Affinage

WLS

Protein wntless homolog · UniProt Q5T9L3

Length
541 aa
Mass
62.3 kDa
Annotated
2026-06-11
100 papers in source corpus 16 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WLS (Wntless/Evi/GPR177) is a conserved multipass transmembrane protein that functions as a dedicated cargo receptor for the secretion of lipid-modified Wnt ligands from Wnt-producing cells, a role first established by genetic epistasis and clonal analysis in Drosophila where evi mutants retain Wg intracellularly (PMID:16678096). WLS binds Wnt in an ER-resident complex, and this recognition depends strictly on PORCN-dependent palmitoleoylation of a conserved Wnt serine (Ser209/S239), since loss of lipidation abolishes both physical and functional engagement with WLS across the Wnt family (PMID:20826466, PMID:22108505). The molecular basis of this interaction was resolved by a 3.2 Å cryo-EM structure of WLS bound to palmitoleated WNT8A, which showed a GPCR-like membrane domain accommodating a Wnt hairpin in a hydrophobic cavity with the palmitoleate protruding between two WLS helices into the bilayer (PMID:33357447). After ER loading, WLS escorts Wnt through the secretory pathway and undergoes an obligatory recycling itinerary to sustain secretion: retromer (Vps35)-dependent retrieval of WLS from endosomes following AP-2-mediated endocytosis prevents its lysosomal degradation (PMID:18193037, PMID:18160347, PMID:18160346), and a C-terminal ER-targeting signal plus ARF/COPI and ERGIC2 drive Golgi-to-ER retrograde transport (PMID:24768165). When Wnt cargo is absent, WLS levels are tuned down by ERAD through UBE2J2/CGRRF1-mediated ubiquitination and VCP-dependent degradation, with a PORCN–VCP triaging complex deciding between secretion and degradation (PMID:29378775). Beyond canonical secretion, at synapses WLS is itself released in MVB-derived exosome-like vesicles via Rab11/Syntaxin1A/Myosin5 to mediate trans-synaptic Wnt transmission (PMID:19837038, PMID:22437826).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2006 High

    Established that Wnt secretion requires a dedicated factor acting within the producing cell, defining WLS as the founding component of the Wnt export machinery.

    Evidence RNAi screen, clonal analysis and epistasis in Drosophila showing Wg is retained intracellularly in evi mutants

    PMID:16678096

    Open questions at the time
    • Did not define the molecular nature of the WLS-Wnt interaction
    • Subcellular trafficking route of WLS not yet mapped
  2. 2008 High

    Answered how WLS is sustained for repeated rounds of secretion by showing retromer retrieves it from endosomes rather than allowing its degradation.

    Evidence Drosophila and C. elegans genetics (Vps35 mutants), co-precipitation, EM, and Wls-overexpression suppression of the Vps35 block

    PMID:18160347 PMID:18193037

    Open questions at the time
    • Did not resolve the endocytic step delivering WLS to endosomes
    • Retromer sorting signal on WLS not defined
  3. 2007 High

    Showed plasma-membrane WLS is endocytosed and retrieved to the Golgi, explaining why loss of recycling makes WLS limiting for Wnt signaling.

    Evidence C. elegans genetics and immunofluorescence showing AP-2 (DPY-23)-dependent endocytosis and lysosomal degradation of MIG-14/WLS without retromer

    PMID:18160346 PMID:18160347

    Open questions at the time
    • Endocytic adaptor recognition motif on WLS not mapped
    • Did not address Golgi-to-ER segment of the itinerary
  4. 2010 High

    Defined the biochemical basis of cargo recognition: WLS binds Wnt in the ER and this requires PORCN-dependent lipid modification of Wnt.

    Evidence Co-IP of WLS-WNT3A, Ser209 mutagenesis, vacuolar acidification inhibitors, and Xenopus functional assays

    PMID:20826466

    Open questions at the time
    • Lipocalin-like binding model was inferred from modeling, not structure
    • Mechanism of pH-dependent Wnt release not molecularly defined
  5. 2011 High

    Generalized lipidation-dependent recognition across the Wnt family, establishing the conserved serine lipid mark as the structural determinant for WLS binding.

