Affinage

ATP6AP2

Renin receptor · UniProt O75787

Round 2 corrected
Length
350 aa
Mass
39.0 kDa
Annotated
2026-04-28
121 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP6AP2 is a multifunctional single-pass transmembrane protein that serves both as an accessory subunit of the vacuolar H⁺-ATPase (V-ATPase) and as a cell-surface receptor for renin and prorenin, coupling extracellular renin-angiotensin signaling to intracellular proton pump function. As a V-ATPase component, its cleaved transmembrane anchor is enclosed within the Vo c-ring, where it is essential for V-ATPase assembly and endosomal/lysosomal acidification (PMID:32165585, PMID:9556572); this acidification function is co-opted by the Wnt signaling pathway, in which ATP6AP2 acts as an adaptor bridging Wnt receptors (LRP6/Frizzled) to V-ATPase to enable β-catenin signal transduction (PMID:20093472). As a renin/prorenin receptor, ligand binding enhances angiotensinogen-to-angiotensin I conversion and activates angiotensin II–independent intracellular signaling through ERK1/2 MAP kinases and, via the transcription factor PLZF, through PI3K-p85α, driving fibrogenic (TGF-β1, fibronectin, collagen I) and proliferative programs in kidney, heart, adipose tissue, placenta, and liver (PMID:12045255, PMID:17082479, PMID:16374430, PMID:27689008). Transgenic overexpression of ATP6AP2 in renal tubules or glomeruli causes hypertension, proteinuria, and glomerulosclerosis independently of angiotensin II, establishing the receptor as a direct contributor to nephropathy (PMID:17494887, PMID:35008728).

Mechanistic history

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

    Identification of a novel 9.2-kDa protein (M9.2) as a membrane-sector component of V-ATPase established that ATP6AP2 is physically part of the proton pump, analogous to yeast Vma21p.

    Evidence Blue native PAGE and amino-terminal sequencing of bovine chromaffin granule V-ATPase

    PMID:9556572

    Open questions at the time
    • Exact topology within the V-ATPase complex was unknown
    • Whether M9.2 had any function beyond V-ATPase assembly was not addressed
  2. 2002 High

    Expression cloning revealed that the same protein is a cell-surface receptor for renin and prorenin, answering how renin signals intracellularly independent of angiotensin II and establishing a dual identity for ATP6AP2.

    Evidence Expression cloning, radioligand binding, angiotensinogen conversion assay, ERK1/2 phosphorylation, and confocal microscopy in human cell lines and tissue sections

    PMID:12045255

    Open questions at the time
    • Structural basis of dual function (receptor vs. V-ATPase subunit) unresolved
    • Downstream signaling beyond ERK1/2 was unknown
  3. 2006 High

    Discovery of PLZF as a direct cytoplasmic interaction partner and demonstration of renin-induced fibrogenic gene programs revealed distinct downstream signaling branches — a PLZF/PI3K-p85α nuclear pathway and an angiotensin II–independent TGF-β1/matrix protein axis.

    Evidence Yeast two-hybrid, co-IP, ChIP, EMSA, PLZF KO mice (PLZF pathway); siRNA knockdown with renin inhibitor and Ang II receptor antagonist controls in mesangial cells (TGF-β1 pathway)

    PMID:16374430 PMID:17082479

    Open questions at the time
    • Whether PLZF and ERK pathways are independent or convergent was not resolved
    • In vivo disease relevance of PLZF axis remained untested
  4. 2007 High

    Transgenic overexpression in rats demonstrated that receptor-level activation is sufficient to cause nephropathy (proteinuria, glomerulosclerosis) with MAPK/TGF-β1 activation, establishing in vivo pathogenic relevance independent of angiotensin II.

    Evidence Transgenic rat model with PRR blocker peptide and ACE inhibitor controls, proteinuria and histology endpoints

    PMID:17494887

    Open questions at the time
    • Whether the blocker peptide acts exclusively at PRR was debated
    • Mechanism linking receptor overexpression to V-ATPase function in vivo was not addressed
  5. 2010 High

    Identification of ATP6AP2 as an essential adaptor between Wnt receptors and V-ATPase for β-catenin signaling revealed a third, renin-independent function and explained how endosomal acidification is coupled to developmental signaling.

    Evidence Co-IP of PRR with LRP6 and V-ATPase subunits, Wnt reporter assays, Xenopus morpholino knockdown with epistasis analysis

    PMID:20093472

    Open questions at the time
    • Structural basis for PRR bridging LRP6 to V-ATPase was unknown
    • Context-dependent repression vs. activation of Wnt signaling was not reconciled
  6. 2012 Medium

    The finding that full-length PRR can repress Wnt signaling through Dishevelled showed that its Wnt-modulatory role is context-dependent and bidirectional, separating V-ATPase-dependent Wnt activation from a Dvl-mediated repressive function.

