Information on EC 4.1.2.27 - sphinganine-1-phosphate aldolase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
4.1.2.27
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RECOMMENDED NAME
GeneOntology No.
sphinganine-1-phosphate aldolase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Sphinganine 1-phosphate = phosphoethanolamine + palmitaldehyde
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
elimination
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
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Sphingolipid metabolism
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sphingolipid recycling and degradation (yeast)
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sphingosine metabolism
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SYSTEMATIC NAME
IUBMB Comments
sphinganine-1-phosphate palmitaldehyde-lyase (phosphoethanolamine-forming)
A pyridoxal-phosphate protein.
CAS REGISTRY NUMBER
COMMENTARY hide
37290-61-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
ecotype Col-0
UniProt
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
strain 130-2
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-
Manually annotated by BRENDA team
strain 130-2
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-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
cultivar Nipponbare
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
yeast
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-
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled sphinganine 1-phosphate
phosphoethanolamine + 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled palmitaldehyde
show the reaction diagram
-
i.e. BODIPY-label, allows fluorescent product detection by HPLC
major aldehyde product is confirmed by reaction with 2,4-dinitrophenylhydrazine
-
?
4D-Hydroxysphinganine 1-phosphate
Phosphoethanolamine + 2-hydroxyhexadecanal
show the reaction diagram
7-nitrobenz-2-oxa-1,3-diazole-sphingosine 1-phosphate
phosphoethanolamine + 7-nitrobenz-2-oxa-1,3-diazole-hexadec-2-enal
show the reaction diagram
boron dipyrromethene difluoride-sphingosine 1-phosphate
phosphoethanolamine + boron dipyrromethene difluoride-hexadec-2-enal
show the reaction diagram
C17-sphinganine-1-phosphate
phosphoethanolamine + pentadecanal
show the reaction diagram
-
-
-
-
?
D-(+)-erythro-sphingosine 1-phosphate
phosphoethanolamine + (2E)-hexadecenal
show the reaction diagram
dihydrosphingosine 1-phosphate
phosphoethanolamine + palmitaldehyde
show the reaction diagram
-
-
-
-
?
Dihydrosphingosine 1-phosphonate
Aminoethylphosphonate + palmidaldehyde
show the reaction diagram
eicosadihydrosphingosine 1-phosphate + H2O
hexadecanal + 2-(icosanoylamino)ethyl phosphate
show the reaction diagram
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-
-
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omega-(7-nitro-2-1,3-benzoxadiazol-4-yl)-D-erythro-sphingosine 1-phosphate
phosphoethanolamine + omega-(7-nitro-2-1,3-benzoxadiazol-4-yl)-D-erythro-(2E)-hexadecenal
show the reaction diagram
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-
-
-
ir
phytosphingosine 1-phosphate
?
show the reaction diagram
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-
-
-
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phytosphingosine-1-phosphate
?
show the reaction diagram
sphinganine 1-phosphate
phosphoethanolamine + palmitaldehyde
show the reaction diagram
sphingosine 1-phosphate
phosphoethanolamine + (2E)-hexadecenal
show the reaction diagram
sphingosine 1-phosphate
phosphoethanolamine + hexadecanal
show the reaction diagram
-
-
?
