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Information on EC 1.21.1.1 - iodotyrosine deiodinase
for references in articles please use BRENDA:EC1.21.1.1
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EC Tree 1 Oxidoreductases
1.21 Catalysing the reaction X-H + Y-H = X-Y
1.21.1 With NAD+ or NADP+ as acceptor
1.21.1.1 iodotyrosine deiodinase
IUBMB Comments
The enzyme activity has only been demonstrated in the direction of 3-deiodination. Present in a transmembrane flavoprotein. Requires FMN.
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 1.21.1.1
- thyroid
- iodide
-
deiodination
- hypothyroidism
- diiodotyrosine
- thyroglobulin
-
dehalogenation
-
halotyrosines
-
iodothyronine
- nitroreductase
- goiter
-
bromo
-
chlorotyrosine
-
organification
- diagnostics
- synthesis
- medicine
Reaction Schemes
show+
2
+
2
=
+
2
+
2
Synonyms
iodotyrosine deiodinase, dehal1, sup-18, dehal1 protein, dehal1b, iodotyrosine dehalogenase 1, nadh oxidase/flavin reductase, sup-18 iyd, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DEHAL1
EC 1.22.1.1
-
-
formerly
-
IYD
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3-iodo-L-tyrosine + NADP+ + iodide = 3,5-diiodo-L-tyrosine + NADPH + H+
(1b)
-
-
-
L-tyrosine + 2 NADP+ + 2 iodide = 3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
overall reaction
-
-
-
L-tyrosine + NADP+ + iodide = 3-iodo-L-tyrosine + NADPH + H+
(1a)
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
NADP+:L-tyrosine oxidoreductase (iodinating)
The enzyme activity has only been demonstrated in the direction of 3-deiodination. Present in a transmembrane flavoprotein. Requires FMN.
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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
3-bromo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + Br-
-
Substrates: -
Products: -
Products: -
?
3-chloro-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + Cl-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + iodide
Substrates: -
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 bromide
3,5-dibromo-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: halide elimination does not appear to limit reactions of bromo- and iodotyrosine since both fully oxidize the reduced enzyme with nearly equivalent second-order rate constants despite the differing strength of their carbon-halogen bonds
Products: -
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r
L-tyrosine + 2 NADP+ + 2 chloride
3,5-dichloro-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: chlorotyrosine reacts with the reduced enzyme approximately 20fold more slowly than bromo- and iodotyrosine and reveals a spectral intermediate that forms at approximately the same rate as the bromo- and iodotyrosine reactions
Products: -
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r
2-iodophenol + NADP+ + iodide
?
Substrates: 2-iodophenol binds very weakly to the enzyme and is dehalogenated with a catalytic efficiency that is more than 4 orders of magnitude lower than that for 3-iodo-L-tyrosine
Products: -
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?
2-iodophenol + NADP+ + iodide
?
Substrates: very weak substrate
Products: -
Products: -
?
2-iodophenol + NADP+ + iodide
?
Substrates: weak substrate
Products: -
Products: -
?
2-iodophenol + NADP+ + iodide
?
Substrates: weak substrate
Products: -
Products: -
?
3,5-diiodo-L-tyrosine + dithionite
3-iodo-L-tyrosine + ? + I-
-
Substrates: solubilized enzyme preparations are active with dithionite, but not with NADPH. Particle-bound enzyme uses both dithionite and NADPH. At concentrations of substrate below 1 microM, 3,5-diiodo-L-tyrosine is more rapidly deiodinated than 3-iodo-L-tyrosine, which is reversed at concentrations greater than 5 microM
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?
3,5-diiodo-L-tyrosine + dithionite
3-iodo-L-tyrosine + ? + I-
Substrates: -
Products: -
Products: -
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
-
Substrates: solubilized enzyme preparations are active with dithionite, but not with NADPH. Particle-bound enzyme uses both dithionite and NADPH. At concentrations of substrate below 1 microM, 3,5-diiodo-L-tyrosine is more rapidly deiodinated than 3-iodo-L-tyrosine, which is reversed at concentrations greater than 5 microM
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Products: -
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
Substrates: -
Products: -
Products: -
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
Substrates: -
Products: -
Products: -
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
Substrates: substrate 3-iodo-L-tyrosine is preferred over 3,5-diiodotyrosine
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Products: -
?
3-bromo-L-tyrosine + NADP+ + bromide
3,5-dibromo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-bromo-L-tyrosine + NADP+ + bromide
3,5-dibromo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-bromo-L-tyrosine + NADP+ + bromide
3,5-dibromo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-bromo-L-tyrosine + NADP+ + bromide
3,5-dibromo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-chloro-L-tyrosine + NADP+ + chloride
3,5-dichloro-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-chloro-L-tyrosine + NADP+ + chloride
3,5-dichloro-L-tyrosine + NADPH + H+
Substrates: low activity
Products: -
Products: -
?
3-chloro-L-tyrosine + NADP+ + chloride
3,5-dichloro-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-chloro-L-tyrosine + NADP+ + chloride
3,5-dichloro-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
Substrates: -
Products: -
Products: -
?
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
Substrates: via mono-iodotyrosine
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: -
Products: -
Products: -
?