    Evidence Systematic RNAi secretion assays of all Drosophila Wnts, serine mutagenesis, and Wnt-Wls co-IP

    PMID:22108505

    Open questions at the time
    • WntD exception's WLS-independence not mechanistically dissected
    • Structural geometry of recognition not yet visualized
  6. 2012 High

    Identified the trafficking machinery for synaptic WLS exosome release, distinguishing it from the canonical secretory route.

    Evidence dsRNA screen, dominant-negative Rab11/Syx1A in motoneurons, EM of MVBs, and mass spectrometry of exosome fractions in Drosophila

    PMID:22437826

    Open questions at the time
    • Conservation of exosomal WLS release in mammals not established
    • Cargo selectivity for MVB sorting unclear
  7. 2014 High

    Completed the trafficking cycle by demonstrating Golgi-to-ER retrograde recycling of WLS and identifying its molecular requirements.

    Evidence Subcellular fractionation, live imaging, ER-targeting sequence mutagenesis, and ARF/ERGIC2 knockdown with Wnt secretion assays

    PMID:24768165

    Open questions at the time
    • How the ER-targeting signal is recognized by COPI machinery not defined
    • Coordination between retromer and COPI arms not resolved
  8. 2018 High

    Revealed cargo-responsive control of WLS abundance through ERAD, coupling WLS levels to Wnt export demand.

    Evidence Co-IP, ubiquitination assays, and siRNA of ERAD components identifying UBE2J2/CGRRF1 and a PORCN-VCP triaging complex

    PMID:29378775

    Open questions at the time
    • Structural basis of the PORCN-VCP triage decision unknown
    • How Wnt occupancy is sensed to spare WLS from ERAD not defined
  9. 2020 High

    Provided the definitive molecular mechanism of cargo loading by visualizing how WLS accommodates a palmitoleated Wnt in a GPCR-like fold.

    Evidence 3.2 Å cryo-EM structure of WLS-WNT8A complex with biochemical mutagenesis validation

    PMID:33357447

    Open questions at the time
    • Conformational switch hypothesized for Wnt transfer not directly tested in vivo
    • Structures of recycling/empty WLS states not determined
  10. 2020 Medium

    Identified accessory factors and additional binding partners modulating WLS-dependent Wnt secretion in mammalian cells.

    Evidence Co-IP, glycosylation assays, Wnt stability and reporter assays implicating TMEM132A, MOR, and N-glycosylation

    PMID:20214800 PMID:20549736 PMID:33324648

    Open questions at the time
    • MOR/GPR177 inhibition of Wnt secretion shown only correlatively
    • Single-lab findings without independent replication
    • Structural basis of TMEM132A and MOR interactions unknown
  11. 2022 Medium

    Placed WLS in a physiological signaling context by linking neuronal WLS-mediated WNT5a secretion to TRPV1 activation and neuropathic pain.

    Evidence Conditional GPR177 knockout in A-fiber neurons, CSF Wnt5a measurement, patch-clamp of WNT5a-TRPV1 currents, and peptide inhibitor behavioral assays

    PMID:35385340

    Open questions at the time
    • Single-lab study without independent replication
    • Generality beyond diabetic neuropathic pain not established
  12. 2018 Medium

    Uncovered a Wnt-independent, cell-autonomous function of WLS in dendrite morphogenesis, expanding its role beyond ligand secretion.

    Evidence C. elegans domain mapping, Wnt mutant analysis, and WASP interaction assays in PVD neurons

    PMID:29673481

    Open questions at the time
    • Molecular mechanism linking WLS to WASP/actin not resolved
    • Conservation in mammals not tested
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple WLS trafficking arms (anterograde loading, endosome retrieval, Golgi-to-ER recycling, ERAD triage) are spatially and temporally coordinated, and whether the structurally inferred Wnt-transfer conformational switch operates at recipient cells, remains unresolved.
  • No integrated structural view of the recycling cycle
  • Mechanism of Wnt release/handoff to receptors undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 3 GO:0008289 lipid binding 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005768 endosome 2 GO:0005794 Golgi apparatus 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-9609507 Protein localization 3 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-392499 Metabolism of proteins 1
Partners
CGRRF1OPRM1PORCNTMEM132AUBE2J2VPS35WNT3AWNT8A
Complex memberships
PORCN-VCP triaging complexWLS-Wnt ER complexretromer (Vps35)

