Affinage

RRAD

GTP-binding protein RAD · UniProt P55042

Length
308 aa
Mass
33.2 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RRAD encodes Rad, a small RGK-family GTPase that serves as a tonic inhibitor of L-type (CaV1.2) calcium channels by binding the auxiliary CaVβ subunit; PKA-dependent phosphorylation of four Rad serine residues during β-adrenergic stimulation disrupts this interaction and augments cardiac Ca²⁺ influx and contractility, constituting the primary molecular mechanism of the cardiac fight-or-flight response (PMID:36424916, PMID:31147441, PMID:19926875). Beyond cardiac electrophysiology, RRAD functions as a p53 transcriptional target that suppresses cancer cell migration through cofilin dephosphorylation and represses aerobic glycolysis (the Warburg effect) by directly binding the NF-κB p65 subunit to block its nuclear translocation and thereby inhibit GLUT1 plasma membrane targeting (PMID:21221513, PMID:25893381, PMID:25114038). Rad is post-translationally regulated by multiple kinases (PKA, CaMKII, PKC, CKII) at C-terminal serines that control calmodulin binding and GTPase cycling, and nm23 serves as both its GTPase-activating protein and a reciprocal enzymatic partner (PMID:9677319, PMID:10611312). A rare RRAD variant (p.R211H) causes electrophysiological and cytoskeletal defects in cardiomyocytes and has been identified in familial Brugada syndrome (PMID:31114854).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1993 High

    Discovery of RRAD as a novel Ras-superfamily GTPase overexpressed in diabetic skeletal muscle established a potential link between small GTPases and metabolic disease, while biochemical characterization revealed GTP binding, low intrinsic GTPase activity, and PKA phosphorylation at C-terminal serines.

    Evidence Bacterial fusion protein expression, GTP binding assays, in vitro GTPase and kinase assays with phosphopeptide mapping

    PMID:7876254

    Open questions at the time
    • Endogenous GAP identity unknown
    • In vivo metabolic function not yet tested
    • Downstream effectors unidentified
  2. 1996 High

    Functional studies showed that Rad overexpression suppresses insulin-stimulated glucose uptake in muscle and adipocyte cells without affecting GLUT4 translocation or insulin receptor signaling, demonstrating that Rad acts downstream of canonical insulin signaling to modulate transporter activity.

    Evidence Adenoviral overexpression in C2C12, L6, and 3T3-L1 cells with 2-deoxyglucose and 3-O-methylglucose uptake assays

    PMID:8798502

    Open questions at the time
    • Mechanism of glucose transporter inhibition unknown
    • No loss-of-function data
    • In vivo relevance not shown
  3. 1998 High

    Comprehensive mapping of Rad phosphorylation sites revealed regulation by four kinases (PKA, CaMKII, PKC, CKII) and showed that phosphorylation by PKC/CKII disrupts calmodulin binding while PKA reduces GTP binding, establishing Rad as a signal integration node.

    Evidence In vitro kinase assays with purified kinases, point mutagenesis of C-terminal serines, calmodulin binding assays, co-precipitation from C2C12 cells

    PMID:9677319

    Open questions at the time
    • Physiological consequences of each phosphorylation event in vivo unknown
    • Relative kinase contributions in intact cells not determined
  4. 1999 High

    Purification of endogenous Rad-GAP activity from skeletal muscle identified nm23 as the cognate GTPase-activating protein and revealed a reciprocal relationship whereby Rad enhances nm23 NDP kinase activity, establishing a bidirectional regulatory circuit.

    Evidence Biochemical purification, antibody depletion, reconstitution with recombinant nm23, GTPase and NDP kinase assays

    PMID:10611312

    Open questions at the time
    • In vivo significance of Rad-nm23 interaction in specific tissues not determined
    • Whether nm23 is the sole physiological GAP for Rad unclear
  5. 2003 High

    The discovery that Rad (and Rem) directly bind CaVβ subunits and abolish L-type Ca²⁺ channel currents upon co-expression redefined RGK GTPases as voltage-gated calcium channel regulators, shifting the field beyond metabolic functions.

    Evidence Co-immunoprecipitation in HEK293 cells, whole-cell patch-clamp of CaV1.2 and CaV3 channels, deletion mutagenesis

    PMID:14623965

    Open questions at the time
    • Endogenous cardiac role not yet demonstrated
    • Mechanism of channel inhibition (trafficking vs. gating) unresolved
    • Physiological regulation of Rad-CaVβ interaction unknown
  6. 2005 High

    Demonstration that Rad inhibits vascular smooth muscle cell migration and neointimal formation through Rho/ROK pathway blockade extended Rad's functional repertoire to cytoskeletal regulation and vascular remodeling.

    Evidence Adenoviral delivery in rat carotid balloon injury model, migration assays, immunofluorescence for focal contacts/stress fibers, GTPase mutant controls

    PMID:15710763

    Open questions at the time
    • Direct biochemical link between Rad and Rho/ROK not established
    • Mechanism of Rad-cytoskeleton interaction not defined
  7. 2006 High

    Transgenic mice overexpressing Rad in muscle confirmed an in vivo role for Rad in worsening high-fat-diet-induced insulin resistance, validating the metabolic function suggested by cell-based studies.

