Affinage

WLS

Protein wntless homolog · UniProt Q5T9L3

Round 2 corrected
Length
541 aa
Mass
62.3 kDa
Annotated
2026-04-28
130 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WLS (Wntless/Evi/GPR177) is a multi-pass transmembrane cargo receptor that is essential in Wnt-producing cells for the secretion of all lipid-modified Wnt ligands across metazoans (PMID:16678096, PMID:16678095, PMID:22784633). Cryo-EM reveals that WLS adopts a GPCR-like seven-transmembrane fold harboring a hydrophobic cavity into which a palmitoylated Wnt hairpin inserts, with the palmitoleate moiety extending into the bilayer; binding requires Porcupine-dependent lipidation of a conserved Wnt serine, and low endosomal pH facilitates Wnt release (PMID:33357447, PMID:20826466, PMID:22108505). The intracellular WLS pool is maintained by retromer-mediated recycling from endosomes to the trans-Golgi network and AP-2-dependent endocytosis from the plasma membrane, while in the absence of Wnt cargo WLS is cleared by ERAD through UBE2J2/CGRRF1-mediated ubiquitination and VCP-dependent extraction (PMID:18160348, PMID:18160346, PMID:29378775). WLS-loaded vesicles released as exosomes at Drosophila synapses—dependent on Rab11, Myosin5, and Syntaxin 1A—enable trans-synaptic Wnt transmission, and tissue-specific Wls deletion in mice disrupts limb patterning, hair follicle development, and skin immune homeostasis (PMID:19837038, PMID:22437826, PMID:22377357, PMID:23918954).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2006 High

    Two independent groups simultaneously identified Wntless/Evi as the first gene specifically required in Wnt-producing cells for Wnt ligand secretion, answering whether a dedicated transmembrane factor exists upstream of Wnt release.

    Evidence RNAi screens, clonal analysis and genetic epistasis in Drosophila, C. elegans, and human cells

    PMID:16678095 PMID:16678096

    Open questions at the time
    • Mechanism of Wnt-WLS binding unknown
    • Unclear whether WLS acts on all Wnt family members
    • Trafficking route of WLS itself not determined
  2. 2007 High

    The intracellular itinerary of WLS was defined: AP-2-mediated endocytosis retrieves WLS from the plasma membrane, and the retromer complex recycles it from endosomes to the TGN, solving how the cell sustains the WLS pool needed for continuous Wnt export.

    Evidence Co-IP of Wls with Vps35, fluorescence localization of MIG-14/Wls in retromer and AP-2 mutants in C. elegans and Drosophila

    PMID:18160346 PMID:18160348

    Open questions at the time
    • Sorting signals on WLS for retromer and AP-2 recognition not mapped
    • Whether additional trafficking machinery participates remains untested
  3. 2009 High

    Discovery that WLS-containing exosome-like vesicles mediate trans-synaptic Wingless delivery at the Drosophila NMJ answered how a lipidated Wnt traverses the synaptic cleft and revealed an unexpected postsynaptic role for Evi in targeting dGRIP.

    Evidence Immunoelectron microscopy of MVBs at synaptic boutons, genetic rescue of pre- and postsynaptic Evi function

    PMID:19837038

    Open questions at the time
    • Whether exosomal WLS-Wnt delivery operates in mammalian synapses is unknown
    • Postsynaptic mechanism of Evi action beyond dGRIP localization is unresolved
  4. 2010 High

    Establishing that Porcupine-dependent palmitoylation of a conserved Wnt serine is a prerequisite for WLS binding, and that low luminal pH triggers Wnt release, defined the biochemical basis of cargo recognition and unloading.

    Evidence Ser209 mutagenesis of WNT3A, co-IP with WLS, V-ATPase inhibition causing WNT3A-WLS accumulation at PM, Xenopus CE assay

    PMID:20826466 PMID:22108505

    Open questions at the time
    • Structural basis for lipid-dependent recognition not yet resolved at this point
    • pH-sensing residues in WLS not identified
  5. 2012 High

    Systematic analysis of all 19 human Wnts confirmed WLS as a universal secretion factor, while exosome release was shown to depend on Rab11, Myosin5, and Syntaxin 1A, answering both the generality and machinery questions for WLS-mediated Wnt export.

