Any feedback?
Information on EC 1.14.18.6 - 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase and Organism(s) Homo sapiens
for references in articles please use BRENDA:EC1.14.18.6Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.14.18.6 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylaseIUBMB Comments
The enzyme, characterized from yeast and mammals, catalyses the hydroxylation of carbon 2 of long- or very-long-chain fatty acids attached to (4R)-4-hydroxysphinganine during de novo ceramide synthesis. The enzymes from yeast and from mammals contain an N-terminal cytochrome b5 domain that acts as the direct electron donor to the desaturase active site. The newly introduced 2-hydroxyl group has R-configuration. cf. EC 1.14.18.7, dihydroceramide fatty acyl 2-hydroxylase.
Specify your search results
Word Map
- 1.14.18.6
- paraplegia
- sphingolipids
-
2-hydroxylation
- leukodystrophy
- nbias
-
atp13a2
- dystonia
- pla2g6
- paraparesis
- galactosylceramide
- sulfatide
-
alpha-hydroxylation
- paucimobilis
-
hydroxylase-associated
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
fa2h, fatty acid 2-hydroxylase, atfah1, fatty acid alpha-hydroxylase, scs7p, sphingolipid alpha-hydroxylase, fatty acid 2-hydroxylase 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
FA2H
-
-
-
-
FA2H
SCS7
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -
SYSTEMATIC NAME
IUBMB Comments
(4R)-4-hydroxysphinganine ceramide,ferrocytochrome-b5:oxygen oxidoreductase (fatty acyl 2-hydroxylating)
The enzyme, characterized from yeast and mammals, catalyses the hydroxylation of carbon 2 of long- or very-long-chain fatty acids attached to (4R)-4-hydroxysphinganine during de novo ceramide synthesis. The enzymes from yeast and from mammals contain an N-terminal cytochrome b5 domain that acts as the direct electron donor to the desaturase active site. The newly introduced 2-hydroxyl group has R-configuration. cf. EC 1.14.18.7, dihydroceramide fatty acyl 2-hydroxylase.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
palmitic acid + 2 ferrocytochrome b5 + O2 + 2 H+
(R)-2-hydroxypalmitic acid + 2 ferricytochrome b5 + H2O
-
FA2H is stereospecific for the production of (R)-enantiomers
-
?
additional information
?
-
2-hydroxylation of fatty acid by FA2H occurs prior to generation of ceramides/glucosylceramides. FA2H expression and 2-hydroxy-free fatty acid production increase early in keratinocyte differentiation, production of 2-hydroxyceramides/2-hydroxyglucosylceramides with longer chain amide-linked fatty acids (more than C24) increases later
-
-
?
additional information
?
-
-
2-hydroxylation of fatty acid by FA2H occurs prior to generation of ceramides/glucosylceramides. FA2H expression and 2-hydroxy-free fatty acid production increase early in keratinocyte differentiation, production of 2-hydroxyceramides/2-hydroxyglucosylceramides with longer chain amide-linked fatty acids (more than C24) increases later
-
-
?
additional information
?
-
initiates fatty acid alpha-oxidation and is also responsible for the biosynthesis of 2-hydroxy fatty acid-containing sphingolipids in mammalian cells
-
-
?
additional information
?