    Evidence Tcf/Lef luciferase reporters and endogenous Axin2 quantification in HEK293T and HepG2 cells stimulated with Wnt3a or constitutively active β-catenin

    PMID:23022225

    Open questions at the time
    • Molecular determinants distinguishing activating vs. repressive modes remain unidentified
    • In vivo relevance of Wnt-repressive function not tested
  7. 2013 Medium

    Genome-wide dissection of V-ATPase versus PLZF transcriptional programs downstream of PRR established that these two functions control distinct but partially overlapping gene networks.

    Evidence siRNA knockdown, stable PLZF overexpression, bafilomycin/genistein treatment, microarray and ChIP-chip in cell lines

    PMID:23469216

    Open questions at the time
    • Physiological relevance of the identified target genes was not validated in vivo
    • Extent of overlap between V-ATPase and PLZF programs was not fully resolved
  8. 2016 Medium

    Adipose-specific knockout demonstrated that PRR regulates fat mass, metabolic rate, and insulin sensitivity, extending its physiological roles beyond the cardiovascular and renal systems.

    Evidence AP2-Cre conditional knockout mice with metabolic cage analysis, glucose tolerance tests, adiponectin measurements

    PMID:27689008

    Open questions at the time
    • Whether the adipose phenotype is V-ATPase-dependent or renin-receptor-dependent was not determined
    • Downstream lipid-metabolic mechanism in adipocytes was not resolved
  9. 2020 High

    Near-atomic cryo-EM of brain V-ATPase resolved how ATP6AP2 integrates into the proton pump: its cleaved transmembrane domain is enclosed within the Vo c-ring, providing the first structural explanation for its dual identity as both a V-ATPase subunit and a receptor.

    Evidence Cryo-EM of SidK-affinity-purified rat brain V-ATPase at near-atomic resolution with atomic model building

    PMID:32165585

    Open questions at the time
    • How uncleaved full-length PRR simultaneously presents the ectodomain for renin binding and integrates into V-ATPase is structurally unresolved
    • Tissue-specific regulation of cleavage and c-ring incorporation is unknown
  10. 2021 Medium

    Tubule-specific overexpression and double-transgenic studies showed that intracellular renin can act as a ligand for PRR within renal tubular epithelium, linking V-ATPase-dependent urinary acidification to intracrine renin signaling.

    Evidence Transgenic mouse overexpression, bafilomycin treatment, double-transgenic crossing with intracellular renin (ARen2), metabolic cage urine analysis and renal histopathology

    PMID:35008728

    Open questions at the time
    • Direct binding of intracellular renin to PRR in tubular cells was not biochemically demonstrated
    • Mechanism of lethal tubular damage in double-transgenics was not resolved
  11. 2023 Medium

    In vivo trophoblast-specific knockdown established that PRR is required for placental labyrinth development and fetal-placental growth, expanding its developmental biology role beyond Xenopus axis patterning to mammalian organogenesis.

    Evidence siRNA in HTR-8/SVneo trophoblast cells plus lentiviral shRNA knockdown in mouse blastocyst trophectoderm with stereological placental morphometry

    PMID:37588662

    Open questions at the time
    • Whether placental phenotype is Wnt-dependent, V-ATPase-dependent, or renin-signaling-dependent is unknown
    • Human placental disease relevance (e.g., pre-eclampsia) not established
  12. 2025 Medium

    Identification of a PRR/ERK/PPARγ axis in hepatic lipid metabolism and demonstration that collecting-duct PRR regulates intrarenal aldosterone biosynthesis extended the tissue-specific signaling repertoire to liver steatosis and renovascular hypertension.

