Information on EC 1.97.1.10 - thyroxine 5'-deiodinase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
1.97.1.10
-
RECOMMENDED NAME
GeneOntology No.
thyroxine 5'-deiodinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
3,5,3'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2
show the reaction diagram
reaction mechanism of thyronine 5'-deiodinase
-
3,5,3'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2
show the reaction diagram
A: cosubstrate, AH2: reduced cosubstrate
-
-
-
3,5,3'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2
show the reaction diagram
type III, inner (tyrosyl) ring deiodination
-
3,5,3'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2
show the reaction diagram
additional product is 3,5',3'-L-triiodo-L-thyronine
-
-
-
3,5,3'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2
show the reaction diagram
type II, outer ring (phenolic) deiodination
-
3,5,3'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2
show the reaction diagram
type I, outer ring (phenolic) deiodination
-
3,5,3'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2
show the reaction diagram
isozyme type I, reaction mechanism, both 5-deiodinase isoforms and 5-deiodinase contain a selenocysteine residue at the active site
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
deiodination
-
-
redox reaction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
thyroid hormone metabolism I (via deiodination)
-
thyroid hormone metabolism II (via conjugation and/or degradation)
-
SYSTEMATIC NAME
IUBMB Comments
acceptor:3,5,3'-triiodo-L-thyronine 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.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5DI
-
-
-
-
5DII
-
-
-
-
5DIII
-
-
-
-
D1 5'-deiodinase
-
-
D2 5'-deiodinase
-
-
diiodothyronine 5'-deiodinase
-
-
-
-
Dio
-
gene name
DIO1
P49895
-
DIO1
Q61153
-
DIO2
-
-
DIO2
Q92813
-
DIO2
-
-
DIO2
-
gene name
DIOI
-
-
-
-
DIOII
-
-
-
-
DIOIII
-
-
-
-
EC 3.8.1.4
-
-
formerly
-
ID-2
-
-
ID-3
-
-
iodothyronine 5'-deiodinase
-
-
iodothyronine 5'-deiodinase
-
iodothyronine 5'-deiodinase type
iodothyronine 5'-deiodinase
-
isoenzymes type I (D1) and type II (D2)
iodothyronine 5'-deiodinase
-
isoenzymes type I (D1) and type II (D2); type II, no selenoprotein, induced by bt2cAMP and hydrocortisone (ED50 4nM); type I, selenoprotein, inducible by T3 (higher synthesis) and angiotensin II (positive chronotropic effect in myocard)
iodothyronine 5'-deiodinase
-
type I, selenoprotein, inducible by T3 (higher synthesis) and angiotensin II (positive chronotropic effect in myocard)
iodothyronine 5'-deiodinase
-
type II, no selenoprotein, induced by bt2cAMP and hydrocortisone (ED50 4nM)
Iodothyronine 5'-monodeiodinase
-
isoenzyme type I
iodothyronine 5-deiodinase
-
iodothyronine 5-deiodinase type
iodothyronine inner ring monodeiodinase
-
isoenzyme type III
iodothyronine inner ring monodeiodinase
-
-
iodothyronine outer ring monodeiodinase
-
-
-
-
L-thyroxine iodohydrolase (reducing)
-
-
-
-
thyroxine 5-deiodinase
-
-
-
-
Thyroxine deiodinase
-
-
-
-
type 1 5'-deiodinase
-
-
type 1 deiodinase
-
-
type 1 deiodinase
Q61153
-
type 1 deiodinase
-
-
Type 1 DI
-
-
-
-
type 1 iodothyronine deiodinase
-
-
type 1 iodothyronine deiodinase
P49895
-
type 1 iodothyronine deiodinase
Q61153
-
type 1 iodothyronine deiodinase
-
-
type 2 5'-deiodinase
-
-
type 2 deiodinase
-
-
type 2 deiodinase
Q92813
-
type 2 deiodinase
-
-
type 2 deiodinase
-
-
type 2 deiodinase
Q9Z148
-
type 2 deiodinase
Q9Z1Y9
-
type 2 deiodinase
-
-
Type 2 DI
-
-
-
-
type 2 iodothyronine deiodinase
-
-
type 2 iodothyronine deiodinase
Q92813
-
type 2 iodothyronine deiodinase
-
-
type 2 iodothyronine deiodinase
-
-
type 2 iodothyronine deiodinase
-
-
type 3 deiodinase
-
-
Type 3 DI
-
-
-
-
type I iodothyronine 5'-deiodinase
-
-
type I iodothyronine deiodinase
-, O42411
-
type I iodothyronine deiodinase
-
-
type I iodothyronine deiodinase
P24389
-
type I-like deiodinase
-
-
type II iodothyronine deiodinase
Q92813
-
type II iodothyronine deiodinase
Q9Z1Y9
-
type II-like deiodinase
-
-
Type-I 5'deiodinase
-
-
-
-
Type-II 5'deiodinase
-
-
-
-
Type-III 5'deiodinase
-
-
-
-
types 1 iodothyronine selenodeiodinase
P49895
-
types 2 iodothyronine selenodeiodinase
Q92813
-
XL-15
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
70712-46-8
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
type I and type II enzyme isoforms
-
-
Manually annotated by BRENDA team
type I enzyme
-
-
Manually annotated by BRENDA team
; tye I enzyme DIO1
SwissProt
Manually annotated by BRENDA team
; tye II enzyme DIO2
SwissProt
Manually annotated by BRENDA team
patients with thyroglobulin transport defect
-
-
Manually annotated by BRENDA team
three deiodinase isozymes Dio1, Dio2, and Dio3
-
-
Manually annotated by BRENDA team
type I and type II enzyme isoforms
-
-
Manually annotated by BRENDA team
Syrian hamster
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
three deiodinase isozymes Dio1, Dio2, and Dio3
-
-
Manually annotated by BRENDA team
type I and type II enzyme isoforms
-
-
Manually annotated by BRENDA team
wild-type and type 3 deiodinase knockdown mice
SwissProt
Manually annotated by BRENDA team
wild-type and type 3 deiodinase knockout mice, infected with Streptococcus pneumoniae
UniProt
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
comparison with placental 5-deiodinase EC 1.97.1.11
-
-
Manually annotated by BRENDA team
enzyme isoforms I, II, and III
-
-
Manually annotated by BRENDA team
male wistar rat
-
-
Manually annotated by BRENDA team
male, Wistar, hypothyroidism and hyperthyroidism is induced by diet
-
-
Manually annotated by BRENDA team
type I and type II enzyme isoforms
-
-
Manually annotated by BRENDA team
Wistar, subjected to 40% food restriction
-
-
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
Rattus norvegicus
-
-
Manually annotated by BRENDA team
type I and type II enzyme isoforms
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
after injury regeneration markedly delays in muscles of mice null for the gene encoding type 2 deiodinase, despite normal circulating 3,5,3'-triiodo-L-thyronine concentrations, Dio2-deficient mice show muscle-specific hypothyroidism
malfunction
-
bones from adult type 2 iodothyronine deiodinase-knockout mice have reduced toughness and are brittle, displaying an increased susceptibility to fracture. This phenotype is characterized by a 50% reduction in bone formation and a generalized increase in skeletal mineralization