    Evidence Gateway library of 19 Wnts with WLS/PORCN knockdown; dsRNA screen, EM, and mass spectrometry of Evi exosomes at Drosophila NMJ

    PMID:22437826 PMID:22784633

    Open questions at the time
    • Whether exosomal versus direct secretion pathways are differentially used for specific Wnts is unknown
    • Stoichiometry of Wnt loading per exosome not determined
  6. 2012 High

    Conditional Wls knockouts in mouse limb mesenchyme, ectoderm, and epidermis demonstrated that WLS-dependent Wnt secretion is essential for limb outgrowth, hair follicle induction, skin barrier integrity, and immune cell homeostasis, establishing broad in vivo requirements.

    Evidence Cre-lox conditional Wls deletion in multiple tissue compartments with histological and immunological phenotyping

    PMID:22377357 PMID:23029304 PMID:23918954

    Open questions at the time
    • Which specific Wnt ligands mediate each tissue phenotype is incompletely resolved
    • Compensatory mechanisms in surviving tissue not characterized
  7. 2013 High

    Demonstration that Wnt/β-catenin signaling in APC-mutant colorectal cancer cells still depends on Evi/WLS-mediated Wnt ligand secretion challenged the assumption that downstream pathway mutations render autocrine Wnt secretion irrelevant, identifying WLS as a potential therapeutic vulnerability.

    Evidence Evi/WLS knockdown in colon cancer cells carrying APC mutations with β-catenin reporter readout

    PMID:24162018

    Open questions at the time
    • In vivo therapeutic efficacy of WLS inhibition in APC-mutant tumors untested
    • Which specific Wnt ligands sustain autocrine signaling not fully defined
  8. 2018 High

    Identification of the ERAD pathway (UBE2J2 as E2, CGRRF1 as E3, VCP/p97 as extractase) that degrades unloaded WLS answered how the cell tunes WLS abundance to match Wnt production demand, with PORCN acting as a triage factor.

    Evidence Co-IP, ubiquitination assays, proteasome inhibitor experiments, siRNA epistasis in mammalian cells

    PMID:29378775

    Open questions at the time
    • Ubiquitination sites on WLS not mapped
    • Whether additional E3 ligases contribute is unclear
    • Structural basis for PORCN-mediated triage not resolved
  9. 2020 High

    The 3.2 Å cryo-EM structure of palmitoleated WNT8A bound to WLS revealed the molecular architecture: WLS adopts a GPCR-like seven-TM fold and captures the Wnt palmitoleate via a hydrophobic cavity, providing the first atomic-resolution view of the cargo receptor mechanism.

    Evidence Cryo-electron microscopy of the human WNT8A–WLS complex with mutagenesis validation

    PMID:33357447

    Open questions at the time
    • No structure of WLS in its apo or endosomal-pH state
    • Conformational changes during Wnt release not captured experimentally
    • Whether the second Wnt hairpin conformational switch occurs in all Wnts is unverified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis for pH-triggered Wnt dissociation from WLS, the identity of sorting signals recognized by retromer and AP-2 on WLS, whether exosomal versus direct secretory routes are differentially utilized for specific Wnt family members, and the in vivo therapeutic potential of targeting WLS in Wnt-dependent cancers.
  • No apo-WLS or low-pH WLS structure available
  • Sorting signals on WLS cytoplasmic domains not mapped
  • In vivo efficacy of WLS-targeted cancer therapy not demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 5 GO:0008289 lipid binding 2
Localization
GO:0005768 endosome 2 GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-1266738 Developmental Biology 3 R-HSA-9609507 Protein localization 3 R-HSA-392499 Metabolism of proteins 1
Partners
CGRRF1PORCNTMEM132AUBE2J2VCPVPS35

