Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol SGPL1 contributors: mct - updated : 23-05-2017
HGNC name sphingosine-1-phosphate lyase 1
HGNC id 10817
Corresponding disease
CMT2G Charcot-Marie-Tooth disease, axonal, type 2G
SRNIA steroid-resistant nephrotic syndrome with ichthyosis and adrenal insufficiency
Location 10q22      Physical location : 72.575.703 - 72.640.930
Synonym name sphingosine-1-phosphate aldolase
Synonym symbol(s) SPL, KIAA1252, FLJ13811, SP-lyase, S1PL
EC.number 4.1.2.27
DNA
TYPE functioning gene
STRUCTURE 64.15 kb     15 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
- splicing 6700 - - highest in liver Veldhoven (2000)
- splicing 4000 - - highest in liver Veldhoven (2000)
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver   highly
Lymphoid/Immunelymph node     Homo sapiens
Urinarykidneynephronrenal capsuleglomerulus  Mus musculus
cells
SystemCellPubmedSpeciesStageRna symbol
Urinarypodocyte Mus musculus
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to murine Sgpl1
Homologene
FAMILY
  • group II decarboxylase family
  • sphingosine-1-phosphate lyase subfamily
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • expressed by CD68+ cells on the parenchymal side of marginal reticular cells in human lymph nodes
    • basic FUNCTION
  • crucial role for SGPL1 in mediating cellular responses to stress
  • endogenous SGPL1 may play a physiological role in stress-induced apoptosis
  • is a key regulator of the levels of multiple sphingolipid substrates
  • catalyzes the degradation of S1P, a potent signaling lysosphingolipid
  • irreversibly cleaves sphingosine 1-phosphate (S1P) in the final step of sphingolipid catabolism
  • critical role of hematopoietic SGPL1 in controlling S1P levels and T cell trafficking in blood and lymphoid tissue
  • leukocyte SGPL1 is a critical factor in monocyte macrophage differentiation and function
  • SGPL1- by facilitating S1PR1 recycling - is essential for S1P-mediated sustained signaling
  • is a novel endogenous suppressor of pulmonary fibrosis in
    • idiopathic pulmonary fibrosis (IPF)
  • executes the final decisive step of the sphingolipid breakdown pathway, mediating the irreversible cleavage of the lipid-signaling molecule sphingosine-1-phosphate (S1P)
  • catalyzes the irreversible degradation of endogenous and dietary S1P, the final step of sphingolipid catabolism, and of other phosphorylated long-chain bases
  • direct role of SGPL1 in neuronal autophagy
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • is a regulator of acid sphingomyelinase (ASMase), the G2 checkpoint and DNA repair and a novel target for radioprotection
  • SGPL1 upregulation stimulates VPS39 recruitment to the mitochondria, thereby enhancing mitochondria-lysosome contacts
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SRNIA , CMT2G
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in fibrotic lung tissues and primary lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF)
    constitutional       loss of function
    produces a pro-inflammatory response while impairing neutrophil trafficking
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerative 
    autophagy modulators (as SGPL1) hold an enormous therapeutic potential in the treatment of neurodegenerative diseases
    ANIMAL & CELL MODELS
  • Sgpl1-/- mice recapitulated the main characteristics of the human disease with abnormal adrenal and renal morphology
  • S1P lyase deficiency in mice causes a severe, lethal phenotype
  • Sgpl1-deficient mice have low numbers of lymphocytes and high numbers of neutrophils in their blood