    Evidence SHR animal model with renin-activated HepG2 cells and HRP blockade (liver); collecting-duct-specific PRR KO and 2K1C surgical model (kidney)

    PMID:40650317 PMID:bio_10.1101_2025.08.24.671658

    Open questions at the time
    • PRR/ERK/PPARγ axis awaits independent replication
    • Direct PRR–aldosterone synthase regulatory mechanism is undefined
    • Both studies are from single laboratories

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how the full-length receptor simultaneously accommodates extracellular renin/prorenin binding and c-ring integration, how tissue-specific proteolytic processing is regulated, and what determines whether PRR activates or represses Wnt signaling in a given cellular context.
  • No structure of full-length uncleaved PRR in complex with renin or prorenin exists
  • Protease(s) and regulation of PRR cleavage are incompletely defined
  • Context-dependent switch between Wnt activation and repression is mechanistically unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0005198 structural molecule activity 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005764 lysosome 2 GO:0005768 endosome 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-382551 Transport of small molecules 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1430728 Metabolism 2 R-HSA-1643685 Disease 2
Partners
ATP6AP1DVL2FZD8LRP6RENZBTB16
Complex memberships
V-ATPase (Vo sector)Wnt signalosome (LRP6/Frizzled/PRR/V-ATPase)

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Expression cloning of the human (pro)renin receptor (ATP6AP2) identified a 350-amino acid single-transmembrane-domain protein with specific renin and prorenin binding. Receptor binding increased the catalytic efficiency of angiotensinogen conversion to angiotensin I by fourfold and induced intracellular signaling including phosphorylation of serine and tyrosine residues and activation of MAP kinases ERK1 and ERK2. Confocal microscopy localized the receptor to glomerular mesangium and subendothelium of coronary and kidney arteries, co-localizing with renin. Expression cloning, radioligand binding assay, stable transfection, in vitro angiotensinogen conversion assay, phosphorylation assay, ERK activation assay, confocal microscopy The Journal of clinical investigation High 12045255
1998 A novel 9.2-kDa protein (M9.2, later identified as ATP6AP2) was identified as a component of the membrane sector of vacuolar proton-translocating ATPase (V-ATPase) isolated from bovine chromaffin granules by blue native PAGE. It showed sequence and structural similarity to yeast Vma21p, required for V-ATPase assembly. Blue native PAGE, biochemical fractionation of chromaffin granule membranes, amino-terminal protein sequencing, sequence analysis The Journal of biological chemistry High 9556572
2006 The transcription factor promyelocytic zinc finger protein (PLZF) was identified as a direct protein interaction partner of the C-terminal domain of ATP6AP2/(pro)renin receptor via yeast two-hybrid screening and co-immunoprecipitation. Upon renin activation of the receptor, PLZF translocates to the nucleus, represses transcription of the receptor itself (negative feedback), and activates transcription of the PI3K p85α subunit. Renin stimulation of cardiomyoblasts increased cell number and decreased apoptosis via this PLZF/PI3K pathway. The receptor also homodimerizes. Yeast two-hybrid screening, co-immunoprecipitation, siRNA knockdown, chromatin immunoprecipitation, electrophoretic mobility-shift assay, site-directed mutagenesis, PLZF knockout mice Circulation research High 17082479
2006 Renin acting through ATP6AP2/(pro)renin receptor on mesangial cells induces TGF-β1 and matrix proteins (PAI-1, fibronectin, collagen I) through a receptor-mediated, angiotensin II-independent mechanism. siRNA knockdown of the renin receptor mRNA abolished these effects, demonstrating the receptor is required for renin-induced TGF-β1 upregulation. siRNA knockdown, recombinant renin treatment, renin enzymatic inhibitor controls, angiotensin receptor antagonist controls, mRNA and protein quantification Kidney international High 16374430
2007 Transgenic rats overexpressing human ATP6AP2/(pro)renin receptor developed proteinuria and glomerulosclerosis with MAPK activation and increased TGF-β1 expression in kidneys, independent of angiotensin II elevation and blood pressure changes. A (pro)renin receptor blocker peptide inhibited these effects, while ACE inhibition did not, establishing that the receptor directly drives Ang II-independent MAPK signaling and nephropathy. Transgenic rat generation, (pro)renin receptor blocker peptide infusion, ACE inhibitor treatment, MAPK activity assays, TGF-β1 expression analysis, histology, proteinuria measurement, cell culture receptor activation Journal of the American Society of Nephrology High 17494887
2010 ATP6AP2/(pro)renin receptor (PRR) was identified as a component of the Wnt receptor complex, functioning as an adaptor between Wnt receptors (LRP6/Frizzled) and the vacuolar H+-ATPase (V-ATPase) complex in a renin-independent manner. PRR and V-ATPase activity (and hence endosomal acidification) were required for Wnt/β-catenin signal transmission and for antero-posterior patterning of Xenopus early central nervous system development. Co-immunoprecipitation, siRNA knockdown in HEK293 and other cell lines, Wnt reporter assays, Xenopus embryo microinjection and morpholino knockdown, epistasis analysis Science High 20093472
