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Information on EC 1.21.99.4 - thyroxine 5'-deiodinase and Organism(s) Mus musculus and UniProt Accession Q9Z148
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1.21.99.4 thyroxine 5'-deiodinaseIUBMB Comments
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.
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Word Map
- 1.21.99.4
- thyroid
- triiodothyronine
- hypothyroidism
- tsh
-
deiodination
- adipose
- pituitary
- selenium
-
euthyroidism
-
selenoproteins
- 3,5,3'-triiodothyronine
- thyrotropin
-
prohormone
-
thermogenesis
-
selenoenzyme
- propylthiouracil
-
photoperiodic
- hypothalamic
-
hypothalamic-pituitary-thyroid
- selenocysteine
-
thyroid-stimulating
-
thyrotropin-releasing
-
iopanoic
-
thermogenic
- iodotyrosine
-
hypophysiotropic
-
t3-dependent
-
polybrominated
-
extrathyroidal
-
hypothyroxinemia
- 3,3',5-triiodothyronine
-
thyroxine-binding
-
mediobasal
-
pbdes
-
5'-deiodination
-
iodine-deficient
- tanycytes
- tuberalis
-
debromination
-
selenocysteine-containing
-
trbeta
- methimazole
- thyrotoxicosis
-
hormone-activating
- thyroperoxidase
-
monocarboxylate
-
nonthyroidal
-
secis
- levothyroxine
- medicine
-
selenium-deficient
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
deiodinase, type 2 deiodinase, type 3 deiodinase, iodothyronine 5'-deiodinase, type 2 iodothyronine deiodinase, type 1 deiodinase, thyroxine 5'-deiodinase, type ii iodothyronine deiodinase, type i iodothyronine deiodinase, type 1 iodothyronine deiodinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5DI
-
-
-
-
5DII
-
-
-
-
5DIII
-
-
-
-
diiodothyronine 5'-deiodinase
-
-
-
-
DIOI
-
-
-
-
DIOII
-
-
-
-
DIOIII
-
-
-
-
iodothyronine outer ring monodeiodinase
-
-
-
-
L-thyroxine iodohydrolase (reducing)
-
-
-
-
thyroxine 5-deiodinase
-
-
-
-
Thyroxine deiodinase
-
-
-
-
Type 1 DI
-
-
-
-
type 2 deiodinase
Type 2 DI
-
-
-
-
Type 3 DI
-
-
-
-
Type-I 5'deiodinase
-
-
-
-
Type-II 5'deiodinase
-
-
-
-
Type-III 5'deiodinase
-
-
-
-
XL-15
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3,3',5-triiodo-L-thyronine + iodide + acceptor + H+ = L-thyroxine + reduced acceptor
isozyme type I, reaction mechanism, both 5-deiodinase isoforms and 5-deiodinase contain a selenocysteine residue at the active site
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -
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
70712-46-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
assay at pH 7.2
-
-
?
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
-
-
-
-
?
3,5,3'-triiodo-L-thyronine + iodide + A + H+
L-thyroxine + AH2
assay at pH 7.2
-
-
?
L-3,5',3'-triiodothyronine + AH2
L-3,3'-diiodothyronine + iodide + A + H+
-
-
-
-
?
L-3,5,3',5'-tetraiodothyronine + AH2
L-3,5,3'-triiodothyronine + iodide + A + H+
-
i.e. thyroxine
-
-
?
L-thyroxine + AH2
3,3',5'-triiodo-L-thyronine + iodide + A + H+
isoenzyme Dio1
-
-
?
L-thyroxine + electron acceptor
3,3',5-triiodothyronine + iodide + reduced electron acceptor
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
-
-
?
3,3',5'-triiodo-L-thyronine + AH2
3,3'-diiodo-L-thyronine + iodide + A + H+
-
isozyme type I
-
-
?
3,3',5'-triiodo-L-thyronine + AH2
3,3'-diiodo-L-thyronine + iodide + A + H+
-
isozyme type I: degradation of 3,3',5'-triiodo-L-thyronine
hormonally inactive
-
?