physiological function
-
convert prohormone T4 to biologicalliy active T3
physiological function
Q9Z1Y9
increase of thyroid hormone in cochlea by type 2 deiodinase, resulting in impairment of 3,3',5-triiodo-L-thyronine, before the onset of hearing
physiological function
-
brain D2 is implicated in adaptative responses to infectious stress
physiological function
-
Dio2 up-regulation is involved in cardiac remodelling in dilated cardiomyopathy through activating the thyroid hormone-signalling pathways involving Akt and p38 MAPK
physiological function
-
type 2 deiodinase is essential for normal mouse myogenesis and muscle regeneration
physiological function
-
type 2 iodothyronine deiodinase plays a role in the optimization of bone strength and mineralization and is essential for normal osteoblast function
physiological function
-
enzyme knock-out mice exhibit greater susceptibility to ventilator-induced lung injury than wild-type mice, as evidenced by poorer alveoli integrity and quantified by lung chemokine and cytokine mRNA induction
physiological function
-
muscle thyronine deiodinase produces physiologically relevant amounts of 3,5,3'-triiodothyronine that can play an important role in muscle thermogenesis and metabolic regulation
physiological function
Mus musculus C57BL/6
-
muscle thyronine deiodinase produces physiologically relevant amounts of 3,5,3'-triiodothyronine that can play an important role in muscle thermogenesis and metabolic regulation
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
-
isozyme type I
-
-
?
3,3',5'-triiodo-L-thyronine + AH2
3,3'-diiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
isozyme type I: degradation of 3,3',5'-triiodo-L-thyronine
hormonally inactive
-
?
3,3',5'-triiodo-L-thyronine + AH2
3,3'-diiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
isozyme type I, degradation of 3,3',5'-triiodo-L-thyronine
hormonally inactive
-
?
3,3',5'-triiodo-L-thyronine + AH2
3,3'-diiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
the reaction is catalyzed by the type 1 and 2 deiodinases
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
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
-
-
-
-
-, ?
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
isoenzyme type I
-
-
-, ?
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
isoenzyme type I
-
-
-
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
isoenzyme type I
-
-
?
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
substrate for type 1 iodothyronine deiodinase
-
-
?
3,3',5,5'-tetraiodo-L-thyronine + AH2
?
show the reaction diagram
Q9Z1Y9
-
-
-
?
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
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
isoenzyme type II and type III
-
-
?
3,3',5-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
rT3 ORD activity
-
-
?
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
Q61153, Q9Z148
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
-
i.e. thyroxine
-
-
?
L-3,5,3',5'-tetraiodothyronine + AH2
L-3,5,3'-triiodothyronine + iodide + A + H+
show the reaction diagram
-
i.e. thyroxine
triiodothyrosine, a small 3,3'-T2 peak also occurs
-
?
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
-
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
Q92813
-
-
-
?
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
-
thyronine 5'-deiodinase type II
-
-
?
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
-
thyronine 5'-deiodinase type II
-
-
-
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
-
thyronine 5'-deiodinase type II
-
-
?
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
P24389
in kidney and liver cells the enzyme can serve as an enzymic barrier to the entry of the prohormone thyroxine and the source of bioactive 3,3',5-triiodothyronine for the cell
-
-
?
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
-
outer ring iodothyronine deiodinase activity, T4 ORD activity
-
-
?
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
-
reaction with dithiothreitol
-
-
?
L-thyroxine + AH2
3,3',5'-triiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
-
L-thyroxine + AH2
3,3',5'-triiodothyronine + iodide + A + H+
show the reaction diagram
-
type II
-
-
?
L-thyroxine + AH2
3,3',5'-triiodothyronine + iodide + A + H+
show the reaction diagram
-
thyronine 5-deiodinase type
-
-
?
L-thyroxine + AH2
3,3',5'-triiodothyronine + iodide + A + H+
show the reaction diagram
-
idothyronine 5'-deiodinase type I
-
-
-
L-thyroxine + AH2
3,3',5'-triiodothyronine + iodide + A + H+
show the reaction diagram
-
idothyronine 5'-deiodinase type I
-
-
?
L-thyroxine + AH2
3,3',5'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
isozymes type II and I, production of 3,3',5-triiodo-L-thyronine
hormonally inactive
-
?
L-thyroxine + AH2
3,3',5'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
Q61153
isoenzyme Dio1
-
-
?
L-thyroxine + AH2
3,3',5-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
-
from microsomal enzyme complex, 3,3',5-triiodo-L-thyronine is thyromimetically active
-
?
L-thyroxine + AH2
3,3',5-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
isozyme type II
hormonally active
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
r
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + 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 + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
Q61153
-
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
isozyme type II
hormonally active
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
isozymes type II and I, production of 3,3',5-triiodo-L-thyronine
hormonally inactive
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
addition of I125 labelled T4 to measure the production of T3
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
addition of I125 labelled T4 to measure the production of T3, using paper chromatography
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
activation and deactivation of thyroid hormone
-
-
r
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
Q61153, Q9Z148
assay at pH 7.2
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
substrate for type 2 iodothyronine deiodinase
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
the reaction is catalyzed by the type 1 and 2 deiodinases
-
-
?