2012 Full-length ATP6AP2/(P)RR acts as a repressor of Wnt signaling in a system pre-activated by Wnt3a or constitutively active β-catenin. The repressive effects are mediated through Dishevelled (Dvl) but are independent of β-catenin mutation status. The V-ATPase complex, but not PLZF translocation or renin enzymatic activity, is necessary for induction of Tcf/Lef-responsive genes by Wnt3a. Tcf/Lef luciferase reporter assays in HEK293T and HepG2 cells, endogenous Axin2 mRNA and protein quantification, Wnt3a stimulation, constitutively active β-catenin overexpression Biochemical pharmacology Medium 23022225
2013 Using siRNA against (P)RR, stable overexpression of PLZF, and specific inhibitors of V-ATPase (bafilomycin) and PLZF (genistein), distinct and overlapping transcriptional signatures downstream of ATP6AP2 were identified by microarray and ChIP-chip analyses. This revealed separate genetic programs controlled by the V-ATPase-associated function versus the PLZF-mediated signaling function of (P)RR, with novel target genes validated by real-time PCR. siRNA knockdown, stable PLZF overexpression, bafilomycin and genistein treatment, microarray transcriptomics, chromatin immunoprecipitation-chip (ChIP-chip), real-time PCR validation PloS one Medium 23469216
2016 Adipose tissue-specific knockout of ATP6AP2/(P)RR (using AP2-Cre) in mice resulted in lower body weight, reduced fat mass, smaller adipocytes, increased locomotor activity, higher circulating adiponectin, and improved insulin sensitivity. These findings establish a role for adipose (P)RR in regulating fat mass, metabolic rate, and insulin sensitivity. Conditional knockout using Cre-loxP (AP2-Cre), metabolic cage analysis, glucose tolerance test, insulin/C-peptide measurements, adiponectin ELISA, body composition analysis Molecular metabolism Medium 27689008
2020 Cryo-electron microscopy of rat brain V-ATPase at near-atomic resolution revealed that ATP6AP2/PRR and ATP6AP1/Ac45 are transmembrane accessory subunits whose cleaved forms have their transmembrane anchors enclosed within the c-ring of the V-ATPase membrane sector (Vo), enabling assembly of the catalytic (V1) and membrane (Vo) regions of the enzyme. The structure defines an ATP:proton ratio of 3:10 for brain V-ATPase. Cryo-electron microscopy, SidK-based affinity purification of native brain V-ATPase, atomic model building Science High 32165585
2021 Tubular epithelial-specific overexpression of ATP6AP2/(P)RR in transgenic mice caused hypertension and alkalized urine with lower osmolality and Na+ excretion. Bafilomycin (V-ATPase antagonist) acidized urine of (P)RR-TG mice, restoring the V-ATPase function phenotype. Double-transgenic mice co-expressing tubular (P)RR and intracellular alternative renin (ARen2) developed lethal renal tubular damage, suggesting intracellular renin acts as a ligand for (P)RR in tubules and that (P)RR functions as V-ATPase in renal tubules. Transgenic mouse generation, ARB/DRI/bafilomycin treatment, metabolic cage urine analysis, double-transgenic crossing, renal histopathology International journal of molecular sciences Medium 35008728
2023 siRNA knockdown of ATP6AP2/(P)RR in HTR-8/SVneo trophoblast cells impaired proliferation, migration, and invasion. In vivo lentiviral knockdown of (P)RR specifically in the trophectoderm of mouse blastocysts reduced placental labyrinth trophoblast number, decreased total surface area available for exchange, increased maternal blood space, and reduced fetal-placental weight ratio, demonstrating (P)RR is necessary for appropriate placental development and function. siRNA knockdown, xCELLigence real-time cell analysis (proliferation, migration, invasion), lentiviral (P)RR shRNA knockdown in mouse blastocysts, embryo transfer to pseudopregnant mice, stereological morphometry of placentae at EA10 and EA18 Frontiers in cell and developmental biology Medium 37588662
2025 Sustained exposure of cells to mycolactone (a Sec61 inhibitor) caused loss of ATP6AP1 and ATP6AP2, which are Sec61-dependent substrates required for V-ATPase assembly, leading to reduced lysosomal biogenesis and acidification. This demonstrates that ATP6AP2 requires co-translational translocation via Sec61 into the ER for its biosynthesis and subsequent V-ATPase assembly. Mycolactone treatment, immunoblotting for ATP6AP2 and ATP6AP1, TFEB nuclear translocation assay, lysosomal acidification assay, autophagy flux assay bioRxiv (preprint)preprint Medium bio_10.1101_2025.08.26.671788
2025 In a model of spontaneous hypertension combined with MAFLD, hepatic (P)RR/ERK/PPARγ pathway and downstream fatty acid synthesis and transport proteins were upregulated. Blocking (P)RR with handle region peptide (HRP) reversed activation of ERK and PPARγ and reduced intracellular lipid accumulation in renin-activated HepG2 cells, identifying a (P)RR/ERK/PPARγ axis in hepatic lipid metabolism. SHR animal model, renin-activated HepG2 cell model, HRP pharmacological blockade, immunoblotting, Nile red fluorescence staining, immunofluorescence, RNA sequencing, liver histology International journal of molecular sciences Medium 40650317
2025 In a two-kidney one-clip mouse model, collecting duct-specific deletion of ATP6AP2/(pro)renin receptor (CD PRR KO) was identified as a key upstream regulator of intrarenal aldosterone biosynthesis. CD PRR KO reduced the hypertensive and fibrotic response to renovascular constriction, establishing (P)RR as a regulator of intrarenal renin-dependent aldosterone generation and ischemic nephropathy. Inducible renal tubule-specific C11B2 KO, collecting duct-specific PRR KO (CD PRR KO) and renin KO mice, 2K1C surgical model, blood pressure measurement, renal fibrosis/inflammation histology, aldosterone assays bioRxiv (preprint)preprint Medium bio_10.1101_2025.08.24.671658