    Evidence MCK-promoter-driven Rad transgenic mice, glucose tolerance tests, hyperinsulinemic-euglycemic clamp, muscle 2-deoxyglucose uptake

    PMID:16537411

    Open questions at the time
    • Loss-of-function (knockout) metabolic phenotype not reported
    • Molecular mechanism of glucose uptake inhibition still undefined
  8. 2009 High

    Bidirectional manipulation of Rad in cardiomyocytes (overexpression suppresses, knockdown enhances ICa,L and contractility) proved that endogenous Rad tonically inhibits cardiac L-type Ca²⁺ channels and mediates β-adrenergic modulation of excitation-contraction coupling.

    Evidence Adenoviral overexpression, RNAi knockdown, and dominant-negative mutant in primary rat cardiomyocytes with patch-clamp, Ca²⁺ imaging, and contractility measurements

    PMID:19926875

    Open questions at the time
    • In vivo cardiac-specific loss-of-function not yet achieved
    • Phosphorylation-dependent release mechanism not demonstrated
  9. 2011 High

    Identification of RRAD as a direct p53 transcriptional target that suppresses cancer cell migration by modulating cofilin phosphorylation linked tumor suppressor signaling to RRAD-mediated cytoskeletal remodeling.

    Evidence ChIP assay confirming p53 binding at Rad promoter, promoter-reporter assays, siRNA knockdown, migration/invasion assays in cancer cells

    PMID:21221513

    Open questions at the time
    • Precise mechanism linking Rad to cofilin Ser3 dephosphorylation not identified
    • In vivo tumor metastasis relevance not shown
  10. 2014 High

    Two convergent studies established RRAD as a suppressor of the Warburg effect: one showing p53-dependent RRAD induction blocks GLUT1 plasma membrane translocation under hypoxia, the other demonstrating Ras-driven epigenetic silencing of RRAD promotes glycolysis in ovarian cancer, collectively positioning RRAD as a metabolic tumor suppressor.

    Evidence RRAD overexpression/knockdown with glycolysis assays and GLUT1 localization (lung cancer cells); bisulfite sequencing, demethylation rescue, xenograft tumor assays (ovarian cancer cells)

    PMID:24648519 PMID:25114038

    Open questions at the time
    • Whether RRAD loss is sufficient for metabolic transformation in vivo unknown
    • GLUT1 trafficking mechanism downstream of RRAD unresolved
  11. 2015 High

    Mechanistic dissection revealed that RRAD represses the Warburg effect by directly binding NF-κB p65 and blocking its nuclear translocation, thereby inhibiting NF-κB-dependent GLUT1 membrane targeting — providing a defined signaling pathway for RRAD's metabolic tumor suppressor activity.

    Evidence Co-immunoprecipitation of RRAD-p65, nuclear fractionation, NF-κB luciferase reporter, glycolysis assays with NF-κB inhibitor epistasis

    PMID:25893381

    Open questions at the time
    • Structural basis of RRAD-p65 interaction unknown
    • Whether GTPase activity is required for p65 binding not tested
  12. 2019 High

    Cardiac-specific inducible Rad knockout mice showed constitutively elevated ICa,L and enhanced contractility without hypertrophy, providing definitive in vivo genetic evidence that endogenous Rad is the primary tonic brake on cardiac L-type Ca²⁺ channels.

    Evidence Inducible cardiac-specific knockout, patch-clamp, Ca²⁺ transients, echocardiography, radiotelemetry

    PMID:31147441

    Open questions at the time
    • Long-term consequences of sustained Rad loss (e.g., arrhythmogenesis, heart failure) under stress not fully explored
    • Whether other RGK GTPases compensate not addressed
  13. 2019 High

    A familial Brugada syndrome RRAD variant (p.R211H), confirmed by CRISPR knock-in in iPSC-cardiomyocytes, caused multi-ion-channel dysfunction and cytoskeletal disruption, establishing RRAD as a Brugada syndrome-associated gene and revealing broader roles beyond CaV1.2 regulation.

    Evidence Whole-exome sequencing of pedigree, patient and isogenic CRISPR-edited iPSC-derived cardiomyocytes, patch-clamp for Na⁺ and Ca²⁺ currents, immunofluorescence for actin/focal adhesions

    PMID:31114854

    Open questions at the time
    • Mechanism by which Rad R211H affects Na⁺ channels not explained
    • Whether this variant acts through loss or gain of function not fully resolved
    • Limited to single family
  14. 2020 High

    The PKA phosphorylation–release mechanism was definitively demonstrated: phosphosite-ablating 4SA-Rad knock-in mice lost both basal contractility and β-adrenergic responsiveness, and rescue with CaVβ mutants unable to bind 4SA-Rad restored function, proving that PKA phosphorylation of Rad disrupts the Rad–CaVβ interaction to relieve CaV1.2 inhibition.

