Affinage

DEGS1

Sphingolipid delta(4)-desaturase DES1 · UniProt O15121

Length
323 aa
Mass
37.9 kDa
Annotated
2026-04-28
100 papers in source corpus 12 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DEGS1 encodes dihydroceramide Δ4-desaturase 1 (DES1), the enzyme that catalyzes the final step of de novo sphingolipid biosynthesis by introducing a trans-double bond at the C4 position of dihydroceramide to generate ceramide (PMID:25352638, PMID:30620337). The enzyme is an integral membrane protein of the endoplasmic reticulum and mitochondria-associated ER membranes (MAMs), containing conserved histidine-rich motifs characteristic of fatty acid desaturases; N-myristoylation of its N-terminal glycine enhances catalytic activity and redirects a fraction to the mitochondrial outer membrane (PMID:9188692, PMID:22139871, PMID:36951944). DEGS1 deficiency disrupts MAM-dependent processes including mitochondrial dynamics (via impaired DRP1 activation), cholesterol esterification, phospholipid remodeling, and lipid droplet biogenesis, and also functions as a retinol isomerase in retinal Müller glial cells (PMID:36951944, PMID:23143414). Loss-of-function mutations in DEGS1 cause pathological accumulation of dihydroceramides and generation of a neurotoxic atypical sphingoid base, resulting in hypomyelinating leukodystrophy (PMID:30620337, PMID:30620338).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1997 Medium

    Establishing that DEGS1 is an ER-resident integral membrane protein of the fatty acid desaturase family provided the first molecular identity and predicted catalytic mechanism for the gene product.

    Evidence Sequence analysis, detergent extraction, and immunolocalization in transfected cells

    PMID:9188692

    Open questions at the time
    • Enzymatic substrate and product not yet identified
    • Functional role of histidine motifs not mutagenetically confirmed
    • No lipid desaturase activity directly measured
  2. 2011 High

    Demonstrating that N-myristoylation of the N-terminal glycine enhances DES1 enzymatic activity and redirects the protein from the ER to the mitochondrial outer membrane revealed a post-translational regulatory mechanism controlling both enzyme activity and subcellular distribution.

    Evidence Site-directed mutagenesis (G→A), subcellular fractionation, and enzymatic activity assay in rat hepatocytes

    PMID:22139871

    Open questions at the time
    • In vivo relevance of mitochondrial DES1 pool unknown
    • Whether myristoylation is regulated physiologically not addressed
  3. 2012 High

    Identifying DES1 as a retinol isomerase (isomerase-2) in Müller glia, with purified protein activity, co-IP with CRALBP, and partial rescue in Rpe65-/- mice, revealed an unexpected non-sphingolipid function for DEGS1.

    Evidence In vitro isomerase assay with purified DES1, co-immunoprecipitation, RNAi knockdown, adenoviral gene therapy in Rpe65-/- mice

    PMID:23143414

    Open questions at the time
    • Conditional KO later showed Müller cell DES1 is dispensable for cone pigment regeneration in mouse (see 2019)
    • Whether isomerase activity is biologically relevant in human retina remains unresolved
  4. 2014 High

    Demonstrating that DEGS1 loss of function blocks adipogenesis with dihydroceramide accumulation, oxidative stress, and cell death established the enzyme as essential for the de novo ceramide biosynthesis pathway and linked its activity to cellular differentiation and survival.

    Evidence Pharmacological inhibition and siRNA knockdown in preadipocytes with lipidomics and in vivo inhibitor treatment

    PMID:25352638

    Open questions at the time
    • Relative contribution of ceramide deficit vs. dihydroceramide accumulation not resolved
    • Mechanism linking sphingolipid imbalance to oxidative stress unclear
  5. 2019 High

    Identification of pathogenic DEGS1 mutations in patients with hypomyelinating leukodystrophy, confirmed by 80% reduction in enzymatic activity, dihydroceramide accumulation in patient cells, and recapitulation in CRISPR knockout cells, established DEGS1 as a Mendelian disease gene and demonstrated that a neurotoxic atypical sphingoid base is produced when the enzyme is defective.