Source papers

Stage 0 corpus · 121 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2002 Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. The Journal of clinical investigation 1101 12045255
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
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
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2010 Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling. Science (New York, N.Y.) 471 20093472
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
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2006 Renin increases mesangial cell transforming growth factor-beta1 and matrix proteins through receptor-mediated, angiotensin II-independent mechanisms. Kidney international 348 16374430
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2003 Comparative toxicity evaluation of cyanobacterial cyclic peptide toxin microcystin variants (LR, RR, YR) in mice. Toxicology 326 12767698
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
2019 Intrinsically Disordered Protein TEX264 Mediates ER-phagy. Molecular cell 296 31006538
1998 Identification and characterization of a novel 9.2-kDa membrane sector-associated protein of vacuolar proton-ATPase from chromaffin granules. The Journal of biological chemistry 259 9556572
2006 A novel signal transduction cascade involving direct physical interaction of the renin/prorenin receptor with the transcription factor promyelocytic zinc finger protein. Circulation research 252 17082479
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2012 Viral immune modulators perturb the human molecular network by common and unique strategies. Nature 219 22810585
2007 Slowly progressive, angiotensin II-independent glomerulosclerosis in human (pro)renin receptor-transgenic rats. Journal of the American Society of Nephrology : JASN 213 17494887
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2011 Next-generation sequencing to generate interactome datasets. Nature methods 200 21516116
2020 Structure of V-ATPase from the mammalian brain. Science (New York, N.Y.) 186 32165585
2007 RR interval variability is inversely related to inflammatory markers: the CARDIA study. Molecular medicine (Cambridge, Mass.) 178 17592552
2022 The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL. Journal for immunotherapy of cancer 159 35580927
2022 Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood 119 35081255
2023 Detailed safety profile of acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia in the ELEVATE-RR trial. Blood 94 37390310
1995 Transposon-mediated chromosomal rearrangements and gene duplications in the formation of the maize R-r complex. The EMBO journal 89 7774593
2004 Dynamic beat-to-beat modeling of the QT-RR interval relationship: analysis of QT prolongation during alterations of autonomic state versus human ether a-go-go-related gene inhibition. The Journal of pharmacology and experimental therapeutics 82 15306635
1991 Meiotic instability of the R-r complex arising from displaced intragenic exchange and intrachromosomal rearrangement. Genetics 63 1682214
1992 Changes in R-R interval at the start of muscle contraction in the decerebrate cat. The Journal of physiology 59 1593459
2009 A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project. Circulation. Cardiovascular genetics 57 20031603
2007 Analytical and functional characterization of microcystins [Asp3]MC-RR and [Asp3,Dhb7]MC-RR: consequences for risk assessment? Environmental science & technology 53 17438823
2008 Acute effects of microcystins MC-LR and MC-RR on acid and alkaline phosphatase activities and pathological changes in intraperitoneally exposed tilapia fish (Oreochromis sp.). Toxicologic pathology 43 18441257
2015 Antiallodynic effects of alpha lipoic acid in an optimized RR-EAE mouse model of MS-neuropathic pain are accompanied by attenuation of upregulated BDNF-TrkB-ERK signaling in the dorsal horn of the spinal cord. Pharmacology research & perspectives 38 26171221
2023 Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: phase 1b PORTIA study results. Blood advances 37 36044388
1998 Contributions of tidal lung inflation to human R-R interval and arterial pressure fluctuations. Journal of the autonomic nervous system 33 9531448
