Affinage

SGPL1

Sphingosine-1-phosphate lyase 1 · UniProt O95470

Round 2 corrected
Length
568 aa
Mass
63.5 kDa
Annotated
2026-04-28
130 papers in source corpus 11 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SGPL1 encodes sphingosine-1-phosphate lyase 1, a pyridoxal 5′-phosphate-dependent, ER-resident integral membrane enzyme that irreversibly cleaves sphingosine-1-phosphate (S1P) into ethanolamine phosphate and hexadecenal, thereby serving as the terminal enzyme in sphingolipid catabolism (PMID:9464245, PMID:15522238). By controlling intracellular and extracellular S1P levels, SGPL1 regulates lymphocyte egress from thymus and lymph nodes in a dose-dependent manner, promotes stress-induced apoptosis through p38 MAPK/p53/caspase-2 signaling, and supports neuronal autophagy by supplying ethanolamine phosphate for phosphatidylethanolamine synthesis required for LC3 lipidation (PMID:19119317, PMID:17090686, PMID:28521611). SGPL1 deficiency causes mitochondrial dysfunction and sphingolipid accumulation, and its loss also activates STAT3 and pro-inflammatory signaling in the kidney (PMID:32682944, PMID:33755599). Biallelic loss-of-function mutations in SGPL1 cause a syndromic steroid-resistant nephrotic syndrome (SPLIS/NPHS14) with adrenal insufficiency, ichthyosis, immunodeficiency, and neurological defects, as demonstrated by human genetic studies, cross-species rescue experiments, and AAV-mediated gene replacement in knockout mice (PMID:28165339, PMID:33755599).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1998 High

    The identification of the mammalian SGPL1 gene established that S1P lyase activity—previously known only in yeast—is conserved in mammals, answering whether an irreversible S1P-degrading enzyme exists in higher eukaryotes.

    Evidence Homology cloning followed by functional complementation of yeast dpl1Δ and in vitro enzyme assay confirming catalytic activity

    PMID:9464245

    Open questions at the time
    • Substrate specificity beyond S1P (e.g., dihydro-S1P) not characterized
    • No structural information on the enzyme
  2. 2004 High

    Topology mapping resolved how SGPL1 accesses its substrate by showing that the catalytic domain faces the cytosol on the ER membrane, placing it in a distinct compartment from S1P phosphohydrolase and establishing spatial partitioning of S1P catabolism.

    Evidence Proteinase K protection assay on microsomal membranes combined with ER co-localization by immunofluorescence

    PMID:15522238

    Open questions at the time
    • Mechanism of S1P access across ER membrane leaflets unknown
    • Whether additional localization sites exist was not addressed
  3. 2006 High

    Demonstration that SGPL1 promotes apoptosis through p38/p53/caspase-2 in a catalytic-activity-dependent but ceramide-independent manner revealed a direct pro-apoptotic signaling role beyond mere lipid catabolism.

    Evidence Overexpression, knockdown, catalytic-dead mutant, and chemical/genetic inhibition of pathway components in HEK293 cells

    PMID:17090686

    Open questions at the time
    • The specific SGPL1-generated metabolite (hexadecenal vs. reduced S1P) responsible for p38 activation was not identified
    • In vivo validation of p38-dependent apoptotic pathway not performed
  4. 2009 High

    KO and hypomorphic knock-in mouse models established that SGPL1 controls lymphocyte egress from thymus and lymph nodes in a dose-sensitive manner, and that complete loss causes multi-organ pathology and early death.

    Evidence Sgpl1 KO and humanized knock-in mice with <10–20% residual activity; flow cytometry of T-cell compartments and histopathology

    PMID:19119317

    Open questions at the time
    • Whether S1P gradient disruption alone explains lymphocyte sequestration or cell-intrinsic effects contribute
    • Contribution of individual organs to lethality not dissected
  5. 2017 High

    Human genetic studies across seven families, coupled with yeast and Drosophila rescue experiments, proved that biallelic SGPL1 loss-of-function mutations cause a syndromic steroid-resistant nephrotic syndrome (SPLIS/NPHS14), definitively linking the enzyme to human Mendelian disease.