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
Substrates: -
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: -
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
Substrates: via mono-iodotyrosine, the reaction might involve an additional ferredoxin reductase
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: halide elimination does not appear to limit reactions of bromo- and iodotyrosine since both fully oxidize the reduced enzyme with nearly equivalent second-order rate constants despite the differing strength of their carbon-halogen bonds
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
Substrates: -
Products: stepwise single electron transfer involving FMN, ferredoxin, and NADPH, overview. Ability of the substrate to provide multiple interactions with the isoalloxazine system ofFMN that are usually provided by protein side chains. Ligand binding acts to template the active site geometry and significantly stabilize the one-electron-reduced semiquinone form of FMN
Products: stepwise single electron transfer involving FMN, ferredoxin, and NADPH, overview. Ability of the substrate to provide multiple interactions with the isoalloxazine system ofFMN that are usually provided by protein side chains. Ligand binding acts to template the active site geometry and significantly stabilize the one-electron-reduced semiquinone form of FMN
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: -
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: -
Products: -
Products: -
r
L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: overall reaction
Products: -
Products: -
?
L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: overall reaction
Products: -
Products: -
?
L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: overall reaction
Products: -
Products: -
?
L-tyrosine + NADP+ + iodide
3-iodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
L-tyrosine + NADP+ + iodide
3-iodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
r
L-tyrosine + NADP+ + iodide
3-iodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
L-tyrosine + NADP+ + iodide
3-iodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with 3-fluoro-L-tyrosine
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with 3-fluoro-L-tyrosine
Products: -
Products: -
?
additional information
?
-
Substrates: analytical detection method for iodotyrosine, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: analytical detection method for iodotyrosine, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: fluorotyrosine is an inert substrate analogue
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme can act as a general dehalogenase, promoting reductive dehalogenation of 3-bromo- and 3-chloro-L-tyrosine, though not 3-fluoro-L-tyrosine
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme can act as a general dehalogenase, promoting reductive dehalogenation of 3-bromo- and 3-chloro-L-tyrosine, though not 3-fluoro-L-tyrosine
Products: -
Products: -
?
additional information
?
-
Substrates: a synergy between substrate selectivity and catalytic activity is created by the enzyme. No activity with the substrate analog 3-fluoro-L-tyrosine
Products: -
Products: -
?
additional information
?
-
-
Substrates: a synergy between substrate selectivity and catalytic activity is created by the enzyme. No activity with the substrate analog 3-fluoro-L-tyrosine
Products: -
Products: -
?
additional information
?
-
Substrates: the substrate analog 3-fluoro-L-tyrosine is inert
Products: -
Products: -
?
additional information
?
-
-
Substrates: while L-iodotyrosines are almost completely dehalogenated, D-iodotyrosines, alpha-methyl-DL-iodotyrosines and 3,5-diiodo-4-hydroxyphenyl-DL-lactic acid are poor substrates for the deiodinase. No substrates are 3,5-diiodo-4-hydroxyphenyl-alpha-guanidyl propionic acid, 3,5-diiodo-4-hydroxyphenyl propionic acid, 3,5-diiodotyramine, 3-iodo-5-nitro-L-tyrosine and 3-iodo-L-phenylalanine
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
-
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
3-iodo-L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
-
Substrates: -
Products: -
Products: -
?
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
Substrates: via mono-iodotyrosine
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: -
Products: -
Products: -
?
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
Substrates: -
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: -
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: -
Products: -
Products: -
r
L-tyrosine + 2 NADP+ + 2 iodide
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
Substrates: -
Products: -
Products: -
r
L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: overall reaction
Products: -
Products: -
?
L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: overall reaction
Products: -
Products: -
?
L-tyrosine + NADP+ + iodide
3,5-diiodo-L-tyrosine + NADPH + H+
Substrates: overall reaction
Products: -
Products: -
?
L-tyrosine + NADP+ + iodide
3-iodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
L-tyrosine + NADP+ + iodide
3-iodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
L-tyrosine + NADP+ + iodide
3-iodo-L-tyrosine + NADPH + H+
Substrates: -
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
flavin
-
presence of a neutral flavin radical during the reaction. Radical is stable and persists at 4°C under aerobic conditions for many days
FMN
-
enzyme is reduced in two successive 1-electron oxidation-reduction steps. The oxidation-reduction potential of the couple semiquinone/fully reduced enzyme is -0.412 V at pH 7 and 25°C. The value for the oxidized/semiquinone couple is -0.190 V at pH 7 and 25°C
FMN
the FMN-binding site of mammalian IYD is conserved in SUP-18, FMN appears to require catalytic activity to function
FMN
FMN binds non-covalently at the dimer interface established by a helix from each of the two identical subunits involving residues Ser102 and Ser128. Iodotyrosine deiodinase utilizes FMN to maintain iodide homeostasis by reductive deiodination of iodotyrosine. In the absence of an active site ligand, only the oxidized and two-electron-reduced forms of FMN are detected
additional information
the cofactors form a redox electron transport chain, overview
-
additional information
-
the cofactors form a redox electron transport chain, overview
-
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
benzyl-C8-18-alkyldimethylammonium chloride
complete inhibition at 1 mM
-
additional information
-
among polychlorinated biphenyls and polybrominated diphenyl ethers without a hydroxyl group tested, including their methoxylated metabolites, none is inhibitory
-
additional information
target for disruption of thyroid hormone homeostasis by environmental halogenated chemicals, e.g. food colorants, pharmaceuticals, agrochemicals, and antiparasitics, effects of environmental halogenated chemicals on iodotyrosine deiodinase activity, overview. Non-hydroxylated PCBs (e.g., 2,2',4,4'-tetrachlorobiphenyl) and PBDEs (e.g., 2,2',4,4'-tetrabromodiphenyl ether), nitrofen, trichlabendazole, miconazole and amiodarone lack IYD-inhibitory activity
-
additional information
-
target for disruption of thyroid hormone homeostasis by environmental halogenated chemicals, e.g. food colorants, pharmaceuticals, agrochemicals, and antiparasitics, effects of environmental halogenated chemicals on iodotyrosine deiodinase activity, overview. Non-hydroxylated PCBs (e.g., 2,2',4,4'-tetrachlorobiphenyl) and PBDEs (e.g., 2,2',4,4'-tetrabromodiphenyl ether), nitrofen, trichlabendazole, miconazole and amiodarone lack IYD-inhibitory activity
-
additional information
not inhibited by bromoxynil, bisphenol A, dibutyl phthalate, and genistein
-
additional information
-
methimazole and propylthiouracil affect the activity of the enzyme in thyrocytes by preventing its lysosomal redistribution
-
additional information
-
not inhibited by 2,6-di-tert-butylphenol, sodium 4-octylbenzenesulfonate, AVE6324, tamoxifen, clomiphene citrate, and 1,4-diaminoanthraquinone
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
an evolutionarily conserved serine-cysteine-rich region in the C-terminal cytoplasmic domain of SUP-9 is required for its specific activation by SUP-18
-
additional information
-
an evolutionarily conserved serine-cysteine-rich region in the C-terminal cytoplasmic domain of SUP-9 is required for its specific activation by SUP-18
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Congenital Hypothyroidism
Mutations in the iodotyrosine deiodinase gene and hypothyroidism.