    Evidence Phosphosite-mutant knock-in mice, echocardiography, electrophysiology, Ca²⁺ transients, radiotelemetry, exercise testing, genetic rescue with CaVβ-binding-deficient transgenic cross

    PMID:36424916

    Open questions at the time
    • Relative contribution of individual phosphosites not dissected
    • Whether CaMKII phosphorylation independently triggers Rad release in vivo not tested
  15. 2020 High

    Structure-function analysis showed that the rigid α-helix in the α1C I-II linker (IS6-AID helix) is mechanistically required for Rad-mediated gating modulation, localizing the downstream effector mechanism within the channel pore-forming subunit.

    Evidence Transgenic mice with polyglycine substitutions in α1C I-II linker, patch-clamp in cardiomyocytes and HEK293 cells

    PMID:33086983

    Open questions at the time
    • Structural model of Rad–CaVβ–α1C ternary complex not available
    • Whether Rad modulates channel gating versus surface expression in native cardiomyocytes still debated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of the Rad–CaVβ interaction and its disruption by phosphorylation; whether Rad's metabolic and cytoskeletal functions operate through the same GTPase cycle as its channel-regulatory role; and the pathophysiological consequences of long-term cardiac Rad loss under hemodynamic stress.
  • No high-resolution structure of Rad–CaVβ complex
  • Integration of channel-regulatory and metabolic tumor-suppressor functions not addressed
  • Long-term cardiac outcomes of Rad deletion under pathological stress unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0003924 GTPase activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 2 R-HSA-397014 Muscle contraction 2
Partners
ACTG1CACNB2CALM1CAMK2AEGFRNME1RELA

