Information on EC 1.21.99.4 - thyroxine 5'-deiodinase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.21.99.4
-
RECOMMENDED NAME
GeneOntology No.
thyroxine 5'-deiodinase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
3,3',5-triiodo-L-thyronine + iodide + acceptor + H+ = L-thyroxine + reduced acceptor
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
deiodination
-
-
redox reaction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
thyroid hormone metabolism I (via deiodination)
-
-
thyroid hormone metabolism II (via conjugation and/or degradation)
-
-
SYSTEMATIC NAME
IUBMB Comments
3,3',5-triiodo-L-thyronine,iodide:acceptor oxidoreductase (iodinating)
The enzyme activity has only been demonstrated in the direction of 5'-deiodination, which renders the thyroid hormone more active. The enzyme consists of type I and type II enzymes, both containing selenocysteine, but with different kinetics. For the type I enzyme the first reaction is a reductive deiodination converting the -Se-H group of the enzyme into an -Se-I group; the reductant then reconverts this into -Se-H, releasing iodide.
CAS REGISTRY NUMBER
COMMENTARY hide
70712-46-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Syrian hamster
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
type I and type II enzyme isoforms
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3,3',5'-triiodo-L-thyronine + AH2
3,3'-diiodo-L-thyronine + iodide + A + H+
show the reaction diagram
3,3',5'-triiodo-L-thyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
3,3',5,5'-tetraiodo-L-thyronine + AH2
?
show the reaction diagram
-
-
-
?
3,3',5-triiodo-L-thyronine sulfate + reduced electron acceptor
diiodothyronine + iodide + electron acceptor
show the reaction diagram
-
-
-
-
?
3,3',5-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
3,3',5-triiodothyronine + AH2
3,5-diiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
3,3',5-triiodothyronine + AH2
diiodothyronine + iodide + A + H+
show the reaction diagram
-
rT3 ORD activity
-
-
?
3,5'-diiodo-L-thyronine + AH2
3-iodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
3,5,3'-triiodo-L-thyronine + iodide + A + H+
L-thyroxine + AH2
show the reaction diagram
assay at pH 7.2
-
-
?
L-3,5',3'-triiodothyronine + AH2
L-3,3'-diiodothyonine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
L-3,5',3'-triiodothyronine + AH2
L-3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
5'-deionination by isozyme Dio1
-
-
?
L-3,5'-diiodothyonine + AH2
L-3-iodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
L-3,5'-diiodothyronine + AH2
L-3-iodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
L-3,5,3',5'-tetraiodothyronine + AH2
L-3,5,3'-triiodothyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + AH2
3,3',5'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + AH2
3,3',5'-triiodothyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + AH2
3,3',5-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + electron acceptor
3,3',5-triiodothyronine + iodide + reduced electron acceptor
show the reaction diagram
L-thyroxine + reduced acceptor
3,3',5-triiodo-L-thyronine + iodide + acceptor + H+
show the reaction diagram
-
-
-
?
L-tyroxine + AH2
3,3',5'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
the reaction is catalyzed by the type 1 deiodinase
-
-
?
reverse triiodothyronine + AH2
diiodothyronine + iodide + A + H+
show the reaction diagram
sulfated reverse triiodothyronine + AH2
diiodothyronine + iodide + A + H+ + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3,3',5'-triiodo-L-thyronine + AH2
3,3'-diiodo-L-thyronine + iodide + A + H+
show the reaction diagram
3,3',5'-triiodo-L-thyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
3,3',5-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
isoenzyme type II and type III
-
-
?