-
-
initiates fatty acid alpha-oxidation and is also responsible for the biosynthesis of 2-hydroxy fatty acid-containing sphingolipids in mammalian cells
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
FA2H is expressed in cultured human keratinocytes and human epidermis, with FA2H expression and fatty acid 2-hydroxylase activity increasing with differentiation
FA2H is expressed in cultured human keratinocytes and human epidermis, with FA2H expression and fatty acid 2-hydroxylase activity increasing with differentiation
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
COS7 cells expressing human FA2H contain 3-20fold higher levels of 2-hydroxyceramides (C16, C18, C24, and C24:1) and 2-hydroxy fatty acids compared with control cells
physiological function
FA2H-siRNA suppresses 2-hydroxylase activity and decreases 2-hydroxyceramide/2-hydroxyglucosylceramide levels. Keratinocytes transduced with FA2H-siRNA contain abnormal epidermal lamellar bodies and do not form the normal extracellular lamellar membranes required for the epidermal permeability barrier
physiological function
silencing of sphingolipid fatty acyl 2-hydroxylase Fa2h turns the cells resistant to synthetic antitumor drug PM02734, i.e. elisidepsin. Overexpression of Fa2H leads to an increased sensitivity to PM02734
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). PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
FA2H lacking the N-terminal cytochrome b5 domain has little activity
additional information
-
FA2H lacking the N-terminal cytochrome b5 domain has little activity
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
DELTA9-tetrahydrocannabinol together with induced levels of peroxisome proliferator-activated receptor alpha significantly stimulate the expression of fatty acid 2 hydroxylase
-
differentiation-dependent up-regulation of ceramide synthesis and fatty acid elongation is accompanied by up-regulation of FA2H
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
in blood and fibroblasts from patients harboring a deleterious FA2H mutatation, hydroxylated fatty acid sphingomyelin is present in normal amounts in patient lymphocytes, but decreases to a different extent in fibroblasts and erythrocytes
medicine
silencing of sphingolipid fatty acyl 2-hydroxylase Fa2h turns the cells resistant to synthetic antitumor drug PM02734, i.e. elisidepsin. Overexpression of Fa2H leads to an increased sensitivity to PM02734. Exogenous addition of the 2-hydroxylated fatty acid 2-hydroxy palmitic acid to different human cell lines increases their sensitivity to the cytotoxic compound
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Herrero, A.B.; Astudillo, A.M.; Balboa, M.A.; Cuevas, C.; Balsinde, J.; Moreno, S.
Levels of SCS7/FA2H-mediated fatty acid 2-hydroxylation determine the sensitivity of cells to antitumor PM02734
Cancer Res.
68
9779-9787
2008
Homo sapiens (Q7L5A8), Homo sapiens, Saccharomyces cerevisiae (Q03529), Saccharomyces cerevisiae
Alderson, N.; Rembiesa, B.; Walla, M.; Bielawska, A.; Bielawski, J.; Hama, H.
The human FA2H gene encodes a fatty acid 2-hydroxylase
J. Biol. Chem.
279
48562-48568
2004
Homo sapiens (Q7L5A8), Homo sapiens
Uchida, Y.; Hama, H.; Alderson, N.L.; Douangpanya, S.; Wang, Y.; Crumrine, D.A.; Elias, P.M.; Holleran, W.M.
Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation
J. Biol. Chem.
282
13211-13219
2007
Homo sapiens (Q7L5A8), Homo sapiens
Guo, L.; Zhang, X.; Zhou, D.; Okunade, A.; Su, X.
Stereospecificity of fatty acid 2-hydroxylase and differential functions of 2-hydroxy fatty acid enantiomers
J. Lipid Res.
53
1327-1335
2012
Homo sapiens (Q7L5A8), Homo sapiens, Mus musculus (Q5MPP0)
Dan, P.; Edvardson, S.; Bielawski, J.; Hama, H.; Saada, A.
2-hydroxylated sphingomyelin profiles in cells from patients with mutated fatty acid 2-hydroxylase
Lipids Health Dis.
10
84
2011
Homo sapiens
Takeda, S.; Ikeda, E.; Su, S.; Harada, M.; Okazaki, H.; Yoshioka, Y.; Nishimura, H.; Ishii, H.; Kakizoe, K.; Taniguchi, A.; Tokuyasu, M.; Himeno, T.; Watanabe, K.; Omiecinski, C.J.; Aramaki, H.
DELTA9-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression possible involvement of induced levels of PPARalpha in MDA-MB-231 breast cancer cells
Toxicology
326
18-24
2014
Homo sapiens
EXTERNAL LINKS (specific for EC-Number 1.14.18.6)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