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 RRAD (Rad, Ras associated with diabetes) was identified as a novel member of the Ras/GTPase superfamily that is overexpressed in skeletal muscle of humans with type II diabetes; it binds GTP specifically and saturably, has low intrinsic GTPase activity stimulated by a tissue-derived GAP activity distinct from known GAPs, and is phosphorylated in vitro by the catalytic subunit of PKA at C-terminal serine residues. Bacterial GST-fusion protein expression, GTP binding assays, in vitro GTPase assays, kinase assays, phosphopeptide mapping The Journal of biological chemistry High 7876254
1996 Overexpression of Rad in C2C12 myotubes, L6 myotubes, and 3T3-L1 adipocytes reduces insulin-stimulated glucose uptake by 50–90% without altering GLUT4 expression levels or GLUT4 translocation, insulin receptor phosphorylation, or PI3-kinase activity, suggesting Rad decreases the intrinsic activity of glucose transporter molecules. Adenoviral/plasmid overexpression in cell lines, 2-deoxyglucose uptake assays, 3-O-methylglucose uptake assays, Western blot, PI3-kinase activity assay The Journal of biological chemistry High 8798502
1998 Rad is phosphorylated by CaMKII and PKA at Ser273, while PKC and CKII phosphorylate multiple C-terminal serines (Ser214, Ser257, Ser273, Ser290, Ser299); phosphorylation by PKC and CKII abolishes Rad's interaction with calmodulin, whereas PKA incubation decreases GTP binding independently of phosphorylation. Rad complexes with CaMKII in C2C12 cells. In vitro kinase assays with purified kinases, deletion and point mutagenesis, calmodulin binding assays, co-precipitation from cell lysates The Biochemical journal High 9677319
1998 Rad associates with cellular membranes and the cytoskeleton in a lipid-independent manner; unlike Ras, Rad is not palmitoylated and lovastatin (isoprenylation inhibitor) does not alter its membrane distribution. The C-terminal 11 residues conserved in the Rad/Gem/Kir family are not required for membrane association. Subcellular fractionation, TX-114 phase partitioning, [3H]palmitic acid biosynthetic labeling, lovastatin treatment, C-terminal truncation and chimeric mutant analysis Experimental cell research High 9683526
1999 Purification of Rad-GAP activity from human skeletal muscle cytosol identified nm23 as the GTPase-activating protein for Rad; nm23 antibodies depleted Rad-GAP activity, bacterially expressed nm23 reconstituted it, and the activity was specific for Rad and absent with dominant-negative Rad(S105N). Additionally, nm23 NDP kinase activity reconverts GDP·Rad to GTP·Rad, while Rad reciprocally enhances nm23 NDP kinase activity and decreases nm23 autophosphorylation. Biochemical purification from muscle cytosol, antibody depletion, reconstitution with recombinant nm23, GTPase assays, NDP kinase assays, cell transfection with DNA synthesis readout Proceedings of the National Academy of Sciences of the United States of America High 10611312
2003 Rem and Rad both bind directly to Ca2+ channel beta-subunits (CaVβ) in vivo; co-expression of Rad or Rem with CaV1.2 and CaVβ2a in HEK293 cells completely abolishes L-type Ca2+ channel currents, while T-type (CaV3) channels not requiring beta-subunits are unaffected. The Rem C-terminus is critical for both CaVβ association and functional channel regulation. Co-immunoprecipitation in HEK293 cells, whole-cell patch-clamp electrophysiology, deletion mutagenesis, overexpression in C2C12 myoblasts Proceedings of the National Academy of Sciences of the United States of America High 14623965
2005 Rad GTPase inhibits vascular smooth muscle cell (VSMC) migration and neointimal formation; adenoviral Rad delivery reduces neointima after balloon injury, while a GDP-binding-only Rad mutant increases it. Rad overexpression reduces focal contact and stress fiber formation in VSMCs by blocking the Rho/ROK signaling pathway. Adenoviral gene delivery in rat carotid balloon injury model, morphometric analysis, in vitro migration assays (attachment and Boyden chamber), immunofluorescence for focal contacts/stress fibers, Rho/ROK pathway analysis Circulation High 15710763
2006 Transgenic mice overexpressing Rad in muscle (6–12-fold) develop more severe glucose intolerance and insulin resistance on a high-fat diet, with a rightward shift in the insulin dose-response curve for muscle 2-deoxyglucose uptake, establishing an in vivo role for Rad in muscle insulin resistance. An unexpected reduction in plasma triglycerides associated with increased lipoprotein lipase levels was also observed. Transgenic mouse model (MCK promoter-driven Rad), glucose tolerance tests, hyperinsulinemic-euglycemic clamp, 2-deoxyglucose uptake in muscle, lipoprotein lipase measurement Proceedings of the National Academy of Sciences of the United States of America High 16537411
2009 Adenoviral overexpression of Rad (~3-fold) in rat cardiomyocytes suppresses L-type Ca2+ channel current (ICa), Ca2+ transients, and contractility; conversely, ~70% Rad knockdown by RNAi increases ICa, Ca2+ transients, and contractility. The dominant negative Rad(S105N) mimics knockdown effects. Rad overexpression negates β-adrenergic receptor effects on ICa and Ca2+ transients, establishing Rad as an endogenous regulator of cardiac excitation-contraction coupling and β-AR signaling. Adenoviral overexpression and RNAi knockdown in primary rat cardiomyocytes, patch-clamp electrophysiology, Ca2+ imaging, contractility measurements, dominant-negative mutant analysis Circulation research High 19926875
2011 Rad is a direct transcriptional target of p53; p53 binds to a -2934/-2905 bp region of the Rad promoter and induces Rad mRNA and protein expression in response to DNA damage in a p53-dependent manner. Rad expression diminishes inhibitory phosphorylation of cofilin at Ser3 and suppresses cancer cell migration and invasion; Rad knockdown promotes migration and abrogates p53-mediated migration suppression. ChIP assay, promoter-reporter assay, Western blot, siRNA knockdown, migration/invasion assays in cancer cell lines Journal of molecular medicine High 21221513
2014 p53 induces RRAD expression under hypoxia, and RRAD in turn represses glycolysis by inhibiting GLUT1 translocation to the plasma membrane in lung cancer cells. Knockdown of RRAD abolishes p53's ability to repress hypoxia-stimulated glycolysis. Ectopic expression and siRNA knockdown in lung cancer cell lines, glycolysis assays (glucose uptake, lactate production), GLUT1 subcellular localization by immunofluorescence/fractionation, p53 induction under hypoxia Oncotarget High 25114038
