help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mandel, S. J.
Right arrow Articles by Larsen, P. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mandel, S. J.
Right arrow Articles by Larsen, P. R.

Journal of Clinical Endocrinology & Metabolism, Vol 75, 1133-1139, Copyright © 1992 by Endocrine Society

ARTICLES

Cloning and in vitro expression of the human selenoprotein, type I iodothyronine deiodinase

SJ Mandel, MJ Berry, JD Kieffer, JW Harney, RL Warne and PR Larsen
Howard Hughes Medical Institute Laboratory, Brigham and Women's Hospital, Boston, Massachusetts.

The type I 5' iodothyronine deiodinase (5' DI) catalyzes the deiodination of T4 to the biologically active hormone T3 and accounts for a significant fraction of its production. We have recently cloned the complementary DNA (cDNA) for the rat 5' DI, which contains the rare amino acid selenocysteine, and used this to screen human liver and kidney cDNA libraries to identify a human 5' DI cDNA clone. From these, we constructed a cDNA encoding a functional 5' DI. The 2222 base pair human 5' DI cDNA is approximately 200 nucleotides shorter than the 2.4- kilobase hybridizing band in Northern blots of human liver, kidney, and thyroid, because of missing 5' untranslated sequence and the poly A tail. The deduced amino acid sequence codes for a protein of 28.7 kilodaltons assuming the UGA codon at position 382 encodes selenocysteine, and is highly homologous (88% similarity) to the rat. We transiently expressed the 5' DI in COS-7 cells to establish that it encodes a functional enzyme and to study its kinetics. These show saturable deiodination of rT3 (Ka 0.52 +/- 0.04 mumol/L and Vmax 63.2 +/- 16.4 pmol min-1 mg-1). T4 and gold thioglucose are competitive inhibitors of rT3 deiodination. 6-n-Propylthiouracil (PTU) is an uncompetitive inhibitor (with rT3) and competitive inhibitor (with dithiothreitol) of rT3 deiodination. 6-n-Propylthiouracil inhibits T4 to T3 conversion. Labeling of COS-7 cells transiently transfected with the human 5' DI cDNA with bromoacetyl-125I-T3 demonstrates a 28- kilodalton protein. This indicates that in the human, as well as in the rat messenger RNA, the UGA encodes selenocysteine and translation terminates at the UAA codon at nucleotides 754 to 756. Reverse T3 and gold thioglucose (100 nmol/L) block bromoacetyl-125I-T3 labeling of the transiently expressed human and rat 5' DI proteins. These results demonstrate that the human 5' DI is a selenoprotein, analogous to the rat enzyme. Given the previously demonstrated critical role of the selenium atom in catalyzing deiodination by this protein, we conclude that this trace element is essential for normal thyroid hormone action in man.


This article has been cited by other articles:


Home page
 EndocrinologyHome page
G. G. J. M. Kuiper, W. Klootwijk, G. Morvan Dubois, O. Destree, V. M. Darras, S. Van der Geyten, B. Demeneix, and T. J. Visser
Characterization of Recombinant Xenopus laevis Type I Iodothyronine Deiodinase: Substitution of a Proline Residue in the Catalytic Center by Serine (Pro132Ser) Restores Sensitivity to 6-Propyl-2-Thiouracil
Endocrinology, July 1, 2006; 147(7): 3519 - 3529.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
P. H. M. Klaren, R. Haasdijk, J. R. Metz, L. M. C. Nitsch, V. M. Darras, S. Van der Geyten, and G. Flik
Characterization of an Iodothyronine 5'-Deiodinase in Gilthead Seabream (Sparus auratus) that Is Inhibited by Dithiothreitol
Endocrinology, December 1, 2005; 146(12): 5621 - 5630.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. H. Canani, C. Capp, J. M. Dora, E. L. S. Meyer, M. S. Wagner, J. W. Harney, P. R. Larsen, J. L. Gross, A. C. Bianco, and A. L. Maia
The Type 2 Deiodinase A/G (Thr92Ala) Polymorphism Is Associated with Decreased Enzyme Velocity and Increased Insulin Resistance in Patients with Type 2 Diabetes Mellitus
J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3472 - 3478.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. G. J. M. Kuiper, F. Wassen, W. Klootwijk, H. van Toor, E. Kaptein, and T. J. Visser
Molecular Basis for the Substrate Selectivity of Cat Type I Iodothyronine Deiodinase
Endocrinology, December 1, 2003; 144(12): 5411 - 5421.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. P. Carvalho
Modulation of Uterine Iodothyronine Deiodinases--A Critical Event for Fetal Development?
Endocrinology, October 1, 2003; 144(10): 4250 - 4252.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Chan, S. Kachilele, E. Hobbs, J. N. Bulmer, K. Boelaert, C. J. McCabe, P. M. Driver, A. R. Bradwell, M. Kester, T. J. Visser, et al.
Placental Iodothyronine Deiodinase Expression in Normal and Growth-Restricted Human Pregnancies
J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4488 - 4495.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Curcio-Morelli, B. Gereben, A. M. Zavacki, B. W. Kim, S. Huang, J. W. Harney, P. R. Larsen, and A. C. Bianco
In Vivo Dimerization of Types 1, 2, and 3 Iodothyronine Selenodeiodinases
Endocrinology, March 1, 2003; 144(3): 937 - 946.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Montero-Pedrazuela, J. Bernal, and A. Guadano-Ferraz
Divergent Expression of Type 2 Deiodinase and the Putative Thyroxine-Binding Protein p29, in Rat Brain, Suggests that They Are Functionally Unrelated Proteins
Endocrinology, March 1, 2003; 144(3): 1045 - 1052.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. H. J. Verhoelst, K. Vandenborne, T. Severi, O. Bakker, B. Zandieh Doulabi, J. L. Leonard, E. R. Kuhn, S. van der Geyten, and V. M. Darras
Specific Detection of Type III Iodothyronine Deiodinase Protein in Chicken Cerebellar Purkinje Cells
Endocrinology, July 1, 2002; 143(7): 2700 - 2707.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
A. C. Bianco, D. Salvatore, B. Gereben, M. J. Berry, and P. R. Larsen
Biochemistry, Cellular and Molecular Biology, and Physiological Roles of the Iodothyronine Selenodeiodinases
Endocr. Rev., February 1, 2002; 23(1): 38 - 89.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
M. M. van Bakel, G. Printzen, B. Wermuth, and U. N Wiesmann
Antioxidant and thyroid hormone status in selenium-deficient phenylketonuric and hyperphenylalaninemic patients
Am. J. Clinical Nutrition, October 1, 2000; 72(4): 976 - 981.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. L. Morrell, J. A. Fuchs, and J. L. Holtzman
Effect of Methoxychlor Administration to Male Rats on Hepatic, Microsomal Iodothyronine 5'-Deiodinase, Form I
J. Pharmacol. Exp. Ther., July 1, 2000; 294(1): 308 - 312.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
J. P. Sanders, S. Van der Geyten, E. Kaptein, V. M. Darras, E. R. Kühn, J. L. Leonard, and T. J. Visser
Cloning and Characterization of Type III Iodothyronine Deiodinase from the Fish Oreochromis niloticus
Endocrinology, August 1, 1999; 140(8): 3666 - 3673.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
C. Buettner, J. W. Harney, and M. J. Berry
