Affinage

MAL

Myelin and lymphocyte protein · UniProt P21145

Audit flag: model fault
Length
153 aa
Mass
16.7 kDa
Annotated
2026-06-13
100 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

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Mechanism profile

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Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 MAL encodes a highly hydrophobic proteolipid protein with four putative transmembrane domains, initially identified as expressed in intermediate and late stages of T-cell differentiation, with predicted configuration resembling integral membrane proteins that form pores or channels. cDNA cloning, sequence analysis, hydrophobicity profiling Proceedings of the National Academy of Sciences of the United States of America Medium 3494249
1994 MAL protein is a proteolipid (soluble in organic lipid-extraction solvents), is encoded by a 4-exon gene where each exon corresponds to one hydrophobic segment, and localizes to the endoplasmic reticulum of T cells. A C-terminal RWKSS motif consistent with ER retention signals was identified. Genomic cloning, RNase protection, recombinant expression in bacteria with lipophilic solvent extraction, immunofluorescence with two distinct anti-peptide antibodies The Journal of biological chemistry Medium 8132541
1995 MAL (MVP17) is a developmentally regulated proteolipid in oligodendrocytes that co-purifies with detergent-insoluble, glycolipid-rich membrane microdomains, consistent with a role in myelin biogenesis. Detergent-insoluble membrane fractionation, 2D gel electrophoresis, N-terminal microsequencing, cDNA cloning from oligodendrocyte library, Northern blot Journal of neuroscience research Medium 8583510
1995 VIP17/MAL is a proteolipid component of apical transport vesicles in MDCK cells, localizing to perinuclear vesicles and the apical cytoplasm, cycling between the Golgi and the apical plasma membrane. cDNA cloning, immunofluorescence of epitope-tagged VIP17/MAL in BHK and MDCK cells FEBS letters Medium 8549777
1997 MAL proteolipid is exclusively incorporated into detergent-resistant, buoyant membrane microdomains (lipid rafts) in both T lymphocytes (Jurkat) and epithelial cells, co-fractionating with p56lck, CD59, and GM1. Stable transfection of epitope-tagged MAL, Triton X-100 extraction, sucrose gradient fractionation, immunofluorescence The Biochemical journal Medium 9003426
1997 MAL and caveolin occupy distinct lipid microenvironments within MDCK cells; MAL is in internal glycolipid-enriched detergent-insoluble membranes while caveolin is additionally found at the cell surface, demonstrating heterogeneity within raft fractions. Sucrose gradient fractionation, immunofluorescence, differential detergent solubilization Biochemical and biophysical research communications Medium 9168919
1998 A C-terminal juxtamembrane tetrapeptide motif LIRW in MAL is necessary for incorporation into glycolipid-enriched membrane (GEM) microdomains; arginine is the most critical residue. Loss of GEM targeting correlates with loss of MAL's response to brefeldin A treatment. Site-directed mutagenesis, sucrose gradient fractionation of GEMs, pulse-chase experiments, brefeldin A treatment The Journal of biological chemistry High 9582298
1998 MAL is expressed specifically in thyroid follicular epithelial cells, localizing to the apical zone, and is a major component of GEM fractions in the polarized thyroid epithelial cell line FRT, consistent with a role in apical sorting in thyroid epithelium. Northern blot, immunohistochemistry with anti-MAL monoclonal antibody, GEM fractionation of FRT cells Endocrinology Medium 9528996
1999 MAL depletion by antisense oligonucleotides in MDCK cells reduces the presence of influenza hemagglutinin (HA) in GEMs, decreases the rate of HA transport to the cell surface, inhibits apical delivery, and causes partial missorting of HA to the basolateral membrane. Ectopic MAL expression rescues these defects, demonstrating that MAL is necessary for both normal apical transport and accurate sorting of HA. Antisense oligonucleotides, newly generated anti-canine MAL monoclonal antibody, surface biotinylation, apical/basolateral sorting assay, ectopic MAL rescue The Journal of cell biology High 10189374
1999 Overexpression of VIP17/MAL in MDCK cells increases apical delivery and expands the apical surface, while antisense-mediated reduction causes accumulation in the Golgi and impairs apical transport of multiple apical markers (HA, clusterin, gp114, GPI-anchored protein) without affecting basolateral E-cadherin distribution. Antisense RNA expression, overexpression, immunofluorescence, transport assays for multiple apical cargo proteins Proceedings of the National Academy of Sciences of the United States of America High 10339572