2015 RRAD inhibits the Warburg effect by directly binding to the p65 subunit of NF-κB and inhibiting p65 nuclear translocation, thereby negatively regulating NF-κB signaling and GLUT1 plasma membrane translocation in lung cancer cells. Blocking NF-κB signaling abolishes RRAD's inhibitory effects on GLUT1 translocation and glycolysis. Co-immunoprecipitation (RRAD-p65 interaction), nuclear fractionation, luciferase NF-κB reporter assay, glycolysis assays, siRNA knockdown and overexpression Oncotarget High 25893381
2014 Ras(V12)-mediated oncogenic transformation induces RRAD promoter hypermethylation and silencing in ovarian cancer cells; restoring RRAD expression inhibits glucose uptake and lactate production by repressing the expression of glucose transporters, and suppresses tumor formation in nude mice. Reduced representation bisulfite sequencing, digital gene expression, 5-aza-2'-deoxycytidine demethylation, farnesyltransferase inhibitor treatment, RRAD knockdown and overexpression, glucose uptake assays, xenograft tumor assays The Journal of biological chemistry High 24648519
2014 RRAD physically associates with EGFR and EEA1 in glioblastoma cells, enhancing EGFR stability and endosome-associated nuclear translocation, thereby promoting STAT3 activation and expression of stem cell factors (OCT4, NANOG, SOX2), self-renewal, and temozolomide resistance. RRAD depletion sensitizes GBM cells to temozolomide. Co-immunoprecipitation (RRAD-EGFR-EEA1), siRNA knockdown and overexpression, STAT3 reporter assays, tumor sphere formation, in vivo tumorigenesis, drug sensitivity assays Molecular cancer therapeutics Medium 25313011
2001 Rad expression is frequently lost in invasive breast carcinoma, but where retained is associated with higher tumor grade. Stable transfection of Rad into Rad-negative breast cancer cells increases growth and colony formation in soft agar and tumor growth in nude mice; these effects map to the NH2- and COOH-terminal regions rather than the GTPase domain. Co-expression of nm23 with Rad inhibits these growth-promoting effects both in vitro and in vivo. Western blot and immunohistochemistry on breast tissue, stable transfection, soft agar colony formation, nude mouse xenograft, domain deletion mutagenesis, nm23 co-transfection Cancer research Medium 11280768
2019 Myocardial-restricted inducible knockout of RAD (RADΔ/Δ mice) results in sustained increase in L-type Ca2+ channel current (ICa,L) that confers a β-AR-modulated basal phenotype, enhanced cytosolic Ca2+ handling, increased contractile function, elevated SERCA2a expression, and faster lusitropy, without structural remodeling or hypertrophy, demonstrating a cardiac-intrinsic role for RAD in regulating ICa,L and Ca2+ dynamics. Inducible cardiac-specific knockout mouse model, patch-clamp electrophysiology, Ca2+ transient recordings, echocardiography, radiotelemetry, Western blot for SERCA2a The Journal of biological chemistry High 31147441
2019 A rare RRAD variant (p.R211H) identified in a familial Brugada syndrome pedigree causes reduced action potential upstroke velocity, prolonged action potentials, early afterdepolarizations, decreased Na+ peak current and increased persistent Na+ current, decreased L-type Ca2+ current, and abnormal actin distribution with fewer focal adhesions in iPSC-derived cardiomyocytes. Genome-editing to introduce p.R211H into control iPSCs confirmed these electrophysiological and cytoskeletal defects. Whole-exome sequencing, iPSC-derived cardiomyocytes from patients, CRISPR genome editing of control iPSCs, patch-clamp electrophysiology, immunofluorescence for actin and focal adhesions European heart journal High 31114854
2020 PKA-mediated phosphorylation of Rad at four residues controls basal CaV1.2 channel activity and is essential for β-adrenergic augmentation of cardiac Ca2+ influx. Transgenic mice bearing phosphosite-ablating mutations in Rad (4SA-Rad) show dramatically reduced basal contractility, near-complete loss of β-adrenergic contractile response, reduced heart rate with pauses, and diminished exercise capacity. Expression of mutant CaVβ subunits that cannot bind 4SA-Rad rescues basal Ca2+ influx and contractility, demonstrating that PKA phosphorylation of Rad releases Rad-mediated inhibition of CaV1.2 through disrupting Rad-CaVβ interaction. Transgenic phospho-site mutant knock-in mice (4SA-Rad), echocardiography, patch-clamp electrophysiology, Ca2+ transients, radiotelemetry, exercise testing, rescue with mutant CaVβ transgenic mice Nature cardiovascular research High 36424916
2020 β-adrenergic activation of CaV1.2 through Rad phosphorylation converges at the α1C I-II loop; introduction of flexibility-disrupting polyglycine substitutions in the IS6-α-interaction domain helix of α1C markedly reduces basal channel open probability and eliminates β-adrenergic stimulation of CaV1.2, even with intact CaVβ binding and Rad, demonstrating that the rigid I-II linker is mechanistically required for Rad-mediated gating regulation. Transgenic mice with engineered α1C variants (GGG substitutions, exon 9* splice variant), patch-clamp electrophysiology in cardiomyocytes and HEK293 cells, Ca2+ current recordings Circulation research High 33086983
2019 RRAD binds to actin gamma 1 (ACTG1) and suppresses aerobic glycolysis in hepatocellular carcinoma by downregulating ACTG1. ACTG1 in turn regulates the cell cycle (cyclins/CDKs) and the mitochondrial apoptosis pathway. Co-immunoprecipitation (RRAD-ACTG1), overexpression and knockdown in HCC cell lines, glycolysis assays, cell cycle analysis, apoptosis assays, in vivo xenograft OncoTargets and therapy Medium 30881024
2018 RRAD expression is upregulated in senescent cells across multiple induction modes and in aging tissues. Functional studies show RRAD upregulation acts as a negative feedback mechanism to counter cellular senescence by reducing reactive oxygen species levels. Both p53 and NF-κB bind to RRAD genomic regions and co-activate RRAD transcription. Transcriptome meta-analysis, qRT-PCR validation, ChIP-seq (p53 and RelA/p65 binding at RRAD locus), ROS measurement in senescent fibroblasts with RRAD knockdown/overexpression Free radical biology & medicine Medium 30391675
1996 Insulin infusion during a euglycemic hyperinsulinemic clamp acutely increases Rad (RRAD) mRNA levels by ~96% in human skeletal muscle, indicating that RRAD gene expression is acutely regulated by insulin in vivo. Euglycemic hyperinsulinemic clamp in human subjects, muscle biopsies, reverse transcription-competitive PCR The Journal of clinical investigation Medium 8690802

