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Information on EC 1.14.18.5 - sphingolipid C4-monooxygenase
for references in articles please use BRENDA:EC1.14.18.5
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EC Tree 1 Oxidoreductases
1.14 Acting on paired donors, with incorporation or reduction of molecular oxygen
1.14.18 With another compound as one donor, and incorporation of one atom of oxygen into the other donor
1.14.18.5 sphingolipid C4-monooxygenase
IUBMB Comments
The enzyme, which belongs to the familiy of endoplasmic reticular cytochrome b5-dependent enzymes, is involved in the biosynthesis of sphingolipids in eukaryotes. Some enzymes are bifunctional and also catalyse EC 1.14.19.17, sphingolipid 4-desaturase .
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 1.14.18.5
- sphingolipids
-
sphingoid
- phytosphingosine
- phytoceramide
-
oxygen-dependent
-
inositolphosphorylceramide
-
c4-hydroxylation
- nidulans
- dihydrosphingosine
Reaction Schemes
showSynonyms
sur2p, sphingolipid c4-hydroxylase, syr2p, sphinganine c4-hydroxylase, sphingolipid hydroxylase, sphingolipid delta(4)-desaturase/c4-monooxygenase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DES2
DHS hydroxylase
dihydroceramide hydrolase
EC 1.14.13.169
-
-
formerly
-
SBH1
-
-
-
-
SBH2
-
-
-
-
sphinganine C4-monooxygenase
-
-
-
-
sphingolipid C4-hydroxylase
SUR2
Sur2p
SYR2
Syr2p
sphingolipid C4-hydroxylase
-
-
-
-
SUR2
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (4R)-4-hydroxysphinganine ceramide + 2 ferricytochrome b5 + H2O
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
sphingolipid biosynthesis (plants), sphingolipid biosynthesis (yeast)
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SYSTEMATIC NAME
IUBMB Comments
dihydroceramide,ferrocytochrome b5:oxygen oxidoreductase (C4-hydroxylating)
The enzyme, which belongs to the familiy of endoplasmic reticular cytochrome b5-dependent enzymes, is involved in the biosynthesis of sphingolipids in eukaryotes. Some enzymes are bifunctional and also catalyse EC 1.14.19.17, sphingolipid 4-desaturase [4].
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
D-erythro-eicosasphinganine + NADH + H+ + O2
4-hydroxyeicosasphinganine + NAD+ + H2O
-
Substrates: -
Products: -
Products: -
?
D-erythro-sphinganine + NADH + H+ + O2
4-hydroxysphinganine + NAD+ + H2O
-
Substrates: -
Products: free 4-hydroxysphinganine is produced in excised corn shoots by the direct hydroxylation of sphinganine and not from the breakdown of complex sphingolipids
Products: free 4-hydroxysphinganine is produced in excised corn shoots by the direct hydroxylation of sphinganine and not from the breakdown of complex sphingolipids
?
D-erythro-sphinganine + NADPH + H+ + O2
4-hydroxysphinganine + NADP+ + H2O
-
Substrates: -
Products: -
Products: -
?
dihydroceramide + reduced acceptor + H+ + O2
phytoceramide + acceptor + H2O
Substrates: -
Products: -
Products: -
?
dihydrosphingosine + NADPH + H+ + O2
phytosphingosine + NADP+ + H2O
Substrates: -
Products: -
Products: -
?
DL-erythro-dihydrosphingosine + reduced acceptor + H+ + O2
phytosphingosine + acceptor + H2O
N-acetylsphinganine + NADPH + H+ + O2
N-acetyl-4-hydroxysphinganine + NADP+ + H2O
-
Substrates: -
Products: -
Products: -
?
N-hexanoylsphinganine + NADPH + H+ + O2
N-hexanoyl-4-hydroxysphinganine + NADP+ + H2O
-
Substrates: -
Products: -
Products: -
?
N-octanoyl-D-erythro-dihydrosphingosine + reduced acceptor + H+ + O2
?
Substrates: -
Products: -
Products: -
?
N-octanoylsphinganine + NADPH + H+ + O2
N-octanoyl-4-hydroxysphinganine + NADP+ + H2O
-
Substrates: -
Products: -
Products: -
?
sphinganine ceramide + 2 ferrocytochrome b5 + O2 + 2 H+
4-hydroxysphinganine ceramide + 2 ferricytochrome b5 + H2O
Substrates: -
Products: plus (E)-sphing-4-enine ceramide, the (E)-sphing-4-enine/4-hydroxysphinganine ratio is 2.5:1
Products: plus (E)-sphing-4-enine ceramide, the (E)-sphing-4-enine/4-hydroxysphinganine ratio is 2.5:1
?
sphingosine + reduced acceptor + H+ + O2
phytosphingosine + acceptor + H2O
Substrates: -
Products: -
Products: -
?
dihydroceramide + reduced acceptor + H+ + O2
?
-
Substrates: -
Products: -
Products: -
?
dihydroceramide + reduced acceptor + H+ + O2
?
-
Substrates: -
Products: -
Products: -
?