L-thyroxine + electron acceptor
3,3',5-triiodothyronine + iodide + reduced electron acceptor
show the reaction diagram
P24389
-
-
-
?
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
-
-
?
reverse triiodothyronine + AH2
diiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
reverse triiodothyronine + AH2
diiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
sulfated reverse triiodothyronine + AH2
diiodothyronine + iodide + A + 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
-
-
?
additional information
?
-
-
L-hormone analogues are preferentially deiodinated via the T4-5'-deiodination pathway, whereas D-analogues produce products via the T4-5-deiodination pathway
-
-
-
additional information
?
-
-
selenium-level of cells influences the enzyme activity
-
-
-
additional information
?
-
-
the catalytic cycle of ID-1 involves a ping-pong bisubstrate reaction in which the selenol form of the enzyme (ESeH) reacts with L-thyroxine to form a selenenyl iodide intermediate (ESeI) with release of the deiodinated compound 3,5,3'-triiodo-L-thyronine, and a subsequent reaction between the selenenyl iodide intermediate and possibly a thiol cofactor regenerates the selenol form
-
-
-
additional information
?
-
-
thyronines and thyronamines are two groups of endogenous iodine-containing signaling molecules that are substrates of three deiodinase isozymes, which catalyze the sequential reductive removal of iodine from the respective precursor molecule. Development of a analytical method applying liquid chromatography/tandem mass spectrometry, overview
-
-
-
additional information
?
-
-
isozyme Dio1 exhibits both phenolic and tyrosyl ring deiodination activity while isozyme Dio2 catalyzes only deiodinations of the phenolic ring, isozyme Dio3 catalyzes only deiodinations of the tyrosyl ring. T3, 3,3'-T2, and 3,5-T2 are also not deiodinated by Dio1 from HepG2 lysates
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
-
isozyme type I
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
isoenzyme type I
-
-
?
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
isoenzyme type I
-
-
-
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
show the reaction diagram
-
isoenzyme type I
-
-
?
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-triiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
-
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
-
thyronine 5'-deiodinase type II
-
-
?
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
-
thyronine 5'-deiodinase type II
-
-
-
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
-
thyronine 5'-deiodinase type II
-
-
?
L-thyroxine + AH2
3,3',5-triiodothyronine + iodide + A + H+
show the reaction diagram
P24389
in kidney and liver cells the enzyme can serve as an enzymic barrier to the entry of the prohormone thyroxine and the source of bioactive 3,3',5-triiodothyronine for the cell
-
-
?
L-thyroxine + AH2
3,3',5'-triiodothyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
-
L-thyroxine + AH2
3,3',5'-triiodothyronine + iodide + A + H+
show the reaction diagram
-
idothyronine 5'-deiodinase type I
-
-
-
L-thyroxine + AH2
3,3',5'-triiodothyronine + iodide + A + H+
show the reaction diagram
-
idothyronine 5'-deiodinase type I
-
-
?
L-thyroxine + AH2
3,3',5'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
isozymes type II and I, production of 3,3',5-triiodo-L-thyronine
hormonally inactive
-
?
L-thyroxine + AH2
3,3',5'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
Q61153
isoenzyme Dio1
-
-
?
L-thyroxine + AH2
3,3',5-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
-
from microsomal enzyme complex, 3,3',5-triiodo-L-thyronine is thyromimetically active
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
-
-
-
r
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + 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 + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
Q61153
-
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
isozymes type II and I, production of 3,3',5-triiodo-L-thyronine
hormonally inactive
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
show the reaction diagram
-
activation and deactivation of thyroid hormone
-
-
r
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
?
-
-
L-hormone analogues are preferentially deiodinated via the T4-5'-deiodination pathway, whereas D-analogues produce products via the T4-5-deiodination pathway
-
-
-
additional information
?
-
-
thyronines and thyronamines are two groups of endogenous iodine-containing signaling molecules that are substrates of three deiodinase isozymes, which catalyze the sequential reductive removal of iodine from the respective precursor molecule. Development of a analytical method applying liquid chromatography/tandem mass spectrometry, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
dithioerythritol
-
can be substituted by dithiothreitol, isozyme type II, 5-20 mM, isozyme type I, 2-5 mM
dithiothreitol
-
can be substituted by dithioerythritol, isozyme type II, 5-20 mM, isozyme type I, 2-5 mM
dithiothreitol
Q9Z1Y9
20 mM
dithiothreitol
-
-
dithiothreitol
-
20 mM dithiothreitol is used in assay conditions
dithiothreitol
-
-
glutathione
-
20 mM glutathione is used in assay conditions
additional information
-
no activity with glutathione or thioredoxin in vivo, isozyme type I
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Se
-
enzyme contains selenocysteine in the highly conserved active senter at position 133. Selenium plays a critical role in deiodination
Se
-
contains selenocysteine in the active center
Se
-
selenoprotein
Se
-
enzyme contains selenocysteine
selenium
Q61153
-
selenium
-
-
selenium
-
selenoprotein
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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'-triiodo-L-thyronine
-
isozyme type II, rapid inactivation in brain
3,3',5'-triiodo-L-thyronine
-