    Evidence WES of affected families; enzyme activity assays; yeast complementation; Drosophila nephrocyte rescue with WT vs. mutant Sply

    PMID:28165339

    Open questions at the time
    • Pathogenic mechanism in podocytes not fully resolved—role of S1P receptor signaling vs. sphingolipid accumulation unclear
    • Genotype–phenotype correlations across the full clinical spectrum not established
  6. 2017 High

    Neural-specific SGPL1 ablation revealed that the enzyme's ethanolamine phosphate product feeds phosphatidylethanolamine synthesis required for LC3 lipidation, establishing SGPL1 as a metabolic regulator of autophagosome formation in the brain.

    Evidence Conditional KO mouse (Nestin-Cre), PE supplementation rescue of LC3-II conversion, autophagic flux reporter, electron microscopy

    PMID:28521611

    Open questions at the time
    • Whether the PE-autophagy link operates outside the CNS not tested
    • Relative contributions of PE deficit vs. S1P accumulation to neurodegeneration not separated
  7. 2018 Medium

    Detection of SGPL1 at the plasma membrane of non-tumorigenic mammary cells expanded its known localization beyond the ER and suggested that loss of surface SGPL1 in breast cancer enables S1P-driven migration.

    Evidence Immunofluorescence, membrane fractionation, flow cytometry in normal vs. cancer cell lines; migration assays

    PMID:29718989

    Open questions at the time
    • Mechanism of SGPL1 trafficking to the plasma membrane unknown
    • Whether plasma membrane activity has distinct substrates or kinetics not determined
    • Single-lab observation; independent confirmation needed
  8. 2020 Medium

    Patient-derived fibroblasts and CRISPR-KO cells demonstrated that SGPL1 deficiency causes mitochondrial dysfunction, linking sphingolipid accumulation to impaired oxidative phosphorylation and providing a mechanistic basis for the adrenal insufficiency seen in patients.

    Evidence Patient fibroblasts and CRISPR-KO HeLa cells; sphingolipid mass spectrometry, mitochondrial imaging, respirometry

    PMID:32682944

    Open questions at the time
    • Whether mitochondrial defects are a direct consequence of specific sphingolipid species or secondary to general lipid imbalance
    • In vivo mitochondrial phenotypes in adrenal tissue not examined
  9. 2021 High

    AAV9-mediated SGPL1 gene replacement rescued survival, renal function, and sphingolipid homeostasis in KO mice and attenuated STAT3/pro-inflammatory cytokine activation in kidneys, providing proof-of-concept for gene therapy and identifying STAT3 as a downstream effector of SGPL1 deficiency.

    Evidence Neonatal AAV9 delivery in Sgpl1-KO mice; survival, histopathology, sphingolipid mass spectrometry, STAT3 and cytokine profiling

    PMID:33755599

    Open questions at the time
    • Duration of therapeutic effect beyond 40 weeks not established
    • Whether STAT3 activation is a direct result of S1P signaling or secondary to inflammation not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of SGPL1 catalysis and substrate selectivity, the mechanism by which hexadecenal (vs. loss of S1P) mediates downstream signaling, the relative pathogenic contributions of individual sphingolipid species in different organs, and how SGPL1 is trafficked to and functions at the plasma membrane.
  • No crystal or cryo-EM structure of mammalian SGPL1
  • Hexadecenal-specific signaling targets uncharacterized
  • Organ-specific pathogenic mechanisms in SPLIS remain incompletely dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016829 lyase activity 5
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-168256 Immune System 1 R-HSA-9612973 Autophagy 1
Partners
CASP2STAT3TP53