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Wntless (Wls/Evi) is a conserved multipass transmembrane protein required in Wnt-producing cells for secretion of Wingless/Wnt ligands. RNAi depletion of Evi in Drosophila phenocopies wg loss-of-function, and Wg is retained intracellularly in evi mutant cells. Epistasis and clonal analysis place Evi in the Wg-producing cell, establishing it as the founding member of a gene family specifically required for Wg/Wnt secretion. RNAi screen, genetic epistasis, clonal analysis, immunofluorescence in Drosophila Cell High 16678096
2006 Wntless (Wls) is required in Wnt-sending cells to promote secretion of Wnt proteins. Loss of Wls blocks Wingless-dependent patterning in Drosophila, MOM-2-governed polarization in C. elegans, and Wnt3a-mediated signaling in cultured human cells, indicating an ancient, dedicated partnership between Wls and all Wnt ligands analyzed. Genetic loss-of-function in Drosophila and C. elegans, siRNA knockdown in human cells, reporter assays Cell High 16678095
2007 The retromer complex is required for Wnt secretion by recycling Wntless (Wls) from endosomes back to the trans-Golgi network (TGN). The retromer subunit Vps35 co-localizes with and co-immunoprecipitates Wls in endosomes; Wls becomes unstable in the absence of retromer activity, depleting the pool available for Wnt secretion. Co-immunoprecipitation, co-localization imaging, genetic loss-of-function (Drosophila and mammalian cells), protein stability assays Developmental cell High 18160348
2007 In C. elegans, the mu subunit of clathrin adaptor AP-2 (DPY-23) acts in Wnt-expressing cells to regulate Wnt function through control of MIG-14/Wntless trafficking. In dpy-23 mutants, MIG-14 accumulates at or near the plasma membrane, whereas in retromer mutants MIG-14 accumulates in intracellular compartments, indicating that AP-2-mediated endocytosis and retromer-mediated recycling together control the intracellular itinerary of MIG-14/Wntless. C. elegans genetics, epistasis, fluorescence localization of MIG-14 in loss-of-function mutants Developmental cell High 18160346
2009 At the Drosophila neuromuscular junction, Wnt/Wingless is transmitted trans-synaptically via exosome-like vesicles containing Evi/Wls. Presynaptic vesicular release of Evi is required for Wingless secretion. Additionally, Evi acts cell-autonomously in the postsynaptic (Wnt-receiving) cell to target dGRIP to postsynaptic sites; loss of Evi in the postsynaptic cell mislocalizes dGRIP and impairs Wnt signal transduction. Live imaging, immunoelectron microscopy, genetic loss-of-function, cell-autonomous rescue experiments at Drosophila NMJ Cell High 19837038
2010 WLS is ER-resident in human cells and WNT3A binding to WLS requires PORCN-dependent lipid modification (palmitoylation) of WNT3A at serine 209. Inhibition of vacuolar acidification blocks release of WNT3A from WLS, causing accumulation of the WNT3A-WLS complex at the plasma membrane, suggesting that low endosomal/vesicular pH is required to dissociate palmitoylated WNT3A from WLS during secretion. Modeling predicts WLS contains a lipocalin-family lipid-binding β-barrel domain. Pharmacological inhibition of V-ATPase, WNT3A Ser209 mutagenesis, co-immunoprecipitation, subcellular fractionation, Xenopus convergent-extension assay Journal of cell science High 20826466
2011 Porcupine-mediated lipidation of a conserved serine residue (equivalent to Wg Ser239) is essential for all Drosophila Wnt family members (except WntD, which lacks this residue) to interact with and be secreted by Wls. WntD neither requires Porcupine nor Wls for secretion. Glycosylation status of Wg does not determine Wls-dependence. Systematic Drosophila genetics, Wnt secretion assays, site-directed mutagenesis of conserved serine, co-immunoprecipitation Developmental biology High 22108505
2012 Release of Evi/Wls-containing exosomes at the Drosophila NMJ requires Rab11, its effector Myosin5, and Syntaxin 1A (Syx1A). These proteins were identified by dsRNA screen in cultured cells and validated in vivo in motoneurons. Ultrastructural analysis revealed multivesicular bodies containing Evi at synaptic boutons. Mass spectrometry and biochemical characterization confirmed that secreted Evi vesicles are bona fide exosomes. dsRNA screen, in vivo motoneuron genetic manipulation, electron microscopy, mass spectrometry, biochemical fractionation The Journal of biological chemistry High 22437826
2012 Wntless (WLS) and Porcupine (PORCN) are essential for all 19 human Wnt ligands to signal through both β-catenin-dependent and independent pathways, establishing WLS as a universal Wnt secretion factor. Wnts show considerable variation in stability, processing, and secretion levels despite similar mRNA expression. Comprehensive Gateway library of all 19 human Wnts, siRNA knockdown of WLS/PORCN, β-catenin reporter assays, LRP6 phosphorylation assays Differentiation; research in biological diversity High 22784633