    Evidence Whole-exome sequencing, patient fibroblast enzymatic assays, CRISPR/Cas9 KO cells, plasma and tissue lipidomics across two independent groups

    PMID:30620337 PMID:30620338 PMID:31186544 PMID:31227640

    Open questions at the time
    • Mechanism by which atypical sphingoid base causes neurotoxicity not elucidated
    • Genotype-phenotype correlation across variant spectrum incomplete
  6. 2019 High

    Conditional knockout of Des1 in Müller cells showed no requirement for cone visual pigment regeneration, refining the earlier isomerase-2 finding and indicating functional redundancy or an alternative isomerase pathway in vivo.

    Evidence Conditional Cre/lox knockout in mouse Müller cells with ERG and single-cell electrophysiology

    PMID:30645148

    Open questions at the time
    • Whether DES1 isomerase activity is relevant under pathological or aging conditions not tested
    • Compensation by other isomerases not investigated
  7. 2022 Medium

    Showing that DES1 catalytic activity is necessary and sufficient for anchorage-independent survival downstream of HER2-driven glucose metabolism placed the enzyme in an oncogenic signaling axis.

    Evidence Loss- and gain-of-function in HER2+ cancer cells, anchorage-independent growth assay, epistasis analysis

    PMID:36165222

    Open questions at the time
    • In vivo tumorigenesis not tested
    • Mechanism connecting ceramide production to anchorage-independent survival unresolved
    • Single cancer cell type studied
  8. 2023 High

    Establishing DEGS1 as a MAM-resident enzyme whose deficiency disrupts mitochondrial dynamics, cholesterol/phospholipid metabolism, and lipid droplet biogenesis broadened the pathomechanism beyond sphingolipid imbalance to encompass global organelle-contact-site dysfunction.

    Evidence Subcellular fractionation, multi-omics, enzymatic assays, and mitochondrial imaging in patient fibroblasts and muscle biopsies

    PMID:36951944

    Open questions at the time
    • Whether MAM dysfunction is a direct consequence of ceramide depletion or dihydroceramide accumulation not separated
    • Structural basis for DES1 enrichment at MAMs unknown
  9. 2023 Medium

    Structural modeling predicted the substrate-binding site and identified an atypical sphingoid base (SPB 18:1(14Z);O2) as a specific biomarker for pathogenic DEGS1 variants, suggesting a regulatory link with FADS3.

    Evidence Computational structural modeling and plasma lipidomics in patients with novel C-terminal variants

    PMID:37890668

    Open questions at the time
    • No experimental structure available
    • FADS3 regulatory link not experimentally validated
    • Biomarker specificity not tested in large cohorts

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of DES1, the mechanism by which dihydroceramide accumulation versus ceramide depletion each contribute to neuropathology, whether the neurotoxic atypical sphingoid base is a primary disease driver, and the physiological relevance of DES1 retinol isomerase activity in humans.
  • No crystal or cryo-EM structure
  • Neurotoxicity mechanism of atypical sphingoid base unknown
  • Relative pathogenic contribution of substrate accumulation vs. product deficit not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0016853 isomerase activity 1
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005739 mitochondrion 2
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-1643685 Disease 3
Partners
CRALBPDRP1