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Identification of the first mammalian sphingosine-1-phosphate lyase (SPL) gene via homology to C. elegans SPL. The mouse gene functionally complemented an S1P lyase-deficient yeast strain (dpl1Δ), restoring sphingosine resistance, and in vitro enzyme assays confirmed SPL catalytic activity in yeast expressing the mouse cDNA. Northern analysis showed tissue-specific expression. Yeast complementation assay, in vitro enzyme assay, Northern blot Biochemical and biophysical research communications High 9464245
2004 SGPL1 (SPL) is an endoplasmic reticulum-resident, integral membrane protein. Its large hydrophilic domain containing the active site (pyridoxal 5'-phosphate binding domain) faces the cytosol, as shown by proteinase K digestion of membrane fractions. This active-site orientation is opposite to that of S1P phosphohydrolase, indicating that two S1P-degrading enzymes act on spatially separated sides of the ER membrane. Immunofluorescence microscopy (ER co-localization), proteinase K protection assay on membrane fractions, immunoblot Biochemical and biophysical research communications High 15522238
2006 SGPL1 potentiates apoptosis in response to DNA damage via a mechanism requiring its enzymatic activity and dependent on p38 MAPK, p53, PIDD, and caspase-2. SPL expression led to constitutive p38 activation. This pro-apoptotic effect was independent of ceramide generation. Endogenous SPL was induced by DNA damage, and SPL knockdown diminished apoptotic responses. SPL expression was significantly down-regulated in human colon cancer tissues compared to normal adjacent tissues. Overexpression and knockdown in HEK293 cells, chemical and molecular inhibition of p38/p53/caspase-2, catalytic-dead mutant analysis, Q-PCR and immunohistochemistry of tumor tissues Proceedings of the National Academy of Sciences of the United States of America High 17090686
2009 Complete genetic ablation of S1P lyase (S1PL/SGPL1) in mice caused lymphopenia with sequestration of mature T cells in thymus and lymph nodes, myeloid cell hyperplasia, and severe lesions in lung, heart, urinary tract, and bone, with markedly reduced lifespan. Humanized knock-in mice expressing <10-20% of normal S1PL activity were protected from lethal non-lymphoid lesions but still showed defective T-cell egress, demonstrating that lymphocyte trafficking is particularly sensitive to S1PL activity levels. Knockout and humanized knock-in mouse models; flow cytometry of T-cell compartments; histopathological analysis PloS one High 19119317
2016 In oral squamous cell carcinoma (OSCC), low SGPL1 expression correlates with reduced S1P catabolism, and S1P enhanced migration/invasion of OSCC cells via S1PR2. SGPL1 manipulation in vitro demonstrated that the enzyme's activity shapes extracellular S1P levels available to drive S1PR2-mediated cell migration. In vitro migration/invasion assays, S1P receptor expression analysis, S1PR2 overexpression/knockdown, FTY720 apoptosis assays Scientific reports Medium 27160553
2017 Recessive mutations in SGPL1 cause a syndromic form of steroid-resistant nephrotic syndrome (SRNS) with ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects. All disease-associated mutations resulted in reduced or absent SGPL1 protein and/or enzyme activity. Overexpression of mutant SGPL1 showed subcellular mislocalization. WT human SGPL1 rescued growth of SGPL1-deficient yeast (dpl1Δ), but disease variants did not. SGPL1 is expressed in mouse podocytes and mesangial cells; Sgpl1 knockdown in rat mesangial cells inhibited cell migration, partially rescued by an S1P receptor antagonist. In Drosophila, Sply mutants displayed a nephrotic syndrome-like nephrocyte phenotype rescued by WT but not mutant Sply. Whole exome sequencing, enzyme activity assays, yeast complementation, immunofluorescence/subcellular localization, siRNA knockdown with migration assay, Drosophila genetic rescue experiments The Journal of clinical investigation High 28165339