Goiter
Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations.
Goiter
Towards the pre-clinical diagnosis of hypothyroidism caused by iodotyrosine deiodinase (DEHAL1) defects.
Goiter
[Quantitative aspects of iodine metabolism in one case of congenital iodotyrosine deiodinase defect (author's transl)]
Hyperthyroidism
A Nonradioactive DEHAL Assay for Testing Substrates, Inhibitors, and Monitoring Endogenous Activity.
Hypothyroidism
Genetic Evaluation of Congenital Hypothyroidism with Gland in situ Using Targeted Exome Sequencing.
Hypothyroidism
Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations.
Hypothyroidism
Molecular characterization of iodotyrosine dehalogenase deficiency in patients with hypothyroidism.
Hypothyroidism
Towards the pre-clinical diagnosis of hypothyroidism caused by iodotyrosine deiodinase (DEHAL1) defects.
Hypothyroidism
Towards the timely diagnosis of hypothyroidism caused by DEHAL1 gene defects.
Hypothyroidism
[Quantitative aspects of iodine metabolism in one case of congenital iodotyrosine deiodinase defect (author's transl)]
Intellectual Disability
Towards the pre-clinical diagnosis of hypothyroidism caused by iodotyrosine deiodinase (DEHAL1) defects.
Intellectual Disability
Towards the timely diagnosis of hypothyroidism caused by DEHAL1 gene defects.
iodotyrosine deiodinase deficiency
Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations.
iodotyrosine deiodinase deficiency
Towards the pre-clinical diagnosis of hypothyroidism caused by iodotyrosine deiodinase (DEHAL1) defects.
iodotyrosine deiodinase deficiency
Towards the timely diagnosis of hypothyroidism caused by DEHAL1 gene defects.
Thyroid Carcinoma, Anaplastic
Characterisation of DEHAL1 expression in thyroid pathologies.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.4
2-iodophenol
mutant enzyme E157S/E158Y/I159E/Y161W/M162A/K163R/M165F/H167D/R168E/T171E/R177N/T178L/N179D/I181R/K182H, at pH 7.4 and 25°C
0.019
3,5-diiodo-L-tyrosine
enzyme expressed in Pichia pastoris, pH not specified in the publication, temperature not specified in the publication
0.04
3,5-diiodo-L-tyrosine
enzyme expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
0.44
3,5-diiodo-L-tyrosine
mutant Y157F, expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
0.008
3-bromo-L-tyrosine
at pH 7.4, temperature not specified in the publication
0.021
3-chloro-L-tyrosine
at pH 7.4, temperature not specified in the publication
0.004
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.0066
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.007
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.0073
3-iodo-L-tyrosine
pH and temperature not specified in the publication
0.008
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.014
3-iodo-L-tyrosine
at pH 7.4, temperature not specified in the publication
0.017
3-iodo-L-tyrosine
mutant enzyme T239S, pH and temperature not specified in the publication
0.019
3-iodo-L-tyrosine
pH not specified in the publication, temperature not specified in the publication
0.031
3-iodo-L-tyrosine
pH 7.6, temperature not specified in the publication, recombinant enzyme
0.031
3-iodo-L-tyrosine
wild type enzyme, pH and temperature not specified in the publication
0.055
3-iodo-L-tyrosine
mutant enzyme T239A, pH and temperature not specified in the publication
0.13
3-iodo-L-tyrosine
mutant enzyme E157D/E158Y/M162A , at pH 7.4 and 25°C
15
3-iodo-L-tyrosine
mutant enzyme E157S/E158Y/I159E/Y161W/M162A/K163R/M165F/H167D/R168E/T171E/R177N/T178L/N179D/I181R/K182H, at pH 7.4 and 25°C
additional information
additional information
-
rapid kinetics of dehalogenation promoted by iodotyrosine deiodinase from human thyroid, substrates chloro-, bromo-, and iodotyrosine bind with similar rate constants, overview. Standard two-state model, no intermediate complex accumulates during closure of the active site lid induced by substrate
-
additional information
additional information
Michaelis-Menten steady-state kinetics. Dissociation constants for different substrate analogues, overview
-
additional information
additional information
-
Michaelis-Menten steady-state kinetics. Dissociation constants for different substrate analogues, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0153
2-iodophenol
mutant enzyme E157S/E158Y/I159E/Y161W/M162A/K163R/M165F/H167D/R168E/T171E/R177N/T178L/N179D/I181R/K182H, at pH 7.4 and 25°C
0.12
3,5-diiodo-L-tyrosine
enzyme expressed in Pichia pastoris, pH not specified in the publication, temperature not specified in the publication
0.16
3,5-diiodo-L-tyrosine
enzyme expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
1.08
3,5-diiodo-L-tyrosine
mutant Y157F, expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
0.069
3-bromo-L-tyrosine
at pH 7.4, temperature not specified in the publication
0.05
3-chloro-L-tyrosine
at pH 7.4, temperature not specified in the publication
0.0102
3-iodo-L-tyrosine
pH and temperature not specified in the publication
0.057
3-iodo-L-tyrosine
mutant enzyme T239A, pH and temperature not specified in the publication
0.07
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.09
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.095
3-iodo-L-tyrosine
mutant enzyme E157S/E158Y/I159E/Y161W/M162A/K163R/M165F/H167D/R168E/T171E/R177N/T178L/N179D/I181R/K182H, at pH 7.4 and 25°C
0.12
3-iodo-L-tyrosine
pH not specified in the publication, temperature not specified in the publication
0.12
3-iodo-L-tyrosine
at pH 7.4, temperature not specified in the publication
0.2