3,3',5-triiodothyronine + AH2
3,5-diiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
3,5'-diiodo-L-thyronine + AH2
3-iodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
L-thyroxine + AH2
3,3',5'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + AH2
3,3',5'-triiodothyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + AH2
3,3',5-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
L-thyroxine + electron acceptor
3,3',5-triiodothyronine + iodide + reduced electron acceptor
show the reaction diagram
Q9Z1Y9
the enzyme is regulated at the pretranslational level
-
-
?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dithioerythritol
dithiothreitol
glutathione
-
20 mM glutathione is used in assay conditions
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
selenium
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2E)-2-(3,4-dihydroxybenzylidene)-4,6-dihydroxy-1-benzofuran-3(2H)-one
-
aurone derivative isolated from plant extract. Comparison with inhibition of 5-deiodinase EC 1.97.1.11
(2E)-2-(3,4-dihydroxybenzylidene)-6-hydroxy-1-benzofuran-3(2H)-one
-
aurone derivative isolated from plant extract. Comparison with inhibition of 5-deiodinase EC 1.97.1.11
(2E)-4,6-dihydroxy-2-(4-hydroxy-3-iodobenzylidene)-1-benzofuran-3(2H)-one
-
aurone derivative isolated from plant extract. Comparison with inhibition of 5-deiodinase EC 1.97.1.11
(2E)-4,6-dihydroxy-2-(4-hydroxybenzylidene)-1-benzofuran-3(2H)-one
-
aurone derivative isolated from plant extract. Comparison with inhibition of 5-deiodinase EC 1.97.1.11
(4-[(E)-(4,6-dihydroxy-3-oxo-1-benzofuran-2(3H)-ylidene)methyl]phenoxy)acetic acid
-
aurone derivative isolated from plant extract. Comparison with inhibition of 5-deiodinase EC 1.97.1.11
2-(3,4-dihydroxybenzyl)-4,6-dihydroxy-1-benzofuran-3(2H)-one
-
aurone derivative isolated from plant extract. Comparison with inhibition of 5-deiodinase EC 1.97.1.11
2-amino-3-[4-[(4-hydroxy-3,5-diiodophenyl)thio]-3,5-diiodophenyl]propanoic acid
-
comparison with 5-deiodinase EC 1.97.1.11
2-Thiouracil
-
-
3',5'-diiodothyronine
-
comparison with 5-deiodinase EC 1.97.1.11
3,3',5'-triiodo-L-thyronine
3,3',5'-triiodothyronine
-
comparison with 5-deiodinase EC 1.97.1.11
3,3',5,5'-tetraiodo-L-thyronine
-
hypoxia has no effect on inhibition of T4
3,5,3'-triiodo-5'-nitrothyronine
-
comparison with 5-deiodinase EC 1.97.1.11
3,5,5'-triiodo-2'-methylthyronine
-
comparison with 5-deiodinase EC 1.97.1.11
3,5-diiodo-2'-hydroxythyronine
-
comparison with 5-deiodinase EC 1.97.1.11
3,5-diiodo-3',5'-dinitrothyronine
-
comparison with 5-deiodinase EC 1.97.1.11
3,5-diiodo-3'-hydroxythyronine
-
comparison with 5-deiodinase EC 1.97.1.11
3,5-diiodo-4'-amino-3',5'-dimethylthyronine
-
comparison with 5-deiodinase EC 1.97.1.11
6-Propyl-2-thiouracil
amiodarone
-
aurothioglucose
Ca2+
-
inhibits expression of isozyme type I in thyroid gland
coumarin
-
anticoagulants
dexamethasone
-
inhibits expression of isozyme type I
dicoumarol
-
-
ethyl 4-(4-hydroxy-3,5-diiodobenzoyl)phenyl carbonate
-
comparison with 5-deiodinase EC 1.97.1.11
gold thioglucose
-
-
Insulin
-
inhibits enzyme expression in glial cell culture
-
interleukin 1 and interleukin 6
-
interleukins are competing for transcriptional coactivators and inhibit thyronine 5'-deiodinase induction by 3,3',5-triiodothyronine
-
iodoacetate
iopanoic acid
ipanoic acid
L-thyroxine
-
isozyme type II
N-acetyl-3,5,3'-triiodo-5'-nitrothyronine
-
comparison with 5-deiodinase EC 1.97.1.11
N-acetyl-3,5-diiodo-3',5'-dinitrothyronine
-
comparison with 5-deiodinase EC 1.97.1.11
N-acetyl-3,5-diiodo-3'-bromo-5'-nitrothyronine
-
comparison with 5-deiodinase EC 1.97.1.11
N-bromoacetyl-L-thyroxine
-
i.e. BrAc-3,3',5-triiodothyronine, all isoenzymes
propanolol
-
type II
propylthiouracil
salicylate
-
-
SH-group blocking reagents
-
-
-
Soybean phospholipids
-
competition with microsomal lipids
-
Tetraiodothyroacetic acid
-
comparison with 5-deiodinase EC 1.97.1.11
thyroxine
-
isozyme type II, rapid inactivation in brain
warfarin
-
-
[4-(4-hydroxy-3,5-diiodophenoxy)phenyl]acetic acid
-
comparison with 5-deiodinase EC 1.97.1.11
[4-(4-hydroxy-3,5-dinitrophenoxy)-3,5-diiodophenyl]acetic acid
-
comparison with 5-deiodinase EC 1.97.1.11