Sphingosine 1-phosphate
Phosphoethanolamine + palmitaldehyde
show the reaction diagram
sphingosine-1-phosphate
phosphoethanolamine + (2E)-hexadecenal
show the reaction diagram
-
-
-
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ir
umbelliferone-labled sphinganine 1-phosphate
phosphoethanolamine + 3-[(2-oxo-2H-chromen-7-yl)oxy]propanal
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
sphinganine 1-phosphate
phosphoethanolamine + palmitaldehyde
show the reaction diagram
Q05567
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-
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ir
Sphingosine 1-phosphate
Phosphoethanolamine + palmitaldehyde
show the reaction diagram
Q54RV9
pathway of sphingomyelin degradation, sphingosine 1-phosphate is an important element of signal transduction pathways that regulate cell proliferation and cell death
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ir
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1R,2S,3R)-1-(1H,1'H-2,2'-biimidazol-4-yl)butane-1,2,3,4-tetraol
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inhibitory to sphinganine 1-phosphate lyase. 53% decrease in circulating lymphocytes after 30 mg/kg oral dose
(1R,2S,3R)-1-(2-(1-benzyl-1H-1,2,4-triazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol
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inhibitory to sphinganine 1-phosphate lyase. 41% decrease in circulating lymphocytes after 30 mg/kg oral dose
(1R,2S,3R)-1-(2-(thiazol-4-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol
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inhibitory to sphinganine 1-phosphate lyase. 33% decrease in circulating lymphocytes after 30 mg/kg oral dose
1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone
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inhibitory to sphinganine 1-phosphate lyase. 25% decrease in circulating lymphocytes after 30 mg/kg oral dose
1-deoxydihydrosphingosine 1-phosphonate
1-desoxysphinganine 1-phosphonate
1-{5-[(1R,2S,3R)-1,2,3,4-tetrahydroxybutyl]-1H-imidazol-2-yl}ethanone
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when given overnight at 25 mg/l in drinking water, tetrahydroxybutylimidazole raises sphingosine 1-phosphate levels and reduces SPL activity
2-acetyl-4(5)-tetrahydroxybutyl imidazole
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inhibitory. Following the oral administration of 10 and 100 mg/kg 2-acetyl-4(5)-tetrahydroxybutyl imidazole to male rats, 2-acetyl-4(5)-tetrahydroxybutyl imidazole is rapidly absorbed and reaches a plasma peak level at 1 h post-dosing. Splenic S1P increases and reaches the peak level at 24 h. Blood lymphocyte count decreases as the splenic S1P level increases. 2-Acetyl-4(5)-tetrahydroxybutyl imidazole plasma concentration is linked to splenic S1P concentration using an indirect model incorporated with a four-step signal transduction model. In turn, the S1P level is directly coupled with blood lymphocyte number
2-acetyl-4-(1R,2S,3R,4-tetrahydroxybutyl)-imidazole
2-acetyl-4-tetrahydroxybutyl-imidazole
2-acetyl-4-tetrahydroxybutylimidazole
2-vinyl dihydrosphingosine
2-vinyl sphinganine phosphate
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50% inhibition at 0.0024 mM
2-vinyldihydro-sphingosine 1-phosphate
2D,3L-sphinganine-phosphate
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competitive
4'-deoxypyridoxine
4-chloromercuribenzoate
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alkylates a cysteine residue
4-deoxypyridoxine
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bisulfite
carboplatin
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cells overexpressing enzyme show increased sensitivity
Chymotrypsin
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cisplatin
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cells overexpressing enzyme show increased sensitivity, mediated by death kinase p38
cyanide
cysteine
deoxypyridoxin phosphate
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inhibits
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deoxypyridoxine
Deoxypyridoxine phosphate
Deoxysphinganine 1-phosphonate
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competitive
doxorubicin
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cells overexpressing enzyme show increased sensitivity
FTY720
FTY720 phosphate
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less potent inhibitor than FTY720, effects only at 0.03 mM
fumonisin B1
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10 mg/kg inhibits the expression of sphingosine 1-phosphate lyase
iodoacetamide
LX2931
N,N-dimethyldodecylamine N-oxide
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50% inhibition at 0.05 mM
N-ethylmaleimide
N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopentenyl)ethyl]octanamide
p-chloromercuribenzoate
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complete inhibition
Semicarbazide
sphinganine 1-phosphonate
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competitive inhibitor
sphinganine phosphate
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2D,3L-isomer is a competitive inhibitor, but 2L,3L-isomer does not influence the enzyme
Subtilisin
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Thermolysin
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threo-dihydro-sphingosine 1-phosphate
Trypsin
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[2-amino-2[2-(4-octylphenyl)ethyl]-3-hydroxypropyl]dihydrogen phosphate
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.035
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled sphinganine 1-phosphate
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37C
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0.006
C17-sphinganine-1-phosphate
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pH 7.4, 37C
0.009
D(+)-erythro-dihydrosphingosine-phosphate
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liver enzyme
0.016
Deoxysphinganine 1-phosphonate
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0.0201
Dihydrosphingosine 1-phosphonate