2012 Conditional deletion of Wls in limb mesenchyme prevents differentiation of distal mesenchyme and arrests limb outgrowth (likely by affecting Wnt5a function), while ectodermal Wls deletion causes agenesis of distal limb tissue, loss of tendon/ligament induction, impaired myoblast migration, and absence of dermis formation, demonstrating that WLS-dependent Wnt secretion from two distinct tissue compartments controls distinct aspects of limb patterning. Conditional Wls knockout (Cre-lox) in limb mesenchyme and ectoderm, histology, marker analysis Developmental biology High 22377357
2012 Conditional deletion of Wls in the epidermis (K14-Cre) causes hair loss after the first cycle, impaired skin barrier function, psoriasis-like inflammation, depletion of dendritic epidermal T cells, and infiltration of γδ-low T cells, demonstrating that epidermal Wnt secretion via Wls is essential for normal skin homeostasis and immune cell homeostasis. Conditional Wls knockout, histology, flow cytometry, expression profiling, comparison to human psoriasis biopsies The Journal of experimental medicine High 23918954
2012 Wls is expressed in the epidermis during embryonic hair follicle induction, and conditional K14-Cre deletion of Wls causes abnormal hair follicle development associated with impaired canonical Wnt/β-catenin signaling. Wnt5a expressed in embryonic epidermis is dispensable for this process, indicating that Wls-dependent canonical Wnt ligands mediate follicle induction. Conditional Wls knockout, immunofluorescence, β-catenin reporter analysis, comparison with Wnt5a null mice PloS one Medium 23029304
2013 Colorectal tumor cells express elevated levels of Wnt3 and Evi/Wls/GPR177, and even in the presence of APC or β-catenin mutations, downstream Wnt/β-catenin signaling remains dependent on Wnt ligand secretion via Evi/Wls. Truncated APC proteins bind β-catenin and destruction complex components, and Evi/Wls knockdown reduces β-catenin signaling in colon cancer cells. siRNA knockdown of Evi/Wls, β-catenin reporter assays, co-immunoprecipitation of APC with destruction complex, tumor expression analysis Nature communications High 24162018
2016 In zebrafish palate morphogenesis, Wls and its ligands Wnt9a and Wnt5b are expressed in the ectoderm, while juxtaposed chondrocytes express Frzb and Gpc4. Genetic analysis using wls, gpc4, frzb, wnt9a, and wnt5b mutants demonstrates that non-canonical Wnt signaling through Wls is required for cell intercalation during convergent-extension, with Wnt5b and Wnt9a controlling extension in distinct axes. Zebrafish mutant analysis, genetic epistasis, in situ hybridization, live imaging of cell intercalation Development (Cambridge, England) Medium 27287801
2016 In zebrafish craniofacial development, disruption of wls causes significant loss of craniofacial bone, whereas loss of gpc4, wnt5b, or wnt9a results in severely delayed endochondral ossification, demonstrating that Wls-dependent non-canonical Wnt signaling regulates coordinated cartilage maturation and the timing of osteogenic differentiation. Zebrafish genetic mutant analysis, Alcian blue/Alizarin red staining, histology, marker analysis Developmental biology Medium 27908786
2018 In the absence of Wnt ligands, Evi/Wls abundance is regulated by ubiquitin-proteasome-mediated endoplasmic reticulum-associated degradation (ERAD). Evi is ubiquitinated by the E2-conjugating enzyme UBE2J2 and the E3-ligase CGRRF1. A triaging complex of Porcupine (PORCN) and VCP/p97 determines whether Evi enters the secretory pathway or is degraded via ERAD, thereby adjusting Evi levels to match Wnt export demand. siRNA knockdown, co-immunoprecipitation, ubiquitination assays, proteasome inhibitor experiments, ERAD pathway dissection The EMBO journal High 29378775
2020 Cryo-EM structure of palmitoleated human WNT8A in complex with WLS resolved at 3.2 Å reveals that the WLS membrane domain has close structural homology to G protein-coupled receptors (GPCRs). A Wnt hairpin inserts into a conserved hydrophobic cavity in the GPCR-like domain of WLS, and the palmitoleate moiety protrudes between two WLS helices into the lipid bilayer. A second conserved Wnt hairpin undergoes a conformational switch that may facilitate Wnt transfer to receiving cells. Cryo-electron microscopy (3.2 Å), biochemical binding experiments, mutagenesis Cell High 33357447
2020 TMEM132A physically interacts with WLS and stabilizes Wnt ligands, enhances the WLS-Wnt ligand interaction, and activates the Wnt signaling pathway, identifying TMEM132A as a novel regulator of Wnt ligand trafficking and secretion. Co-immunoprecipitation, Wnt luciferase reporter assays, siRNA knockdown, protein stability assays Frontiers in cell and developmental biology Medium 33324648
2011 Evi/Wls/GPR177 is a specific regulator of pan-Wnt protein secretion affecting both canonical and non-canonical signaling. Depletion of Evi/Wls in glioma and glioma stem-like cells reduces cell proliferation, induces apoptosis, and reduces cell migration and tumor formation in vivo. Evi/Wls overexpression is sufficient to promote downstream Wnt signaling. siRNA/shRNA knockdown of Evi/Wls, cell proliferation assays, apoptosis assays, migration assays, in vivo xenograft tumor formation, Wnt reporter assays EMBO molecular medicine Medium 22147553