2023 Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: a 3-year follow-up. Blood advances 32 37352266
2000 The thylakoid delta pH-dependent pathway machinery facilitates RR-independent N-tail protein integration. The Journal of biological chemistry 32 10816594
2012 The proteomic study on cellular responses of the testes of zebrafish (Danio rerio) exposed to microcystin-RR. Proteomics 31 22140076
2021 Anti-CD19 CAR-T cell therapy bridge to HSCT decreases the relapse rate and improves the long-term survival of R/R B-ALL patients: a systematic review and meta-analysis. Annals of hematology 30 33587155
2016 Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight. Molecular metabolism 30 27689008
1999 Characterization of the regulatory elements of the maize P-rr gene by transient expression assays. Plant molecular biology 30 10080705
2022 The differential effects of tumor burdens on predicting the net benefits of ssCART-19 cell treatment on r/r B-ALL patients. Scientific reports 28 35013456
1996 PR/RR interval ratio during rapid atrial pacing: a simple method for confirming the presence of slow AV nodal pathway conduction. Journal of cardiovascular electrophysiology 26 8777476
2012 The (pro)renin receptor ((P)RR) can act as a repressor of Wnt signalling. Biochemical pharmacology 25 23022225
2022 Timing of Tocilizumab Administration Under the Guidance of IL-6 in CAR-T Therapy for R/R Acute Lymphoblastic Leukemia. Frontiers in immunology 24 35799791
2006 Association of decreased variation of R-R interval and elevated serum C-reactive protein level in a general population in Japan. International heart journal 24 17268121
1991 The alpha- and beta-adrenoceptor blocking activities of labetalol and its RR-SR (50:50) stereoisomers. British journal of pharmacology 21 1687367
2000 Generation of antibodies directed against the low-immunogenic peptide-toxins microcystin-LR/RR and nodularin. International journal of immunopharmacology 19 10708882
2018 Allogeneic hematopoietic stem cell transplantation in r/r Hodgkin lymphoma after treatment with checkpoint inhibitors: Feasibility and safety. European journal of haematology 18 30341987
2017 Hepatotoxicity and metabolic effects of cellular extract of cyanobacterium Radiocystis fernandoi containing microcystins RR and YR on neotropical fish (Hoplias malabaricus). Chemosphere 17 28242458
1990 Effects of carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP) and of ruthenium red (RR) on capsaicin-evoked neuropeptide release from peripheral terminals of primary afferent neurones. Naunyn-Schmiedeberg's archives of pharmacology 17 1697404
2021 Serial surveillance by circulating tumor DNA profiling after chimeric antigen receptor T therapy for the guidance of r/r diffuse large B cell lymphoma precise treatment. Journal of Cancer 16 34405005
1991 Leucine repeats in the large subunit of herpes simplex virus type 2 ribonucleotide reductase (RR; ICP10) are involved in RR activity and subunit complex formation. The Journal of general virology 16 1851814
2022 High proportion of RR-TB and mutations conferring RR outside of the RRDR of the rpoB gene detected in GeneXpert MTB/RIF assay positive pulmonary tuberculosis cases, in Addis Ababa, Ethiopia. PloS one 15 36584037
2014 Draft Genome Sequence of Phaeomoniella chlamydospora Strain RR-HG1, a Grapevine Trunk Disease (Esca)-Related Member of the Ascomycota. Genome announcements 14 24723699
1984 Antitumor activity and toxicity in animals of RR-150 (7-cysteaminomitosane), a new mitomycin derivative. Cancer research 14 6437670
2024 OUTREACH: phase 2 study of lisocabtagene maraleucel as outpatient or inpatient treatment at community sites for R/R LBCL. Blood advances 13 39347584
2023 Salvage therapy with brentuximab-vedotin and bendamustine for patients with R/R PTCL: a retrospective study from the LYSA group. Blood advances 13 36477770
2013 Appearance of Planktothrix rubescens bloom with [D-Asp3, Mdha7]MC-RR in gravel pit pond of a shallow lake-dominated area. Toxins 13 24351711
2012 Genotype- and Sex-Specific QT-RR Relationship in the Type-1 Long-QT Syndrome. Journal of the American Heart Association 12 23130128
2025 Impact of vein-to-vein time in patients with R/R LBCL treated with axicabtagene ciloleucel. Blood advances 11 39883946