L-thyroxine + AH2
3,3',5-triiodo-L-thyronine + iodide + A + H+
-
-
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+
-
isozyme type II
hormonally active
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
-
-
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
-
isozymes type II and I, production of 3,3',5-triiodo-L-thyronine
hormonally inactive
-
?
L-thyroxine + electron acceptor
3,3',5-triiodothyronine + iodide + reduced electron acceptor
-
-
-
?
L-thyroxine + electron acceptor
3,3',5-triiodothyronine + iodide + reduced electron acceptor
the enzyme is regulated at the pretranslational level
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3,3',5'-triiodo-L-thyronine + AH2
3,3'-diiodo-L-thyronine + iodide + A + H+
-
isozyme type I
-
-
?
3,3',5'-triiodothyronine + AH2
3,3'-diiodothyronine + iodide + A + H+
-
-
-
-
?
L-thyroxine + AH2
3,3',5'-triiodo-L-thyronine + iodide + A + H+
isoenzyme Dio1
-
-
?
L-thyroxine + AH2
3,3',5-triiodo-L-thyronine + iodide + A + H+
-
-
from microsomal enzyme complex, 3,3',5-triiodo-L-thyronine is thyromimetically active
-
?
L-thyroxine + electron acceptor
3,3',5-triiodothyronine + iodide + reduced electron acceptor
the enzyme is regulated at the pretranslational level
-
-
?
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
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
-
-
-
-
?
L-thyroxine + AH2
3,5,3'-triiodo-L-thyronine + iodide + A + H+
-
isozymes type II and I, production of 3,3',5-triiodo-L-thyronine
hormonally inactive
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0000000005
pituitary type 2 deiodinase activity, type 3 deiodinase knockout mice after infection with Streptococcus pneumoniae
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
0.000000013
-
eight weeks high-fat diet, interscapular white fat, 3,3'-diiodothyronine
0.000000015
-
eight weeks low-fat diet, interscapular white fat, 3,3'-diiodothyronine
0.000000033
-
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
0.000000058
-
eight weeks low-fat diet, epididymal white fat, 3,3'-diiodothyronine
0.000000063
-
two weeks high-fat diet, dorsolumbar white fat, 3,3'-diiodothyronine
0.000000093
-
two weeks low-fat diet, epididymal white fat, 3,3'-diiodothyronine
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
0.000000187
-
eight weeks high-fat diet, dorsolumbar white fat, 3,3'-diiodothyronine
0.0000002
-
eight weeks high-fat diet, epididymal white fat, 3,3'-diiodothyronine
0.000001
type 3 deiodinase knockout mice after infection with Streptococcus pneumoniae
0.00000125
wild-type mice after infection with Streptococcus pneumoniae
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
wild-type and type 3 deiodinase knockout mice, infected with Streptococcus pneumoniae
UniProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
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
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
-
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
activity in white fat is stimulated by a high-fat diet, leptin injections increases activity
-
decrease of liver type 1 deiodinase levels after infection only in wild-type mice, low expression levels in type 3 deiodinase knockout mice
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 Krüppel-like transcription factor 9, KLF9, functions together with HNF4alpha and GATA4 to synergistically activate the promoter through direct interaction between these transcriptional factors
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
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yu, J.; Koenig, R.J.
Regulation of hepatocyte thyroxine 5'-deiodinase by T3 and nuclear receptor coactivators as a model of the sick euthyroid syndrome
J. Biol. Chem.
275
38296-38301
2000
Homo sapiens, Mus musculus, Rattus sp.
Santini, F.; Chopra, I.J.; Hurd, R.E.; Chua Teco, G.N.
A study of the characteristics of hepatic iodothyronine 5'-monodeiodinase in various vertebrate species
Endocrinology
131
830-834
1992
Bos taurus, Cavia porcellus, Gallus gallus, Ovis aries, Homo sapiens, Mus musculus, Rattus sp., Sus scrofa
Koehrle, J.
Iodothyronine deiodinases
Methods Enzymol.
347
125-167
2002
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus, vertebrata
Song, S.; Sorimachi, K.; Adachi, K.; Oka, T.
Biochemical and molecular biological evidence for the presence of type II iodothyronine deiodinase in mouse mammary gland
Mol. Cell. Endocrinol.
