BRENDA - Enzyme Database show
show all sequences of 1.21.1.1

Towards the pre-clinical diagnosis of hypothyroidism caused by iodotyrosine deiodinase (DEHAL1) defects

Iglesias, A.; Garcia-Nimo, L.; Cocho de Juan, J.A.; Moreno, J.C.; Best Pract. Res. Clin. Endocrinol. Metab. 28, 151-159 (2014)

Data extracted from this reference:

Application
Application
Commentary
Organism
diagnostics
improvement of pre-clinical detection of iodotyrosine deiodinase deficiency during the neonatal time
Homo sapiens
Cloned(Commentary)
Commentary
Organism
gene DEHAL1, DNA and amino acid sequence determination and analysis, genotyping of healthy and iodotyrosine deiodinase deficiency samples
Homo sapiens
Engineering
Amino acid exchange
Commentary
Organism
A220T
naturally occuring mutation involved in iodotyrosine deiodinase
Homo sapiens
I116T
naturally occuring mutation involved in iodotyrosine deiodinase deficiency, the mutant shows highly reduced activity compared to te wild-type enzyme
Homo sapiens
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
Homo sapiens
R101W
naturally occuring mutation involved in iodotyrosine deiodinase deficiency, the mutant shows highly reduced activity compared to te wild-type enzyme
Homo sapiens
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
L-tyrosine + 2 NADP+ + 2 iodide
Homo sapiens
via mono-iodotyrosine
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
-
r
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
Q6PHW0
gene DEHAL1
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
thyroid
-
Homo sapiens
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
L-tyrosine + 2 NADP+ + 2 iodide
via mono-iodotyrosine
733237
Homo sapiens
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
-
-
r
L-tyrosine + 2 NADP+ + 2 iodide
via mono-iodotyrosine, the reaction might involve an additional ferredoxin reductase
733237
Homo sapiens
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
-
-
r
additional information
analytical detection method for iodotyrosine, overview
733237
Homo sapiens
?
-
-
-
-
Cofactor
Cofactor
Commentary
Organism
Structure
Ferredoxin
-
Homo sapiens
FMN
dependent on
Homo sapiens
additional information
the cofactors form a redox electron transport chain, overview
Homo sapiens
NADPH
NADPH is a necessary donor of electrons for the reductive reaction
Homo sapiens
Application (protein specific)
Application
Commentary
Organism
diagnostics
improvement of pre-clinical detection of iodotyrosine deiodinase deficiency during the neonatal time
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
gene DEHAL1, DNA and amino acid sequence determination and analysis, genotyping of healthy and iodotyrosine deiodinase deficiency samples
Homo sapiens
Cofactor (protein specific)
Cofactor
Commentary
Organism
Structure
Ferredoxin
-
Homo sapiens
FMN
dependent on
Homo sapiens
additional information
the cofactors form a redox electron transport chain, overview
Homo sapiens
NADPH
NADPH is a necessary donor of electrons for the reductive reaction
Homo sapiens
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
A220T
naturally occuring mutation involved in iodotyrosine deiodinase
Homo sapiens
I116T
naturally occuring mutation involved in iodotyrosine deiodinase deficiency, the mutant shows highly reduced activity compared to te wild-type enzyme
Homo sapiens
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
Homo sapiens
R101W
naturally occuring mutation involved in iodotyrosine deiodinase deficiency, the mutant shows highly reduced activity compared to te wild-type enzyme
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
L-tyrosine + 2 NADP+ + 2 iodide
Homo sapiens
via mono-iodotyrosine
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
-
r
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
thyroid
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
L-tyrosine + 2 NADP+ + 2 iodide
via mono-iodotyrosine
733237
Homo sapiens
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
-
-
r
L-tyrosine + 2 NADP+ + 2 iodide
via mono-iodotyrosine, the reaction might involve an additional ferredoxin reductase
733237
Homo sapiens
3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+
-
-
-
r
additional information
analytical detection method for iodotyrosine, overview
733237
Homo sapiens
?
-
-
-
-
General Information
General Information
Commentary
Organism
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
Homo sapiens
additional information
the human enzyme harbors a conserved nitroreductase domain
Homo sapiens
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
Homo sapiens
General Information (protein specific)
General Information
Commentary
Organism
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
Homo sapiens
additional information