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Evi/WLS is a conserved multipass transmembrane protein specifically required for Wg/Wnt secretion in Wnt-producing cells. Epistasis experiments and clonal analysis place Evi in the Wg-producing cell, and evi mutants retain Wg intracellularly, demonstrating its essential role in Wnt release. RNAi screen in Drosophila, clonal analysis, epistasis experiments, immunostaining for Wg retention Cell High 16678096
2009 At the Drosophila NMJ, Evi/WLS is released in exosome-like vesicles to mediate trans-synaptic Wnt (Wingless) transmission. Additionally, Evi acts cell-autonomously in the postsynaptic cell to target dGRIP (a Wg-receptor-interacting protein) to postsynaptic sites, enabling Wnt signal transduction in the receiving cell. Live imaging, genetic loss-of-function, immunostaining at NMJ, vesicle fractionation Cell High 19837038
2008 Retromer-dependent endosome-to-Golgi recycling of Wntless/Evi is required for efficient Wnt secretion. In the absence of Vps35 (retromer component), Wntless is diverted to a degradative compartment. Biochemical evidence confirms that Wntless engages the retromer complex, and overexpression of Wntless overcomes the Vps35 secretion block. Drosophila genetics (Vps35 mutant analysis), biochemical co-precipitation, electron microscopy, epistasis (Wls overexpression suppresses Vps35 mutant) Nature cell biology High 18160347 18193037
2007 In C. elegans, retromer-dependent recycling retrieves MIG-14/WLS from the plasma membrane back to the Golgi. Without retromer function, MIG-14/WLS is degraded in lysosomes, becoming limiting for Wnt signaling. AP-2 (DPY-23) mediates endocytosis of MIG-14 from the plasma membrane, and in dpy-23 mutants MIG-14 accumulates at the plasma membrane. C. elegans genetics, RNAi, subcellular localization by immunofluorescence, lysosomal degradation assays Developmental cell High 18160346 18160347
2010 WLS binds WNT3A in an ER-resident complex, and this binding requires PORCN-dependent lipid modification (palmitoylation) of WNT3A at Ser209. Inhibition of vacuolar acidification blocks WNT3A release from the WLS complex and causes accumulation of the WNT3A-WLS complex at the plasma membrane. Structural modeling suggests WLS has a lipocalin-like lipid-binding β-barrel that interacts with the Wnt palmitoyl moiety. Co-immunoprecipitation of WLS-WNT3A complex, small molecule inhibitor screen, site-directed mutagenesis of WNT3A Ser209, subcellular fractionation, Xenopus embryo functional assays Journal of cell science High 20826466
2011 Porcupine-mediated lipidation of a conserved serine residue (equivalent to Wg S239) is required for Wnt's physical and functional interaction with Wls in Drosophila. All Drosophila Wnts (except WntD, which lacks this serine) require both Porcupine and Wls for secretion, demonstrating that lipidation at this site is the structural determinant for Wls recognition. Systematic RNAi-based secretion assays of all Drosophila Wnt family members, site-directed mutagenesis of the conserved serine, co-immunoprecipitation of Wnt-Wls interaction Developmental biology High 22108505
2012 Evi/WLS vesicle release at Drosophila synaptic boutons requires Rab11, Syntaxin 1A (Syx1A), and the Rab11 effector Myosin5. Multivesicular bodies (MVBs) containing Evi are present at synaptic boutons and serve as organelles for exosome production. Secreted Evi vesicles have biochemical characteristics conserved with exosomes. dsRNA screen in cultured cells, motoneuron-specific expression of dominant-negative Rab11 and Syx1A, ultrastructural analysis (electron microscopy), mass spectrometry characterization of exosome fraction The Journal of biological chemistry High 22437826