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 DEGS1 (MLD gene product) is a member of the membrane fatty acid desaturase family, contains three consensus histidine-rich motifs (HX3H, HX2HH, HX2HHXFP) characteristic of membrane fatty acid desaturases, is extractable from particulate fractions only with detergent, and localizes to the endoplasmic reticulum. Overexpression inhibits biosynthesis of the EGF receptor without affecting PDGF receptor expression, suggesting a role in biosynthetic processing. Sequence analysis, subcellular fractionation, detergent/salt/urea extraction, immunolocalization to ER, cotransfection overexpression assay Biochemistry Medium 9188692
2012 DES1 (DEGS1) functions as a retinol isomerase (isomerase-2) in Müller glial cells of the retina; it coimmunoprecipitates with cellular retinaldehyde binding protein (CRALBP), purified DES1 has high isomerase-2 activity in the presence of appropriate cofactors, adenoviral DES1 gene therapy partially rescues biochemical and physiological phenotypes in Rpe65-/- mice, and RNAi knockdown reduces isomerase-2 activity in cultured Müller cells. Co-immunoprecipitation, in vitro isomerase assay with purified protein, RNAi knockdown, adenoviral gene therapy rescue in Rpe65-/- mice Nature chemical biology High 23143414
2014 DEGS1 is the desaturase catalyzing the last step in the main ceramide biosynthetic pathway (dihydroceramide to ceramide). Loss-of-function (pharmacological or genetic ablation) in preadipocytes prevents adipogenesis and decreases lipid accumulation, associated with elevated dihydroceramide content, oxidative stress, cell death, and cell cycle blockage. In vivo pharmacological inhibition of DEGS1 impairs adipocyte differentiation. Pharmacological inhibition, siRNA/genetic knockdown in preadipocytes, lipidomics, in vivo inhibitor treatment Diabetes High 25352638
2019 DEGS1 catalyzes the conversion of dihydroceramide (DhCer) to ceramide (Cer) as the final step of de novo ceramide biosynthesis. Mutations in DEGS1 cause marked accumulation of dihydroceramide species and elevated DhCer/Cer ratios in patient fibroblasts and muscle, recapitulated in CRISPR/Cas9 DEGS1-knockout cells and by pharmacological inhibition. Patient fibroblast enzymatic activity was reduced by 80% vs. wild-type. A potentially neurotoxic atypical sphingosine isomer was identified in patient plasma and in cells expressing mutant DEGS1. Whole-exome sequencing, lipidomics in patient fibroblasts and plasma, CRISPR/Cas9 knockout cells, pharmacological inhibition, enzymatic activity assay The Journal of clinical investigation High 30620337 30620338
2019 DEGS1 encodes C4-dihydroceramide desaturase; missense variants cause accumulation of dihydroceramides, dihydrosphingosine, dihydrosphingosine-1-phosphate, and dihydrosphingomyelins with reduced ceramide, sphingosine, sphingosine-1-phosphate, and monohexosylceramides in patient blood, confirming the enzymatic role in ceramide synthesis pathway. Whole-exome sequencing, Sanger sequencing, lipidomics of whole blood European journal of human genetics Medium 31186544
2019 A rare DEGS1 variant (L175Q) significantly reduces DEGS1 enzymatic activity; CRISPR/Cas9 editing of HepG2 cells confirmed partial loss of function, with heterozygotes showing dramatically reduced indexes of DEGS1 enzymatic activity and large increases in plasma dihydroceramides. CRISPR/Cas9 genome editing, plasma lipidomics, enzymatic activity assay Journal of lipid research High 31227640
2019 Conditional knockout of Des1 in Müller cells of the retina (using Pdgfrα-Cre) causes no gross changes in retinal structure and no effect on cone sensitivity or dark adaptation, but slightly accelerates cone phototransduction termination rate. This indicates Des1 expression in Müller cells is not required for cone visual pigment regeneration in the mouse. Conditional knockout (Cre/lox), electrophysiology (ERG/single-cell recordings), tissue-selective gene recombination, Des1 catalytic activity assay FASEB journal High 30645148
2011 Myristic acid increases native DES1 (dihydroceramide Δ4-desaturase 1) enzymatic activity in cultured rat hepatocytes through N-myristoylation of the N-terminal glycine. The wild-type myristoylable form localizes to both ER and mitochondria, whereas a non-myristoylable mutant (N-terminal Gly→Ala) is almost exclusively in the ER, demonstrating that N-myristoylation targets a portion of DES1 from the ER to the mitochondrial outer membrane and increases ceramide levels and apoptosis. Site-directed mutagenesis (Gly→Ala), subcellular fractionation, organelle immunolocalization, enzymatic activity assay in hepatocytes and cell lysates Lipids High 22139871
2023 DEGS1 is a mitochondria-associated endoplasmic reticulum membrane (MAM)-resident enzyme. DEGS1 deficiency disrupts core MAM functions: (a) mitochondrial dynamics — hyperfused mitochondrial network with decreased DRP1 activation; (b) cholesterol metabolism — impaired sterol O-acyltransferase activity and decreased cholesteryl esters; (c) phospholipid metabolism — increased phosphatidic acid and phosphatidylserine, decreased phosphatidylethanolamine; (d) lipid droplet biogenesis — increased size and numbers. Increased mitochondrial superoxide production and impaired mitochondrial respiration were also detected. Subcellular fractionation, multiomics (lipidomics, proteomics), enzymatic assays, patient fibroblasts, patient muscle biopsy, mitochondrial morphology imaging, superoxide measurement The Journal of clinical investigation High 36951944
2022 DES1 (DEGS1) catalytic activity is necessary for anchorage-independent survival (AIS) in HER2+ cancer cells; DES1 acts downstream of HER2-driven glucose uptake and metabolism. Overexpression of DES1 is sufficient to drive AIS and in vitro tumorigenicity. DES1 functions as a transducer of HER2-driven glucose metabolic signals. Loss-of-function and gain-of-function (overexpression), anchorage-independent growth assay, epistasis with HER2 pathway FASEB journal Medium 36165222
2023 Two novel DEGS1 missense variants near the C-terminus are characterized; a structural model predicts the substrate-binding site. A regulatory link between DEGS1 and fatty acid desaturase 3 (FADS3) is proposed, as the atypical sphingoid base SPB 18:1(14Z);O2 — formed when DEGS1 is non-functional — is a specific biomarker for pathogenic DEGS1 variants. Structural modeling, plasma lipidomics (dihydrosphingolipids and atypical sphingoid base measurement), variant functional assessment Journal of lipid research Medium 37890668