3-iodo-L-tyrosine
mutant enzyme T239S, pH and temperature not specified in the publication
0.208
3-iodo-L-tyrosine
pH 7.6, temperature not specified in the publication, recombinant enzyme
0.217
3-iodo-L-tyrosine
wild type enzyme, pH and temperature not specified in the publication
0.23
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.29
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.533
3-iodo-L-tyrosine
mutant enzyme E157D/E158Y/M162A , at pH 7.4 and 25°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0045
2-iodophenol
mutant enzyme E157S/E158Y/I159E/Y161W/M162A/K163R/M165F/H167D/R168E/T171E/R177N/T178L/N179D/I181R/K182H, at pH 7.4 and 25°C
2.5
3,5-diiodo-L-tyrosine
mutant Y157F, expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
3.83
3,5-diiodo-L-tyrosine
enzyme expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
6
3,5-diiodo-L-tyrosine
enzyme expressed in Pichia pastoris, pH not specified in the publication, temperature not specified in the publication
9000
3-bromo-L-tyrosine
at pH 7.4, temperature not specified in the publication
2400
3-chloro-L-tyrosine
at pH 7.4, temperature not specified in the publication
0.0065
3-iodo-L-tyrosine
mutant enzyme E157S/E158Y/I159E/Y161W/M162A/K163R/M165F/H167D/R168E/T171E/R177N/T178L/N179D/I181R/K182H, at pH 7.4 and 25°C
1
3-iodo-L-tyrosine
mutant enzyme T239A, pH and temperature not specified in the publication
4.17
3-iodo-L-tyrosine
mutant enzyme E157D/E158Y/M162A , at pH 7.4 and 25°C
6
3-iodo-L-tyrosine
pH not specified in the publication, temperature not specified in the publication
6.67
3-iodo-L-tyrosine
wild type enzyme, pH and temperature not specified in the publication
6.72
3-iodo-L-tyrosine
pH 7.6, temperature not specified in the publication, recombinant enzyme
8.5
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
9.7
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
11.67
3-iodo-L-tyrosine
mutant enzyme T239S, pH and temperature not specified in the publication
41.7
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
58.3
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
9000
3-iodo-L-tyrosine
at pH 7.4, temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.3
4,5-dichloro-2-octyl-3(2H)-isothiazolone
Homo sapiens
IC50 above 0.3 mM, at pH 7.4 and 37°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
activity ranges from 0.0001 to 0.0003 microg/min/mg of tissue
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
pH dependence of IYD binding and turnover, tightest binding was measured near a neutral pH of 7.67.7
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
during metamorphosis, DEHAL1 enzyme activity is higher on diiodotyrosine as compared to monoiodotyrosine. Using diiodotyrosine as a substrate, maximal activity is detected at stage 44 in the brain, while it is higher at stage 42 in the tail. With monoiodotyrosine as a substrate, highest activity is detected in the brain at stage 42
brenda
-
tadpole tail fin. During metamorphosis, DEHAL1 enzyme activity is higher on diiodotyrosine as compared to monoiodotyrosine. Using diiodotyrosine as a substrate, maximal activity is detected at stage 44 in the brain, while it is higher at stage 42 in the tail (138.5 U/mg protein). With monoiodotyrosine as a substrate, highest activity is detected in the brain at stage 42
brenda
additional information
additional information
-
tissue expression analysis of the enzyme in conditions such as iodine deficiency and excess, overview
brenda
additional information
-
tissue expression analysis of the enzyme in conditions such as iodine deficiency and excess, overview
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
enzyme SUP-18 is a type-I transmembrane protein that can function independently of membrane anchoring
brenda
transmembrane protein, partly exposed to cell surface, protein accumulates at the apical pole of thyrocytes
brenda
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
evolution
domain swaps at each N and C terminus consistent with the nitro-FMN reductase superfamily
malfunction
metabolism
physiological function
additional information
malfunction
increased sup-18(+) expression in body-wall muscles specifically enhances the behavioral defects of sup-10(n983gf) mutants
malfunction
loss-of-function mutations of the enzyme lead to the iodotyrosine deiodinase deficiency (ITDD), characterized by accumulation of mono- and diiodotyrosines in thyroid gland, plasma, and urine, hypothyroidism, compressive goiter and variable mental retardation, whose diagnostic hallmark is the elevation of iodotyrosines in serum and urine. Patients harboring DEHAL1 defects so far described all belong to consanguineous families, phenotype, overview. Lack of biochemical expression of the disease at the beginning of life
malfunction
thyroid dysfunction can have very serious consequences, including mental retardation
malfunction
-
loss of function or chemical inhibition of the enzyme reduces available iodide for thyroid hormone synthesis, which leads to hormone insufficiency in tissues
metabolism
genetic analyses suggest that SUP-10 can function with SUP-18 to activate SUP-9 through a pathway that is independent of the presumptive SUP-9 regulatory subunit UNC-93. The SUP-9 two-pore domain K+ channel is most closely related to human TASK-3. unc-93 encodes a conserved multi-pass transmembrane protein. An evolutionarily conserved serine-cysteine-rich region in the C-terminal cytoplasmic domain of SUP-9 is required for its specific activation by SUP-10 and SUP-18 but not by UNC-93