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Deriving genotypes from RAD-seq short-read data using Stacks. Nature protocols 268 29189774
2015 RAD Capture (Rapture): Flexible and Efficient Sequence-Based Genotyping. Genetics 251 26715661
1980 The Role of Radiation (rad) Genes in Meiotic Recombination in Yeast. Genetics 233 17248996
2012 Special features of RAD Sequencing data: implications for genotyping. Molecular ecology 230 23110438
2011 Next-generation RAD sequencing identifies thousands of SNPs for assessing hybridization between rainbow and westslope cutthroat trout. Molecular ecology resources 221 21429168
1995 Reconstitution of yeast nucleotide excision repair with purified Rad proteins, replication protein A, and transcription factor TFIIH. The Journal of biological chemistry 209 7768886
2012 Inferring phylogenies from RAD sequence data. PloS one 202 22493668
2003 Genetic and cytological characterization of the recombination protein RAD-51 in Caenorhabditis elegans. Chromosoma 194 12684824
2003 Regulation of voltage-gated calcium channel activity by the Rem and Rad GTPases. Proceedings of the National Academy of Sciences of the United States of America 187 14623965
2015 Restriction Site-Associated DNA Sequencing (RAD-seq) Reveals an Extraordinary Number of Transitions among Gecko Sex-Determining Systems. Molecular biology and evolution 186 25657328
2011 Construction and application for QTL analysis of a Restriction Site Associated DNA (RAD) linkage map in barley. BMC genomics 183 21205322
2001 Purification and characterization of human DNA damage checkpoint Rad complexes. Proceedings of the National Academy of Sciences of the United States of America 164 11572977
1995 DNA structure-dependent requirements for yeast RAD genes in gene conversion. Nature 158 7800045
2014 Demystifying the RAD fad. Molecular ecology 140 25319241
2001 C. elegans RAD-5/CLK-2 defines a new DNA damage checkpoint protein. Current biology : CB 133 11747819
2014 Amplification biases and consistent recovery of loci in a double-digest RAD-seq protocol. PloS one 121 25188270
1996 Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle. The Journal of clinical investigation 120 8690802
2011 Identification of SNP and SSR markers in eggplant using RAD tag sequencing. BMC genomics 114 21663628
2002 Roles for Caenorhabditis elegans rad-51 in meiosis and in resistance to ionizing radiation during development. Genetics 109 11861554
1999 Interaction of the Ras-related protein associated with diabetes rad and the putative tumor metastasis suppressor NM23 provides a novel mechanism of GTPase regulation. Proceedings of the National Academy of Sciences of the United States of America 108 10611312
1996 Overexpression of Rad inhibits glucose uptake in cultured muscle and fat cells. The Journal of biological chemistry 108 8798502
2009 Lenalidomide, adriamycin, and dexamethasone (RAD) in patients with relapsed and refractory multiple myeloma: a report from the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom). Blood 103 19182205
2018 RAD-ical New Insights into RAD51 Regulation. Genes 100 30551670
2014 Sequencing degraded DNA from non-destructively sampled museum specimens for RAD-tagging and low-coverage shotgun phylogenetics. PloS one 98 24828244
1997 Rem is a new member of the Rad- and Gem/Kir Ras-related GTP-binding protein family repressed by lipopolysaccharide stimulation. The Journal of biological chemistry 92 9268335
2016 Multiplex quantification of four DNA targets in one reaction with Bio-Rad droplet digital PCR system for GMO detection. Scientific reports 88 27739510
2010 Overlapping mechanisms promote postsynaptic RAD-51 filament disassembly during meiotic double-strand break repair. Molecular cell 83 20122407
2001 Regulation of growth and tumorigenicity of breast cancer cells by the low molecular weight GTPase Rad and nm23. Cancer research 83 11280768
2014 Empirical assessment of RAD sequencing for interspecific phylogeny. Molecular biology and evolution 80 24497030
2014 Tumor suppressor p53 negatively regulates glycolysis stimulated by hypoxia through its target RRAD. Oncotarget 80 25114038
2012 A RAD tag derived marker based eggplant linkage map and the location of QTLs determining anthocyanin pigmentation. PloS one 79 22912903
2012 Characterisation of QTL-linked and genome-wide restriction site-associated DNA (RAD) markers in farmed Atlantic salmon. BMC genomics 75 22702806
2012 Mapping phenotypic, expression and transmission ratio distortion QTL using RAD markers in the Lake Whitefish (Coregonus clupeaformis). Molecular ecology 74 23181719
2012 Rainbow: an integrated tool for efficient clustering and assembling RAD-seq reads. Bioinformatics (Oxford, England) 64 22942077
2009 Radiation protection by a new chemical entity, Ex-Rad: efficacy and mechanisms. Radiation research 64 19267542
2009 Rad as a novel regulator of excitation-contraction coupling and beta-adrenergic signaling in heart. Circulation research 63 19926875