Source papers

Stage 0 corpus · 130 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
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nature genetics 958 22504420
1994 Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer research 755 7954421
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
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
1999 Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance. Biochimica et biophysica acta 629 10581368
2006 Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell 590 16678095
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2009 Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nature genetics 552 19801982
2006 Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell 453 16678096
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
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2009 Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell 364 19837038
1995 The leukotriene LTD4 receptor antagonist MK571 specifically modulates MRP associated multidrug resistance. Biochemical and biophysical research communications 358 7887949
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2003 Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. Oncogene 331 12761501
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
1998 The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting Smad3. Nature 301 9665135
2003 The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome research 285 12975309
2007 The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network. Developmental cell 257 18160348
2012 Mechanism of evenness interrupted (Evi)-exosome release at synaptic boutons. The Journal of biological chemistry 230 22437826
2007 R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proceedings of the National Academy of Sciences of the United States of America 223 17804805
1996 Multidrug resistance mediated by the multidrug resistance protein (MRP) gene. Biochemical pharmacology 217 8831715
2013 Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells. Nature communications 202 24162018
1994 The RNA of RNase MRP is required for normal processing of ribosomal RNA. Proceedings of the National Academy of Sciences of the United States of America 194 8290578
2010 Of proteins and RNA: the RNase P/MRP family. RNA (New York, N.Y.) 186 20627997
2003 Myeloid cell function in MRP-14 (S100A9) null mice. Molecular and cellular biology 180 12640137
2000 Expression of various multidrug resistance-associated protein (MRP) homologues in brain microvessel endothelial cells. Brain research 174 10973603
2007 C. elegans AP-2 and retromer control Wnt signaling by regulating mig-14/Wntless. Developmental cell 170 18160346
2010 WLS-dependent secretion of WNT3A requires Ser209 acylation and vacuolar acidification. Journal of cell science 162 20826466
2010 An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits. PLoS genetics 155 20548944
2011 Porcupine-mediated lipidation is required for Wnt recognition by Wls. Developmental biology 153 22108505
1997 Function, evolution and structure of multidrug resistance protein (MRP). Seminars in cancer biology 148 9441948
2012 Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction. American journal of respiratory and critical care medicine 147 22837378
1998 Expression of multidrug resistance-associated protein (MRP) in brain microvessel endothelial cells. Biochemical and biophysical research communications 147 9500978
2006 The DNA sequence and biological annotation of human chromosome 1. Nature 144 16710414
2001 MRP subfamily transporters and resistance to anticancer agents. Journal of bioenergetics and biomembranes 138 11804191
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2017 RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC biology 135 29117863
1993 Loss of erythropoietin responsiveness in erythroid progenitors due to expression of the Evi-1 myeloid-transforming gene. Proceedings of the National Academy of Sciences of the United States of America 135 8341654
2012 A uniform human Wnt expression library reveals a shared secretory pathway and unique signaling activities. Differentiation; research in biological diversity 126 22784633
2019 The Functional Proximal Proteome of Oncogenic Ras Includes mTORC2. Molecular cell 124 30639242