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone marrow transplantation 489 12203137
1989 Insulin-like growth factor (IGF)-binding proteins inhibit the biological activities of IGF-1 and IGF-2 but not des-(1-3)-IGF-1. The Biochemical journal 185 2539101
1993 The nature of the trophic action of brain-derived neurotrophic factor, des(1-3)-insulin-like growth factor-1, and basic fibroblast growth factor on mesencephalic dopaminergic neurons developing in culture. Neuroscience 172 8095710
1991 IGF-I and the truncated analogue des-(1-3)IGF-I enhance growth in rats after gut resection. The American journal of physiology 148 1996625
2012 Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina. Nature chemical biology 91 23143414
1991 Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I), IGF-II and des(1-3)IGF-I in rats. The Journal of endocrinology 86 2005410
2019 Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy. The Journal of clinical investigation 79 30620337
2019 DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans. The Journal of clinical investigation 79 30620338
1994 Role of the NH2-terminal domain of angiotensin II (ANG II) and [Sar1]angiotensin II on conformation and activity. NMR evidence for aromatic ring clustering and peptide backbone folding compared with [des-1,2,3]angiotensin II. The Journal of biological chemistry 71 8106515
2000 Cooperative interaction between mutant p53 and des(1-3)IGF-I accelerates mammary tumorigenesis. Oncogene 70 10702797
1991 Increased weight gain, nitrogen retention and muscle protein synthesis following treatment of diabetic rats with insulin-like growth factor (IGF)-I and des(1-3)IGF-I. The Biochemical journal 67 1710892
2018 Withaferin-A attenuates multiple low doses of Streptozotocin (MLD-STZ) induced type 1 diabetes. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 63 30119216
1975 Selective inhibition by des-1-Asp-8-lle-angiotensin ii of the steroidogenic response to restricted sodium intake in the rat. Circulation research 61 1157223
1984 Comparison of coagulation factor Xa and des-(1-44)factor Xa in the assembly of prothrombinase. The Journal of biological chemistry 59 6698966
1983 Myelin basic protein deposition in the optic and sciatic nerves of dysmyelinating mutants quaking, jimpy, Trembler, mld, and shiverer during development. Journal of neurochemistry 59 6194264
1975 Des-1-Asp-angiotensin II. Possible intrarenal role in homeostasis in the dog. Circulation research 58 1149185
2014 Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function. Diabetes 56 25352638
1991 Two new arylsulfatase A (ARSA) mutations in a juvenile metachromatic leukodystrophy (MLD) patient. American journal of human genetics 55 1684088
1992 des-(1-3)-IGF-I, an insulin-like growth factor analog used to mimic a potential IGF-II autocrine loop, promotes the differentiation of human colon-carcinoma cells. International journal of cancer 49 1281142
1994 Generation of des-(1-3) insulin-like growth factor-I in serum by an acid protease. Endocrinology 45 7988428
2011 Prevention of multiple low-dose streptozotocin (MLD-STZ) diabetes in mice by an extract from gum resin of Boswellia serrata (BE). Phytomedicine : international journal of phytotherapy and phytopharmacology 44 21831620
1997 The product of the MLD gene is a member of the membrane fatty acid desaturase family: overexpression of MLD inhibits EGF receptor biosynthesis. Biochemistry 38 9188692
2019 DEGS1 variant causes neurological disorder. European journal of human genetics : EJHG 37 31186544
1988 Gene organization and transcription of duplicated MBP genes of myelin deficient (shi(mld)) mutant mouse. The EMBO journal 37 2452084
1984 Myelination in the CNS of mld mutant mice: comparison between composition and structure. Brain research 37 6202376
1991 IGF-I and its variant, des-(1-3)IGF-I, enhance growth in rats with reduced renal mass. The American journal of physiology 35 1928375
2023 Sphingolipid desaturase DEGS1 is essential for mitochondria-associated membrane integrity. The Journal of clinical investigation 34 36951944