2014 Endogenous WLS undergoes a full ER→plasma membrane→Golgi→ER retrograde transport cycle during Wnt secretion. A C-terminal ER-targeting sequence on WLS is critical for ER retrograde recycling and Wnt secretory function. Golgi-to-ER recycling requires ARF (COPI regulator) and ERGIC2, an ER-Golgi intermediate compartment protein also required for efficient Wnt secretion. Subcellular fractionation, live imaging, mutagenesis of ER-targeting sequence, siRNA knockdown of ARF and ERGIC2, functional Wnt secretion assays Developmental cell High 24768165
2020 Cryo-EM structure of palmitoleated human WNT8A in complex with WLS at 3.2 Å resolution reveals: (1) the WLS membrane domain has close structural homology to GPCRs; (2) a Wnt hairpin inserts into a conserved hydrophobic cavity in the GPCR-like domain; (3) the palmitoleate of WNT8A protrudes between two WLS helices into the lipid bilayer; (4) a conformational switch of conserved residues on a separate Wnt hairpin may contribute to Wnt transfer to receiving cells. Cryo-EM structure determination at 3.2 Å, biochemical mutagenesis experiments to validate observed interactions Cell High 33357447
2018 WLS abundance is regulated by ER-associated degradation (ERAD) via the ubiquitin-proteasome system. In the absence of Wnt ligands, WLS is ubiquitinated and degraded via ERAD in a VCP-dependent manner. The E2-conjugating enzyme UBE2J2 and E3-ligase CGRRF1 mediate WLS ubiquitination. A triaging complex of Porcupine (Porcn) and VCP determines whether WLS enters the secretory pathway or ERAD, thereby adjusting WLS levels to meet Wnt export demand. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown of ERAD components, functional Wnt secretion assays The EMBO journal High 29378775
2010 WLS/GPR177 physically interacts with the mu-opioid receptor (MOR). This interaction, validated by pulldown, co-immunoprecipitation, and colocalization in mammalian cells and in rodent striatal neurons, is enhanced by morphine treatment, which causes GPR177 to redistribute from cytosol to cell surface. MOR/GPR177 complex formation at the cell periphery inhibits Wnt protein secretion. Split-ubiquitin yeast two-hybrid screen, co-immunoprecipitation, pulldown assay, colocalization in brain tissue, morphine treatment functional assays BMC neuroscience Medium 20214800
2010 Gpr177 (mouse WLS ortholog) is a glycoprotein that primarily accumulates in the Golgi apparatus in Wnt signal-producing cells. Glycosylation of Gpr177 is necessary for proper transportation in the secretory pathway. Subcellular fractionation, immunofluorescence localization, glycosylation assays (tunicamycin treatment, Western blot mobility shift) Developmental dynamics Medium 20549736
2020 TMEM132A physically interacts with WLS, stabilizes Wnt ligand, enhances the WLS-Wnt ligand interaction, and activates the Wnt signaling pathway. Co-immunoprecipitation, Wnt ligand stability assays, Wnt signaling reporter assays Frontiers in cell and developmental biology Medium 33324648
2022 GPR177/WLS in A-fiber dorsal root ganglion neurons mediates the secretion of WNT5a into cerebrospinal fluid, which is necessary for maintenance of diabetic neuropathic pain. WNT5a directly activates TRPV1 ion channels by binding residues at the extracellular S5-S6 loop. A peptide disrupting the WNT5a/TRPV1 interaction suppressed neuropathic pain. Conditional knockout of GPR177 in A-fiber neurons, CSF Wnt5a measurement, electrophysiological patch-clamp recordings of WNT5a-induced TRPV1 currents, computer simulation of WNT5a-TRPV1 binding, peptide inhibitor in rodent behavioral assays Science translational medicine Medium 35385340
2018 MIG-14/WLS has a cell-autonomous, Wnt-independent function in dendrite self-avoidance in C. elegans PVD neurons. Functions of dendrite self-avoidance and Wnt secretion map to distinct MIG-14 domains (genetically separable), and MIG-14 engages WASP-dependent actin assembly to regulate dendrite self-avoidance. C. elegans genetics, domain mapping with deletion constructs, Wnt mutant analysis showing lack of self-avoidance defects, WASP interaction assays Neuron Medium 29673481