metabolism
-
reductive dehalogenation such as that catalyzed by iodotyrosine deiodinase is highly unusual in aerobic organisms but necessary for iodide salvage from iodotyrosine generated during thyroxine biosynthesis
physiological function
-
the enzyme, catalyzing the reductive dehalogenation, is a critical enzyme in maintaining iodine homeostasis
physiological function
the NADH oxidase/flavin reductase, an orthologue of mammalian iodotyrosine deiodinase (IYD), functions in iodine recycling and is important for the biosynthesis of thyroid hormones that regulate metabolism. The enzyme SUP-18 is a type-I transmembrane protein with an NADH oxidase/flavin reductase domain that resides intracellularly and can function without plasma membrane localization. The enzyme regulates the activity of the muscle two-pore domain potassium SUP-9 channel using NADH as a coenzyme and thus couples the metabolic state of muscle cells to muscle membrane excitability
physiological function
the thyroidal enzyme deiodinates mono- and diiodotyrosines (MIT, DIT) and recycles iodine, a scarce element in the environment, for the efficient synthesis of thyroid hormone, function and proposed components of the iodotyrosine deiodinase system, overview
physiological function
-
reductive dehalogenation such as that catalyzed by iodotyrosine deiodinase is highly unusual in aerobic organisms but necessary for iodide salvage from iodotyrosine generated during thyroxine biosynthesis
physiological function
a FMN moiety that is involved in reduced NADPH-dependent reductive deiodination of 3-iodo-Ltyrosine (MIT) and 3,5-diiodo-L-tyrosine (DIT), which are released along with the thyroid hormones T4 and T3 during thyroglobulin proteolysis. Iodotyrosine deiodinase is involved in iodide salvage by catalyzing deiodination of iodinated by-products of thyroid hormone production. Thyroid hormones play important roles in growth, development, differentiation, and basal metabolic homeostasis, as well as in brain development in human fetus and children
physiological function
iodotyrosine deiodinase utilizes FMN to maintain iodide homeostasis by reductive deiodination of iodotyrosine
physiological function
-
the enzyme, catalyzing the reductive dehalogenation, is a critical enzyme in maintaining iodine homeostasis
-
additional information
the human enzyme harbors a conserved nitroreductase domain
additional information
-
the human enzyme harbors a conserved nitroreductase domain
additional information
a synergy between substrate selectivity and catalytic activity is created by the enzyme, active site and cofactor and substrate binding structures, overview
additional information
-
a synergy between substrate selectivity and catalytic activity is created by the enzyme, active site and cofactor and substrate binding structures, overview
Show AA Sequence and Transmembrane Helices (963 entries)
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Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
33000
30000
two identical subunits of human IYD form an alphabeta fold, 2 * 30000, recombinant enzyme, SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
heterodimer
two identical subunits of human IYD form an alphabeta fold, 2 * 30000, recombinant enzyme, SDS-PAGE
additional information
additional information
the enzyme contains three domains: an N-terminal transmembrane region, an intermediate domain, and a catalytic domain
additional information
-
the enzyme contains three domains: an N-terminal transmembrane region, an intermediate domain, and a catalytic domain
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
putative signal peptide with a possible cleavage site between Ala23 and Asp24
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 80 mM Tris-HCl pH 8.5, 100 mM MgCl2, 24% (w/v) PEG 4000 and 20% glycerol
mutant enzyme T239A co-crystallized with 3-fluoro-L-tyrosine, hanging drop vapor diffusion method, using 0.17 M sodium acetate, 85 mM Tris-HCl pH 8.5, 22.5% (w/v) polyethylene glycol 4000 and 15% (v/v) glycerol
purified enzyme in complex with substrate 3-iodo-L-tyrosine, method optimization, hanging drop diffusion method, mixing of 0.001 ml of 12 mg/ml protein in 50mM sodium phosphate, pH 7.4, 100 mM NaCl, 1 mM DTT, and 10% glycerol with 0.001 ml of precipitant solution containing 0.05 M ammonium sulfate, 50 mM BisTris, pH 6.5, and 25% pentaerythritol ethoxylate, 2 days, 20°C. To generate co-crystals the enzyme is treated with 1.5 mM 3-iodo-L-tyrosine overnight and then subjected to the same hanging drop procedure using a well solution of 0.15 M sodium acetate, 85mM Tris-HCl, pH 8.5, 25.5% w/v PEG 4000, and 15% glycerol at 20 °C, 24 h, X-ray diffraction structure determination and analysis at 2.45-2.65 A resolution, molecular replacement
hanging dop vapor diffusion method, using 0.2 M ammonium acetate, 0.1 M BisTris (pH 6.5), and 45% v/v 2-methyl-2,4-pentanediol
structure of a truncated derivative lacking the membrane domain, residues 2-33, at its N-terminal, and its complex with substrate monoiodotyrosine. In the absence of substrate, the active site appears very accessible to solvent due to a lack of detectable structure in two surrounding regions of the polypeptide. In the presence of substrate, an active site lid comprised of a helix and loop is detected from the diffraction data. This lid effectively sequesters the substrate-flavin complex from solvent