1992 An evaluation of different enzymatic cleavage methods for recombinant fusion proteins, applied on des(1-3)insulin-like growth factor I. Journal of protein chemistry 34 1388667
1992 Two different Ca2+ ion binding sites in factor VIIa and in des(1-38) factor VIIa. FEBS letters 34 1633884
1996 Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. The international journal of biochemistry & cell biology 33 8930132
2000 A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD). Journal of inherited metabolic disease 31 10682309
1987 Structure and expression of myelin basic protein gene sequences in the mld mutant mouse: reiteration and rearrangement of the MBP gene. Genetics 31 2440764
2014 Long-term correction of biochemical and neurological abnormalities in MLD mice model by neonatal systemic injection of an AAV serotype 9 vector. Gene therapy 27 24572788
2001 Inability of overexpressed des(1-3)human insulin-like growth factor I (IGF-I) to inhibit forced mammary gland involution is associated with decreased expression of IGF signaling molecules. Endocrinology 27 11250928
1991 The effects of insulin-like growth factor-I (IGF-I), IGF-II and des(1-3)IGF-I, a potent IGF analogue, on growth hormone and IGF-binding protein secretion from cultured rat anterior pituitary cells. The Journal of endocrinology 27 1715381
1999 Effect of insulin-like growth factor (IGF)-I and Des (1-3) IGF-I on the level of IGF binding protein-3 and IGF binding protein-3 mRNA in cultured porcine embryonic muscle cells. Journal of cellular physiology 26 10048587
2020 The coordination of guard-cell autonomous ABA synthesis and DES1 function in situ regulates plant water deficit responses. Journal of advanced research 25 33318877
1994 Des (1-3) IGF-I potently enhances differentiated cell growth in olfactory bulb organ culture. Growth factors (Chur, Switzerland) 25 7779409
2019 Conditional deletion of Des1 in the mouse retina does not impair the visual cycle in cones. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 30645148
2019 Rare DEGS1 variant significantly alters de novo ceramide synthesis pathway. Journal of lipid research 23 31227640
2018 IL-33 Prevents MLD-STZ Induction of Diabetes and Attenuate Insulitis in Prediabetic NOD Mice. Frontiers in immunology 23 30498495
1994 The des(1-6)antennapedia homeodomain: comparison of the NMR solution structure and the DNA-binding affinity with the intact Antennapedia homeodomain. Proceedings of the National Academy of Sciences of the United States of America 23 7909611
1983 Intrinsic myelin proteins are normally synthesized in vitro in the myelin-deficient (mld) mutant mouse. Developmental neuroscience 23 6680688
1996 Late juvenile metachromatic leukodystrophy (MLD) in three patients with a similar clinical course and identical mutation on one allele. Clinical genetics 22 9007312
2020 Electrochemically Active In Situ Crystalline Lithium-Organic Thin Films by ALD/MLD. ACS applied materials & interfaces 20 32818370
2003 Identification of nine novel arylsulfatase a (ARSA) gene mutations in patients with metachromatic leukodystrophy (MLD). Human mutation 20 14517960
1987 Immunohistochemical, biochemical and electron microscopic analysis of myelin formation in the central nervous system of myelin deficient (mld) mutant mice. Brain research 20 2443219
1986 Mice heterozygous for the mld mutation have intermediate levels of myelin basic protein mRNA and its translation products. Brain research 20 2431744
1983 Immunocytochemical investigations of murine leukodystrophies. A study of the mutants 'jimpy' (jp) and 'myelin deficient' (mld). Brain research 20 6191832
2005 Overexpression of des(1-3) insulin-like growth factor 1 in the mammary glands of transgenic mice delays the loss of milk production with prolonged lactation. Biology of reproduction 19 16079306
2002 Biochemical-genetic analysis and distribution of DES-1, an Ambler class A extended-spectrum beta-lactamase from Desulfovibrio desulfuricans. Antimicrobial agents and chemotherapy 19 12234847