[4-(4-hydroxy-3-iodo-5-nitrophenoxy)-3,5-diiodophenyl]acetic acid
-
comparison with 5-deiodinase EC 1.97.1.11
[4-(4-hydroxy-3-iodo-5-nitrophenoxy)phenyl]acetic acid
-
comparison with 5-deiodinase EC 1.97.1.11
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(Bu)2cAMP
3,3',5-triiodo-L-thyronine
-
induces isozyme type I
atrial natriuretic protein
-
induces isozyme type II via cGMP
-
beta-adrenergic agonists
-
stimulates isozyme type II
-
C-type natriuretic protein
-
induces isozyme type II via cGMP
-
carbobenzoxy-L-leucyl-L-leucyl-L-leucinal
-
MG132, proteasome inhibitor, increases type 2 deiodinase
DEX
-
-
-
dithiothreitol
EDTA
-
-
Epidermal growth factor
-
-
fibroblast growth factor
-
induces isozymes type II, and I
-
forskolin
isoproterenol
-
type II
lipopolysaccharide
after stimulation by lipopolysaccharide, mRNA expression level in haemocytes is 25fold increased at 12 h and 7-8fold at 24 h. The concentration of T3 in haemolymph increases significantly at 12 h, the concentration of T4 does not change significantly
Nicotine
-
stimulates isozyme type II
Phorbol esters
-
induce isozyme type II via protein kinase C
propranolol
propanolol does not prevent muscle Dio2 induction, but impairs a decrease of Dio2 in the brown adipose tissue and soleus after 10 days at 4C
reduced thiols
retinoic acid
testosterone
-
stimulates isozyme type I in liver
thyroid hormone
-
-
thyroid hormone L-thyroxine and 3,3',5'-triiodothyronine
-
thyroid stimulating hormone
-
induces isozyme type I
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02
3,3',5'-triiodo-L-thyronine
-
pH 7.4, 37C
0.0067 - 2.7
3,3',5'-triiodothyronine
0.0015 - 0.0045
3,3',5-triiodo-L-thyronine sulfate
0.00256 - 0.005
3,3',5-triiodothyronine
0.01
3,5'-diiodo-L-thyronine
-
pH 7.4, 37C
0.003 - 0.57
L-3,5',3'-triiodothyronine
0.0000000017 - 0.009
L-thyroxine
0.00000101 - 0.015
reverse triiodothyronine
0.0007
sulfated reverse triiodothyronine
-
wild-type enzyme
0.00003 - 0.003
thyroxine
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000467 - 0.00107
3,3',5'-triiodothyronine
additional information
additional information
Homo sapiens
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001
(2E)-2-(3,4-dihydroxybenzylidene)-4,6-dihydroxy-1-benzofuran-3(2H)-one
Rattus norvegicus
-
pH 7.4, 37C
0.01
(2E)-2-(3,4-dihydroxybenzylidene)-6-hydroxy-1-benzofuran-3(2H)-one
Rattus norvegicus
-
pH 7.4, 37C
0.0005
(2E)-4,6-dihydroxy-2-(4-hydroxy-3-iodobenzylidene)-1-benzofuran-3(2H)-one
Rattus norvegicus
-
pH 7.4, 37C
0.001
(2E)-4,6-dihydroxy-2-(4-hydroxybenzylidene)-1-benzofuran-3(2H)-one
Rattus norvegicus
-
pH 7.4, 37C
0.005
(4-[(E)-(4,6-dihydroxy-3-oxo-1-benzofuran-2(3H)-ylidene)methyl]phenoxy)acetic acid
Rattus norvegicus
-
pH 7.4, 37C
0.008
2-(3,4-dihydroxybenzyl)-4,6-dihydroxy-1-benzofuran-3(2H)-one
Rattus norvegicus
-
pH 7.4, 37C
0.003
2-amino-3-[4-[(4-hydroxy-3,5-diiodophenyl)thio]-3,5-diiodophenyl]propanoate
Rattus norvegicus
-
-
0.001
3',5'-diiodothyronine
Rattus norvegicus
-
pH 7.4, 37C
0.0003
3,3',5'-triiodothyronine
Rattus norvegicus
-
pH 7.4, 37C
0.008
3,5,3'-triiodo-5'-nitrothyronine
Rattus norvegicus
-
pH 7.4, 37C
0.007
3,5,5'-triiodo-2'-methylthyronine
Rattus norvegicus
-
pH 7.4, 37C
0.008
3,5-diiodo-2'-hydroxythyronine
Rattus norvegicus
-
pH 7.4, 37C
0.014
3,5-diiodo-3',5'-dinitrothyronine
Rattus norvegicus
-
pH 7.4, 37C
0.013
3,5-diiodo-3'-hydroxythyronine
Rattus norvegicus
-
pH 7.4, 37C
0.012
3,5-diiodo-4'-amino-3',5'-dimethylthyronine
Rattus norvegicus
-
pH 7.4, 37C
0.008
aurothioglucose
Rattus norvegicus
-
pH 7.4, 37C
0.002
ethyl 4-(4-hydroxy-3,5-diiodobenzoyl)phenyl carbonate
Rattus norvegicus
-
pH 7.4, 37C
0.0015
N-acetyl-3,5,3'-triiodo-5'-nitrothyronine
Rattus norvegicus
-
pH 7.4, 37C
0.007
N-acetyl-3,5-diiodo-3',5'-dinitrothyronine
Rattus norvegicus
-
pH 7.4, 37C
0.004
N-acetyl-3,5-diiodo-3'-bromo-5'-nitrothyronine
Rattus norvegicus
-
pH 7.4, 37C
0.005 - 0.01
propylthiouracil
Felis catus
-
native and recombinant enzyme, IC50: 0.005-0.01 mM
0.0002
Tetraiodothyroacetic acid
Rattus norvegicus
-
pH 7.4, 37C
0.0003
[4-(4-hydroxy-3,5-diiodophenoxy)phenyl]acetic acid
Rattus norvegicus
-
pH 7.4, 37C
0.0015
[4-(4-hydroxy-3,5-dinitrophenoxy)-3,5-diiodophenyl]acetic acid