the human enzyme harbors a conserved nitroreductase domain
Homo sapiens
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
Homo sapiens
Other publictions for EC 1.21.1.1
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
744171
Sun
The distribution and mechanis ...
Homo sapiens
Arch. Biochem. Biophys.
632
77-87
2017
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744363
Ingavat
Active site binding is not su ...
Homo sapiens
Biochemistry
56
1130-1139
2017
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2
746394
Phatarphekar
Functional analysis of iodoty ...
Drosophila melanogaster
Protein Sci.
25
2187-2195
2016
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733360
Bobyk
Rapid kinetics of dehalogenati ...
Homo sapiens
Biochemistry
54
4487-4494
2015
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733459
Sun
Expression of iodotyrosine dei ...
Rattus norvegicus, Rattus norvegicus Wistar
Biol. Trace Elem. Res.
167
272-279
2015
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1
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170
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734321
Hu
A switch between one- and two- ...
Homo sapiens
J. Biol. Chem.
290
590-600
2015
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3
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1
1
728285
Phatarphekar
Iodotyrosine deiodinase: a uni ...
Danio rerio, Daphnia pulex, Haliscomenobacter hydrossis, Hydra vulgaris, Mus musculus
Mol. Biosyst.
10
86-92
2014
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10
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733237
Iglesias
Towards the pre-clinical diagn ...
Homo sapiens
Best Pract. Res. Clin. Endocrinol. Metab.
28
151-159
2014
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3
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733452
Shimizu
Iodotyrosine deiodinase, a nov ...
Homo sapiens
Biol. Pharm. Bull.
37
1430-1434
2014
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1
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23
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734996
de la Cruz
The Caenorhabditis elegans iod ...
Caenorhabditis elegans
PLoS Genet.
10
e1004175
2014
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728830
Shimizu
Structure-activity relationshi ...
Homo sapiens
Toxicology
314
22-29
2013
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726449
Buss
Expression of a soluble form o ...
Mus musculus
Protein Sci.
21
351-361
2012
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701712
Gaupale
Localization and enzyme activi ...
Microhyla ornata
Ann. N. Y. Acad. Sci.
1163
402-406
2009
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704182
McTamney
A mammalian reductive deiodina ...
Homo sapiens
J. Am. Chem. Soc.
131
14212-14213
2009
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704506
Thomas
Crystal structure of iodotyros ...
Mus musculus
J. Biol. Chem.
284
19659-19667
2009
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703541
Krause
Characterisation of DEHAL1 exp ...
Homo sapiens
Eur. J. Endocrinol.
156
295-301
2007
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704417
Friedman
Iodotyrosine deiodinase is the ...
Mus musculus, Sus scrofa
J. Biol. Chem.
281
2812-2819
2006
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703608
Gnidehou
Iodotyrosine dehalogenase 1 (D ...
Homo sapiens, Sus scrofa
FASEB J.
18
1574-1576
2004
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704839
Solis-S
Comparative kinetic characteri ...
Rattus norvegicus
J. Endocrinol.
181
385-392
2004
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704368
Rosenberg
Purification and characterizat ...
Bos taurus
J. Biol. Chem.
254
12318-12325
1979
4
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1
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1
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704369
Goswami
Characterization of a flavopro ...
Bos taurus
J. Biol. Chem.
254
12326-12330
1979
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703835
Chiu
The snake thyroid gland. III. ...
Elaphe taeniura
Gen. Comp. Endocrinol.
35
93-95
1978
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1
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703460
Goswami
Studies on a soluble thyroid i ...
Bos taurus
Endocrinology
101
331-341
1977
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3
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702475
Dumas
Specificity of thyroidal and h ...
Rattus norvegicus
Biochim. Biophys. Acta
293
36-47
1973
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705504
Rosenberg
Purification of iodotyrosine d ...
Bos taurus
Metab. Clin. Exp.
19
785-798
1970
2
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