1999 Transgenic hypersecretion of des(1-3) human insulin-like growth factor I in mouse milk has limited effects on the gastrointestinal tract in suckling pups. The Journal of nutrition 19 9915875
1983 In vitro myelin basic protein synthesis in the PNS and CNS of myelin deficient (mld) mutant mice. Brain research 19 6196085
2023 Nutrient scoring for the DEGS1-FFQ - from food intake to nutrient intake. BMC nutrition 18 36639712
2009 VGD and MLD-motifs containing heterodimeric disintegrin viplebedin-2 from Vipera lebetina snake venom. Purification and cDNA cloning. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 17 19296915
2002 Des (1-3) IGF-I-stimulated growth of human stromal BPH cells is inhibited by a vitamin D3 analogue. Molecular and cellular endocrinology 17 12573816
1998 The Des-1 protein, required for central spindle assembly and cytokinesis, is associated with mitochondria along the meiotic spindle apparatus and with the contractile ring during male meiosis in Drosophila melanogaster. Molecular & general genetics : MGG 17 9819060
1997 Biodistribution of 125I-labeled des(1-3) insulin-like growth factor I in tumor-bearing nude mice and its in vitro catabolism. Cancer research 17 9205087
2009 DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD-STZ diabetes. Journal of immune based therapies and vaccines 16 19754943
2003 Des(1-3)IGF-1 treatment normalizes type 1 IGF receptor and phospho-Akt (Thr 308) immunoreactivity in predegenerative retina of diabetic rats. International journal of experimental diabesity research 16 12745670
1999 Leflunomide protects mice from multiple low dose streptozotocin (MLD-SZ)-induced insulitis and diabetes. Clinical and experimental immunology 16 10403914
1986 The stimulation by monovalent cations of the amidase activity of bovine des-1-41 light chain activated protein C. The Journal of biological chemistry 15 3771560
2023 A retrospective cohort study of Libmeldy (atidarsagene autotemcel) for MLD: What we have accomplished and what opportunities lie ahead. JIMD reports 14 37701322
2021 Emodin inhibits viability, proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting miR-244-5p/DEGS1 axis. BMC pulmonary medicine 14 34332565
2020 DES1: A Key Driver of Lipotoxicity in Metabolic Disease. DNA and cell biology 14 32181687
2003 Spectrum of mutations in the arylsulfatase A gene in a Canadian DNA collection including two novel frameshift mutations, a new missense mutation (C488R) and an MLD mutation (R84Q) in cis with a pseudodeficiency allele. Molecular genetics and metabolism 14 12809638
1993 Insulin-like growth factor binding protein-1 from Hep G2 cells is potently inhibited by the truncated IGF-I analogue des-(1-3) IGF-I. Acta endocrinologica 14 7680515
1985 Des-1-25-fructose-1,6-bisphosphatase, a nonallosteric derivative produced by trypsin treatment of the native protein. The Journal of biological chemistry 14 2997170
2000 Adult-onset MLD: a gene mutation with isolated polyneuropathy. Neurology 13 11061266
1995 Metachromatic leucodystrophy (MLD) in a patient with a constitutional ring chromosome 22. Journal of medical genetics 13 8558556
1989 The duplicated myelin basic protein gene in mld mutant mice does not impair transcription. Brain research 13 2467724
1989 A comparison between activated protein C and des-1-41-light chain-activated protein C in reactions with type 1 plasminogen activator inhibitor. Blood 13 2787675
1983 des-(1-13) human beta-endorphin interacts with calmodulin. Peptides 13 6312432
1982 Initial Stages in the Biodegradation of the Surfactant Sodium Dodecyltriethoxy Sulfate by Pseudomonas sp. Strain DES1. Applied and environmental microbiology 13 16346108
2007 A multiplex PCR method discriminating between the TYLCV and TYLCV-Mld clades of tomato yellow leaf curl virus. Journal of virological methods 12 17485124
1987 The effect of divalent cations on the amidolytic activity of bovine plasma activated protein C and des-1-41-light chain activated protein C. The Journal of biological chemistry 12 3597424
2023 DEGS1 -related leukodystrophy: a clinical report and review of literature. Clinical dysmorphology 11 37195341