2017 SGPL1 modulates autophagy in neurons through production of phosphatidylethanolamine (PE). SGPL1 cleaves S1P into ethanolamine phosphate, which is directed toward PE synthesis; PE anchors LC3-I to phagophore membranes as LC3-II. Neural-specific SGPL1 ablation (SGPL1fl/fl/Nes mice) reduced brain PE levels, decreased LC3-I to LC3-II conversion, increased BECN1 and SQSTM1/p62, altered lysosomal markers, and accumulated APP and α-synuclein. Addition of exogenous PE rescued LC3-I to LC3-II conversion and normalized SQSTM1, APP, and SNCA levels. Electron and immunofluorescence microscopy showed accumulation of unclosed phagophore-like structures. Conditional knockout mouse (Cre-lox), PE supplementation rescue, LC3 lipidation assay, EGFP-mRFP-LC3 autophagic flux reporter, electron microscopy, immunofluorescence, pharmacological inhibition Autophagy High 28521611
2018 SGPL1 is expressed not only in the ER but also at the plasma membrane of non-tumorigenic mammary epithelial cells, as demonstrated by three independent methods (immunofluorescence, Western blot of membrane fractions, and flow cytometry). Loss of this plasma membrane SGPL1 expression in breast cancer cell lines correlated with S1P-dependent stimulation of migration. Overexpression of SGPL1 significantly reduced both S1P-stimulated and general migratory activity in breast cancer cells. Immunofluorescence microscopy, membrane fractionation Western blot, flow cytometry, migration assays with SGPL1 overexpression PloS one Medium 29718989
2020 SGPL1 deficiency is associated with mitochondrial dysfunction. Patient-derived dermal fibroblasts and CRISPR-engineered SGPL1-knockout HeLa cells showed reduced cortisol output, elevated sphingolipid intermediates (S1P, sphingosine, ceramides, sphingomyelin), reduced total mitochondrial volume, and altered mitochondrial dynamics and oxidative phosphorylation parameters compared to matched controls. Patient-derived fibroblasts, CRISPR-KO HeLa cells, mass spectrometric sphingolipid analysis, mitochondrial morphology imaging, oxidative phosphorylation measurement The Journal of steroid biochemistry and molecular biology Medium 32682944
2021 AAV9-mediated delivery of human SGPL1 to newborn Sgpl1-KO mice dramatically prolonged survival and prevented nephrosis, neurodevelopmental delay, anemia, and hypercholesterolemia. SGPL1 expression and activity were measurable for at least 40 weeks post-treatment. Plasma and tissue sphingolipids were reduced in treated KO pups. STAT3 pathway activation and elevated pro-inflammatory/profibrogenic cytokines in KO kidneys were attenuated by treatment, establishing enzymatic SGPL1 activity as required for normal renal and systemic function. AAV9 gene delivery in KO mice, survival analysis, histopathology, sphingolipid mass spectrometry, cytokine profiling, STAT3 pathway analysis JCI insight High 33755599
2022 In a cell model of non-alcoholic fatty liver disease, SGPL1 overexpression abolished the anti-apoptotic effect of ginsenoside Rg1, downregulating pro-survival proteins Bcl-2, p-Akt, and p-Erk1/2 while upregulating pro-apoptotic Bax. This placed SGPL1 activity upstream of the Akt and Erk1/2 pro-survival signaling pathways in hepatocytes, consistent with its role in reducing S1P-dependent survival signaling. SGPL1 overexpression in HHL-5 hepatocytes, Western blot for Bcl-2/Bax/p-Akt/p-Erk1/2, apoptosis assays Molecular medicine reports Low 35322862