1999 MAL is an itinerant protein that cycles between the trans-Golgi network and the plasma membrane: it is expressed at the cell surface, rapidly internalized via an endosomal pathway requiring endosomal acidification, and ~30% of internalized MAL is delivered back to the TGN to restart the transport cycle. Epitope-tagged and O-glycosylatable/biotinylatable MAL constructs, surface biotinylation, anti-FLAG surface binding, neuraminidase sensitivity assay, resialylation experiment, drug treatments (chloroquine, monensin, NH4Cl), flow cytometry Molecular biology of the cell High 10512878
2001 MAL (MyD88-adapter-like) is a TIR-domain-containing cytoplasmic adapter protein that activates NF-κB, JNK, and ERK1/2; forms homodimers and heterodimers with MyD88; associates with TLR4 and with IRAK-2 via its TIR domain; and acts as an adapter specifically in TLR-4 signal transduction. A dominant-negative form of Mal inhibits NF-κB activated by TLR-4 or LPS but not by IL-1RI or IL-18R. Co-immunoprecipitation, overexpression, dominant-negative constructs, NF-κB/JNK/ERK reporter assays, two-hybrid interaction assays Nature High 11544529
2003 Purified TIR domains of MAL and MyD88 form stable heterodimers in vitro; MAL homodimers/oligomers are dissociated by ATP. Structural modeling and GST pull-down/co-IP experiments indicate MAL and MyD88 bind to different, non-overlapping surfaces on TLR2 and TLR4 TIR domains, suggesting a heterotetrameric receptor-adapter complex. A sequence relationship between Drosophila Tube and MAL was identified. In vitro TIR domain purification, gel filtration, GST pull-down, co-immunoprecipitation, computational structural modeling and docking The Journal of biological chemistry High 12888566
2004 Genetic ablation of MAL in mice results in cytoplasmic inclusions in compact myelin, everted paranodal loops, disorganized transverse bands, and reduced levels of contactin-associated protein/paranodin, NF155, Kv1.2, MAG, and MBP in myelin and myelin-derived rafts, demonstrating MAL is required for maintenance of CNS paranode structure, likely by controlling NF155 trafficking/sorting in oligodendrocytes. MAL knockout mice, electron microscopy, immunofluorescence, Western blotting of myelin fractions and raft fractions The Journal of cell biology High 15337780
2006 MAL undergoes tyrosine phosphorylation at positions 86, 187 (and 106) during TLR2 and TLR4 signaling. Bruton's tyrosine kinase (Btk) is identified as the kinase: Btk immunoprecipitated from LPS-activated THP-1 cells directly phosphorylates MAL in vitro, and the Btk inhibitor LFM-A13 blocks endogenous MAL tyrosine phosphorylation. Tyrosine-to-phenylalanine mutations at positions 86 and 187 act as dominant-negative inhibitors of LPS-induced NF-κB activation. Phosphotyrosine immunoprecipitation, site-directed mutagenesis (Y86F, Y187F), Btk kinase inhibitor (LFM-A13), in vitro kinase assay with immunoprecipitated Btk, THP-1 cell stimulation The Journal of biological chemistry High 16439361
2006 MAL interacts with SRF through a conserved seven-residue B1 region sequence that is essential and sufficient for complex formation; the neighboring Q-box facilitates interaction. MAL directly contacts DNA flanking the SRF-protected region in the MAL-SRF-DNA complex, and these contacts are required for effective MAL-SRF complex formation. SRF-induced DNA bending facilitates MAL-DNA contact. MAL-SRF and TCF-SRF use different mechanisms to engage the same SRF hydrophobic groove/pocket. Deletion and point mutagenesis of MAL B1/Q-box regions, GST pull-downs, gel mobility shift assays, DNase I footprinting, SRF mutagenesis Molecular and cellular biology High 16705166
2006 MAL/MKL1 (SRF co-activator) is expressed in developing neurons, localizes to neuronal cell bodies and apical dendrites, and is required for dendritic morphology: dominant-negative MAL constructs or MAL siRNA reduce the number of dendritic processes in cultured cortical neurons and decrease basal SRF-mediated transcription. Immunohistochemistry of mouse brain, dominant-negative construct expression, siRNA knockdown, dendritic morphology analysis, SRF reporter assay in primary cortical neurons Journal of neurochemistry Medium 16945101