2023 The atypical sphingolipid SPB 18:1(14Z);O2 is a biomarker for DEGS1 related hypomyelinating leukodystrophy. Journal of lipid research 11 37890668
2000 Brazilin augments cellular immunity in multiple low dose streptozotocin (MLD-STZ) induced type I diabetic mice. Archives of pharmacal research 11 11156186
2017 Metachromatic Leukodystrophy (MLD): a Pakistani Family with Novel ARSA Gene Mutation. Journal of molecular neuroscience : MN 10 28799099
2004 Late onset MLD with normal nerve conduction associated with two novel missense mutations in the ASA gene. Journal of neurology, neurosurgery, and psychiatry 10 15026521
1991 The endogenous lectin cerebellar soluble lectin and its ligands in central nervous system myelin of myelin-deficient (mld) mutant mice. Journal of neurochemistry 10 1703219
1991 Expression, purification and characterization of secreted recombinant human insulin-like growth factor-I (IGF-I) and the potent variant des(1-3) IGF-I in Chinese hamster ovary cells. Journal of molecular endocrinology 10 1883485
1988 The role of myelination in learning performance observed in two strains of myelin-deficient mutant mice (shiverer and mld). Behavioral and neural biology 10 2465759
2012 Profile of fatty acids, muscle structure and shear force of musculus longissimus dorsi (MLD) in growing pigs as affected by energy and protein or protein restriction followed by realimentation. Meat science 9 22424756
2011 Myristic acid increases dihydroceramide Δ4-desaturase 1 (DES1) activity in cultured rat hepatocytes. Lipids 9 22139871
1987 The binding of Mn2+ to bovine plasma protein C, des(1-41)-light chain protein C, and activated des(1-41)-light chain activated protein C. Archives of biochemistry and biophysics 9 3579297
1982 Density distribution of 2?,3?-cyclic nucleotide 3?-phosphodiesterase and myelin proteins in particulate material from myelin deficient (mld) mutant and control brains. Neurochemistry international 9 20487852
1992 Insulin-like growth factor I and its variant, des(1-3)IGF-I, improve nitrogen balance and food utilization in rats with renal failure. Mineral and electrolyte metabolism 8 1465072
1981 Heterozygote detection in MLD. allelic mutations at the ARA locus. Human genetics 8 6120139
2019 Heterogeneity of Mesenchymal Stromal Cells in Myelodysplastic Syndrome-with Multilineage Dysplasia (MDS-MLD). Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 7 30988556
2019 Three novel variants in the arylsulfatase A (ARSA) gene in patients with metachromatic leukodystrophy (MLD). BMC research notes 6 31694723
1997 The growth hormone dependent serine protease inhibitor, Spi 2.1 inhibits the des (1-3) insulin-like growth factor-I generating protease. Endocrinology 6 9389551
1987 The effect of monovalent cations on the pre-steady state reaction kinetics of bovine activated plasma protein C and des-1-41-light chain activated plasma protein C. The Journal of biological chemistry 6 3793723
2022 Dihydroceramide desaturase 1 (DES1) promotes anchorage-independent survival downstream of HER2-driven glucose uptake and metabolism. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 36165222
2018 Clinical, Molecular, and Computational Analysis Showed a Novel Homozygous Mutation Among the Substrate-Binding Site of ARSA Protein in Consanguineous Family with Late-Infantile MLD. Journal of molecular neuroscience : MN 5 30083785
1992 Molecular genetic analysis of the mldr mouse: a spontaneous revertant at the mld locus containing a recombinant myelin basic protein gene. Genetics 5 1371758
1987 205Tl+ as a spectroscopic probe of the monovalent cation binding sites of bovine plasma activated protein C and des-1-41-light-chain-activated protein C. The Journal of biological chemistry 5 3584107
2012 Brain MRI and biological diagnosis in five Tunisians MLD patients. Diagnostic pathology 4 22284439
1984 Anticonvulsive treatment of myelin-deficient (mld) mice improves survival and confirms the delayed increase of myelin basic protein. Neurochemical pathology 4 6085770