Any feedback?
Information on EC 1.14.11.8 - trimethyllysine dioxygenase
for references in articles please use BRENDA:EC1.14.11.8Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.14.11.8 trimethyllysine dioxygenaseIUBMB Comments
Requires Fe2+ and ascorbate.
Specify your search results
Word Map
- 1.14.11.8
- carnitine
- gamma-butyrobetaine
-
autism
-
inborn
-
proliferator-activated
- hydroxymethyltransferase
-
transporter-2
- aldolase
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
trimethyllysine hydroxylase, tmlh-b, epsilon-n-trimethyllysine hydroxylase, 6-n-trimethyllysine dioxygenase, tmlh-a, trimethyllysine dioxygenase, tml hydroxylase, tml dioxygenase, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
6-N-trimethyllysine dioxygenase
epsilon-N-trimethyllysine hydroxylase
epsilon-trimethyllysine 2-oxoglutarate dioxygenase
-
-
-
-
eta-N-trimethyllysine hydroxylase
oxygenase, trimethyllysine di-
-
-
-
-
TML dioxygenase
TML hydroxylase
-
-
-
-
TML-alpha-ketoglutarate dioxygenase
-
-
-
-
TMLD
TMLH
TMLH-a
TMLH-b
trimethyllysine alpha-ketoglutarate dioxygenase
-
-
-
-
trimethyllysine hydroxylase
TML dioxygenase
-
-
-
-
TMLD
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2 = (3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
N6,N6,N6-trimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)
Requires Fe2+ and ascorbate.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
84012-77-1
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
N5,N5,N5-trimethyl-L-ornithine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N5,N5,N5-trimethyl-L-ornithine + succinate + CO2
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
N6,N6-dimethyl-N6-ethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6-dimethyl-N6-ethyl-L-lysine + succinate + CO2
-
-
-
?
N6,N6-dimethyl-N6-isopropyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6-dimethyl-N6-isopropyl-L-lysine + succinate + CO2
-
-
-
?
N6,N6-dimethyl-N6-propyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6-dimethyl-N6-propyl-L-lysine + succinate + CO2
-
-
-
?
N6-fluoromethyl-N6,N6-dimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6-fluoromethyl-N6,N6-dimethyl-L-lysine + succinate + CO2
Nepsilon-trimethyllysine analogue that contains the fluoromethyl group can be used as a 1H and 19F NMR probe for studies on TMLH catalysis
-
-
?
N7,N7,N7-trimethyl-L-alpha-homolysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N7,N7,N7-trimethyl-L-alpha-homolysine + succinate + CO2
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
the enzymatic hydroxylation occurs at the C-3 site of (2S)-Nepsilon-trimethyllysine substrate. Comparative NMR spectroscopic studies (with two enantiopure synthetic standards that possess 3R and 3S stereochemistry) on the enzymatically produced (2S)-3-hydroxy-Nepsilon-trimethyllysine reveal that TMLH exclusively catalyzes the formation of (3S)-3-hydroxy-Nepsilon-trimethyl-L-lysine, not forming any (3R)-3-hydroxy-Nepsilon-trimethyl-L-lysine diastereoisomer
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
recognition sites that contribute to the enzymatic activity of the enzyme (TMLH): the Fe(II)-binding H242-D244-H389 residues, R391-R398 involved in 2-oxoglutarate-binding, and several residues (D231, N334, and the aromatic cage comprised of W221, Y217 and Y234) associated with binding of (2S)-Nepsilon-trimethyllysine
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
N6,N6, N6-trimethyl-L-lysine is epsilon-N-trimethyl-L-lysine
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
N6,N6, N6-trimethyl-L-lysine is epsilon-N-trimethyl-L-lysine
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
N6,N6, N6-trimethyl-L-lysine is epsilon-N-trimethyl-L-lysine
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
N6,N6, N6-trimethyl-L-lysine is epsilon-N-trimethyl-L-lysine
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
carnitine biosynthesis
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
first enzyme of the L-carnitine biosynthesis
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
-
?
additional information
?
-
determination of the (2S,3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine and N6,N6,N6-trimethyl-L-lysine is performed by ultraperformance liquid chromatographytandem mass spectrometry (UPLC/MS/MS) in positive ion electrospray mode
-
-
?
additional information
?
-
NMR spectrosopic structure analysis of substrates and products
-
-
?
additional information
?
-
NMR spectrosopic structure analysis of substrates and products, substrate specificity, overview. No or poor activity with dimethyllysine, methyllysine, lysine, D-trimethyllysine, 5-trimethylamino-1-aminopentane, trimethyllysine, 6-trimethylaminohexanoic acid, hexamethyllysine, N-acetyltrimethyllysine, trimethyldiaminobutyric acid, triethyllysine, symmetric and asymmetric dimethylarginines, mildronate, and gamma-butyrobetaine, structure-activity relationship study
-
-
?
additional information
?
-
-
NMR spectrosopic structure analysis of substrates and products, substrate specificity, overview. No or poor activity with dimethyllysine, methyllysine, lysine, D-trimethyllysine, 5-trimethylamino-1-aminopentane, trimethyllysine, 6-trimethylaminohexanoic acid, hexamethyllysine, N-acetyltrimethyllysine, trimethyldiaminobutyric acid, triethyllysine, symmetric and asymmetric dimethylarginines, mildronate, and gamma-butyrobetaine, structure-activity relationship study
-
-
?
additional information
?