inhibits expression of isozyme type II
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
-
competes with thiol cofactor; type I mutant with exchange of selenocysteine by cystein is 300fold less sensitive
6-Propyl-2-thiouracil
-
only type II sensitive to inhibition
6-Propyl-2-thiouracil
-
-
6-Propyl-2-thiouracil
-
inhibits selectively only thyronine 5'-deiodinase type I activity not type II activity
amiodarone
Q61153
-
aurothioglucose
-
type I, selenium-containing enzyme, competitive
aurothioglucose
-
competitive
aurothioglucose
-
-
aurothioglucose
-
isoyzme type I
aurothioglucose
Q9Z1Y9
-
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
-
isozyme type I
iodoacetate
-
-
iopanoic acid
-
both isozyme type I and type II
ipanoic acid
-
-
ipanoic acid
-
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
-
isozyme type I
propylthiouracil
-
wild-type and mutant enzymes A131C and A131S are insensitive to propylthiouracil in presence ogf 20 mM dithiothreitol. When tested in presence of 0.2 mM dithiothreitol the Ic50 value for propylthiouracil is reduced to about 0.1 mM
propylthiouracil
-
native and recombinant enzyme, IC50: 0.005-0.01 mM
propylthiouracil
-
-
propylthiouracil
-
partially, uncompetitively
propylthiouracil
-
D1 inhibitor
propylthiouracil
Q61153
-
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
L-thyroxine
-
isozyme type II
additional information
-
L-thyroxine inhibited competitively 3,3',5'-triiodothyronine utilization of isoenzyme type II
-
additional information
-
3,3',5'-triiodothyronine blocks 5'-deiodination of L-thyroxine blocks 5'-deiodination of 3,3',5'-triiodothyronine
-
additional information
-
expression and function of the 5-deiodinase and 5-deiodinase isozymes are sensitive to thyroid hormone status, various cytokines and growth factors, severe illness, reactive oxygen species, a variety of hormones and signaling compounds, circadian rythm, and pharmacological agents, and therefore might be useful in sensor function of physiology and pathophysiology
-
additional information
-
substrate-induced loss of activity of the type 2 deiodinase is due to proteasomal degradation of the enzyme and requires interaction with the catalytic center
-
additional information
-
no inhibition by propylthiouracil, type II-like enzyme
-
additional information
Q9Z1Y9
no inhibition by propylthiouracil
-
additional information
-
the wild type enzyme is insensitive to 6-propyl-2-thiouracil
-
additional information
-
lipopolysaccharide-induced type 2 deiodinase activity is not inhibited by 1 mM 6-propyl-2-thiouracil
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(Bu)2cAMP
-
significantly stimulates deiodinating activity in TT cells
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
-
cAMP
-
induces isozyme type I in thyroid gland only, induces isozyme type II
carbobenzoxy-L-leucyl-L-leucyl-L-leucinal
-
MG132, proteasome inhibitor, increases type 2 deiodinase
DEX
-
-
-
dithiothreitol
-
high concentrations of cofactor increases type I activity
dithiothreitol
-
high concentrations increase type II activity
dithiothreitol
-
10 mM required; type II-like enzyme from liver microsomes: 15 mM required. Type II-like enzyme from gut and kidney microsomes: 20 mM required
Epidermal growth factor
-
-
fibroblast growth factor
-
induces isozymes type II, and I
-
forskolin
-
increases mRNA expression and type 2 deiodinase activity, hypoxia stimulates forskolin induces activation of type 2 deiodinase
forskolin
-
significantly stimulates deiodinating activity in TT cells
Nicotine
-
stimulates isozyme type II
Phorbol esters
-
induce isozyme type II via protein kinase C
reduced thiols
-
e.g. dithiothreitol; e.g. ethanethiol, glutathione
reduced thiols
-
e.g. dithiothreitol
reduced thiols
-
e.g. dithiothreitol
retinoic acid
-
-
retinoic acid
-
stimulates isozyme type I
Se2+
-
severe selenium deficiency leads to a decrease in activity of isozyme type I in liver, kidney, and several other organs, but not in the thyroid gland, the central nervous system, and several other endrocrine organs
Se2+
-
stimulates isozyme type I, absolutely required, isozymes of the deiodinase enzyme family are selenoproteins
testosterone
-
stimulates isozyme type I in liver
thyroid hormone
Q61153
-
-
thyroid hormone L-thyroxine and 3,3',5'-triiodothyronine
-
extra-nuclear site of action
-
thyroid hormone L-thyroxine and 3,3',5'-triiodothyronine
-
type I
-
thyroid stimulating hormone
-
induces isozyme type I
-
isoproterenol
-
type II
additional information
-
phospholipid required
-
additional information
-
thiol cofactor reaction stimulation reduced in type I mutant with exchange of selenocysteine by cysteine
-
additional information
-
no effect of insulin and dexamethasone on type I activity
-
additional information
-
hypothyroidism enhances type II activity and decreases type I activity
-
additional information
-
growth hormone increases plasma T3 and decreases plasma T4 levels in 8-day old chicken embryos, in newly hatched chicks and in adult chickens within 2 h after injection. Growth hormone has no effect at all on the amount of hepatic type I enzyme catalyzing T4 deiodination to T3 but acutely decreases the amount of type III enzyme catalyzing T3 deiodination
-
additional information
-
expression and function of the deiodinase isozymes are sensitive to thyroid hormone status, various cytokines and growth factors, severe illness, reactive oxygen species, a variety of hormones and signaling compounds, circadian rythm, and pharmacological agents
-
additional information
-
hypoxia activates type 2 deiodinase by a posttranslational mechanism, glucose depletion decrased hypoxia induced type 2 deiodinase activation, agents promoting hypoxia like desferrioxamine, dimethyloxalylglycine, diethylsuccinatecobalt chloride activate type 2 deiodinase
-
additional information
-