2009 MAL directly interacts with the p85α regulatory subunit of PI3K in an inducible manner upon TLR2/6 stimulation with diacylated lipoproteins, driving PI3K-dependent Akt phosphorylation, PIP3 generation, and macrophage polarization independently of MyD88. Co-immunoprecipitation (inducible Mal-p85α interaction), PI3K activity assay, Akt phosphorylation assay, PIP3 measurement, MyD88-deficient cell analysis The EMBO journal High 19574958
2009 Actin-MAL-SRF signaling induces Mig6/Errfi-1 expression, a negative regulator of EGFR. MAL is inducibly recruited to and activates the mig6 promoter. Upregulation of Mig6 correlates with decreased EGFR, MAPK/Erk, and c-fos activation; overexpression of MAL has antiproliferative effects requiring domains for SRF binding and transactivation. Gene expression profiling, chromatin immunoprecipitation (ChIP) of MAL at mig6 promoter, MAL overexpression/siRNA knockdown, EGFR/MAPK activation assays Molecular cell High 19683494
2009 MAL clusters laterally concentrate sphingolipid raft markers and exclude phosphatidylethanolamine analogues. MAL forms oligomers via intramembrane protein-protein binding motifs (demonstrated by site-directed mutagenesis and bimolecular fluorescence complementation). MAL-raft association is driven in part by positive hydrophobic mismatch between MAL transmembrane helices and membrane lipids. Antibody-mediated cross-linking of FLAG-tagged MAL, tandem dimer DiHcRED-MAL spontaneous clustering, site-directed mutagenesis of intramembrane motifs, bimolecular fluorescence complementation (BiFC), exogenous cholesterol/ceramide membrane modulation Molecular biology of the cell High 19553470
2010 IRAK1 and IRAK4 directly phosphorylate MAL (but not MyD88). Co-expression of Mal with either IRAK causes depletion of Mal from cell lysates; LPS stimulation triggers ubiquitination and degradation of Mal; this is inhibited by IRAK1/4 kinase inhibitor or IRAK1/4 knockdown. Phosphorylation by IRAKs thus promotes ubiquitination and degradation of Mal, serving as a negative regulatory mechanism for TLR2/TLR4 signaling. In vitro kinase assay (direct phosphorylation of Mal by IRAK1/4), kinase-inactive IRAK mutants, co-expression degradation assay, ubiquitination assay, IRAK1/4 siRNA knockdown, IRAK inhibitor treatment The Journal of biological chemistry High 20400509
2010 MAL interacts with Inverted Formin 2 (INF2) in Jurkat T cells, where they colocalize at the cell periphery, pericentriolar endosomes, and along microtubules. MAL+ vesicles transport Lck to the plasma membrane along microtubule tracks. INF2 knockdown greatly reduces MAL+ transport vesicle formation and Lck plasma membrane levels and impairs immunological synapse formation. Both actin polymerization and depolymerization activities of INF2 are required. Cdc42 and Rac1 regulate this Lck transport process. Co-immunoprecipitation, videomicroscopy (live imaging of MAL+ vesicle movement), INF2 siRNA knockdown, INF2 activity mutants, Cdc42/Rac1 manipulation in Jurkat and primary T cells Blood High 20881207
2010 MAL/VIP17 coimmunoprecipitates with NKCC2 (Na+-K+-2Cl- cotransporter) in LLC-PK1 cells and rat kidney medullae; a 150-amino-acid stretch of the NKCC2 C-terminal tail mediates the interaction. MAL/VIP17 overexpression increases NKCC2 cell surface retention by attenuating internalization and coincides with increased cotransporter phosphorylation. Transgenic mice overexpressing MAL/VIP17 show cyst formation in distal nephron with highly glycosylated and phosphorylated NKCC2. Co-immunoprecipitation, truncation mutagenesis of NKCC2, surface biotinylation internalization assay, Western blotting for phosphorylation, transgenic mouse model Molecular biology of the cell High 20861303
2011 MAL localizes to the central SMAC (cSMAC) of the immunological synapse (IS) in T cells, where it colocalizes with condensed membranes. Mislocalization of MAL to the peripheral SMAC (pSMAC) reduces membrane condensation at the cSMAC, redistributes microtubule/vesicle docking machinery, and causes missorting of raft-associated Lck and LAT (but not TCR) to the pSMAC. MAL thus regulates membrane order and protein sorting at the IS. Live imaging, Laurdan fluorescent probe for membrane condensation, MAL mislocalization constructs, co-localization analysis in Jurkat and primary T cells Journal of immunology High 21508261
2011 Mal is required for TLR2- and TLR4-induced CREB activation in macrophages. Mal-deficient macrophages fail to express CREB-responsive genes IL-10 and COX-2 in response to TLR2/TLR4 ligands. This pathway requires Pellino3, TRAF6, p38 MAPK, and MAPK-activated protein kinase 2 (MK2), which is directly activated by Mal. Mal-deficient murine macrophages (BMDM), CREB reporter/phosphorylation assays, Pellino3 siRNA knockdown, TRAF6-deficient cells, p38 MAPK inhibitor, MK2 inhibition, overexpression assays Journal of immunology Medium 21398611