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2009 miR156-regulated SPL transcription factors define an endogenous flowering pathway in Arabidopsis thaliana. Cell 1040 19703399
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
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
2011 Negative regulation of anthocyanin biosynthesis in Arabidopsis by a miR156-targeted SPL transcription factor. The Plant cell 654 21487097
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2011 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 507 21565611
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2016 Developmental Functions of miR156-Regulated SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) Genes in Arabidopsis thaliana. PLoS genetics 398 27541584
2014 Arabidopsis miR156 Regulates Tolerance to Recurring Environmental Stress through SPL Transcription Factors. The Plant cell 395 24769482
2008 Dual effects of miR156-targeted SPL genes and CYP78A5/KLUH on plastochron length and organ size in Arabidopsis thaliana. The Plant cell 387 18492871
2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Science signaling 383 24255178
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2011 Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Immunity 286 21903422
2010 Temporal control of trichome distribution by microRNA156-targeted SPL genes in Arabidopsis thaliana. The Plant cell 244 20622149
2015 The miR156/SPL Module, a Regulatory Hub and Versatile Toolbox, Gears up Crops for Enhanced Agronomic Traits. Molecular plant 240 25617719
2002 Hairy/E(spl)-related (Her) genes are central components of the segmentation oscillator and display redundancy with the Delta/Notch signaling pathway in the formation of anterior segmental boundaries in the zebrafish. Development (Cambridge, England) 225 12050140
2011 The SOC1-SPL module integrates photoperiod and gibberellic acid signals to control flowering time in Arabidopsis. The Plant journal : for cell and molecular biology 199 21988498
2006 Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer. Proceedings of the National Academy of Sciences of the United States of America 194 17090686
1992 The Enhancer of split [E(spl)] locus of Drosophila encodes seven independent helix-loop-helix proteins. Proceedings of the National Academy of Sciences of the United States of America 187 1528887
2001 HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling. Molecular and cellular biology 185 11486045
1987 cDNA and deduced amino acid sequence of human pulmonary surfactant-associated proteolipid SPL(Phe). Proceedings of the National Academy of Sciences of the United States of America 183 3035561
2013 Functional Evolution in the Plant SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) Gene Family. Frontiers in plant science 176 23577017
2014 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Molecular cell 173 25544563
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
1996 Functional relationships between Notch, Su(H) and the bHLH genes of the E(spl) complex: the E(spl) genes mediate only a subset of Notch activities during imaginal development. Development (Cambridge, England) 163 8787746
2012 The transcription factors BEL1 and SPL are required for cytokinin and auxin signaling during ovule development in Arabidopsis. The Plant cell 160 22786869
1999 her4, a zebrafish homologue of the Drosophila neurogenic gene E(spl), is a target of NOTCH signalling. Development (Cambridge, England) 160 10101116
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2020 The miR156/SPL module regulates apple salt stress tolerance by activating MdWRKY100 expression. Plant biotechnology journal 157 32885918
2017 Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency. The Journal of clinical investigation 149 28165339
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
1998 Identification of the first mammalian sphingosine phosphate lyase gene and its functional expression in yeast. Biochemical and biophysical research communications 143 9464245
2014 microRNA156-targeted SPL/SBP box transcription factors regulate tomato ovary and fruit development. The Plant journal : for cell and molecular biology 142 24580734
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2022 A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets. Nature biotechnology 140 36217030
2009 Incomplete inhibition of sphingosine 1-phosphate lyase modulates immune system function yet prevents early lethality and non-lymphoid lesions. PloS one 139 19119317
2005 A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. American journal of human genetics 137 16385451
2004 Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5'-phosphate binding domain exposed to the cytosol. Biochemical and biophysical research communications 131 15522238
2014 Progressive regulation of sesquiterpene biosynthesis in Arabidopsis and Patchouli (Pogostemon cablin) by the miR156-targeted SPL transcription factors. Molecular plant 129 25578275
1988 cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal). The Journal of biological chemistry 121 3335510
1998 A subset of notch functions during Drosophila eye development require Su(H) and the E(spl) gene complex. Development (Cambridge, England) 110 9655811
2017 Non-canonical regulation of SPL transcription factors by a human OTUB1-like deubiquitinase defines a new plant type rice associated with higher grain yield. Cell research 103 28776570
2020 MiR156 regulates anthocyanin biosynthesis through SPL targets and other microRNAs in poplar. Horticulture research 100 32821401