Rattus norvegicus
-
pH 7.4, 37C
0.0005
[4-(4-hydroxy-3-iodo-5-nitrophenoxy)-3,5-diiodophenyl]acetate
Rattus norvegicus
-
pH 7.4, 37C
0.0008
[4-(4-hydroxy-3-iodo-5-nitrophenoxy)phenyl]acetic acid
Rattus norvegicus
-
pH 7.4, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0000000003
-
medium alone
0.00000000041
-
medullary thyroid carcinoma
0.00000000043
-
normal thyroid tissue
0.0000000005
pituitary type 2 deiodinase activity, type 3 deiodinase knockout mice after infection with Streptococcus pneumoniae
0.0000000006
-
hypoxia
0.00000000075
pituitary type 2 deiodinase activity, wild-type mice after infection with Streptococcus pneumoniae
0.0000000014
value about, pituitary type 2 deiodinase activity, type 3 deiodinase knockout mice
0.0000000015
value about, pituitary type 2 deiodinase activity, wild-type mice
0.0000000058
-
normal tissues
0.000000013
-
eight weeks high-fat diet, interscapular white fat, 3,3'-diiodothyronine
0.000000015
-
eight weeks low-fat diet, interscapular white fat, 3,3'-diiodothyronine
0.000000025
-
in presence of carbobenzoxy-L-leucyl-L-leucyl-L-leucinal
0.0000000286
-
normal tissues
0.00000003
-
10 micromol forskolin
0.000000033
-
two weeks low-fat diet, interscapular white fat, 3,3'-diiodothyronine
0.000000035
-
two weeks high-fat diet, interscapular white fat, 3,3'-diiodothyronine
0.000000037
-
two weeks low-fat diet, dorsolumbar white fat, 3,3'-diiodothyronine
0.0000000429
-
McCune-Albright syndrome patients
0.0000000543
-
toxic adenoma patient
0.000000058
-
eight weeks low-fat diet, epididymal white fat, 3,3'-diiodothyronine
0.000000063
-
two weeks high-fat diet, dorsolumbar white fat, 3,3'-diiodothyronine
0.0000000714
-
toxic adenoma patient
0.00000009
-
10 micromol forskolin and hypoxia
0.000000093
-
two weeks low-fat diet, epididymal white fat, 3,3'-diiodothyronine
0.0000001
-
two weeks high-fat diet, epididymal white fat, 3,3'-diiodothyronine
0.000000102
-
effect of leptin on iodothyronine 5'-deiodinase activity, control
0.000000108
-
eight weeks low-fat diet, dorsolumbar white fat, 3,3'-diiodothyronine
0.000000165
-
effect of leptin on iodothyronine 5'-deiodinase activity, mice are injected with three doses, 3 mg/kg, leptin for three days
0.0000001857
-
McCune-Albright syndrome patients
0.000000187
-
eight weeks high-fat diet, dorsolumbar white fat, 3,3'-diiodothyronine
0.0000002
-
eight weeks high-fat diet, epididymal white fat, 3,3'-diiodothyronine
0.00000075
type 3 deiodinase knockout mice
0.000001
0.00000125
wild-type mice after infection with Streptococcus pneumoniae
0.000002
wild-type mice
0.0000025
-
patient with mutation in thyroglobulin gene
0.0000146
-
eight weeks low-fat diet, liver, 3,3'-diiodothyronine
0.0000215
-
two weeks low-fat diet, liver, 3,3'-diiodothyronine
0.0000363
-
two weeks high-fat diet, liver, 3,3'-diiodothyronine
0.0000394
-
eight weeks high-fat diet, liver, 3,3'-diiodothyronine
0.0001
0.0002
0.0003
-
isoenzyme type I
0.0004
-
isoenzyme type I
0.002
-
isoenzyme type I
0.2
-
isoenzyme D2 (type II) in cerebral cortex
2
-
isoenzyme D2 (type II) induced in cultured astrocytes
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 6
-
isoform III
5.8 - 6.3
-
isoform II
6.5
-
-
6.8
-
isoform I
6.9
-
activity assay
7 - 7.4
-
-
7.5
-
activity assay
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 30
-
T4 ORD activity of type II-like enzyme from gut and kidney microsomes
30 - 35
-
rT3 ORD activity of type I-like enzme; T4 ORD activity of type II-like enzyme from liver microsomes
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
hepatocellular carcinoma
Manually annotated by BRENDA team
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isozyme type I
Manually annotated by BRENDA team
low level of activity
Manually annotated by BRENDA team
low level of activity
Manually annotated by BRENDA team
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isozyme Dio3
Manually annotated by BRENDA team
after 10 days of cold exposure an increase of 2.8fold in Dio2 activity is detected in white glycolytic gastrocnemius but not in red oxidative gastrocnemius fibers
Manually annotated by BRENDA team