2012 MAL/MRTF-A upregulates cytoskeleton-associated genes including integrin α5, plakophilin 2 (Pkp2), and FHL1 via direct SRF recruitment to their cis-regulatory elements (shown by ChIP). Elevated MAL expression impairs migration of fibroblasts and epithelial cells, while dominant-negative MAL or partial knockdown enhances motility. Knockdown of Pkp2 and FHL1 partially reverses MAL-induced migration inhibition. ChIP of MAL and SRF at integrin α5 and Pkp2 gene regulatory elements, active MAL and dominant-negative constructs, MAL knockdown, siRNA of target genes, cell migration assay Journal of cell science High 22223881
2013 Mal interacts with multiple protein kinase C (PKC) isoforms in intestinal epithelial cells (Caco-2). Inhibition of Mal or PKC increases paracellular permeability and bacterial invasion. Mal-deficient mice show altered expression of tight junction proteins (occludin, ZO-1, claudin-3) and increased susceptibility to oral Salmonella infection; bone marrow chimeras indicate the role is in non-hematopoietic (epithelial) cells. Co-immunoprecipitation (Mal-PKC), transepithelial resistance measurement, Mal−/− mice, bone marrow chimeras, oral vs. intraperitoneal infection comparison, tight junction protein Western blot/IF Mucosal immunology Medium 23612054
2014 Genetic evidence in both Drosophila and human cellular models establishes that actin is the key MAL/SRF target gene required for invasive cell migration. Actin protein feeds back on actin mRNA production via MAL/SRF, constituting a dedicated homeostatic feedback loop ensuring sufficient actin supply. Genetic epistasis in Drosophila (MAL-D mutants rescued by actin overexpression), human cell models with specific actin manipulation, gene expression analysis Genes & development High 24831700
2015 MAL (myelin and lymphocyte protein) is required for binding of Clostridium perfringens ε-toxin (ETX) to mammalian cells and for ETX-mediated cytotoxicity. Native CHO cells are resistant to ETX; exogenous MAL expression confers ETX binding and cell death susceptibility. FLAG insertion into the second extracellular loop of MAL abolishes ETX binding. MAL-knockout mice show complete absence of ETX binding to tissues and complete resistance to ETX at doses >1000x the symptomatic dose for wild-type mice. Exogenous MAL expression in CHO cells, FLAG epitope insertion mutagenesis, ETX binding assay, cytotoxicity assay, MAL knockout mice, immunofluorescence tissue binding PLoS pathogens High 25993478
2016 Mal has a TLR-independent role in IFN-γ receptor (IFNGR) signaling: Mal-dependent IFNGR signaling leads to p38 MAPK phosphorylation and autophagy, is required for phagosome maturation and killing of intracellular M. tuberculosis. The common S180L Mal polymorphism (S200L in mice) reduces Mal's affinity for the IFNGR, thereby compromising IFNGR signaling in macrophages. Mal-deficient macrophages, IFNGR co-immunoprecipitation with Mal, p38 phosphorylation assays, autophagy assays, phagosome maturation assay, Mtb killing assay, S200L knock-in mice Immunity High 26885859
2017 MAL TIR domains spontaneously and reversibly form filaments in vitro; they form co-filaments with TLR4 TIR domains and induce MyD88 assembly. A 7-Å cryo-EM structure reveals a stable MAL protofilament of two parallel TIR-domain strands in a BB-loop-mediated head-to-tail arrangement. Structure-guided mutagenesis of interface residues combined with in vivo interaction assays shows these MAL interactions represent a conserved mode of TIR-domain interaction for TLR and IL-1R signaling. Cryo-EM (7-Å resolution), in vitro TIR domain filament reconstitution, site-directed mutagenesis of interface residues, in vivo interaction assays Nature structural & molecular biology High 28759049
2017 Src family kinase (SFK) activation induces tyrosine phosphorylation of TLR4, which dissociates both MyD88 and Mal/TIRAP from TLR4 and suppresses LPS-induced NFκB and JNK1/2 activation, constituting a negative feedback loop. Kinase-dead SFK-Lyn inhibits TLR4 tyrosine phosphorylation and has reduced binding to TLR4, whereas constitutively active SFK-Lyn strongly promotes TLR4 phosphorylation. Chemical rescuing approach for temporal SFK activation, TLR4 co-immunoprecipitation with MyD88/Mal, kinase-dead and constitutively active SFK-Lyn mutants, NFκB/JNK reporter assays Biochemical pharmacology Medium 29175418