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell 458 16678096
2009 Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell 366 19837038
1994 Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. The EMBO journal 350 8313895
1998 The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting Smad3. Nature 302 9665135
2008 Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells. Cell stem cell 243 18682242
2012 Mechanism of evenness interrupted (Evi)-exosome release at synaptic boutons. The Journal of biological chemistry 233 22437826
2008 Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex. Nature cell biology 217 18193037
2007 Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells. Developmental cell 204 18160347
2001 The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling. Blood 194 11313276
1988 Identification of a common ecotropic viral integration site, Evi-1, in the DNA of AKXD murine myeloid tumors. Molecular and cellular biology 184 2827004
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
2009 Smed-Evi/Wntless is required for beta-catenin-dependent and -independent processes during planarian regeneration. Development (Cambridge, England) 155 19211673
2011 Porcupine-mediated lipidation is required for Wnt recognition by Wls. Developmental biology 153 22108505
1992 Expression of the Evi-1 zinc finger gene in 32Dc13 myeloid cells blocks granulocytic differentiation in response to granulocyte colony-stimulating factor. Molecular and cellular biology 148 1370341
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
1993 Four of the seven zinc fingers of the Evi-1 myeloid-transforming gene are required for sequence-specific binding to GA(C/T)AAGA(T/C)AAGATAA. Molecular and cellular biology 127 8321231
1988 Localization of Evi-2 to chromosome 11: linkage to other proto-oncogene and growth factor loci using interspecific backcross mice. Oncogene research 121 2851124
1991 Evi-1, a murine zinc finger proto-oncogene, encodes a sequence-specific DNA-binding protein. Molecular and cellular biology 119 2017172
1992 Evi-1 expression in leukemic patients with rearrangements of the 3q25-q28 chromosomal region. Leukemia 106 1552747
1995 Dual functions of the AML1/Evi-1 chimeric protein in the mechanism of leukemogenesis in t(3;21) leukemias. Molecular and cellular biology 105 7739522
2014 WLS retrograde transport to the endoplasmic reticulum during Wnt secretion. Developmental cell 104 24768165
2000 The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death. The EMBO journal 98 10856240
1990 Unique expression of the human Evi-1 gene in an endometrial carcinoma cell line: sequence of cDNAs and structure of alternatively spliced transcripts. Oncogene 98 2115646
1991 Patterns of Evi-1 expression in embryonic and adult tissues suggest that Evi-1 plays an important regulatory role in mouse development. Development (Cambridge, England) 97 1893871
1994 The carboxyl domain of zinc fingers of the Evi-1 myeloid transforming gene binds a consensus sequence of GAAGATGAG. Oncogene 89 8183551
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
1994 Evi-1 raises AP-1 activity and stimulates c-fos promoter transactivation with dependence on the second zinc finger domain. The Journal of biological chemistry 88 7929053
2011 Gpr177/mouse Wntless is essential for Wnt-mediated craniofacial and brain development. Developmental dynamics : an official publication of the American Association of Anatomists 86 21246653
1990 Evi-2, a common integration site involved in murine myeloid leukemogenesis. Molecular and cellular biology 86 2167436
2001 Evi-1 transforming and repressor activities are mediated by CtBP co-repressor proteins. The Journal of biological chemistry 85 11328817
1998 The t(3;21) fusion product, AML1/Evi-1, interacts with Smad3 and blocks transforming growth factor-beta-mediated growth inhibition of myeloid cells. Blood 79 9834202
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 77 22147553
2010 Evi-1 is a transcriptional target of mixed-lineage leukemia oncoproteins in hematopoietic stem cells. Blood 77 21190993
1990 Identification, nuclear localization, and DNA-binding activity of the zinc finger protein encoded by the Evi-1 myeloid transforming gene. Molecular and cellular biology 76 2106070