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low type I-like activity, type II-like activity is the predominant activity; type II-like activity is the predominant activity
Manually annotated by BRENDA team
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isozyme Dio1
Manually annotated by BRENDA team
high expression level
Manually annotated by BRENDA team
expression of type 2 iodothyronine deiodinase D2, which converts T4 to T3, and TR1 in HUVECs
Manually annotated by BRENDA team
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thyronine 5'-deiodinase type II
Manually annotated by BRENDA team
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thyronine 5'-deiodinase type II
Manually annotated by BRENDA team
low level of activity
Manually annotated by BRENDA team
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high expression
Manually annotated by BRENDA team
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the enzyme is restricted to mature primary osteoblasts
Manually annotated by BRENDA team
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thyroid tissue samples are collected from five patients, three affected by toxic nodule, and from areas of normal thyroid parenchyma from five patients undergoing total thyroidectomy for thyroid cancer
Manually annotated by BRENDA team
low level of activity
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
at the inner leaflet of the basolateral plasma membrane, isozyme type I, kidney
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
49900
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gel filtration
55400
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type I, sucrose density gradient centrifugation and gel filtration
56000
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SDS-PAGE
198700
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type II, sucrose density gradient centrifugation and gel filtration
200000
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 29000, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
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heterogeneity is not caused by N-linked glycosylation, but probably by a combination of O-linked glycosylation and phosphorylation
no glycoprotein
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no glycosylation of substrate binding subunits of both isoenzymes
phosphoprotein
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heterogeneity is not caused by N-linked glycosylation, but probably by a combination of O-linked glycosylation and phosphorylation
additional information
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both type I and type II enzyme as well as type III enzyme EC 1.97.1.11 are selenoproteins. All tissues studied maintain more than 50% deiodinase activity during prolonged selenium-deficiency. Only when selenium levels decrease by more than 80%, deiodinase activity markedly decreases
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
-
inactivation after 30 min
56
-
inactivation after 30 min
60
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inactivation after 30 min
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
activity mostly lost during purification procedures, catalytic activity lost in detergent solution
-
very short lifetime in vivo of isoenzyme type II (D2) from brain
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, presence of 3 mM dithiothreitol, stable for at least 6 weeks, after 3 months, loss of55% of activity
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
isoenzyme type I and type II
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Sephadex LH20 gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a promoter reporter gene for a luciferase assay is constructed
different splicing variants of DOI1 are cloned into the vector pGEM-T for sequencing, 11 variants are identified
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expression in COS cells
expression in Escherichia coli via phage lambda infection; overexpression in rat astrocytes of 29 kD subunit with and without GFP-tag via adenovirus infection
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expression in HEK-293 cells
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expression in HEK-293 cells; expression in HEK-293 cells