2019 MAL is required for ETX-induced blood-brain barrier permeability through caveolae-dependent transcytosis in brain endothelial cells. ETX binding to CNS microvasculature is MAL-dependent (absent in MAL-/- mice). ETX-induced BBB permeability additionally requires caveolin-1: MAL-/- or caveolin-1-/- mice do not show ETX-induced BBB permeability. ETX treatment increases caveolae in brain endothelial cells and causes loss of EEA1+ early endosomes with accumulation of RAB7+ late endosomes/MVBs. MAL-/- and caveolin-1-/- mice, intravascular ETX injection, molecular tracer extravasation (fluorescein, albumin, dextran, IgG), primary murine brain endothelial cell analysis, EEA1/RAB7 immunofluorescence, electron microscopy of caveolae PLoS pathogens High 31703116
2024 Upon LPS stimulation, lysine acetyltransferase CBP is recruited to the TLR4 signalosome, leading to acetylation of the TIR domains of TLR4, MAL, and MyD88. This TIR domain acetylation enhances NF-κB (but not IRF3) pathway activation and M1 macrophage polarization. HDAC1 deacetylates the TIR domains; pharmacological modulation of CBP or HDAC1 plays opposite roles in sepsis. LPS stimulation of macrophages, CBP co-immunoprecipitation with TLR4 signalosome, acetylation mass spectrometry, NF-κB/IRF3 reporter assays, HDAC1 inhibitor, CBP inhibitor, patient monocyte analysis The EMBO journal Medium 39294473
2006 Protein kinase Cδ (PKCδ) binds to TIRAP/Mal via the TIR domain of TIRAP/Mal. TLR2- and TLR4-mediated phosphorylation of p38 MAPK, IKK, and IκB in RAW264.7 cells is abolished by depletion of PKCδ. GST-fusion pull-down, co-immunoprecipitation from macrophage and THP1 lysates, TIRAP/Mal truncation mutants, PKCδ depletion (siRNA), p38/IKK/IκB phosphorylation assays Molecular immunology Medium 17161867
2011 Poxvirus A46 protein binds to MAL/TIRAP via a dimeric α-helical C-terminal domain. Biophysical analysis shows this A46 segment adopts a dimeric α-helical structure and interacts with monomeric Mal in vitro. The A46-derived peptide VIPER does not interact with Mal in vitro. Biophysical binding assays (in vitro), A46 C-terminal domain expression and dimerization characterization, Mal binding assay Molecular immunology Medium 21831443
2009 In epithelial cells, dissociation of E-cadherin-dependent cell-cell junctions activates SRF-mediated transcription via monomeric actin and MAL. This pathway requires Rac1 (not RhoA) and actomyosin contractility as a prerequisite. Rac1 inhibition blocks MAL/SRF activation during junction disassembly in contrast to the Rho-ROCK pathway used in serum-stimulated fibroblasts. Ca2+-dependent junction dissociation, clostridial cytotoxin inhibition of Rac vs. RhoA, MAL reporter assays, direct evidence of actin-MAL signaling Journal of cell science Medium 18334560
2004 Border cell migration in Drosophila oogenesis requires SRF and its cofactor MAL-D; nuclear accumulation of MAL-D is induced by cell stretching/tension. Border cells that cannot migrate lack nuclear MAL-D but accumulate it when pulled by other cells. MAL-D responds to activated Diaphanous (affecting actin dynamics). MAL-D/SRF activity builds a robust actin cytoskeleton in migrating cells; mutant cells break apart during migration initiation. Drosophila genetics (MAL-D and SRF mutants), live imaging of border cell migration, nuclear localization assay under tension, activated Diaphanous expression Developmental cell High 15239956
2009 MAL/SRF complex directly regulates MYL9 (MLC2) and MMP9 transcription in megakaryocytes, as demonstrated by luciferase assays and ChIP in primary megakaryocytes. MAL knockdown reduces filopodia/lamellipodia/stress fiber formation, proplatelet formation, and megakaryocyte migration (via MMP9). MAL expression increases during late megakaryopoiesis and localizes to the nucleus after Rho GTPase activation by adhesion. ChIP in primary megakaryocytes, luciferase assays (HEK293T), MAL siRNA knockdown, gene expression profiling, migration assay through Matrigel, MYL9 shRNA knockdown Blood High 19724058
2016 In urothelial umbrella cells, MAL facilitates apical fusion of uroplakin-delivering fusiform vesicles (FVs). Sequential action is established: Rab8/11 and Rab27b/Slac2-a mediate apical transport along actin; Rab27b/Slp2-a mediates membrane anchorage; then SNARE-mediated and MAL-facilitated apical fusion occurs. Rab27b acts upstream of MAL in this pathway. Immunomicroscopy of normal and mutant mouse urothelia, Rab27b knockout mice, epistasis analysis placing Rab27b upstream of MAL Molecular biology of the cell Medium 27009205

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 940 11544529