2012 Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice. Journal of radiation research 62 22843617
2016 RAD sequencing enables unprecedented phylogenetic resolution and objective species delimitation in recalcitrant divergent taxa. Molecular phylogenetics and evolution 61 26993764
2007 Diversification and co-option of RAD-like genes in the evolution of floral asymmetry. The Plant journal : for cell and molecular biology 58 17672842
2020 Phylogenomic Relationships and Evolution of Polyploid Salix Species Revealed by RAD Sequencing Data. Frontiers in plant science 55 32765560
2006 CeBRC-2 stimulates D-loop formation by RAD-51 and promotes DNA single-strand annealing. Journal of molecular biology 55 16843491
1995 Characterization of Rad, a new member of Ras/GTPase superfamily, and its regulation by a unique GTPase-activating protein (GAP)-like activity. The Journal of biological chemistry 55 7876254
2007 Stabilization of RAD-51-DNA filaments via an interaction domain in Caenorhabditis elegans BRCA2. Proceedings of the National Academy of Sciences of the United States of America 54 17483448
2018 Double-digest RAD sequencing outperforms microsatellite loci at assigning paternity and estimating relatedness: A proof of concept in a highly promiscuous bird. Molecular ecology resources 50 29455472
2018 BRCA1-BARD1 associate with the synaptonemal complex and pro-crossover factors and influence RAD-51 dynamics during Caenorhabditis elegans meiosis. PLoS genetics 50 30383754
1993 Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe. Molecular and cellular biology 46 8413238
2020 Adrenergic CaV1.2 Activation via Rad Phosphorylation Converges at α1C I-II Loop. Circulation research 44 33086983
2013 Comparative evaluation of the Bio-Rad Geenius HIV-1/2 Confirmatory Assay and the Bio-Rad Multispot HIV-1/2 Rapid Test as an alternative differentiation assay for CLSI M53 algorithm-I. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 43 24342484
2022 Rad regulation of CaV1.2 channels controls cardiac fight-or-flight response. Nature cardiovascular research 42 36424916
2019 RRAD mutation causes electrical and cytoskeletal defects in cardiomyocytes derived from a familial case of Brugada syndrome. European heart journal 42 31114854
2016 Using RAD-seq to recognize sex-specific markers and sex chromosome systems. Molecular ecology 42 27213697
2012 Promoter hypermethylation of Ras-related GTPase gene RRAD inactivates a tumor suppressor function in nasopharyngeal carcinoma. Cancer letters 41 22487779
2006 Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level. Proceedings of the National Academy of Sciences of the United States of America 40 16537411
2013 ON01210.Na (Ex-RAD®) mitigates radiation damage through activation of the AKT pathway. PloS one 39 23505494
2005 Rad GTPase attenuates vascular lesion formation by inhibition of vascular smooth muscle cell migration. Circulation 39 15710763
1975 The effect of three rad genes on survival, inter- and intragenic mitotic recombination in Saccharomyces. I. UV irradiation without photoreactivation or liquid-holding post-treatment. Molecular & general genetics : MGG 38 16094968
2014 Selective intra-arterial infusion of rAd-p53 with chemotherapy for advanced oral cancer: a randomized clinical trial. BMC medicine 37 24479409
2020 Simultaneous aerobic denitrification and antibiotics degradation by strain Marinobacter hydrocarbonoclasticus RAD-2. Bioresource technology 36 32506034
2000 Ges, A human GTPase of the Rad/Gem/Kir family, promotes endothelial cell sprouting and cytoskeleton reorganization. The Journal of cell biology 36 10831614
1981 Changes in DNA during meiosis in a repair-deficient mutant (rad 52) of yeast. Science (New York, N.Y.) 36 7010606
2014 RRAD promotes EGFR-mediated STAT3 activation and induces temozolomide resistance of malignant glioblastoma. Molecular cancer therapeutics 35 25313011
2015 RRAD inhibits the Warburg effect through negative regulation of the NF-κB signaling. Oncotarget 34 25893381
2022 Population Genomics Analysis with RAD, Reprised: Stacks 2. Methods in molecular biology (Clifton, N.J.) 33 35727543
2014 Key points of basic theories and clinical practice in rAd-p53 ( Gendicine ™) gene therapy for solid malignant tumors. Expert opinion on biological therapy 32 25496374
1998 Effects of phosphorylation on function of the Rad GTPase. The Biochemical journal 32 9677319
2015 RAD mapping reveals an evolving, polymorphic and fuzzy boundary of a plant pseudoautosomal region. Molecular ecology 31 26139514
2004 The rapamycin derivative RAD inhibits mesangial cell migration through the CDK-inhibitor p27KIP1. Laboratory investigation; a journal of technical methods and pathology 31 15064772
2020 Estimating and accounting for genotyping errors in RAD-seq experiments. Molecular ecology resources 30 32142201