expression in JEG-3 cells, transient transfection
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expression of mutant enzymes, in which selenocysteine residues in the core catalytic center is replaced by cysteine, in Saccharomyces cerevisiae
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into a D10 vector
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isozyme type I, mapping on chromosome 1p32-p33, DNA sequence analysis
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isozyme type I, mapping on chromosome 4
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overexpression in LLC-PK1 cells
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the P135S mutant enzyme is expressed in HEK-293 cells
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transcription in vitro, translation in Xenopus laevis oocytes
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transfection in HEK 293 cells; transfection in HEK 293 cells
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translation of purified rat RNA in Xenopus laevis oocytes
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
3,5,3'-triiodothyronine decreases mRNA levels in TT cell, addition of thyroxine or 3,3',5'-triiodothyronine decreases the deiodinating activity
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5'-deiodinase is increased in McCune-Albright syndrome-associated hyperthyroidism pathogenesis
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activity in white fat is stimulated by a high-fat diet, leptin injections increases activity
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bacterial lipopolysaccharide induces type 2 iodothyronine deiodinase (D2) activity with a lag-time of 4-8 h and a maximum at 24 h at 0.001 mg /ml. Glucocorticoids (0.001 mM cortisol, 10 nM dexamethasone) enhance both the basal and LPS-stimulated D2 activity and mRNA accumulation. RU486 and sulfasalazine block the effects of lipopolysaccharide on both D2 activity and mRNA accumulation. In astrocytes, co-expression of p65 nuclear factor-kappaB with the 3.8 kb form of the rat dio2 promoter leads to a 7fold increase in the transcriptional activity
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caloric restriction decreases activity in white fat
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decrease of liver type 1 deiodinase levels after infection only in wild-type mice, low expression levels in type 3 deiodinase knockout mice; decrease of pituitary type 2 deiodinase levels after infection
expression of the Dio1 gene is dependent on HNF4alpha expression, the Dio1 promoter is directly regulated by HNF4alpha
expression of the Dio1 gene is dependent on HNF4alpha expression, the Dio1 promoter is directly regulated by HNF4alpha, the Krppel-like transcription factor 9, KLF9, functions together with HNF4alpha and GATA4 to synergistically activate the promoter through direct interaction between these transcriptional factors
increase of expression levels postnatal until day 8
increased local generation of triiodothyronine in prostate might be related to the differentiation, maturation that occurs at puberty, and, or, the energy expenditure associated with maintaining the secretory activity of the glandular epithelium
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incubation (for 2-12 h at 37C) of confluent primary cultures of astroglial cells, maintained in a chemically defined medium devoid of growth factors and hormones, with various concentrations of adenosine, AMP, ADP, ATP (highest activity at 0. 1 mM after 4 h), and a series of their analogues causes a marked induction of type 2 iodothyronine deiodinase activity (up to 30fold basal level). Preincubation of cells with all-trans-retinoic acid multiplies the inducing effect of the purines (up to 42fold increase of type 1 iodothyronine deiodinase); all-trans retinoic acid itself enhances the activity of type 2 iodothyronine deiodinase, and also of type 1 iodothyronine deiodinase, only a little
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substrate-dependent down-regulation, WSB-1-mediated ubiquitination inactivates the enzyme and targets it for proteasomal degradation, TEB4 interacts with the enzyme and mediates loss of activity and protein