1999 VIP17/MAL, a lipid raft-associated protein, is involved in apical transport in MDCK cells. Proceedings of the National Academy of Sciences of the United States of America 176 10339572
2001 Mutations in the gene encoding SLURP-1 in Mal de Meleda. Human molecular genetics 170 11285253
2006 MyD88 adapter-like (Mal) is phosphorylated by Bruton's tyrosine kinase during TLR2 and TLR4 signal transduction. The Journal of biological chemistry 165 16439361
2003 Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88. The Journal of biological chemistry 159 12888566
2004 Evidence for tension-based regulation of Drosophila MAL and SRF during invasive cell migration. Developmental cell 152 15239956
2017 Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling. Nature structural & molecular biology 151 28759049
1987 cDNA cloning and sequence of MAL, a hydrophobic protein associated with human T-cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 150 3494249
1999 The MAL proteolipid is necessary for normal apical transport and accurate sorting of the influenza virus hemagglutinin in Madin-Darby canine kidney cells. The Journal of cell biology 149 10189374
2015 Amygdala-prefrontal interactions in (mal)adaptive learning. Trends in neurosciences 143 25583269
2002 Toll-like receptor signal transduction and the tailoring of innate immunity: a role for Mal? Trends in immunology 128 12072368
1989 Molecular evolution of the telomere-associated MAL loci of Saccharomyces. Genetics 122 2548922
1995 Cloning and characterization of MVP17: a developmentally regulated myelin protein in oligodendrocytes. Journal of neuroscience research 119 8583510
2004 The raft-associated protein MAL is required for maintenance of proper axon--glia interactions in the central nervous system. The Journal of cell biology 118 15337780
2012 Disconnection and reconnection: the morphological basis of (mal)adaptation to stress. Trends in neurosciences 110 23000140
2013 CADM1 and MAL promoter methylation levels in hrHPV-positive cervical scrapes increase proportional to degree and duration of underlying cervical disease. International journal of cancer 107 23456988
2002 MAL expression in lymphoid cells: further evidence for MAL as a distinct molecular marker of primary mediastinal large B-cell lymphomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 106 12429796
1995 VIP17/MAL, a proteolipid in apical transport vesicles. FEBS letters 101 8549777
2009 Mal connects TLR2 to PI3Kinase activation and phagocyte polarization. The EMBO journal 96 19574958
1999 The MAL gene is expressed in primary mediastinal large B-cell lymphoma. Blood 93 10552968
2004 Caveolin-1 and MAL are located on prostasomes secreted by the prostate cancer PC-3 cell line. Journal of cell science 92 15466889
2009 Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction. Molecular cell 90 19683494
2014 CADM1, MAL and miR124-2 methylation analysis in cervical scrapes to detect cervical and endometrial cancer. Journal of clinical pathology 86 25281766
2012 Triangulated mal-signaling in Alzheimer's disease: roles of neurotoxic ceramides, ER stress, and insulin resistance reviewed. Journal of Alzheimer's disease : JAD 86 22337830
2009 Repression of MAL tumour suppressor activity by promoter methylation during cervical carcinogenesis. The Journal of pathology 86 19662663
2015 Engineered VEGF-releasing PEG-MAL hydrogel for pancreatic islet vascularization. Drug delivery and translational research 85 25787738
2006 MAL and ternary complex factor use different mechanisms to contact a common surface on the serum response factor DNA-binding domain. Molecular and cellular biology 84 16705166
2008 Epithelial cell-cell contacts regulate SRF-mediated transcription via Rac-actin-MAL signalling. Journal of cell science 81 18334560
2000 MAL, a proteolipid in glycosphingolipid enriched domains: functional implications in myelin and beyond. Progress in neurobiology 81 10739088
1999 MAL, an integral element of the apical sorting machinery, is an itinerant protein that cycles between the trans-Golgi network and the plasma membrane. Molecular biology of the cell 80 10512878
2015 The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of Clostridium perfringens ε-Toxin. PLoS pathogens 73 25993478
2009 MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9. Blood 66 19724058
2011 Mal mediates TLR-induced activation of CREB and expression of IL-10. Journal of immunology (Baltimore, Md. : 1950) 61 21398611
2003 Mal and MyD88: adapter proteins involved in signal transduction by Toll-like receptors. Journal of endotoxin research 60 12691620