1991 Pre-excited RR intervals during atrial fibrillation in the Wolff-Parkinson-White syndrome: influence of the atrioventricular node refractory period. Journal of the American College of Cardiology 11 1960320
2017 Cannabinoid receptor 2-63 RR variant is independently associated with severe necroinflammation in HIV/HCV coinfected patients. PloS one 10 28759568
2016 A genome-wide interaction analysis of tricyclic/tetracyclic antidepressants and RR and QT intervals: a pharmacogenomics study from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Journal of medical genetics 10 28039329
2007 Identifying coronary artery flow reduction and ischemia using quasistationary QT/RR-interval hysteresis measurements. Journal of electrocardiology 10 17993337
2025 Real-world data for tisagenlecleucel in patients with R/R B-ALL: subgroup analyses from the CIBMTR registry. Blood advances 9 40554426
2008 Growth-compromised HSV-2 vector Delta RR protects from N-methyl-D-aspartate-induced neuronal degeneration through redundant activation of the MEK/ERK and PI3-K/Akt survival pathways, either one of which overrides apoptotic cascades. Journal of neuroscience research 9 17893911
2025 Efficacy of zanubrutinib versus acalabrutinib for relapsed or refractory chronic lymphocytic leukemia (R/R CLL): a matching-adjusted indirect comparison (MAIC). Therapeutic advances in medical oncology 8 40656602
2022 Transcriptome-Wide Identification of CCCH-Type Zinc Finger Proteins Family in Pinus massoniana and RR-TZF Proteins in Stress Response. Genes 8 36140811
2024 Comparative efficacy and safety of tisagenlecleucel and axicabtagene ciloleucel among adults with r/r follicular lymphoma. Leukemia & lymphoma 7 38179688
2024 Daratumumab and venetoclax combined with CAGE for late R/R T-ALL/LBL patients: Single-arm, open-label, phase I study. Annals of hematology 7 38662205
2024 Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE. Annals of hematology 7 38888616
2021 Blood Pressure Elevation of Tubular Specific (P)RR Transgenic Mice and Lethal Tubular Degeneration due to Possible Intracellular Interactions between (P)RR and Alternative Renin Products. International journal of molecular sciences 7 35008728
2018 In vivo evidence that the cannabinoid receptor 2-63 RR variant is associated with the acquisition and/or expansion of HIV infection. HIV medicine 7 29932291
2001 Imprinting of R-r, paramutation of B-I and Pl, and epigenetic silencing of MuDR/Mu transposons in Zea mays L. are coordinately affected by inbred background. Genetical research 7 11486505
2000 Multiple AV nodal pathways with multiple peaks in the RR interval histogram of the Holter monitoring ECG during atrial fibrillation. Pacing and clinical electrophysiology : PACE 7 11139958
2025 Lisocabtagene maraleucel for R/R LBCL in patients not intended for HSCT: final results of the phase 2 PILOT study. Blood advances 6 40305658
2013 Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses. PloS one 6 23469216
2024 Rituximab potentially improves clinical outcomes of CAR-T therapy for r/r B-ALL via sensitizing leukemia cells to CAR-T-mediated cytotoxicity and reducing CAR-T exhaustion. Cellular oncology (Dordrecht, Netherlands) 5 38662336
2024 Efficacy and safety of bendamustine-containing bridging therapy in R/R LBCL patients receiving CD19 CAR T-cells. HemaSphere 5 38948924
2024 Outcomes of patients with R/R B-cell NHL and limited (<5 sites) pre-CART disease bridged with or without radiotherapy. Blood advances 5 39028948
2024 Genome-wide characterization of RR gene family members in Zanthoxylum armatum and the subsequent functional characterization of the C-type RR. Plant physiology and biochemistry : PPB 5 39032447
2023 Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity. Frontiers in cell and developmental biology 5 37588662
2017 Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Michaelson MD, McKay RR, Werner L, Atkins MB, Van Allen EM, Olivier KM, Song J, Signoretti S, McDermott DF, Choueiri TK.Cancer. 2015 Oct 1;121(19):3435-43. [Epub 2015 Jun 8]. doi: 10.1002/cncr.29503. Urologic oncology 5 28159495
2025 The dual role of the RR-2 cuticular protein gene in development and acaricide susceptibility of Panonychus citri (Acari: Tetranychidae). Experimental & applied acarology 4 40423860
2021 The (pro)renin receptor ((P)RR) and soluble (pro)renin receptor (s(P)RR) in pregnancy. Placenta 4 34020806