-
-
enzyme is localized to the mitochondrial matrix, product formation is limited by 6-N-trimethyllysine transport across the mitochondrial inner membrane
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL 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
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
additional information
?
-
-
enzyme is localized to the mitochondrial matrix, product formation is limited by 6-N-trimethyllysine transport across the mitochondrial inner membrane
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
(3S)-3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
carnitine biosynthesis
-
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
first enzyme of the L-carnitine biosynthesis
-
?
N6,N6,N6-trimethyl-L-lysine + 2-oxoglutarate + O2
3-hydroxy-N6,N6,N6-trimethyl-L-lysine + succinate + CO2
-
-
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Fe2+
Fe2+
-
preincubation with Fe2+ in absence of other cofactors inactivates (ascorbate or dithiothreitol prevents inactivation)
Fe2+
dependent on, non-heme Fe(II) and 2-oxoglutarate dependent oxygenase, Fe2+ is required for catalysis
Fe2+
-
absence of the cofactor Fe2+ does not completely abolish enzyme activity, even when endogenous Fe2+ is removed from the homogenate with a gel filtration column
Fe2+
-
absence of the cofactor Fe2+ does not completely abolish enzyme activity, even when endogenous Fe2+ is removed from the homogenate with a gel filtration column
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Michaelis-Menten kinetics
-
0.636
N6,N6,N6-Trimethyl-L-lysine
recombinant MBP-tagged enzyme, pH 7.0, 37°C
0.696
N6,N6,N6-Trimethyl-L-lysine
recombinant detagged enzyme, pH 7.0, 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
tissue-dependent enzyme expression in case of high-lysine diet, overview
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
no activity found in microsomal or soluble fractions of liver
-
brenda
-
mitochondrial matrix, product formation is limited by 6-N-trimethyllysine transport across the mitochondrial inner membrane
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
metabolism
physiological function
additional information
evolution
the enzyme belongs to the family of 2-oxoglutarate (2OG)-dependent oxygenases
evolution
the enzyme belongs to the family of 2-oxoglutarate (2OG)-dependent oxygenases. Members of Fe(II) and 2-oxoglutarate-dependent oxygenases catalyze stereoselective hydroxylations of unactivated C-H bonds in various (bio)molecules, including proteins, DNA, and small molecule metabolites
evolution
the enzyme belongs to the non-heme Fe(II) and 2-oxoglutarate dependent oxygenases
metabolism
the enzyme catalyzes the first step in the biosynthesis of carnitine
metabolism
-
the enzyme catalyzes the first step in the biosynthesis of carnitine, i.e. L-3-hydroxy-4-N-N-N-trimethylaminobutyrate. Lysine in protein peptide linkages undergoes methylation of the 1-amino group to yield trimethyllysine, TML, which is released upon protein degradation. Muscle is the major source of TML. The released TML is further oxidised to gamma-butyrobetaine by the action of trimethyllysine dioxygenase, 3-hydroxy-N-trimethyllysine aldolase and 4-N-trimethylaminobutyraldehyde dehydrogenase
metabolism
the enzyme catalyses the first step in mammalian biosynthesis of carnitine, which plays a crucial role in fatty acid metabolism. Carnitine biosynthesis patway, overview
metabolism
trimethyllysine hydroxylase (TMLH) catalyses C-3 hydroxylation of Nepsilon-trimethyllysine in the first step of carnitine biosynthesis
metabolism
trimethyllysine hydroxylase (TMLH) catalyses C-3 hydroxylation of Nepsilon-trimethyllysine in the first step of carnitine biosynthesis in humans
metabolism
trimethyllysine hydroxylase (TMLH) catalyses the first step in carnitine biosynthesis, the conversion of N6,N6,N6-trimethyl-L-lysine to 3-hydroxy-N6,N6,N6-trimethyl-L-lysine
metabolism
trimethyllysine hydroxylase (TMLH) is involved in the first step of the physiologically important carnitine biosynthesis pathway. The enzyme catalyzes C-3 hydroxylation of (2S)-Nepsilon-L-trimethyllysine, to produce 3-hydroxy-Nepsilon-L-trimethyllysine, which then undergoes three additional enzymatic steps to the final L-carnitine
physiological function
trimethyllysine hydroxylase (TMLH) catalyses C-3 hydroxylation of Nepsilon-trimethyllysine in the first step of carnitine biosynthesis
physiological function
trimethyllysine hydroxylase (TMLH) catalyses C-3 hydroxylation of Nepsilon-trimethyllysine in the first step of carnitine biosynthesis in humans
physiological function
the enzyme catalyzes the first step in carnitine biosynthesis
additional information
residue Asp131 in TMLHis responsible for specific binding of the alpha-ammonium group of trimethyllysine
additional information
-
residue Asp131 in TMLHis responsible for specific binding of the alpha-ammonium group of trimethyllysine
Show AA Sequence and Transmembrane Helices (1739 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
the enzyme is synthesized as a 47500 Da precursor and processed to a mature protein of 43000 Da, presumably upon import into mitochondria
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D244E