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the enzymatic activity of type 1 iodothyronine deiodinase is low in liver hemangioma
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there is no significant difference between the thyroidal type 2 iodothyronine deiodinase mRNA level in patients with with 3,5,3'-triiodothyronine-predominant Graves' disease and that in patients with common type-Graves' disease
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thyroidal type 1 iodothyronine deiodinase mRNA level and activity in patients with 3,5,3'-triiodothyronine-predominant Graves' disease is significantly higher than that in patients with common type-Graves' disease
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type 2 deiodinase is induced in muscle regeneration, forkhead box O3 is a key molecule inducing type 2 deiodinase expression
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type 2 iodothyronine deiodinase (Dio2) is up-regulated in dilated cardiomyopathy mice hearts whereas the expression of type 1 iodothyronine deiodinase remains unchanged. Dio2 gene expression is also markedly up-regulated in the mice hearts developing similar eccentric hypertrophy after myocardial infarction
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ubiquitinated enzyme can be reactivated and rescued from proteosomal degradation by the von Hippel-Lindau protein-interacting deubiquitinating enzyme-1, TEB4 knockdown increases activity and protein level of iodothyronine deiodinase 2
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A131C
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similar Km-values for L-thyroxine and 3,3',5-triiodothyronine as the wild-type enzyme. Mutation improves the interaction with the reducing cofactor dithiothreitol
A131S
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similar Km-values for L-thyroxine and 3,3',5-triiodothyronine as the wild-type enzyme. Mutation improves the interaction with the reducing cofactor dithiothreitol
P135S
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the mutant type 2 iodothyronine deiodinase has many type 1 iodothyronine deiodinase-like properties, a Km (L-thyroxine) in the micromolar range, ping-pong kinetics with dithiothreitol, and sensitivity to 6n-propylthiouracil in vitro. When the P135S mutant is expressed in HEK-293 cells and exposed to 2-200 pM free L-thyroxine, the rate of L-thyroxine to 3,5,3'-triiodo-L-thyronine conversion is identical with type 2 iodothyronine deiodinase and conversion is insensitive to 6n-propylthiouracil. Using glutathione as a cofactor in vitro results in a marked decrease in the Km (L-thyroxine) (as also occurs for type 1 iodothyronine deiodinase), it shows sequential kinetics with L-thyroxine and is sensitive to 6n-propylthiouracil but is resistant when HEK-293 cytosol is used as a cofactor
SeC133A
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inactive mutant enzyme
SeC133C
SeC133C/A131C
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mutant enzyme with more than 1000fold increase in Km-value for L-thyroxine
N203Q
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decrease in Km-value for 3,3',5-triiodo-L-thyronine sulfate
N94Q
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decrease in Km-value for 3,3',5-triiodo-L-thyronine sulfate
N94Q/N203Q
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increase in Km-value for 3,3',5-triiodo-L-thyronine sulfate
S101A
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Km-value for 3,3',5-triiodo-L-thyronine sulfate is nearly identical
S101A/S176A
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increase in Km-value for 3,3',5-triiodo-L-thyronine sulfate
Y209F/Y217F
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increase in Km-value for 3,3',5-triiodo-L-thyronine sulfate
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partly reconstitution of activity of delipinated purified thyronine 5'-deiodinase from liver microsomes in soybean phospholipids
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
additional information