2021 Characteristics of the Dynamic Electrocardiogram in the Elderly with Nonvalvular Atrial Fibrillation Combined with Long R-R Intervals. Evidence-based complementary and alternative medicine : eCAM 4 34804179
2008 Renin/prorenin receptor, (P)RR, in end-organ damage: current issues in 2007. Journal of the American Society of Hypertension : JASH 4 20409904
2001 LFA-1 expression on CD4(+)CD45RO(+) peripheral blood T-lymphocytes in RR MS: effects induced by rIFNbeta-1a. Journal of the neurological sciences 4 11412874
2025 Tocilizumab Dosing for Management of T Cell-Engaging Bispecific Antibody-Related CRS in Patients With R/R B-Cell NHL. Clinical pharmacology and therapeutics 3 40576759
2014 Novel approach to cardiovascular diseases: a promising probability of (pro)renin receptor [(P)RR]. Current pharmaceutical design 3 23844810
2025 Population-based validation of the CAR-HEMATOTOX for hematotoxicity, infections, and survival after CART in R/R LBCL. Blood advances 2 40668622
2025 Pirtobrutinib, a highly selective, noncovalent (reversible) BTKi in R/R follicular lymphoma: phase 1/2 BRUIN study. Blood advances 2 40845254
2024 Efficacy and Safety of Ibrutinib as Monotherapy or Combination Therapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL): A Systematic Review and Meta-analysis. American journal of therapeutics 2 39413356
2024 Microcystin-RR is a biliary toxin selective for neonatal extrahepatic cholangiocytes. JHEP reports : innovation in hepatology 2 39687604
2008 The RR genotype of codon 72 of p53 gene reduces the development of intestinal metaplasia. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2 18567547
2025 QT and RR interval analysis in genetic cardiac diseases using the AccuQT and advanced heart rate variability methods. Journal of electrocardiology 1 40915048
2024 Early evaluation of CAR-T cell therapy response in R/R DLBCL patients using 18F-FDG PET/CT. Hellenic journal of nuclear medicine 1 38629814
2024 PKM2/Hif-1α signal suppression involved in therapeutics of pulmonary fibrosis with microcystin-RR but not with pirfenidone. Toxicon : official journal of the International Society on Toxinology 1 38908528
2023 Narrow QRS Complex Tachycardia With Variable R-R Intervals and Discrete P Waves. JACC. Case reports 1 36974046
2019 Prediction of bortezomib-induced peripheral neuropathy with the R-R interval variation of the electrocardiogram in plasma cell myeloma: a retrospective study. Leukemia & lymphoma 1 31642372
2026 Pirtobrutinib, a highly selective, noncovalent (reversible) BTKi in R/R marginal zone lymphoma: phase 1/2 BRUIN study. Blood advances 0 41544219
2026 Limited contribution of compensatory mutations to MDR/RR-TB clustering in Hunan Province, China: a population-based whole-genome sequencing study. Microbiology spectrum 0 41773868
2026 OUTCOMES OF PATIENTS OVER 70 YEARS TREATED WITH BREXU-CEL FOR R/R MANTLE CELL LYMPHOMA: A STUDY FROM THE CTIWP OF EBMT. Blood advances 0 41779968
2025 Indirect Comparisons of Efficacy of Zanubrutinib Versus Orelabrutinib in Patients with R/R MCL: An Extended Follow-up Analysis. Advances in therapy 0 40317419
2025 Overexpression of (P)RR in SHR and Renin-Induced HepG2 Cells Leads to Spontaneous Hypertension Combined with Metabolic Dysfunction-Associated Fatty Liver Disease. International journal of molecular sciences 0 40650317
2025 First-line lenvatinib and sorafenib in RR-DTC from a shared real-life context. Endocrine-related cancer 0 41051352
2025 Immune reconstitution after CD7 CAR-T cell therapy for refractory/relapsed acute T-lymphoblastic leukaemia/lymphoblastic lymphoma (R/R T-ALL/LBL). British journal of haematology 0 41111252
2024 Cardiovascular effect of preeclampsia upon offspring development: Are (Pro) renin-renin receptor ((P)RR) and gender related? Iranian journal of basic medical sciences 0 38629095
2024 Soluble (pro)renin receptor (s(P)RR) levels in women carrying Aboriginal and/or Torres Strait Islander babies; the Gomeroi Gaaynggal study. Pregnancy hypertension 0 39577063
2014 [Isolation and cultivation of a wild microcytin-RR-producing cyanobacterium and verification of its toxin by high performance liquid chromatography and acute oral toxicity]. Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 0 25312573