with hearing impairment in humans. PLoS genetics 39 24039609
2020 miR-15a-5p and miR-21-5p contribute to chemoresistance in cytogenetically normal acute myeloid leukaemia by targeting PDCD4, ARL2 and BTG2. Journal of cellular and molecular medicine 37 33270982
2010 The small GTPase ARL2 is required for cytokinesis in Trypanosoma brucei. Molecular and biochemical parasitology 33 20653091
2006 ADP ribosylation factor like 2 (Arl2) protein influences microtubule dynamics in breast cancer cells. Experimental cell research 32 17188265
2019 Long non-coding RNA ANRIL enhances mitochondrial function of hepatocellular carcinoma by regulating the MiR-199a-5p/ARL2 axis. Environmental toxicology 27 31670868
2018 ARL2 overexpression inhibits glioma proliferation and tumorigenicity via down-regulating AXL. BMC cancer 26 29843637
2008 Expression of Arl2 is associated with p53 localization and chemosensitivity in a breast cancer cell line. Cell cycle (Georgetown, Tex.) 26 18818514
2019 MiR-195-5p inhibits the cell migration and invasion of cervical carcinoma through suppressing ARL2. European review for medical and pharmacological sciences 25 31858533
2020 Circ_0084927 Facilitates Cervical Cancer Development via Sponging miR-142-3p and Upregulating ARL2. Cancer management and research 24 33061617
2009 ADP ribosylation factor like 2 (Arl2) regulates breast tumor aggressivity in immunodeficient mice. PloS one 22 19829707
2020 Long non-coding RNA SNHG3, induced by IL-6/STAT3 transactivation, promotes stem cell-like properties of gastric cancer cells by regulating the miR-3619-5p/ARL2 axis. Cellular oncology (Dordrecht, Netherlands) 21 32930970
2017 The ARL2 GTPase regulates mitochondrial fusion from the intermembrane space. Cellular logistics 21 28944094
2007 Beta-tubulin cofactor D and ARL2 take part in apical junctional complex disassembly and abrogate epithelial structure. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 17704193
2016 Arl2- and Msps-dependent microtubule growth governs asymmetric division. The Journal of cell biology 20 26953351
2019 ELMOD2 regulates mitochondrial fusion in a mitofusin-dependent manner, downstream of ARL2. Molecular biology of the cell 19 30865555
2019 Role of Arf-like proteins (Arl1 and Arl2) of Mucor circinelloides in virulence and antifungal susceptibility. Fungal genetics and biology : FG & B 19 31014992
2008 ARG1 and ARL2 form an actin-based gravity-signaling chaperone complex in root statocytes? Plant signaling & behavior 19 19704815
2016 Higher order signaling: ARL2 as regulator of both mitochondrial fusion and microtubule dynamics allows integration of 2 essential cell functions. Small GTPases 18 27400436
2021 LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression. Open life sciences 17 33817293
2017 Nucleotide Binding to ARL2 in the TBCD∙ARL2∙β-Tubulin Complex Drives Conformational Changes in β-Tubulin. Journal of molecular biology 17 28970104
2020 GAS6-AS2 Promotes Hepatocellular Carcinoma via miR-3619-5p/ARL2 Axis Under Insufficient Radiofrequency Ablation Condition. Cancer biotherapy & radiopharmaceuticals 16 32799553
2019 Whole-exome sequencing identified ARL2 as a novel candidate gene for MRCS (microcornea, rod-cone dystrophy, cataract, and posterior staphyloma) syndrome. Clinical genetics 16 30945270
2015 Effect of the N-Terminal Helix and Nucleotide Loading on the Membrane and Effector Binding of Arl2/3. Biophysical journal 16 26488653
2018 ADP-Ribosylation Factor-Like 2 (ARL2) regulates cilia stability and development of outer segments in rod photoreceptor neurons. Scientific reports 13 30446707
2011 BART inhibits pancreatic cancer cell invasion by inhibiting ARL2-mediated RhoA inactivation. International journal of oncology 13 21833473
2005 Assays used in the analysis of Arl2 and its binding partners. Methods in enzymology 13 16413291
2001 Coexpression, copurification, crystallization and preliminary X-ray analysis of a complex of ARL2-GTP and PDE delta. Acta crystallographica. Section D, Biological crystallography 13 11468408
2016 The Function of Arf-like Proteins ARL2 and ARL3 in Photoreceptors. Advances in experimental medicine and biology 12 26427472
2013 The dual role of fission yeast Tbc1/cofactor C orchestrates microtubule homeostasis in tubulin folding and acts as a GAP for GTPase Alp41/Arl2. Molecular biology of the cell 11 23576550
2021 Circ_0000527 promotes osteosarcoma cell progression through modulating miR-646/ARL2 axis. Aging 10 33617480
2018 Arl2-Mediated Allosteric Release of Farnesylated KRas4B from Shuttling Factor PDEδ. The journal of physical chemistry. B 10 29961325
2008 The structure of binder of Arl2 (BART) reveals a novel G protein binding domain: implications for function. The Journal of biological chemistry 10 18981177
2020 Arf-like proteins (Arl1 and Arl2) are involved in mitochondrial homeostasis in Mucor circinelloides. Fungal biology 9 32540185
2022 Circ_0085616 contributes to the radio-resistance and progression of cervical cancer by targeting miR-541-3p/ARL2 signaling. Histology and histopathology 6 36300495
2022 Herpes Simplex Type 1 UL43 Multiple Membrane-Spanning Protein Increases Energy Metabolism in Host Cells through Interacting with ARL2. Cells 5 36429022
2024 Arl2 GTPase associates with the centrosomal protein Cdk5rap2 to regulate cortical development via microtubule organization. PLoS biology 2 39137170
2022 ARL2 is required for homologous recombination repair and colon cancer stem cell survival. FEBS open bio 2 35567502
2022 Arf-like Protein 2 (ARL2) Controls Microtubule Neogenesis during Early Postnatal Photoreceptor Development. Cells 2 36611941
2021 Regulation of ARL2 in colorectal cancer cell proliferation and tumorigenicity, and its negative association with AXL. Oncology letters 2 33574935
2008 1H, 13C and 15N resonance assignments for Binder of Arl2, BART. Biomolecular NMR assignments 2 19636941
2023 Long Non-Coding RNA ZSCAN16-AS1 Promotes the Malignant Progression of Melanoma Through Regulating the miR-503-5p/ARL2 Axis. Clinical, cosmetic and investigational dermatology 1 37483470
2023 Retraction Note: MiR-195-5p inhibits the cell migration and invasion of cervical carcinoma through suppressing ARL2. European review for medical and pharmacological sciences 1 37916316

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