DL-erythro-dihydrosphingosine + reduced acceptor + H+ + O2
phytosphingosine + acceptor + H2O
-
Substrates: -
Products: -
Products: -
?
DL-erythro-dihydrosphingosine + reduced acceptor + H+ + O2
phytosphingosine + acceptor + H2O
-
Substrates: -
Products: -
Products: -
?
sphinganine + reduced acceptor + H+ + O2
phytosphinganine + acceptor + H2O
Substrates: -
Products: -
Products: -
?
sphinganine + reduced acceptor + H+ + O2
phytosphinganine + acceptor + H2O
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: enzyme is a bifunctional sphingolipid DELTA4-desaturase/C4-hydroxylase, with the desaturase activity being one order of magnitude higher than the hydroxylase activity
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Leishmania major has four genes occurring in tandem arrays, with at least three of them encoding active bifunctional enzymes
UniProt
brenda
bifunctional sphingolipid delta(4)-desaturase/C4-monooxygenase
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
not detected in heart, liver, spleen, skeletal muscle, thymus or placenta
brenda
additional information
-
not detected in heart, liver, spleen, skeletal muscle, thymus or placenta
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
deleting the SUR2 gene reduces hydroxylation of ceramides and suppresses Ca2+ sensitivity of csg2 mutants
malfunction
-
yeast strains deficient in Syr2 lack the sphingoid long chain base phytosphingosine
malfunction
-
yeast strains deficient in Syr2 lack the sphingoid long chain base phytosphingosine
-
physiological function
-
sphingolipid C4 hydroxylation by the enzyme influences properties of detergent-insoluble glycolipid-enriched membranes
physiological function
-
Sur2p is required for the hydroxylation of C-4 of the sphingoid moiety of ceramide. The enzyme is not essential for growth
physiological function
-
SYR2 is necessary for growth inhibition by the cyclic lipodepsipeptide syringomycin E. The SYR2 gene is required for the 4-hydroxylation reaction of sphingolipid long chain bases and is not essential for growth. SYR2 does not play a role in sterol biosynthesis
physiological function
the enzyme plays an essential role in phytosphingolipid synthesis in human skin and other phytosphingolipid-containing tissues
physiological function
C-4 hydroxylation of sphingolipids is important for the antifungal action of syringomycin E. Mutants with defects in C-4 hydroxylated sphingoid base biosynthesis are resistant to this antifungal agent
physiological function
-
SYR2 is necessary for growth inhibition by the cyclic lipodepsipeptide syringomycin E. The SYR2 gene is required for the 4-hydroxylation reaction of sphingolipid long chain bases and is not essential for growth. SYR2 does not play a role in sterol biosynthesis
-
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DEGS2_BOVIN
323
0
37319
Swiss-Prot
other Location (Reliability: 3)
DEGS2_CAEEL
362
3
42316
Swiss-Prot
other Location (Reliability: 3)
DEGS2_HUMAN
323
1
37197
Swiss-Prot
other Location (Reliability: 4)
SBH1_ARATH
260
3
29819
Swiss-Prot
Secretory Pathway (Reliability: 2)
SBH2_ARATH
259
3
29831
Swiss-Prot
Secretory Pathway (Reliability: 1)
DEGS2_MOUSE
323
0
37491
Swiss-Prot
other Location (Reliability: 3)
DEGS2_RAT
323
5
37441
Swiss-Prot
other Location (Reliability: 3)
B7FLU5_MEDTR
263
1
30186
TrEMBL
other Location (Reliability: 5)
A0A5B7A8L7_DAVIN
257
3
29511
TrEMBL
Secretory Pathway (Reliability: 1)
A0A084G5A8_PSEDA
377
2
42936
TrEMBL
other Location (Reliability: 5)
A0A6J8B6B3_MYTCO
219
3
25945
TrEMBL
other Location (Reliability: 3)
A0A5B7A3E9_DAVIN
257
3
29649
TrEMBL
Secretory Pathway (Reliability: 2)
A0A396JTI8_MEDTR
140
2
16019
TrEMBL
other Location (Reliability: 2)
A0A812CFK5_SEPPH
162
2
19072
TrEMBL
Mitochondrion (Reliability: 2)
A0A2P6PAH8_ROSCH
243
2
28067
TrEMBL
Secretory Pathway (Reliability: 1)
A0A2P6P809_ROSCH
118
0
13713
TrEMBL
other Location (Reliability: 5)
A0A2P6P811_ROSCH
275
2
31445
TrEMBL
Secretory Pathway (Reliability: 2)
A0A2P6P827_ROSCH
139
2
15524
TrEMBL
Secretory Pathway (Reliability: 4)
A0A2G9HHX5_9LAMI
263
3
30326
TrEMBL
Secretory Pathway (Reliability: 5)
A0A2P6PRK1_ROSCH
260
4
29756
TrEMBL
Secretory Pathway (Reliability: 5)
A0A5B7A0U3_DAVIN
257
4
29527
TrEMBL
other Location (Reliability: 4)
A0A072VZX3_MEDTR
255
5
29296
TrEMBL
Secretory Pathway (Reliability: 5)
A0A5B7A6X4_DAVIN
257
3