2019 Myocardial-restricted ablation of the GTPase RAD results in a pro-adaptive heart response in mice. The Journal of biological chemistry 30 31147441
2014 Ras-induced epigenetic inactivation of the RRAD (Ras-related associated with diabetes) gene promotes glucose uptake in a human ovarian cancer model. The Journal of biological chemistry 30 24648519
2023 Leveraging the microbiome to understand clinical heterogeneity in depression: findings from the T-RAD study. Translational psychiatry 29 37117195
2019 RRAD suppresses the Warburg effect by downregulating ACTG1 in hepatocellular carcinoma. OncoTargets and therapy 29 30881024
2014 Evaluation of the Bio-Rad Geenius HIV-1/2 test as a confirmatory assay. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 28 24932737
1998 The ras-related protein rad associates with the cytoskeleton in a non-lipid-dependent manner. Experimental cell research 28 9683526
2018 RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation. BMC genomics 27 30419821
2017 Predicting the genetic impact of stocking in Brook Charr (Salvelinus fontinalis) by combining RAD sequencing and modeling of explanatory variables. Evolutionary applications 26 29875804
2015 Identification of Laying-Related SNP Markers in Geese Using RAD Sequencing. PloS one 26 26181055
2015 Loss of RAD-23 Protects Against Models of Motor Neuron Disease by Enhancing Mutant Protein Clearance. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 26490867
2014 Reassessment of QTLs for late blight resistance in the tomato accession L3708 using a restriction site associated DNA (RAD) linkage map and highly aggressive isolates of Phytophthora infestans. PloS one 25 24788810
2006 Ras triggers ataxia-telangiectasia-mutated and Rad-3-related activation and apoptosis through sustained mitogenic signaling. The Journal of biological chemistry 25 16968694
2018 Differential RPA-1 and RAD-51 recruitment in vivo throughout the C. elegans germline, as revealed by laser microirradiation. Nucleic acids research 24 29244155
2018 Oncolytic Adenovirus rAd.DCN Inhibits Breast Tumor Growth and Lung Metastasis in an Immune-Competent Orthotopic Xenograft Model. Human gene therapy 24 30032645
1994 Repair of 6-4 photoproducts and cyclobutane pyrimidine dimers in rad mutants of Saccharomyces cerevisiae. Mutation research 24 7526203
2019 HPV 16 E6/E7 up-regulate the expression of both HIF-1α and GLUT1 by inhibition of RRAD and activation of NF-κB in lung cancer cells. Journal of Cancer 23 31839825
2011 Rad is a p53 direct transcriptional target that inhibits cell migration and is frequently silenced in lung carcinoma cells. Journal of molecular medicine (Berlin, Germany) 23 21221513
2000 The novel immunosuppressant FTY720 induces peripheral lymphodepletion of both T- and B-cells in cynomolgus monkeys when given alone, with Cyclosporine Neoral or with RAD. Transplant immunology 23 11147698
1997 DNA repair: RAD alert. Current biology : CB 23 9259545
2018 A RAD-Based Genetic Map for Anchoring Scaffold Sequences and Identifying QTLs in Bitter Gourd (Momordica charantia). Frontiers in plant science 21 29706980
2018 Pan-senescence transcriptome analysis identified RRAD as a marker and negative regulator of cellular senescence. Free radical biology & medicine 21 30391675
2019 Genome-wide genetic diversity detection and population structure analysis in sweetpotato (Ipomoea batatas) using RAD-seq. Genomics 20 31756427
2001 Identification and characterization of newt rad (ras associated with diabetes), a gene specifically expressed in regenerating limb muscle. Developmental dynamics : an official publication of the American Association of Anatomists 20 11146509
2023 RAD-TGTs: high-throughput measurement of cellular mechanotype via rupture and delivery of DNA tension probes. Nature communications 19 37117218
2018 Population genomic analyses of RAD sequences resolves the phylogenetic relationship of the lichen-forming fungal species Usneaantarctica and Usneaaurantiacoatra. MycoKeys 19 30588165
2022 Acute Myocarditis From the Use of Selective Androgen Receptor Modulator (SARM) RAD-140 (Testolone). Cureus 18 35233331
2020 Poor performance of DNA barcoding and the impact of RAD loci filtering on the species delimitation of an Iberian ant-eating spider. Molecular phylogenetics and evolution 17 33164854
2018 ddSeeker: a tool for processing Bio-Rad ddSEQ single cell RNA-seq data. BMC genomics 17 30583719
2014 Rapid SNP discovery and a RAD-based high-density linkage map in jujube (Ziziphus Mill.). PloS one 17 25303289
1975 The effects of three rad genes on UV induced mutation rates in haploid and diploid Saccharomyces cells. Molecular & general genetics : MGG 17 16094977
2023 Analysis of the Proteomic Profile in Serum of Irradiated Nonhuman Primates Treated with Ex-Rad, a Radiation Medical Countermeasure. Journal of proteome research 16 36977373
2016 Application of RAD Sequencing for Evaluating the Genetic Diversity of Domesticated Panax notoginseng (Araliaceae). PloS one 16 27846268