structures of soluble enzyme lacking codons for amino acids 2-33 and two co-crystals containing substrates, mono- and diiodotyrosine, alternatively, at resolutions of 2.0 A, 2.45 A, and 2.6 A, respectively. Substrate coordination induces formation of an additional helix and coil that act as an active site lid to shield the resulting substrateflavin complex from solvent. This complex is stabilized by aromatic stacking and extensive hydrogen bonding between the substrate and flavin. The carbon-iodine bond of the substrate is positioned directly over the C-4a/N-5 region of the flavin to promote electron transfer
hanging drop vapor diffusion method, using 100 mM sodium citrate pH 4.5 with 3 M NaCl
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E154Q
the mutation diminishes the affinity of the enzyme for 3,5-diiodo-L-tyrosine by 30fold
K179Q
the mutation diminishes the affinity of the enzyme for 3,5-diiodo-L-tyrosine by 46fold
Y158F
the mutation results in a 7fold decrease in the enzyme's affinity for 3,5-diiodo-L-tyrosine
E157D/E158Y/M162A
the mutant TM01 binds 3-iodo-L-tyrosine 240fold more weakly than mutant enzyme DM01 and exhibits a higher Km, by more than 90fold. However, the kcat for 3-iodo-L-tyrosine increases, relative to that of DM01, by more than 7fold to hold the loss in catalytic efficiency of TM01 to 12fold
E157S/E158Y/I159E/Y161W/M162A/K163R/M165F/H167D/R168E/T171E/R177N/T178L/N179D/I181R/K182H
the mutant UD08 supports a 4.5fold increase in turnover of 2-iodophenol and suppresses turnover of 3-iodo-L-tyrosine by 2000fold relative to the native enzyme
E158Y/M162A
the mutant DM01 binds 3-iodo-L-tyrosine more strongly than its parent and shows was 5fold lower Km and almost 4fold higher kcat/Km with 3-iodo-L-tyrosine as compared to the wild type enzyme
I116T
naturally occuring mutation involved in iodotyrosine deiodinase deficiency, the mutant shows highly reduced activity compared to te wild-type enzyme
R101W
naturally occuring mutation involved in iodotyrosine deiodinase deficiency, the mutant shows highly reduced activity compared to te wild-type enzyme
T239A
the catalytic efficiency of this variant is lower than wild type by 7fold
T239S
the dissociation constants of F-Tyr and I-Tyr increase by a similar 2fold for the T239S variant relative to those for wild type enzyme. The catalytic efficiency of this variant is greater than wild type by almost 2fold
E153Q
Y157F
M41A
the substitution weakens the enzyme's affinity for L-Tyr by 3.6fold, but its effect on 3-iodo-L-tyrosine is slightly greater (5fold) as compared to the wild type
M41A/Y112A
the mutant binds both 3-iodo-L-tyrosine and L-Tyr with nearly the same affinities as the native enzyme
M41F
the mutation enhances binding of L-Tyr by 5fold and concurrently decreases binding of 3-iodo-L-tyrosine by 10fold resulting in a protein with an inverted selectivity that now favouring L-Tyr over 3-iodo-L-tyrosine by 5fold
M41K
the mutation decreases affinity for 3-iodo-L-tyrosine and L-Tyr by 22fold and 16fold, respectively, as compared to the wild type
W82A/F88A/Y112A
the mutations noticeably weaken binding of 3-iodo-L-tyrosine by 18fold but also re-establish selectivity for this substrate by a much more substantial destabilization of L-Tyr binding of more than 2600fold
Y112A
the mutant binds both 3-iodo-L-tyrosine and L-Tyr with nearly the same affinities as the native enzyme
Y122A
the mutant binds both 3-iodo-L-tyrosine and L-Tyr with nearly the same affinities as the native enzyme
M41A
-
the substitution weakens the enzyme's affinity for L-Tyr by 3.6fold, but its effect on 3-iodo-L-tyrosine is slightly greater (5fold) as compared to the wild type
-
M41A/Y112A
-
the mutant binds both 3-iodo-L-tyrosine and L-Tyr with nearly the same affinities as the native enzyme
-
M41K
-
the mutation decreases affinity for 3-iodo-L-tyrosine and L-Tyr by 22fold and 16fold, respectively, as compared to the wild type
-
Y112A
-
the mutant binds both 3-iodo-L-tyrosine and L-Tyr with nearly the same affinities as the native enzyme
-
Y122A
-
the mutant binds both 3-iodo-L-tyrosine and L-Tyr with nearly the same affinities as the native enzyme
-
additional information
E153Q
the mutant exhibits no measurable binding affinity for 3-chloro-L-tyrosine
E153Q
mutation reduces the deiodinase activity to an undetectable level. Mutant exhibits no measurable binding affinity for the substrate
Y157F
lack of the phenolic -OH of Y157F increases the kcat and KM values for deiodination by more than sevenfold and decreases the kcat/KM value more modestly by less than 40%
additional information
naturally occuring sup-18 loss-of-function mutations, e.g. splice-junction mutants and spontaneaous mutations, overview
additional information
-
naturally occuring sup-18 loss-of-function mutations, e.g. splice-junction mutants and spontaneaous mutations, overview
additional information
mutations occuring in enzyme deficiency include homozygous one inframe-deletion of three base pairs (F105-I106L) and two missense (R101W, I116T). The mutations are located in close vicinity of each other within exon 2 of the gene encoding a putative FMN-binding site at the nitroreductase catalytic domain of the protein. All three mutations dramatically reduce the in vitro activity of the enzyme, one is also prematurely degraded
additional information
-
mutations occuring in enzyme deficiency include homozygous one inframe-deletion of three base pairs (F105-I106L) and two missense (R101W, I116T). The mutations are located in close vicinity of each other within exon 2 of the gene encoding a putative FMN-binding site at the nitroreductase catalytic domain of the protein. All three mutations dramatically reduce the in vitro activity of the enzyme, one is also prematurely degraded