160
173-181
2000
Mus musculus (Q9Z1Y9), Mus musculus
Ng, L.; Hernandez, A.; He, W.; Ren, T.; Srinivas, M.; Ma, M.; Galton, V.A.; St Germain, D.L.; Forrest, D.
A protective role for type 3 deiodinase, a thyroid hormone-inactivating enzyme, in cochlear development and auditory function
Endocrinology
150
1952-1960
2009
Mus musculus (Q9Z1Y9)
Boelen, A.; Kwakkel, J.; Wieland, C.W.; St Germain, D.L.; Fliers, E.; Hernandez, A.
Impaired bacterial clearance in type 3 deiodinase-deficient mice infected with Streptococcus pneumoniae
Endocrinology
150
1984-1990
2009
Mus musculus (Q61153), Mus musculus (Q9Z148), Mus musculus
Ohguchi, H.; Tanaka, T.; Uchida, A.; Magoori, K.; Kudo, H.; Kim, I.; Daigo, K.; Sakakibara, I.; Okamura, M.; Harigae, H.; Sasaki, T.; Osborne, T.F.; Gonzalez, F.J.; Hamakubo, T.; Kodama, T.; Sakai, J.
Hepatocyte nuclear factor 4alpha contributes to thyroid hormone homeostasis by cooperatively regulating the type 1 iodothyronine deiodinase gene with GATA4 and Kruppel-like transcription factor 9
Mol. Cell. Biol.
28
3917-3931
2008
Mus musculus (Q61153), Mus musculus
Macek Jilkova, Z.; Pavelka, S.; Flachs, P.; Hensler, M.; Kus, V.; Kopecky, J.
Modulation of type I iodothyronine 5-deiodinase activity in white adipose tissue by nutrition: possible involvement of leptin
Physiol. Res.
59
561-569
2010
Mus musculus
Wang, Y.Y.; Morimoto, S.; Du, C.K.; Lu, Q.W.; Zhan, D.Y.; Tsutsumi, T.; Ide, T.; Miwa, Y.; Takahashi-Yanaga, F.; Sasaguri, T.
Up-regulation of type 2 iodothyronine deiodinase in dilated cardiomyopathy
Cardiovasc. Res.
87
636-646
2010
Mus musculus
Dentice, M.; Marsili, A.; Ambrosio, R.; Guardiola, O.; Sibilio, A.; Paik, J.H.; Minchiotti, G.; DePinho, R.A.; Fenzi, G.; Larsen, P.R.; Salvatore, D.
The FoxO3/type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration
J. Clin. Invest.
120
4021-4030
2010
Mus musculus
Bassett, J.H.; Boyde, A.; Howell, P.G.; Bassett, R.H.; Galliford, T.M.; Archanco, M.; Evans, H.; Lawson, M.A.; Croucher, P.; St Germain, D.L.; Galton, V.A.; Williams, G.R.
Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts
Proc. Natl. Acad. Sci. USA
107
7604-7609
2010
Mus musculus
Piehl, S.; Heberer, T.; Balizs, G.; Scanlan, T.S.; Kohrle, J.
Development of a validated liquid chromatography/tandem mass spectrometry method for the distinction of thyronine and thyronamine constitutional isomers and for the identification of new deiodinase substrates
Rapid Commun. Mass Spectrom.
22
3286-3296
2008
Homo sapiens, Mus musculus
Ramadan, W.; Marsili, A.; Huang, S.; Larsen, P.R.; Silva, J.E.
Type-2 iodothyronine 5-deiodinase in skeletal muscle of C57BL/6 mice. I. Identity, subcellular localization, and characterization
Endocrinology
152
3082-3092
2011
Mus musculus, Mus musculus C57BL/6
Barca-Mayo, O.; Liao, X.H.; DiCosmo, C.; Dumitrescu, A.; Moreno-Vinasco, L.; Wade, M.S.; Sammani, S.; Mirzapoiazova, T.; Garcia, J.G.; Refetoff, S.; Weiss, R.E.
Role of type 2 deiodinase in response to acute lung injury (ALI) in mice
Proc. Natl. Acad. Sci. USA
108
E1321-E1329
2011
Mus musculus
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