1994 Subcellular partitioning of MRP RNA assessed by ultrastructural and biochemical analysis. The Journal of cell biology 110 7510714
1994 Expression of the multidrug resistance-associated protein (MRP) in acute leukaemia. Leukemia 109 7808005
2017 Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing. Genes & development 101 28115465
1996 M-related protein (Mrp) contributes to group A streptococcal resistance to phagocytosis by human granulocytes. Molecular microbiology 97 8830235
2003 Interplay between MRP inhibition and metabolism of MRP inhibitors: the case of curcumin. Chemical research in toxicology 90 14680379
1993 Secondary structure of RNase MRP RNA as predicted by phylogenetic comparison. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 89 7678563
1991 Retroviral insertions 90 kilobases proximal to the Evi-1 myeloid transforming gene activate transcription from the normal promoter. Molecular and cellular biology 89 1848663
2017 Mrp Antiporters Have Important Roles in Diverse Bacteria and Archaea. Frontiers in microbiology 87 29218041
1996 hPop1: an autoantigenic protein subunit shared by the human RNase P and RNase MRP ribonucleoproteins. The EMBO journal 85 8918471
2001 Evi-1 transforming and repressor activities are mediated by CtBP co-repressor proteins. The Journal of biological chemistry 84 11328817
2016 Active Yeast Telomerase Shares Subunits with Ribonucleoproteins RNase P and RNase MRP. Cell 81 27156450
1997 Multidrug resistance protein (MRP) expression in retinoblastoma correlates with the rare failure of chemotherapy despite cyclosporine for reversal of P-glycoprotein. Cancer research 80 9192801
1996 Increased Evi-1 expression is frequently observed in blastic crisis of chronic myelocytic leukemia. Leukemia 79 8656673
2011 The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis. EMBO molecular medicine 76 22147553
1996 Reduction of expression of the multidrug resistance protein (MRP) in human tumor cells by antisense phosphorothioate oligonucleotides. Biochemical pharmacology 74 8619891
1997 Do cMOAT (MRP2), other MRP homologues, and LRP play a role in MDR? Seminars in cancer biology 72 9441949
2005 Repression of bone morphogenetic protein and activin-inducible transcription by Evi-1. The Journal of biological chemistry 70 15849193
2008 Pharmacogenomics of MRP transporters (ABCC1-5) and BCRP (ABCG2). Drug metabolism reviews 68 18464048
2007 RNase MRP RNA and human genetic diseases. Cell research 65 17189938
2005 Nuclear MRP genes and mitochondrial disease. Gene 65 15908146
2002 mig-14 is a Salmonella gene that plays a role in bacterial resistance to antimicrobial peptides. Journal of bacteriology 65 12029036
2009 EVI-1 interacts with histone methyltransferases SUV39H1 and G9a for transcriptional repression and bone marrow immortalization. Leukemia 64 19776757
2004 Molecular mechanisms of leukemogenesis by AML1/EVI-1. Oncogene 64 15156182
1997 A novel protein shared by RNase MRP and RNase P. RNA (New York, N.Y.) 64 9085845
2020 Structural Basis of WLS/Evi-Mediated Wnt Transport and Secretion. Cell 63 33357447
2000 Expression of multidrug resistance-associated protein (MRP) in human gliomas. Journal of neuro-oncology 63 11206006
2012 Wls-mediated Wnts differentially regulate distal limb patterning and tissue morphogenesis. Developmental biology 61 22377357
2006 Induction of hepatic transporters multidrug resistance-associated proteins (Mrp) 3 and 4 by clofibrate is regulated by peroxisome proliferator-activated receptor alpha. The Journal of pharmacology and experimental therapeutics 60 16467456
2001 The MRP family and anticancer drug metabolism. Current drug metabolism 60 11766988
1999 RNA-protein interactions in the human RNase MRP ribonucleoprotein complex. RNA (New York, N.Y.) 59 10199568
2010 RNase MRP and disease. Wiley interdisciplinary reviews. RNA 57 21956908
1996 Cellular and in vitro transport of glutathione conjugates by MRP. Biochemistry 56 8639531
2009 Mrp-8 and -14 mediate CNS injury in focal cerebral ischemia. Biochimica et biophysica acta 53 19835955
1997 The role of multidrug resistance-associated protein (MRP) expression in multidrug resistance. Anti-cancer drugs 51 9147606
2002 Identity of the RNase MRP- and RNase P-associated Th/To autoantigen. Arthritis and rheumatism 50 12483731