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant SUMO-tagged enzyme from Escherichia coli strain Rosetta 2(DE3) by nickel affinity chromatography, tag removal, and gel filtration
solubilization by 0.1% CHAPS
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of a derivative lacking codons for amino acids 233 to gain a soluble protein
gene DEHAL1, DNA and amino acid sequence determination and analysis, genotyping of healthy and iodotyrosine deiodinase deficiency samples
gene DEHAL1, recombinant expression of N-terminally SUMO-tagged enzyme in Escherichia coli strain Rosetta 2(DE3)
gene sup-18, genotyping, encodes the Caenorhabditis elegans orthologue of mammalian iodotyrosine deiodinase (IYD)
transfection of HEK-293 cells results in active protein, but not of CHO cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
iodine deficiency results in an increased enzyme expression in thyroid
study on enzyme expression in thyroid pathology. The highest DEHAL1 mRNA levels are found in Graves' disease thyroids, while downregulation of DEHAL1 and DEHAL1B mRNA occurrs in papillary thyroid carcinomas and anaplastic thyroid carcinomas. DEHAL1 protein is overexpressed in toxic thyroid nodules and Graves' disease thyroids with predominant apical staining in all samples. A weaker and patchy staining pattern is found in benign cold thyroid nodules and normal thyroids. In differentiated thyroid cancers such as follicular thyroid carcinomas and papillary thyroid carcinomas, a diffuse cytoplasmic DEHAL1 expression is found. In partially differentiated thyroid cancers and anaplastic thyroid carcinomas, DEHAL1 expression is faint or absent
-
the enzyme is suppressed in liver and kidney by iodine intake. Excess iodine decreases the expression of thyroidal enzyme
the enzyme mRNA level is suppressed by iodine and a follicular concentration of thyroglobulin. Methimazole and propylthiouracil significantly suppress enzyme expression induced by TSH, insulin and serum to 43% and 21% of the original levels, respectively
-
the enzyme is suppressed in liver and kidney by iodine intake. Excess iodine decreases the expression of thyroidal enzyme
-
the enzyme is suppressed in liver and kidney by iodine intake. Excess iodine decreases the expression of thyroidal enzyme
-
-
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
activation of purified enzyme by dithionite, methyl viologen, or ferredoxin, but not by photo-reduced FMN or by reducing agents having more positive oxidation-reduction potentials than the ferredoxin-NADP system
-
apoprotein binds FMN with an almost complete restoration of enzymatic activity. It can also bind FAD with partial restoration of activity, but does not bind riboflavin
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
improvement of pre-clinical detection of iodotyrosine deiodinase deficiency during the neonatal time
medicine
-
study on enzyme expression in thyroid pathology. The highest DEHAL1 mRNA levels are found in Graves' disease thyroids, while downregulation of DEHAL1 and DEHAL1B mRNA occurrs in papillary thyroid carcinomas and anaplastic thyroid carcinomas. DEHAL1 protein is overexpressed in toxic thyroid nodules and Graves' disease thyroids with predominant apical staining in all samples. A weaker and patchy staining pattern is found in benign cold thyroid nodules and normal thyroids. In differentiated thyroid cancers such as follicular thyroid carcinomas and papillary thyroid carcinomas, a diffuse cytoplasmic DEHAL1 expression is found. In partially differentiated thyroid cancers and anaplastic thyroid carcinomas, DEHAL1 expression is faint or absent
synthesis
high expression of a truncated derivative lacking the membrane domain, residues 2-33, at its N-terminal is observed in Sf9 cells, whereas expression in Pichia pastoris remains low despite codon optimization. The desired expression in Escherichia coli can be achieved after replacing the two conserved Cys residues of the deiodinase with Ala and fusing the resulting protein to thioredoxin. This construct provides abundant enzyme for crystallography and mutagenesis
additional information
additional information
target for disruption of thyroid hormone homeostasis by environmental halogenated chemicals
additional information
-
target for disruption of thyroid hormone homeostasis by environmental halogenated chemicals
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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Rattus norvegicus
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Goswami, A.; Rosenberg, I.
Studies on a soluble thyroid iodotyrosine deiodinase: activation by NADPH and electron carriers
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Goswami, A.; Rosenberg, I.
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254
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Bos taurus
brenda
Friedman, J.E.; Watson, J.A.; Lam, D.W.; Rokita, S.E.
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281
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Mus musculus (Q9DCX8), Mus musculus, Sus scrofa (Q6TA49), Sus scrofa
brenda
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284
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Mus musculus (Q9DCX8)
brenda
Solis-S, J.C.; Villalobos, P.; Orozco, A.; Valverde-R, C.