29517
TrEMBL
Secretory Pathway (Reliability: 2)
A0A2G9I2U3_9LAMI
263
1
30289
TrEMBL
Secretory Pathway (Reliability: 5)
A0A2P6R2X2_ROSCH
257
2
29476
TrEMBL
Secretory Pathway (Reliability: 3)
A0A5B7BCE3_DAVIN
194
3
22111
TrEMBL
Secretory Pathway (Reliability: 4)
SUR2_YEAST
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
349
0
40734
Swiss-Prot
-
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the replacement of any one of conserved His residues of three histidine-rich motifs with an alanine eliminates hydroxylase activity in vivo and in vitro. Residues Phe 174, Asn 182, Ser 191, Leu 196, Pro 199, Asn 266, Tyr 269, Asp 271 and Gln 275 appear to be additionally important elements of the active site but their conversion into corresponding yeast DELTA7-sterol-C5(6)-desaturase Erg3p residues does not lead to a gain in desaturase activity
additional information
-
the replacement of any one of conserved His residues of three histidine-rich motifs with an alanine eliminates hydroxylase activity in vivo and in vitro. Residues Phe 174, Asn 182, Ser 191, Leu 196, Pro 199, Asn 266, Tyr 269, Asp 271 and Gln 275 appear to be additionally important elements of the active site but their conversion into corresponding yeast DELTA7-sterol-C5(6)-desaturase Erg3p residues does not lead to a gain in desaturase activity
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
sphinganine hydroxylase activity in microsomes isolated from corn shoots treated with fumonisin B1 increases more than 3fold compared to controls
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sperling, P.; Ternes, P.; Moll, H.; Franke, S.; Zaehringer, U.; Heinz, E.
Functional characterization of sphingolipid C4-hydroxylase genes from Arabidopsis thaliana
FEBS Lett.
494
90-94
2001
Arabidopsis thaliana (Q9AST3), Arabidopsis thaliana
brenda
Mizutani, Y.; Kihara, A.; Igarashi, Y.
Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation
FEBS Lett.
563
93-97
2004
Homo sapiens (Q6QHC5), Homo sapiens
brenda
Idkowiak-Baldys, J.; Grilley, M.; Takemoto, J.
Sphingolipid C4 hydroxylation influences properties of yeast detergent-insoluble glycolipid-enriched membranes
FEBS Lett.
569
272-276
2004
Saccharomyces cerevisiae
brenda
Haak, D.; Gable, K.; Beeler, T.; Dunn, T.
Hydroxylation of Saccharomyces cerevisiae ceramides requires Sur2p and Scs7p
J. Biol. Chem.
272
29704-29710
1997
Saccharomyces cerevisiae
brenda
Grilley, M.; Stock, S.; Dickson, R.; Lester, R.; Takemoto, J.
Syringomycin action gene SYR2 is essential for sphingolipid 4-hydroxylation in Saccharomyces cerevisiae
J. Biol. Chem.
273
11062-11068
1998
Saccharomyces cerevisiae, Saccharomyces cerevisiae W303C
brenda
Moreno-Perez, A.J.; Martinez-Force, E.; Garces, R.; Salas, J.J.
Sphingolipid base modifying enzymes in sunflower (Helianthus annuus): cloning and characterization of a C4-hydroxylase gene and a new paralogous DELTA8-desaturase gene
J. Plant Physiol.
168
831-839
2011
Helianthus annuus
brenda
Bae, J.H.; Sohn, J.H.; Park, C.S.; Rhee, J.S.; Choi, E.S.
Cloning and functional characterization of the SUR2/SYR2 gene encoding sphinganine hydroxylase in Pichia ciferrii
Yeast
21
437-443
2004
Wickerhamomyces ciferrii (Q6YGT5), Wickerhamomyces ciferrii
brenda
Wright, B.S.; Snow, J.W.; OBrien, T.C.; Lynch, D.V.
Synthesis of 4-hydroxysphinganine and characterization of sphinganine hydroxylase activity in corn
Arch. Biochem. Biophys.
415
184-192
2003
Zea mays
brenda
Idkowiak-Baldys, J.; Takemoto, J.Y.; Grilley, M.M.
Structure-function studies of yeast C-4 sphingolipid long chain base hydroxylase
Biochim. Biophys. Acta
1618
17-24
2003
Saccharomyces cerevisiae (P38992), Saccharomyces cerevisiae
brenda
Ternes, P.; Franke, S.; Zaehringer, U.; Sperling, P.; Heinz, E.
Identification and characterization of a sphingolipid delta 4-desaturase family
J. Biol. Chem.
277
25512-25518
2002
Mus musculus (Q8R2F2)
brenda
Vacchina, P.; Tripodi, K.E.; Escalante, A.M.; Uttaro, A.D.
Characterization of bifunctional sphingolipid DELTA4-desaturases/C4-hydroxylases of trypanosomatids by liquid chromatography-electrospray tandem mass spectrometry
Mol. Biochem. Parasitol.
184
29-38
2012
Leishmania major (G3FCJ2)
brenda
EXTERNAL LINKS (specific for EC-Number 1.14.18.5)
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Release 2023.1 (January 2023)
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