2005 Mig-14 is an inner membrane-associated protein that promotes Salmonella typhimurium resistance to CRAMP, survival within activated macrophages and persistent infection. Molecular microbiology 73 15661016
1990 The human homolog of murine Evi-2 lies between two von Recklinghausen neurofibromatosis translocations. Genomics 72 2117565
2005 Repression of bone morphogenetic protein and activin-inducible transcription by Evi-1. The Journal of biological chemistry 70 15849193
1989 Retroviral insertions in the CB-1/Fim-3 common site of integration activate expression of the Evi-1 gene. Oncogene 70 2542863
1990 The Evi-1 zinc finger myeloid transforming gene is normally expressed in the kidney and in developing oocytes. Oncogene 69 1699199
2022 GPR177 in A-fiber sensory neurons drives diabetic neuropathic pain via WNT-mediated TRPV1 activation. Science translational medicine 67 35385340
1997 The Evi-1 proto-oncogene encodes a transcriptional repressor activity associated with transformation. Oncogene 67 9053855
2020 Structural Basis of WLS/Evi-Mediated Wnt Transport and Secretion. Cell 66 33357447
2002 mig-14 is a Salmonella gene that plays a role in bacterial resistance to antimicrobial peptides. Journal of bacteriology 66 12029036
2009 EVI-1 interacts with histone methyltransferases SUV39H1 and G9a for transcriptional repression and bone marrow immortalization. Leukemia 65 19776757
2004 Molecular mechanisms of leukemogenesis by AML1/EVI-1. Oncogene 64 15156182
2012 Wls-mediated Wnts differentially regulate distal limb patterning and tissue morphogenesis. Developmental biology 61 22377357
1996 Expression of the zinc finger gene EVI-1 in ovarian and other cancers. British journal of cancer 61 8932329
1988 Chromosomal location of Evi-1, a common site of ecotropic viral integration in AKXD murine myeloid tumors. Oncogene research 59 2897103
1990 The human Evi-1 gene is located on chromosome 3q24-q28 but is not rearranged in three cases of acute nonlymphocytic leukemias containing t(3;5)(q25;q34) translocations. Oncogene research 56 2108405
2009 Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells. Oncogene 55 19767769
1990 Alternative splicing of the Evi-1 zinc finger gene generates mRNAs which differ by the number of zinc finger motifs. Oncogene 55 2113669
2010 Interaction of the mu-opioid receptor with GPR177 (Wntless) inhibits Wnt secretion: potential implications for opioid dependence. BMC neuroscience 52 20214800
1995 Retroviral integration at the Evi-2 locus in BXH-2 myeloid leukemia cell lines disrupts Nf1 expression without changes in steady-state Ras-GTP levels. Journal of virology 50 7609078
2021 WLS-Wnt signaling promotes neuroendocrine prostate cancer. iScience 49 33437943
1995 EVI-1 zinc finger protein works as a transcriptional activator via binding to a consensus sequence of GACAAGATAAGATAAN1-28 CTCATCTTC. Oncogene 47 7761097
1996 Structurally altered Evi-1 protein generated in the 3q21q26 syndrome. Oncogene 46 8700545
2018 ERAD-dependent control of the Wnt secretory factor Evi. The EMBO journal 45 29378775
2013 Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis. The Journal of experimental medicine 45 23918954
2001 The leukaemia-associated transcription factors EVI-1 and MDS1/EVI1 repress transcription and interact with histone deacetylase. British journal of haematology 45 11552981
1998 The AML1/ETO(MTG8) and AML1/Evi-1 leukemia-associated chimeric oncoproteins accumulate PEBP2beta(CBFbeta) in the nucleus more efficiently than wild-type AML1. Blood 44 9473235
1995 Evi-5, a common site of retroviral integration in AKXD T-cell lymphomas, maps near Gfi-1 on mouse chromosome 5. Journal of virology 44 7474133
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
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
2012 EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia. Leukemia 40 22828445
2007 Regulation of anchor cell invasion and uterine cell fates by the egl-43 Evi-1 proto-oncogene in Caenorhabditis elegans. Developmental biology 40 17573066
2005 Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP. Oncogene 40 15897867
1992 Analysis of proviruses integrated in Fli-1 and Evi-1 regions in Cas-Br-E MuLV-induced non-T-, non-B-cell leukemias. Virology 40 1448920