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181
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Rattus norvegicus
brenda
Rosenberg, I.
Purification of iodotyrosine deiodinase from bovine thyroid
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19
785-798
1970
Bos taurus
brenda
Buss, J.M.; McTamney, P.M.; Rokita, S.E.
Expression of a soluble form of iodotyrosine deiodinase for active site characterization by engineering the native membrane protein from Mus musculus
Protein Sci.
21
351-361
2012
Mus musculus (Q9DCX8), Mus musculus
brenda
Phatarphekar, A.; Buss, J.M.; Rokita, S.E.
Iodotyrosine deiodinase: a unique flavoprotein present in organisms of diverse phyla
Mol. Biosyst.
10
86-92
2014
Danio rerio, Daphnia pulex, Haliscomenobacter hydrossis, Hydra vulgaris, Mus musculus (Q9DCX8)
brenda
Shimizu, R.; Yamaguchi, M.; Uramaru, N.; Kuroki, H.; Ohta, S.; Kitamura, S.; Sugihara, K.
Structure-activity relationships of 44 halogenated compounds for iodotyrosine deiodinase-inhibitory activity
Toxicology
314
22-29
2013
Homo sapiens
brenda
Iglesias, A.; Garcia-Nimo, L.; Cocho de Juan, J.A.; Moreno, J.C.
Towards the pre-clinical diagnosis of hypothyroidism caused by iodotyrosine deiodinase (DEHAL1) defects
Best Pract. Res. Clin. Endocrinol. Metab.
28
151-159
2014
Homo sapiens (Q6PHW0), Homo sapiens
brenda
Bobyk, K.D.; Ballou, D.P.; Rokita, S.E.
Rapid kinetics of dehalogenation promoted by iodotyrosine deiodinase from human thyroid
Biochemistry
54
4487-4494
2015
Homo sapiens
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Shimizu, R.
Iodotyrosine deiodinase, a novel target of environmental halogenated chemicals for disruption of the thyroid hormone system in mammals
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37
1430-1434
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Homo sapiens (Q6PHW0), Homo sapiens
brenda
Sun, X.; Zhang, X.; Jiang, Y.; Bao, S.; Shan, Z.; Teng, W.
Expression of iodotyrosine deiodinase in thyroid and other organs in iodine-deficient and iodine-excess rats
Biol. Trace Elem. Res.
167
272-279
2015
Rattus norvegicus, Rattus norvegicus Wistar
brenda
Hu, J.; Chuenchor, W.; Rokita, S.E.
A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate
J. Biol. Chem.
290
590-600
2015
Homo sapiens (Q6PHW0), Homo sapiens
brenda
de la Cruz, I.P.; Ma, L.; Horvitz, H.R.
The Caenorhabditis elegans iodotyrosine deiodinase ortholog SUP-18 functions through a conserved channel SC-box to regulate the muscle two-pore domain potassium channel SUP-9
PLoS Genet.
10
e1004175
2014
Caenorhabditis elegans (Q17374), Caenorhabditis elegans
brenda
Sun, Z.; Su, Q.; Rokita, S.E.
The distribution and mechanism of iodotyrosine deiodinase defied expectations
Arch. Biochem. Biophys.
632
77-87
2017
Homo sapiens (Q6PHW0), Homo sapiens
brenda
Ingavat, N.; Kavran, J.M.; Sun, Z.; Rokita, S.E.
Active site binding is not sufficient for reductive deiodination by iodotyrosine deiodinase
Biochemistry
56
1130-1139
2017
Homo sapiens (F4KU78), Homo sapiens
brenda
Phatarphekar, A.; Rokita, S.E.
Functional analysis of iodotyrosine deiodinase from Drosophila melanogaster
Protein Sci.
25
2187-2195
2016
Drosophila melanogaster (E1JIB2), Drosophila melanogaster
brenda
Sun, Z.; Rokita, S.
Toward a halophenol dehalogenase from iodotyrosine deiodinase via computational design
ACS Catal.
8
11783-11793
2018
Homo sapiens (Q6PHW0)
-
brenda
Olker, J.H.; Korte, J.J.; Haselman, J.T.; Hornung, M.W.; Degitz, S.J.
Cross-species comparison of chemical inhibition of human and Xenopus iodotyrosine deiodinase
Aquat. Toxicol.
249
106227
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Homo sapiens (Q6PHW0), Xenopus laevis
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Yoshihara, A.; Luo, Y.; Ishido, Y.; Usukura, K.; Oda, K.; Sue, M.; Kawashima, A.; Hiroi, N.; Suzuki, K.
Inhibitory effects of methimazole and propylthiouracil on iodotyrosine deiodinase 1 in thyrocytes
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66
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Rattus norvegicus
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Sun, Z.; Xu, B.; Spisak, S.; Kavran, J.M.; Rokita, S.E.
The minimal structure for iodotyrosine deiodinase function is defined by an outlier protein from the thermophilic bacterium Thermotoga neapolitana
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297
101385
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Thermotoga neapolitana (B9K712), Thermotoga neapolitana ATCC 49049 (B9K712)
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Hu, J.; Su, Q.; Schlessman, J.L.; Rokita, S.E.
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28
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Homo sapiens (Q6PHW0)
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In vitro screening for chemical inhibition of the iodide recycling enzyme, iodotyrosine deiodinase
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71
105073
2021
Homo sapiens (Q6PHW0)
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Evaluating iodide recycling inhibition as a novel molecular initiating event for thyroid axis disruption in amphibians
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Xenopus laevis
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