exposure of animals to ventilator-induced lung injury leads to ignificant increases in enzyme immunorectivity and activity. Treatment of knock-out mice with 3,3',5-triiodothyronine reverses many of the lung chemokine and cytokine profiles seen in response to ventilator-induced lung injury
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.02
-
3,3',5'-triiodo-L-thyronine
-
pH 7.4, 37C
0.0067
-
3,3',5'-triiodothyronine
-
recombinant isoenzyme D2 (type II) from induced brain astrocytes with cosubstrate dithiothreitol KM: 18 mM
0.065
-
3,3',5'-triiodothyronine
-
DTT 10 mM; type I, myocardial
0.1
-
3,3',5'-triiodothyronine
-
DTT 20 mM; type I
0.18
-
3,3',5'-triiodothyronine
-
type I, liver
0.21
-
3,3',5'-triiodothyronine
-
DTT 10 mM; type I
0.24
-
3,3',5'-triiodothyronine
-
DTT 10 mM; type I, liver
0.25
-
3,3',5'-triiodothyronine
-
DTT 30 mM; type I
0.28
-
3,3',5'-triiodothyronine
-
DTT 10 mM; type I, liver
0.33
-
3,3',5'-triiodothyronine
-
DTT 10 mM; type I, liver
0.51
-
3,3',5'-triiodothyronine
-
DTT 10 mM; type I, liver
0.66
-
3,3',5'-triiodothyronine
-
DTT 10 mM; type I,l iver
0.69
-
3,3',5'-triiodothyronine
-
DTT 10 mM; type I, liver
0.7
-
3,3',5'-triiodothyronine
-
DTT 10 mM; type I, liver
2.7
-
3,3',5'-triiodothyronine
-
type I mutant, exchange of selenocysteine by cysteine
0.0015
-
3,3',5-triiodo-L-thyronine sulfate
-
mutant enzyme G2A, duplicate determination give the values: 0.0015 mM and 0.0024 mM
0.0018
-
3,3',5-triiodo-L-thyronine sulfate
-
mutant enzyme N94Q
0.002
-
3,3',5-triiodo-L-thyronine sulfate
-
mutant enzyme S176A, duplicate determination give the values: 0.0024 mM and 0.0024 mM; mutant enzyme S176A, duplicate determination give the values: 0.002 mM and 0.0024 mM; mutant enzymes, in which selenocysteine residues in the core catalytic center is replaced by cysteine
0.0022
-
3,3',5-triiodo-L-thyronine sulfate
-
mutant enzyme S101A, duplicate determination give the values: 0.0022 mM and 3.2 mM
0.0024
-
3,3',5-triiodo-L-thyronine sulfate
-
mutant enzyme G2A, duplicate determination give the values: 0.0015 mM and 0.0024 mM
0.0028
-
3,3',5-triiodo-L-thyronine sulfate
-
native enzyme from rat liver microsomes
0.0029
-
3,3',5-triiodo-L-thyronine sulfate
-
mutant enzymeN94Q/N203Q
0.0032
-
3,3',5-triiodo-L-thyronine sulfate
-
mutant enzyme S101A, duplicate determination give the values: 0.0022 mM and 0.0032 mM
0.0045
-
3,3',5-triiodo-L-thyronine sulfate
-
mutant enzyme N203Q
0.00256
-
3,3',5-triiodothyronine
-
type I-like activity in kidney microsomes
0.005
-
3,3',5-triiodothyronine
-
type I-like activity in liver microsomes
0.01
-
3,5'-diiodo-L-thyronine
-
pH 7.4, 37C
0.003
-
L-3,5',3'-triiodothyronine
-
pH 7.4, 37C, isozyme Dio2
-
0.57
-
L-3,5',3'-triiodothyronine
-
pH 7.4, 37C, isozyme Dio1
-
0.0000000017
-
L-thyroxine
-
mutant P135S type 2 iodothyronine deiodinase, with 20 mM glutathione as cofactor, in Tris-EDTA buffer (pH 7.5), at 37C
0.0000000029
-
L-thyroxine
-
wild type type 2 iodothyronine deiodinase, with 20 mM glutathione as cofactor, in Tris-EDTA buffer (pH 7.5), at 37C
0.0000000059
-
L-thyroxine
-
wild type type 2 iodothyronine deiodinase, with 20 mM dithiothreitol as cofactor, in Tris-EDTA buffer (pH 7.5), at 37C
0.000001
-
L-thyroxine
-
pH and temperature not specified in the publication
0.0000014
-
L-thyroxine
-
wild-type enzyme
0.0000023
-
L-thyroxine
-
neoplastic tissue, apparent Km
0.0000026
-
L-thyroxine
-
TT cell, apparent Km
0.0000044
-
L-thyroxine
Q9Z1Y9
-
0.0000045
-
L-thyroxine
-
mutant enzyme A131C, in presence of 20 mM dithiothreitol
0.0000045
-
L-thyroxine
-
mutant P135S type 2 iodothyronine deiodinase, with 20 mM dithiothreitol as cofactor, in Tris-EDTA buffer (pH 7.5), at 37C
0.0000049
-
L-thyroxine
-
wild-type enzyme, in presence of 20 mM dithiothreitol
0.0000054
-
L-thyroxine
-
mutant enzyme A131S, in presence of 20 mM dithiothreitol
0.0002
0.0006
L-thyroxine
-
isoform III, 37C, pH 6.0
0.001
0.005
L-thyroxine
-
type II
0.001
-
L-thyroxine
-
isoform II, 37C, pH 6.0
0.002
0.0035
L-thyroxine
-
isoform I, 37C, pH 6.8
0.002
-
L-thyroxine
-
pH 7.4, 37C
0.0021
-
L-thyroxine
-
mutant enzyme SeC133C
0.005
-
L-thyroxine
-
mutant enzyme SeC133C, in presence of 20 mM dithiothreitol
0.0066
-
L-thyroxine
-
mutant enzyme SeC133C/A131C, in presence of 20 mM dithiothreitol
0.00000101
-
reverse triiodothyronine
-
mutant enzyme A131S, in presence of 20 mM dithiothreitol
0.0000089
-
reverse triiodothyronine
-
wild-type enzyme, in presence of 20 mM dithiothreitol
0.0000098
-
reverse triiodothyronine
-
mutant enzyme A131C, in presence of 20 mM dithiothreitol
0.00036
-
reverse triiodothyronine
-
-
0.015
-
reverse triiodothyronine
-
wild-type enzyme
0.0007
-
sulfated reverse triiodothyronine
-
wild-type enzyme
0.00003
-
thyroxine
-
-
0.003
-
thyroxine
-
-
0.009
-
L-thyroxine
-
0.0105 mM during hypothyroidism; DTT 20 mM; type II, thymus
additional information
-
additional information
-
review on enzyme isoforms type I and II and 5-deiodinase, type III
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
mutant enzymes S101A/S176A and Y209F/Y217F show KM-values above 0.005 mM
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.000467
-
3,3',5'-triiodothyronine
-
-
0.00107
-
3,3',5'-triiodothyronine
-
in hypothyroid medium
additional information
-
additional information
-
-
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.001
-
(2E)-2-(3,4-dihydroxybenzylidene)-4,6-dihydroxy-1-benzofuran-3(2H)-one
-
pH 7.4, 37C
0.01
-
(2E)-2-(3,4-dihydroxybenzylidene)-6-hydroxy-1-benzofuran-3(2H)-one
-
pH 7.4, 37C
0.0005
-
(2E)-4,6-dihydroxy-2-(4-hydroxy-3-iodobenzylidene)-1-benzofuran-3(2H)-one
-
pH 7.4, 37C
0.001
-
(2E)-4,6-dihydroxy-2-(4-hydroxybenzylidene)-1-benzofuran-3(2H)-one
-
pH 7.4, 37C
0.005
-
(4-[(E)-(4,6-dihydroxy-3-oxo-1-benzofuran-2(3H)-ylidene)methyl]phenoxy)acetic acid
-
pH 7.4, 37C
0.008
-
2-(3,4-dihydroxybenzyl)-4,6-dihydroxy-1-benzofuran-3(2H)-one
-
pH 7.4, 37C
0.003
-
2-amino-3-[4-[(4-hydroxy-3,5-diiodophenyl)thio]-3,5-diiodophenyl]propanoate
-
-
0.001