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in 0.6 mM EDTA, 0.4 mM pyridoxal 5'-phosphate, 3 mM dithiothreitol mM sucrose, 36 mM potassium phosphate buffer, and 36 mM NaF containing 0.08% Triton X-100
0.009 - 0.11
sphinganine 1-phosphate
0.11
sphinganine-phosphate
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0.0057 - 0.0146
sphingosine 1-phosphate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.5
Deoxypyridoxine phosphate
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0.005
sphinganine 1-phosphonate
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-
0.0097
sphinganine phosphate
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2D,3L-isomer
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0524
FTY720
Mus musculus
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in 35 mM potassium phosphate buffer (pH 7.4), 0.6 mM EDTA, 70 mM sucrose, 36 mM sodium fluoride, 0.57 mM pyridoxal 5'-phosphate, at 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
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assay at
7.4 - 7.6
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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CRL 1444 (ATCC)
Manually annotated by BRENDA team
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high expression rate
Manually annotated by BRENDA team
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circulating T lymphocyte
Manually annotated by BRENDA team
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CRL 1443 (ATCC)
Manually annotated by BRENDA team
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CRL 1772 (ATCC)
Manually annotated by BRENDA team
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high expression rate
Manually annotated by BRENDA team
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high expression rate
Manually annotated by BRENDA team
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the cells expressing sphingosine-1-phosphate lyase in the parenchyma o lymph nodes are CD68+ antigen-presenting cells. CD68+ antigen-presenting cells generated from human monocytes are able to internalize and irreversibly degrade sphingosine 1-phosphate
Manually annotated by BRENDA team
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high expression rate
Manually annotated by BRENDA team
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embryonal carcinoma cell
Manually annotated by BRENDA team
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weak expression
Manually annotated by BRENDA team
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CCL2 (ATCC)
Manually annotated by BRENDA team
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HB 8065 (ATTC)
Manually annotated by BRENDA team
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inhibition of sphingosine-1-phosphate lyase activity rendes sphingosine 1-phosphate an efficient S1P1 receptor internalizing compound and abrogated sphingosine-1-phosphate-mediated sustained signaling, suggesting that sphingosine-1-phosphate lyase by facilitating S1P1 receptor recycling is essential for sphingosine-1-phosphate-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not sphingosine-1-phosphate lyase substrates
Manually annotated by BRENDA team
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CRL 1392 (ATCC)
Manually annotated by BRENDA team
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silencing of sphingosine 1-phosphate lyase enhances survival after irradiation or chemotherapy by decreasing expression of proteins involved in sensing and repairing DNA damage or apoptosis, respectively. Enforced expression of sphingosine 1-phosphate lyase sensitizes cancer cells to irradiation or docetaxel by tilting the ceramide/sphingosine 1-phosphate balance toward cell death
Manually annotated by BRENDA team
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sphingosine-1-phosphate lyase expression is almost exclusively restricted to cells on the parenchymal side of marginal reticular cells, consistent with a role in maintaining the S1P gradient between the sinuses and the parenchyma
Manually annotated by BRENDA team
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CCL 34 (ATCC)
Manually annotated by BRENDA team
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sphingosine-1-phosphate lyase is induced during myoblast differentiation
Manually annotated by BRENDA team
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of the olfactory bulb, cerebral cortex, midbrain, hindbrain, and cerebellum, high expression rate
Manually annotated by BRENDA team
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the enzyme is highly enriched in olfactory mucosal epithelium
Manually annotated by BRENDA team
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silencing of sphingosine 1-phosphate lyase enhances survival after irradiation or chemotherapy by decreasing expression of proteins involved in sensing and repairing DNA damage or apoptosis, respectively. Enforced expression of sphingosine 1-phosphate lyase sensitizes cancer cells to irradiation or docetaxel by tilting the ceramide/sphingosine 1-phosphate balance toward cell death
Manually annotated by BRENDA team
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higher enzyme activity than in F9 EC cells
Manually annotated by BRENDA team
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in fresh human prostatectomy specimens, a remarkable decrease in sphingosine 1-phosphate lyase enzymatic activity is found in tumor samples, as compared with normal adjacent tissues. A significant relationship between loss of sphingosine 1-phosphate lyase expression and higher Gleason score is confirmed. Sphingosine 1-phosphate lyase protein expression and activity are inversely correlated with those of sphingosine kinase-1, the enzyme producing sphingosine 1-phosphate. Sphingosine 1-phosphate lyase and sphingosine kinase expressions are independently predictive of aggressive cancer on tissue microarray
Manually annotated by BRENDA team
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moderate expression
Manually annotated by BRENDA team