2002 Drosophila Sir2 is required for heterochromatic silencing and by euchromatic Hairy/E(Spl) bHLH repressors in segmentation and sex determination. Cell 98 12086602
2013 SPL8 and miR156-targeted SPL genes redundantly regulate Arabidopsis gynoecium differential patterning. The Plant journal : for cell and molecular biology 95 23621152
2019 A Regulatory Network for miR156-SPL Module in Arabidopsis thaliana. International journal of molecular sciences 93 31817723
2017 SGPL1 (sphingosine phosphate lyase 1) modulates neuronal autophagy via phosphatidylethanolamine production. Autophagy 89 28521611
2020 FHY3 and FAR1 Integrate Light Signals with the miR156-SPL Module-Mediated Aging Pathway to Regulate Arabidopsis Flowering. Molecular plant 84 32017999
2020 Characterizing the Role of the miR156-SPL Network in Plant Development and Stress Response. Plants (Basel, Switzerland) 81 32942558
1994 Neuroectodermal transcription of the Drosophila neurogenic genes E(spl) and HLH-m5 is regulated by proneural genes. Development (Cambridge, England) 75 7600959
2003 Two modes of recruitment of E(spl) repressors onto target genes. Development (Cambridge, England) 66 12466194
2014 Molecular characterization of the SPL gene family in Populus trichocarpa. BMC plant biology 65 24884654
2017 Response of miR156-SPL Module during the Red Peel Coloration of Bagging-Treated Chinese Sand Pear (Pyrus pyrifolia Nakai). Frontiers in physiology 62 28824447
2016 The Spl Serine Proteases Modulate Staphylococcus aureus Protein Production and Virulence in a Rabbit Model of Pneumonia. mSphere 61 27747296
2013 Genome-wide analysis and molecular dissection of the SPL gene family in Salvia miltiorrhiza. Journal of integrative plant biology 60 24112769
2020 Genome-wide identification, phylogeny and expression analysis of the SPL gene family in wheat. BMC plant biology 58 32912142
2002 Evidence of dual sites of action of dendrimers: SPL-2999 inhibits both virus entry and late stages of herpes simplex virus replication. Antiviral research 57 12103432
2018 Genome-wide analysis of the SPL/miR156 module and its interaction with the AP2/miR172 unit in barley. Scientific reports 55 29728569
2018 Exploiting SPL genes to improve maize plant architecture tailored for high-density planting. Journal of experimental botany 54 29992284
2004 her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling. Development (Cambridge, England) 51 15169758
1995 Suppressor of hairless, the Drosophila homologue of RBP-J kappa, transactivates the neurogenic gene E(spl)m8. Idengaku zasshi 50 7546844
2013 Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes. PLoS genetics 46 23300480
2005 Inhibition of neurogenesis at the zebrafish midbrain-hindbrain boundary by the combined and dose-dependent activity of a new hairy/E(spl) gene pair. Development (Cambridge, England) 45 15590746
2020 MiR529a controls plant height, tiller number, panicle architecture and grain size by regulating SPL target genes in rice (Oryza sativa L.). Plant science : an international journal of experimental plant biology 43 33288029
2017 MicroRNA 157-targeted SPL genes regulate floral organ size and ovule production in cotton. BMC plant biology 42 28068913
2006 Functional and structural characterization of Spl proteases from Staphylococcus aureus. Journal of molecular biology 42 16516230
2019 Roles of the SPL gene family and miR156 in the salt stress responses of tamarisk (Tamarix chinensis). BMC plant biology 38 31438851
2019 Evolutionary Analyses Reveal Diverged Patterns of SQUAMOSA Promoter Binding Protein-Like (SPL) Gene Family in Oryza Genus. Frontiers in plant science 37 31139200
2016 Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2. Scientific reports 37 27160553
2016 Trichome patterning control involves TTG1 interaction with SPL transcription factors. Plant molecular biology 36 27631431
2011 Probing the reaction mechanism of spore photoproduct lyase (SPL) via diastereoselectively labeled dinucleotide SP TpT substrates. Journal of the American Chemical Society 36 21671623
2007 Identification of neural progenitor pools by E(Spl) factors in the embryonic and adult brain. Brain research bulletin 36 18331883
1993 Drosophila evolution challenges postulated redundancy in the E(spl) gene complex. Proceedings of the National Academy of Sciences of the United States of America 36 8516287
2008 Synthesis of oligosaccharides derived from lactulose and pectinex ultra SP-L. Journal of agricultural and food chemistry 35 18412359
2019 An Early Arising Role of the MicroRNA156/529-SPL Module in Reproductive Development Revealed by the Liverwort Marchantia polymorpha. Current biology : CB 34 31543452
2021 Involvement of the miR156/SPL module in flooding response in Medicago sativa. Scientific reports 33 33547346
2017 Nephrotic syndrome and adrenal insufficiency caused by a variant in SGPL1. Clinical kidney journal 33 30090628
2018 Molecular Characterization of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) Gene Family in Betula luminifera. Frontiers in plant science 32 29780401
2014 Genomic organization, differential expression, and functional analysis of the SPL gene family in Gossypium hirsutum. Molecular genetics and genomics : MGG 32 25159110
2019 Roles of the GA-mediated SPL Gene Family and miR156 in the Floral Development of Chinese Chestnut (Castanea mollissima). International journal of molecular sciences 30 30934840
2022 Low-affinity SPL binding sites contribute to subgenome expression divergence in allohexaploid wheat. Science China. Life sciences 29 36417050
2016 Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling. PLoS genetics 29 27070787