2000 Architecture and function of the human endonucleases RNase P and RNase MRP. IUBMB life 50 10995027
1996 Expression of multidrug resistance-associated protein (MRP) mRNA in blast cells from acute myeloid leukemia (AML) patients. Leukemia 50 8558937
1999 MARCKS-related protein (MRP) is a substrate for the Leishmania major surface protease leishmanolysin (gp63). The Journal of biological chemistry 48 10464270
1995 EVI-1 zinc finger protein works as a transcriptional activator via binding to a consensus sequence of GACAAGATAAGATAAN1-28 CTCATCTTC. Oncogene 47 7761097
2010 Eukaryotic ribonucleases P/MRP: the crystal structure of the P3 domain. The EMBO journal 46 20075859
2001 Multidrug resistance protein (MRP) activity in normal mature leukocytes and CD34-positive hematopoietic cells from peripheral blood. Life sciences 46 11233999
2000 Use of RNA secondary structure for studying the evolution of RNase P and RNase MRP. Journal of molecular evolution 46 11029064
2013 Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis. The Journal of experimental medicine 45 23918954
2009 Conserved and variable domains of RNase MRP RNA. RNA biology 45 19395864
2001 The leukaemia-associated transcription factors EVI-1 and MDS1/EVI1 repress transcription and interact with histone deacetylase. British journal of haematology 45 11552981
2000 A comparison of human S100A12 with MRP-14 (S100A9). Biochemical and biophysical research communications 45 10973813
2018 ERAD-dependent control of the Wnt secretory factor Evi. The EMBO journal 44 29378775
2006 Differential association of protein subunits with the human RNase MRP and RNase P complexes. RNA (New York, N.Y.) 44 16723659
1995 The AML1/Evi-1 fusion protein in the t(3;21) translocation exhibits transforming activity on Rat1 fibroblasts with dependence on the Evi-1 sequence. Oncogene 44 7675444
2022 A disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis. Nature communications 43 35115551
2020 Structural insight into precursor ribosomal RNA processing by ribonuclease MRP. Science (New York, N.Y.) 41 32586950
2016 Roles of Wnt pathway genes wls, wnt9a, wnt5b, frzb and gpc4 in regulating convergent-extension during zebrafish palate morphogenesis. Development (Cambridge, England) 41 27287801
2016 Distinct requirements of wls, wnt9a, wnt5b and gpc4 in regulating chondrocyte maturation and timing of endochondral ossification. Developmental biology 41 27908786
2001 hPop5, a protein subunit of the human RNase MRP and RNase P endoribonucleases. The Journal of biological chemistry 41 11413139
2000 The human multidrug resistance-associated protein (MRP) gene family: from biological function to drug molecular design. Clinical chemistry and laboratory medicine 41 11097346
2012 EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia. Leukemia 40 22828445
2005 Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP. Oncogene 39 15897867
1999 hPop4: a new protein subunit of the human RNase MRP and RNase P ribonucleoprotein complexes. Nucleic acids research 39 10352175
2016 Crocin suppresses multidrug resistance in MRP overexpressing ovarian cancer cell line. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 37 27342070
2015 Genome-wide identification and expression characterization of ABCC-MRP transporters in hexaploid wheat. Frontiers in plant science 37 26191068
2008 Evi-1 promotes para-aortic splanchnopleural hematopoiesis through up-regulation of GATA-2 and repression of TGF-b signaling. Cancer science 37 18452556
2012 Wls is expressed in the epidermis and regulates embryonic hair follicle induction in mice. PloS one 36 23029304
2002 Phylogenetic analysis of the structure of RNase MRP RNA in yeasts. RNA (New York, N.Y.) 36 12088147
1996 Functional chemotactic factor CP-10 and MRP-14 are abundant in murine abscesses. Infection and immunity 36 8606099
2000 Functional equivalence of hairpins in the RNA subunits of RNase MRP and RNase P in Saccharomyces cerevisiae. RNA (New York, N.Y.) 35 10836786
1995 Expression of the Evi-1 gene in myelodysplastic syndromes. Leukemia 35 7845018
2020 Cryo-EM structure of catalytic ribonucleoprotein complex RNase MRP. Nature communications 34 32651392
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