-
3',5'-diiodothyronine
-
pH 7.4, 37C
0.0003
-
3,3',5'-triiodothyronine
-
pH 7.4, 37C
0.008
-
3,5,3'-triiodo-5'-nitrothyronine
-
pH 7.4, 37C
0.007
-
3,5,5'-triiodo-2'-methylthyronine
-
pH 7.4, 37C
0.008
-
3,5-diiodo-2'-hydroxythyronine
-
pH 7.4, 37C
0.014
-
3,5-diiodo-3',5'-dinitrothyronine
-
pH 7.4, 37C
0.013
-
3,5-diiodo-3'-hydroxythyronine
-
pH 7.4, 37C
0.012
-
3,5-diiodo-4'-amino-3',5'-dimethylthyronine
-
pH 7.4, 37C
0.008
-
aurothioglucose
-
pH 7.4, 37C
0.002
-
ethyl 4-(4-hydroxy-3,5-diiodobenzoyl)phenyl carbonate
-
pH 7.4, 37C
0.0015
-
N-acetyl-3,5,3'-triiodo-5'-nitrothyronine
-
pH 7.4, 37C
0.007
-
N-acetyl-3,5-diiodo-3',5'-dinitrothyronine
-
pH 7.4, 37C
0.004
-
N-acetyl-3,5-diiodo-3'-bromo-5'-nitrothyronine
-
pH 7.4, 37C
0.005
0.01
propylthiouracil
-
native and recombinant enzyme, IC50: 0.005-0.01 mM
0.0002
-
Tetraiodothyroacetic acid
-
pH 7.4, 37C
0.0003
-
[4-(4-hydroxy-3,5-diiodophenoxy)phenyl]acetic acid
-
pH 7.4, 37C
0.0015
-
[4-(4-hydroxy-3,5-dinitrophenoxy)-3,5-diiodophenyl]acetic acid
-
pH 7.4, 37C
0.0005
-
[4-(4-hydroxy-3-iodo-5-nitrophenoxy)-3,5-diiodophenyl]acetate
-
pH 7.4, 37C
0.0008
-
[4-(4-hydroxy-3-iodo-5-nitrophenoxy)phenyl]acetic acid
-
pH 7.4, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0000000003
-
-
medium alone
0.00000000041
-
-
medullary thyroid carcinoma
0.00000000043
-
-
normal thyroid tissue
0.0000000005
-
Q61153, Q9Z148
pituitary type 2 deiodinase activity, type 3 deiodinase knockout mice after infection with Streptococcus pneumoniae
0.0000000006
-
-
hypoxia
0.00000000075
-
Q61153, Q9Z148
pituitary type 2 deiodinase activity, wild-type mice after infection with Streptococcus pneumoniae
0.0000000014
-
Q61153, Q9Z148
value about, pituitary type 2 deiodinase activity, type 3 deiodinase knockout mice
0.0000000015
-
Q61153, Q9Z148
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
-
Q61153, Q9Z148
type 3 deiodinase knockout mice
0.000001
-
-
healthy control
0.000001
-
Q61153, Q9Z148
type 3 deiodinase knockout mice after infection with Streptococcus pneumoniae
0.00000125
-
Q61153, Q9Z148
wild-type mice after infection with Streptococcus pneumoniae
0.000002
-
Q61153, Q9Z148
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
-
-
isoenzyme type I
0.0002
-
-
isoenzyme type I
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
-
-
overview on assay methods
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
-
-
7.2
-
-
-
7.2
-
Q61153, Q9Z148
assay at; assay at
7.2
-
Q61153
activity assay
7.4
-
-
assay at
7.5
-
-
activity assay
8
-
-
-
8
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
8
-
-
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
37
-
Q61153
activity assay
37
-
-
activity assay
37
-
-
activity assay
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
thyronine 5'-deiodinase type II
Manually annotated by BRENDA team
-
isoenzyme D2
Manually annotated by BRENDA team
-
isozyme type II
Manually annotated by BRENDA team
-
astrocytes and tanycytes express type 2 deiodinase
Manually annotated by BRENDA team
-
mediobasal hypothalamus
Manually annotated by BRENDA team
-
thyronine 5'-deiodinase type II
Manually annotated by BRENDA team
Q9Z1Y9
low level of activity
Manually annotated by BRENDA team
Q9Z1Y9
low level of activity
Manually annotated by BRENDA team
-
isozyme Dio3
Manually annotated by BRENDA team
-
of kidney, isozyme type I
Manually annotated by BRENDA team
-
thyronine 5'-deiodinase type II
Manually annotated by BRENDA team
-
i.e. brain astrocytes in culture
Manually annotated by BRENDA team
-
measurable activity only during induction with bt2cAMP
Manually annotated by BRENDA team
-
isoenzyme type II (D2)
Manually annotated by BRENDA team
-
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
-
thyronine 5'-deiodinase type II
Manually annotated by BRENDA team
-
isozyme type II vertebrata
Manually annotated by BRENDA team
Q9Z1Y9
low level of activity
Manually annotated by BRENDA team
-
isozyme type I
Manually annotated by BRENDA team
-
thyronine 5'-deiodinase type II
Manually annotated by BRENDA team
Q61153, Q9Z148
-
Manually annotated by BRENDA team
-
thyronine 5'-deiodinase type II
Manually annotated by BRENDA team
Q9Z1Y9
low level of activity
Manually annotated by BRENDA team
-
thyronine 5'-deiodinase type I
Manually annotated by BRENDA team
-
isoenzyme type I (D1)
Manually annotated by BRENDA team
O42411
expression is associated with the tubular epithelial cells and with the transitional epithelium, and the inner longotudinal and outer circular muscle layers of the ureter, maximal expression in a thin layer of hepatocates bordering the blood veins
Manually annotated by BRENDA team
-
type I-like activity
Manually annotated by BRENDA team
Q9Z1Y9
low level of activity
Manually annotated by BRENDA team
-
isoenzyme typ I (D1)
Manually annotated by BRENDA team
-
type I and II
Manually annotated by BRENDA team
-
type II and III
Manually annotated by BRENDA team
-
thyronine 5'-deiodinase type I
Manually annotated by BRENDA team
-
thyronine 5'-deiodinase type I
Manually annotated by BRENDA team
O42411
expressionis associated with tubular epithelial cells and with the transitional epithelium, and the inner longitudinal and outer circular muscle layers of the ureter
Manually annotated by BRENDA team
-
low type II-like activity, type I-like activity is the predominant activity
Manually annotated by BRENDA team
O42411
maximum protein expression is shown in a thin layer of hepatocytes bordering the blood veins
Manually annotated by BRENDA team
-
type I-like activity is the predominant activity
Manually annotated by BRENDA team
-
healthy liver tissue expresses a high level of type 1 iodothyronine deiodinase
Manually annotated by BRENDA team
Q9Z1Y9
low level of activity
Manually annotated by BRENDA team
-
mesothelioma cell line, high expression of type 2 iodothyronine deiodinase
Manually annotated by BRENDA team
-
thyronine 5'-deiodinase type I