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thymic and splenic stromal cell
Manually annotated by BRENDA team
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circulating T lymphocyte
Manually annotated by BRENDA team
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lowest expression detected
Manually annotated by BRENDA team
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high expression rate
Manually annotated by BRENDA team
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spingosine 1-phosphate lyase is modestly expressed at day 20 of pregnancy antd then decreases. In contrast, sphingosine 1-phosphate receptor mRNA increases in endometrium and caruncular stroma of the gravid uterine horn
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Legionella pneumophila (strain Paris)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Symbiobacterium thermophilum (strain T / IAM 14863)
Symbiobacterium thermophilum (strain T / IAM 14863)
Symbiobacterium thermophilum (strain T / IAM 14863)
Symbiobacterium thermophilum (strain T / IAM 14863)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55000
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x * 55000, SDS-PAGE
61000 - 65000
63000
-
x * 63000, SDS-PAGE
63480
-
calculated from amino acid sequence
63490
-
calculated from amino acid sequence
63710
calculation from cDNA nucleotide sequence
65520
-
calculation from sequence of genomic DNA
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer or hexamer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
nitrosylation
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nitrosylation on tyrosine residues Y356 and Y366
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
embedded in its lipid environment liver enzyme is quite stable
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stable towards Triton X-100 and no significant inhibition of the enzyme is observed up to a concentration of 15 mg/ml
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, liver enzyme loses 25% of activity for up to 2 month
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-20C, lyophilized microsomal preparations retain their full activity
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-80C, activity is well preserved in tissues or cells
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-80C, liver enzyme loses 10-15% of activity for up to 2 months
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
FLAG-tagged purification is performed
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA overexpressed in yeast strain-deltabst1
expressed in Escherichia coli
expressed in Saccharomyces cerevisiae
expression in HEK-293 cell
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expression in Mus musculus
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fusion protein with green fluorescence protein, expressed in HEK293 cells
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fusion protein with green fluorescence protein, expressed in Saccharomyces cerevisiae
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the plasmids pRS415, pRS416 and pESC are used
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
basal SPL activity is low in wild type cardiac tissue but is activated 3fold in response to 50 min of ischemia
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high SPL transcription of H1155 cells is regulated by specificity protein 1 and GATA-4 protein/specificity protein 1 complex formation
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mRNA expression for both sphingosine kinase and sphingosine 1-phosphate lyase are up-regulated throughout all four stages in human breast cancer patients. Exogenous administration of S1P produces a bell-shaped dose response for apoptosis in normal mammary gland MCF12A cells but a sigmoid-shaped apoptotic response in breast cancer MCF7 cells. Co-administration of S1P enhances the cytotoxicity of anticancer drug docetaxel against MCF7 cells
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SGPL1 gene expression is downregulated in colon cancer and is upregulated in certain malignant tissues, for example, in ovarian cancers as well as in the skin of patients suffering from atopic dermatitis
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C218G
-
reduced enzyme activity
C317S
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reduced enzyme activity
C344A
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
C65L
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
C65L/K67L
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
C65L/K67L/S70L/N71L
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
DELTA1-16
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
DELTA1-31
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
DELTA1-31/C65L/K67L/S70L/N71L
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
DELTA1-54
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
DELTA1-57
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
DELTA1-81
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
H129A
-
the mutation drastically impairs enzyme activity
H268A
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
H340A
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
K380A
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
K386A
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
K67L
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
K67L/S70L
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
N6A
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
N71L
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
S70L
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
S70L/N71L
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
Y105F
-
inactive
Y174F
-
the mutant is partially active
Y554A
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
Y554F
mutant constructed for structure-function analysis of Dpl1p to discover possible modes of regulation
H129A
-
the mutation drastically impairs enzyme activity
additional information
-
enzyme null mutant, exhibits dihydrosphingosine-1-phosphate lyase activity
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
medicine