2012 MAL/MRTF-A controls migration of non-invasive cells by upregulation of cytoskeleton-associated proteins. Journal of cell science 59 22223881
1995 Differential expression of mal genes under cAMP and endogenous inducer control in nutrient-stressed Escherichia coli. Molecular microbiology 59 7651130
1998 Expression of the MAL gene in the thyroid: the MAL proteolipid, a component of glycolipid-enriched membranes, is apically distributed in thyroid follicles. Endocrinology 57 9528996
2010 Formin INF2 regulates MAL-mediated transport of Lck to the plasma membrane of human T lymphocytes. Blood 55 20881207
2008 Adaptation and mal-adaptation to ambient hypoxia; Andean, Ethiopian and Himalayan patterns. PloS one 53 18523639
2016 NDE1 and NDEL1 from genes to (mal)functions: parallel but distinct roles impacting on neurodevelopmental disorders and psychiatric illness. Cellular and molecular life sciences : CMLS 52 27742926
2010 IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88 adaptor-like (Mal). The Journal of biological chemistry 52 20400509
2015 DNA hypermethylation and decreased mRNA expression of MAL, PRIMA1, PTGDR and SFRP1 in colorectal adenoma and cancer. BMC cancer 51 26482433
2011 MAL protein controls protein sorting at the supramolecular activation cluster of human T lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 51 21508261
2009 Clustering and lateral concentration of raft lipids by the MAL protein. Molecular biology of the cell 51 19553470
1999 Protease activation in apoptosis induced by MAL. Experimental cell research 51 10366425
2013 Mal, more than a bridge to MyD88. IUBMB life 50 23983209
2010 Elevated MAL expression is accompanied by promoter hypomethylation and platinum resistance in epithelial ovarian cancer. International journal of cancer 48 19642140
1996 Expression, purification, and ligand-binding analysis of recombinant keratinocyte lipid-binding protein (MAL-1), an intracellular lipid-binding found overexpressed in neoplastic skin cells. Biochemistry 48 8608126
2007 The Troll in Toll: Mal and Tram as bridges for TLR2 and TLR4 signaling. Journal of leukocyte biology 47 17449723
1997 The MAL proteolipid is a component of the detergent-insoluble membrane subdomains of human T-lymphocytes. The Biochemical journal 47 9003426
2010 SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda. The British journal of dermatology 44 20854438
2010 Epigenetic silencing of MAL, a putative tumor suppressor gene, can contribute to human epithelium cell carcinoma. Molecular cancer 43 21092172
2018 HPV E4 expression and DNA hypermethylation of CADM1, MAL, and miR124-2 genes in cervical cancer and precursor lesions. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 42 30135508
2006 Protein kinase Cdelta binds TIRAP/Mal to participate in TLR signaling. Molecular immunology 42 17161867
1997 Myelin and lymphocyte protein (MAL/MVP17/VIP17) and plasmolipin are members of an extended gene family. Gene 42 9168137
1997 Caveolin and MAL, two protein components of internal detergent-insoluble membranes, are in distinct lipid microenvironments in MDCK cells. Biochemical and biophysical research communications 41 9168919
2013 Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer. Oncology reports 40 23381221
2013 Differential role of MyD88 and Mal/TIRAP in TLR2-mediated gastric tumourigenesis. Oncogene 40 23728346
2004 Expression of MAL and MAL2, two elements of the protein machinery for raft-mediated transport, in normal and neoplastic human tissue. Histology and histopathology 40 15168355
2019 Conservation through the lens of (mal)adaptation: Concepts and meta-analysis. Evolutionary applications 39 31417615
2017 Structure of the Major Apple Allergen Mal d 1. Journal of agricultural and food chemistry 38 28161953
2013 Current methods for photodynamic therapy in the US: comparison of MAL/PDT and ALA/PDT. Journal of drugs in dermatology : JDD 36 23986167
2006 Developmental expression of the SRF co-activator MAL in brain: role in regulating dendritic morphology. Journal of neurochemistry 36 16945101
1994 Genomic structure and subcellular localization of MAL, a human T-cell-specific proteolipid protein. The Journal of biological chemistry 36 8132541
2017 Src family kinase tyrosine phosphorylates Toll-like receptor 4 to dissociate MyD88 and Mal/Tirap, suppressing LPS-induced inflammatory responses. Biochemical pharmacology 35 29175418
2016 Mal de Meleda: A Focused Review. American journal of clinical dermatology 35 26445964