Manually annotated by BRENDA team
-
the enzyme is restricted to mature primary osteoblasts
Manually annotated by BRENDA team
-
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
-
thyronine 5'-deiodinase type II
Manually annotated by BRENDA team
Q61153, Q9Z148
-
Manually annotated by BRENDA team
-
anterior, isozyme type I
Manually annotated by BRENDA team
-
anterior, isozyme type II, isozyme type I
Manually annotated by BRENDA team
Q9Z1Y9
low level of activity
Manually annotated by BRENDA team
-
isozyme type II
Manually annotated by BRENDA team
Q9Z1Y9
low level of activity
Manually annotated by BRENDA team
-
increase in the prepubertal testis
Manually annotated by BRENDA team
-
thyronine 5'-deiodinase type II
Manually annotated by BRENDA team
-
isozyme type II
Manually annotated by BRENDA team
-
thyronine 5'-deiodinase type I
Manually annotated by BRENDA team
-
isozyme types I and II
Manually annotated by BRENDA team
additional information
-
no type II activity in spleen
Manually annotated by BRENDA team
additional information
-
severe selenium deficiency leads to a decrease in activity of isozyme type I in liver, kidney, and several other organs, but not in the thyroid gland, the central nervous system, and several other endrocrine organs
Manually annotated by BRENDA team
additional information
-
no type-II-like activity in kidney
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
liver, smooth and rough, isozyme type I, at the cytosolic surface
Manually annotated by BRENDA team
-
anterior pituitary gland, isozyme type I
Manually annotated by BRENDA team
-
integral membrane protein
Manually annotated by BRENDA team
-
bound, type II integral in neurolemmal membranes
Manually annotated by BRENDA team
-
isoenzyme type I and type II are both integral membrane proteins
Manually annotated by BRENDA team
-
type II in membranes of stromal cells and thymocytes
Manually annotated by BRENDA team
-
integral membrane protein. Once assembled the D1 holoenzyme is sorted to the plasma membrane in both kidney and liver cells, where it can serve as an enzymic barrier to the entry of the prohormone thyroxine and the source of bioactive 3,3',5-triiodothyronine for the cell
Manually annotated by BRENDA team
-
isozyme type I, liver
-
Manually annotated by BRENDA team
-
enzyme isoforms I, II
-
Manually annotated by BRENDA team
-
at the inner leaflet of the basolateral plasma membrane, isozyme type I, kidney
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
additional information
-
membrane association is not essential for maintenance of functional activity
-
Manually annotated by BRENDA team
additional information
-
subcellular localization of the different isozyme types in different tissues, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
49900
-
-
gel filtration
55400
-
-
type I, sucrose density gradient centrifugation and gel filtration
56000
-
-
SDS-PAGE
198700
-
-
type II, sucrose density gradient centrifugation and gel filtration
200000
-
-
-
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 29000, SDS-PAGE
dimer
-
-
dimer
-
2 * 27000
dimer
-
2 * 27000, isozyme type I
dimer
P49895, Q92813
overexpressed enzyme can homodimerize probably through disulfide bridges, type 1 iodothyronine selenodeiodinase
dimer
P49895, Q92813
overexpressed enzyme can homodimerize probably through disulfide bridges, type 2 iodothyronine selenodeiodinase
dimer
P49895, Q92813
x * 55000, SDS-PAGE, overexpressed enzyme can homodimerize probably through disulfide bridges. Monomeric form is also catalytically active
dimer
P49895, Q92813
x * 62000, SDS-PAGE, overexpressed enzyme can homodimerize probably through disulfide bridges. Monomeric form is also catalytically active
additional information
-
substrate binding unit type I
additional information
-
several subunits, thereof 1 * 29000 substrate binding subunit + 1 * 60000 cAMP-activation subunit + unknown number of other subunits, sequence analysis
additional information
-
substrate binding unit type I 31 kD
additional information
-
substrate binding subunit of multimeric isoenzyme type I has 27 kD and of multimeric isoenzyme type II 29 kD, SDS-PAGE
additional information
-
substrate binding unit type I 29 kD, SDS-PAGE
additional information
-
substrate binding unit type I 33 kD
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
heterogeneity is not caused by N-linked glycosylation, but probably by a combination of O-linked glycosylation and phosphorylation
no glycoprotein
-
no glycosylation of substrate binding subunits of both isoenzymes
glycoprotein
-
heterogeneity is not caused by N-linked glycosylation, but probably by a combination of O-linked glycosylation and phosphorylation
additional information
-
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
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
-
-
inactivation after 30 min
56
-
-
inactivation after 30 min
60
-
-
inactivation after 30 min
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
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
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, presence of 3 mM dithiothreitol, stable for at least 6 weeks, after 3 months, loss of55% of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Sephadex LH20 gel filtration
-
isoenzyme type I and type II
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in COS cells
-
different splicing variants of DOI1 are cloned into the vector pGEM-T for sequencing, 11 variants are identified
-
expression in COS cells
-
expression in HEK-293 cells
-
expression in HEK-293 cells; expression in HEK-293 cells
P49895, Q92813
into a D10 vector
-
isozyme type I, mapping on chromosome 1p32-p33, DNA sequence analysis
-
the P135S mutant enzyme is expressed in HEK-293 cells
-
transfection in HEK 293 cells; transfection in HEK 293 cells
-
-
Q9Z1Y9
a promoter reporter gene for a luciferase assay is constructed
Q61153
isozyme type I, mapping on chromosome 4