2013 Gpr177, a novel locus for bone mineral density and osteoporosis, regulates osteogenesis and chondrogenesis in skeletal development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 38 23188710
2008 Evi-1 promotes para-aortic splanchnopleural hematopoiesis through up-regulation of GATA-2 and repression of TGF-b signaling. Cancer science 38 18452556
1994 Identification of Evi-3, a novel common site of retroviral integration in mouse AKXD B-cell lymphomas. Journal of virology 38 8107195
2015 Primary acute myeloid leukemia cells with overexpression of EVI-1 are sensitive to all-trans retinoic acid. Blood 36 26582376
2014 Wls provides a new compartmental view of the rhombic lip in mouse cerebellar development. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 25209290
2012 Wls is expressed in the epidermis and regulates embryonic hair follicle induction in mice. PloS one 36 23029304
1995 Expression of the Evi-1 gene in myelodysplastic syndromes. Leukemia 35 7845018
2020 TMEM132A, a Novel Wnt Signaling Pathway Regulator Through Wntless (WLS) Interaction. Frontiers in cell and developmental biology 33 33324648
2011 Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer. Molecular carcinogenesis 33 22161860
1998 Evi-1 ZF1 DNA binding activity and a second distinct transcriptional repressor region are both required for optimal transformation of Rat1 fibroblasts. Oncogene 32 9619838
2013 Gpr177 regulates pulmonary vasculature development. Development (Cambridge, England) 31 23884445
2010 Evi-1 as a critical regulator of leukemic cells. International journal of hematology 30 20532840
2010 Expression of Gpr177, a Wnt trafficking regulator, in mouse embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 30 20549736
2000 The EVI-1 gene--its role in pathogenesis of human leukemias. Leukemia research 30 10867128
1999 The transcription factor Evi-1. The international journal of biochemistry & cell biology 30 10641791
2014 Focal chromosomal copy number aberrations identify CMTM8 and GPR177 as new candidate driver genes in osteosarcoma. PloS one 29 25551557
2010 Expression of GPR177 (Wntless/Evi/Sprinter), a highly conserved Wnt-transport protein, in rat tissues, zebrafish embryos, and cultured human cells. Developmental dynamics : an official publication of the American Association of Anatomists 29 20652957
2000 mig-14 is a horizontally acquired, host-induced gene required for salmonella enterica lethal infection in the murine model of typhoid fever. Infection and immunity 29 11083839
2002 The t(3;21) fusion product, AML1/Evi-1 blocks AML1-induced transactivation by recruiting CtBP. Oncogene 28 11965542
2013 Inactivation of evenness interrupted (EVI) reduces experimental fibrosis by combined inhibition of canonical and non-canonical Wnt signalling. Annals of the rheumatic diseases 27 24257024
2014 Survivin modulates genes with divergent molecular functions and regulates proliferation of hematopoietic stem cells through Evi-1. Leukemia 26 24903482
2010 The role of Runx1/AML1 and Evi-1 in the regulation of hematopoietic stem cells. Journal of cellular physiology 26 19847803
1992 Expression and regulation of the evi-1 gene in the human factor-dependent leukemia cell line, UCSD/AML1. Leukemia 26 1593910
2002 The human promyelocytic leukemia zinc finger gene is regulated by the Evi-1 oncoprotein and a novel guanine-rich site binding protein. Leukemia 25 12200691
1999 Loss of cell cycle control by deregulation of cyclin-dependent kinase 2 kinase activity in Evi-1 transformed fibroblasts. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 25 10511310
2018 Cell-Autonomous Regulation of Dendrite Self-Avoidance by the Wnt Secretory Factor MIG-14/Wntless. Neuron 24 29673481
2014 Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 24 25258105
2012 WLS inhibits melanoma cell proliferation through the β-catenin signalling pathway and induces spontaneous metastasis. EMBO molecular medicine 24 23129487
2015 Wls promotes the proliferation of breast cancer cells via Wnt signaling. Medical oncology (Northwood, London, England) 23 25801232
2015 Gpr177-mediated Wnt Signaling Is Required for Secondary Palate Development. Journal of dental research 23 25922332

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