2010 Characterization and expression analysis of a maltose-utilizing (MAL) cluster in Aspergillus oryzae. Fungal genetics and biology : FG & B 35 19850146
2014 The core and conserved role of MAL is homeostatic regulation of actin levels. Genes & development 34 24831700
2019 CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions. International journal of molecular sciences 33 31067838
2008 Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-talk between MyD88 and FAK pathways. Journal of immunology (Baltimore, Md. : 1950) 32 18292575
2003 Features of influenza HA required for apical sorting differ from those required for association with DRMs or MAL. Traffic (Copenhagen, Denmark) 32 14617347
2015 Preliminary evaluation of [18F]AlF-NOTA-MAL-Cys39-exendin-4 in insulinoma with PET. Journal of drug targeting 31 25758750
1992 Chromosome mal-orientation and reorientation during mitosis. Cell motility and the cytoskeleton 31 1423661
2019 HSV-1/TLR9-Mediated IFNβ and TNFα Induction Is Mal-Dependent in Macrophages. Journal of innate immunity 30 31851971
2004 Characterisation of Mal d 1-related genes in Malus. Plant molecular biology 30 15604687
2010 MAL/VIP17, a new player in the regulation of NKCC2 in the kidney. Molecular biology of the cell 29 20861303
2017 Human Papillomavirus Genotypes and Methylation of CADM1, PAX1, MAL and ADCYAP1 Genes in Epithelial Ovarian Cancer Patients. Asian Pacific journal of cancer prevention : APJCP 28 28240513
2016 A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling. Immunity 28 26885859
2013 MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C. Mucosal immunology 28 23612054
2006 Characterization of recombinant Mal d 4 and its application for component-resolved diagnosis of apple allergy. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 28 16911365
1999 Functional domain analysis of the Saccharomyces MAL-activator. Current genetics 28 10447589
2023 Cancer CD39 drives metabolic adaption and mal-differentiation of CD4+ T cells in patients with non-small-cell lung cancer. Cell death & disease 27 38062068
2019 On The Role of Myelin and Lymphocyte Protein (MAL) In Cancer: A Puzzle With Two Faces. Journal of Cancer 26 31258734
2016 MAL and TMEM220 are novel DNA methylation markers in human gastric cancer. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 26 27329150
1998 A short peptide motif at the carboxyl terminus is required for incorporation of the integral membrane MAL protein to glycolipid-enriched membranes. The Journal of biological chemistry 26 9582298
2024 Acetylation of TIR domains in the TLR4-Mal-MyD88 complex regulates immune responses in sepsis. The EMBO journal 25 39294473
2019 Clostridium perfringens epsilon toxin induces blood brain barrier permeability via caveolae-dependent transcytosis and requires expression of MAL. PLoS pathogens 25 31703116
2020 Myelin-Associated MAL and PLP Are Unusual among Multipass Transmembrane Proteins in Preferring Ordered Membrane Domains. The journal of physical chemistry. B 24 32436385
2016 Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells. Molecular biology of the cell 24 27009205
2013 Synthesis and preclinical characterization of [64Cu]NODAGA-MAL-exendin-4 with a Nε-maleoyl-L-lysyl-glycine linkage. Nuclear medicine and biology 24 23932646
2023 From Non-Alcoholic Fatty Liver to Hepatocellular Carcinoma: A Story of (Mal)Adapted Mitochondria. Biology 23 37106795
2021 The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer. Cells 23 33946345
2018 RAC2 promotes abnormal proliferation of quiescent cells by enhanced JUNB expression via the MAL-SRF pathway. Cell cycle (Georgetown, Tex.) 22 29895215
2014 MyD88 adaptor-like (Mal) regulates intestinal homeostasis and colitis-associated colorectal cancer in mice. American journal of physiology. Gastrointestinal and liver physiology 21 24603458
2004 Mutations in SIN4 and RGR1 cause constitutive expression of MAL structural genes in Saccharomyces cerevisiae. Genetics 21 15514050
2022 The Role of Microglia in the (Mal)adaptive Response to Traumatic Experience in an Animal Model of PTSD. International journal of molecular sciences 20 35806185
2022 Combined Liquid Biopsy Methylation Analysis of CADM1 and MAL in Cervical Cancer Patients. Cancers 20 36010947
2011 MAL-PDT for difficult to treat nonmelanoma skin cancer. Dermatologic therapy 20 21276161
2022 Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia. Scientific reports 19 35241698
2011 Poxvirus A46 protein binds to TIR domain-containing Mal/TIRAP via an α-helical sub-domain. Molecular immunology 19 21831443

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