2019 SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency. The Journal of clinical endocrinology and metabolism 28 30517686
2015 Effect of SPL (Spent Pot Liner) and its main components on root growth, mitotic activity and phosphorylation of Histone H3 in Lactuca sativa L. Ecotoxicology and environmental safety 28 26615478
2006 Regulatory mechanisms of ROI generation are affected by rice spl mutations. Plant & cell physiology 28 16816407
2015 Paralogous SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes differentially regulate leaf initiation and reproductive phase change in petunia. Planta 27 26445769
2020 Genome-wide characterization of the SPL gene family involved in the age development of Jatropha curcas. BMC genomics 26 32434522
2018 Characterization of Vv-miR156: Vv-SPL pairs involved in the modulation of grape berry development and ripening. Molecular genetics and genomics : MGG 26 29943289
2008 Cytogenetic alterations induced by SPL (spent potliners) in meristematic cells of plant bioassays. Ecotoxicology and environmental safety 26 18395259
2023 Meristem dormancy in Marchantia polymorpha is regulated by a liverwort-specific miRNA and a clade III SPL gene. Current biology : CB 25 36696899
2021 Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome. JCI insight 25 33755599
2019 Genome-wide characterization of SPL family in Medicago truncatula reveals the novel roles of miR156/SPL module in spiky pod development. BMC genomics 25 31277566
1999 Notchspl is deficient for inductive processes in the eye, and E(spl)D enhances split by interfering with proneural activity. Developmental biology 25 10191054
2022 The miR157-SPL-CNR module acts upstream of bHLH101 to negatively regulate iron deficiency responses in tomato. Journal of integrative plant biology 24 35297168
2019 Regulation of Notch output dynamics via specific E(spl)-HLH factors during bristle patterning in Drosophila. Nature communications 24 31375669
2017 Genome-wide identification and characterization of the SPL gene family in Ziziphus jujuba. Gene 24 28652183
2014 E(spl): genetic, developmental, and evolutionary aspects of a group of invertebrate Hes proteins with close ties to Notch signaling. Current topics in developmental biology 24 25248478
2017 Heteroblastic Development of Transfer Cells Is Controlled by the microRNA miR156/SPL Module. Plant physiology 23 28082719
2004 Drosophila CK2 regulates eye morphogenesis via phosphorylation of E(spl)M8. Mechanisms of development 23 15003630
1990 Defective ommatidial cell assembly leads to defective morphogenesis: a phenotypic analysis of the E(spl) D mutation of Drosophila melanogaster. Roux's archives of developmental biology : the official organ of the EDBO 23 28305667
2021 Intra-articular injection of loaded sPL sustained-release microspheres inhibits osteoarthritis and promotes cartilaginous repairs. Journal of orthopaedic surgery and research 22 34717689
2020 Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction. The Journal of steroid biochemistry and molecular biology 22 32682944
2018 First evidence of SGPL1 expression in the cell membrane silencing the extracellular S1P siren in mammary epithelial cells. PloS one 22 29718989
2022 Conservation and Divergence of SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) Gene Family between Wheat and Rice. International journal of molecular sciences 21 35216210
2004 Role of the Sc C terminus in transcriptional activation and E(spl) repressor recruitment. The Journal of biological chemistry 21 15507447
2023 Molecular characterization of SPL gene family during flower morphogenesis and regulation in blueberry. BMC plant biology 20 36650432
2022 Genome-wide identification and expression analysis of the SPL transcription factor family and its response to abiotic stress in Quinoa (Chenopodium quinoa). BMC genomics 20 36434504
2019 Characterization and Rapid Gene-Mapping of Leaf Lesion Mimic Phenotype of spl-1 Mutant in Soybean (Glycine max (L.) Merr.). International journal of molecular sciences 20 31058828
1999 Overexpression of the m4 and malpha genes of the E(spl)-complex antagonizes notch mediated lateral inhibition. Mechanisms of development 20 10446264
2023 The SPL transcription factor TaSPL6 negatively regulates drought stress response in wheat. Plant physiology and biochemistry : PPB 19 38091935
1995 A Drosophila E(spł) gene is "neurogenic" in Xenopus: a green fluorescent protein study. Developmental biology 19 7729602
2023 Distinct function of SPL genes in age-related resistance in Arabidopsis. PLoS pathogens 18 36947557
2019 Comparative genome analysis of the SPL gene family reveals novel evolutionary features in maize. Genetics and molecular biology 18 31271590
2018 Notch Target Gene E(spl)mδ Is a Mediator of Methylmercury-Induced Myotoxicity in Drosophila. Frontiers in genetics 18 29379520
2018 Genome-wide identification and expression analysis of the SPL gene family in woodland strawberry Fragaria vesca. Genome 18 30067072
2014 The Notch target E(spl)mδ is a muscle-specific gene involved in methylmercury toxicity in motor neuron development. Neurotoxicology and teratology 18 24632433
2023 Identification of Alfalfa SPL gene family and expression analysis under biotic and abiotic stresses. Scientific reports 17 36596810
2022 Ginsenoside Rg1 exerts anti‑apoptotic effects on non‑alcoholic fatty liver cells by downregulating the expression of SGPL1. Molecular medicine reports 16 35322862
2019 Expression Pattern of FT/TFL1 and miR156-Targeted SPL Genes Associated with Developmental Stages in Dendrobium catenatum. International journal of molecular sciences 16 31163611