-
expression of mutant enzymes, in which selenocysteine residues in the core catalytic center is replaced by cysteine, in Saccharomyces cerevisiae
-
overexpression in LLC-PK1 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
-
expression in JEG-3 cells, transient transfection
-
transcription in vitro, translation in Xenopus laevis oocytes
-
translation of purified rat RNA in Xenopus laevis oocytes
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
3,5,3'-triiodothyronine decreases mRNA levels in TT cell, addition of thyroxine or 3,3',5'-triiodothyronine decreases the deiodinating activity
-
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
-
the enzymatic activity of type 1 iodothyronine deiodinase is low in liver hemangioma
-
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
-
5'-deiodinase is increased in McCune-Albright syndrome-associated hyperthyroidism pathogenesis
-
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
-
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
-
caloric restriction decreases activity in white fat
-
decrease of liver type 1 deiodinase levels after infection only in wild-type mice, low expression levels in type 3 deiodinase knockout mice
Q61153, Q9Z148
decrease of pituitary type 2 deiodinase levels after infection
Q61153, Q9Z148
expression of the Dio1 gene is dependent on HNF4alpha expression, the Dio1 promoter is directly regulated by HNF4alpha
Q61153
activity in white fat is stimulated by a high-fat diet, leptin injections increases activity
-
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
Q61153
increase of expression levels postnatal until day 8
Q9Z1Y9
type 2 deiodinase is induced in muscle regeneration, forkhead box O3 is a key molecule inducing type 2 deiodinase expression
-
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
-
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
-
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
-
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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ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
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mutant enzyme with a 1000fold increase in Km-value for L-thyroxine
SeC133C
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the Km-value for L-thyroxine is 1500fold higher than the wild-type value, the turnover-number is 10fold lower than the wild-type value
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
SeC133C/A131C
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mutant enzyme with more than 1000fold increase in Km-value for L-thyroxine
additional information
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mutant enzymes, in which selenocysteine residues in the core catalytic center is replaced by cysteine, shows a 10fold increase in Km-value for 3,3',5-triiodo-L-thyronine sulfate. Deletion of the endoplasmic reticulum (ER)-signal sequence and the membrane-spanning domain, amino acids 2-35, does not result in the production of a soluble type I-like enzyme. This mutant protein is inactive but is still membrane-bound
Y209F/Y217F
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increase in Km-value for 3,3',5-triiodo-L-thyronine sulfate
additional information
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exchange selenocysteine to cysteine by site-directed mutagenesis of isoenzyme type I
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
partly reconstitution of activity of delipinated purified thyronine 5'-deiodinase from liver microsomes in soybean phospholipids
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APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
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expression and function of the 5-deiodinase and 5-deiodinase isozymes are sensitive to thyroid hormone status, various cytokines and growth factors, severe illness, reactive oxygen species, a variety of hormones and signaling compounds, circadian rythm, and pharmacological agents, and therefore might be useful in sensor function of physiology and pathophysiology
medicine
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thyroglobulin gene mutations induce defective intracellular transport of thyroglobulin leading to increased thyroidal type 2 iodothyronine deiodinase activity, increased thyroidal type 2 deiodinase activity accounts for a relatively high serum free T3 level with a disproportionately low serum free T4 level
medicine
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expression and alternative splicing of DIO mRNA is disturbed in renal cancer, possibly due to changes in expression of splicing factors SF2/ASF and hnRNPA1
medicine
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Dio2 plays a significant role in the photoperiodic response of gonads, melatonin is involved in the signal transduction mechanisms controlling the photoperiodic response of gonads by acting on Dio2 expression
medicine
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exposure of animals to ventilator-induced lung injury leads to ignificant increases in enzyme immunorectivity and activity. Treatment of knock-out mice with 3,3',5-triiodothyronine reverses many of the lung chemokine and cytokine profiles seen in response to ventilator-induced lung injury
additional information
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food restriction leads to reduced liver type 1 deiodinase activity, administration of 3,3,5,5-tetraiodo-L-thyronine restores type 1 deiodinase activity and promotes body protein loss
additional information
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type 2 deiodinase is inactivated via WSB-1 mediated ubiquination but can be rescued from proteasomal degradation by USP-33 mediated deubiquination, expression of WSB-1 and USP-33 underlie cell specific posttranslational control of type 2 deiodinase