The Caenorhabditis elegans Homologue of Thioredoxin Reductase Contains a Selenocysteine Insertion Sequence (SECIS) Element That Differs from Mammalian SECIS Elements but Directs Selenocysteine Incorporation
J. Biol. Chem., July 30, 1999; 274(31): 21598 - 21602.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Gereben, T. Bartha, H. M. Tu, J. W. Harney, P. Rudas, and P. R. Larsen
Cloning and Expression of the Chicken Type 2 Iodothyronine 5'-Deiodinase
J. Biol. Chem., May 14, 1999; 274(20): 13768 - 13776.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Hernández, G. J. Lyon, M. J. Schneider, and D. L. St. Germain
Isolation and Characterization of the Mouse Gene for the Type 3 Iodothyronine Deiodinase
Endocrinology, January 1, 1999; 140(1): 124 - 130.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
S. Van der Geyten, J. P. Sanders, E. Kaptein, V. M. Darras, E. R. Kuhn, J. L. Leonard, and T. J. Visser
Expression of Chicken Hepatic Type I and Type III Iodothyronine Deiodinases during Embryonic Development
Endocrinology, December 1, 1997; 138(12): 5144 - 5152.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. P. Sanders, S. Van der Geyten, E. Kaptein, V. M. Darras, E. R. Kuhn, J. L. Leonard, and T. J. Visser
Characterization of a Propylthiouracil-Insensitive Type I Iodothyronine Deiodinase
Endocrinology, December 1, 1997; 138(12): 5153 - 5160.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. C. Sun, J. W. Harney, M. J. Berry, and P. R. Larsen
The Role of the Active Site Cysteine in Catalysis by Type 1 Iodothyronine Deiodinase
Endocrinology, December 1, 1997; 138(12): 5452 - 5458.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. Navarro, A. Landa, C. Valverde-R, and C. Aceves
Mammary Gland Type I Iodothyronine Deiodinase Is Encoded by a Short Messenger Ribonucleic Acid
Endocrinology, October 1, 1997; 138(10): 4248 - 4254.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Pallud, A.-M. Lennon, M. Ramauge, J.-M. Gavaret, W. Croteau, M. Pierre, F. Courtin, and D. L. St. Germain
Expression of the Type II Iodothyronine Deiodinase in Cultured Rat Astrocytes Is Selenium-dependent
J. Biol. Chem., July 18, 1997; 272(29): 18104 - 18110.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. A. Mol, S. van der Geyten, V. M. Darras, T. J. Visser, and E. R. Kuhn
Characterization of Iodothyronine Outer Ring and Inner Ring Deiodinase Activities in the Blue Tilapia, Oreochromis Aureus
Endocrinology, May 1, 1997; 138(5): 1787 - 1793.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
I. J. Chopra
Euthyroid Sick Syndrome: Is It a Misnomer?
J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 329 - 334.
[Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Valverde-R, W. Croteau, G. J. LaFleur Jr., A. Orozco, and D. L. St. Germain
Cloning and Expression of a 5'-Iodothyronine Deiodinase from the Liver of Fundulus heteroclitus
Endocrinology, February 1, 1997; 138(2): 642 - 648.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. Toyoda, E. Kaptein, M. J. Berry, J. W. Harney, P. R. Larsen, and T. J. Visser
Structure-Activity Relationships for Thyroid Hormone Deiodination by Mammalian Type I Iodothyronine Deiodinases
Endocrinology, January 1, 1997; 138(1): 213 - 219.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. C. Davey, K. B. Becker, M. J. Schneider, D. L. St. Germain, and V. A. Galton
Cloning of a cDNA for the Type II Iodothyronine Deiodinase
J. Biol. Chem., November 10, 1995; 270(45): 26786 - 26789.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. C. Low, J. W. Harney, and M. J. Berry
Cloning and Functional Characterization of Human Selenophosphate Synthetase, an Essential Component of Selenoprotein Synthesis
J. Biol. Chem., September 15, 1995; 270(37): 21659 - 21664.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
W. Croteau, S. L. Whittemore, M. J. Schneider, and D. L. St. Germain
Cloning and Expression of a cDNA for a Mammalian Type III Iodothyronine Deiodinase
J. Biol. Chem., July 14, 1995; 270(28): 16569 - 16575.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Toyoda, M. J. Berry, J. W. Harney, and P. R. Larsen
Topological Analysis of the Integral Membrane Protein, Type 1 Iodothyronine Deiodinase (D1)
J. Biol. Chem., May 19, 1995; 270(20): 12310 - 12318.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
G. N. Burrow, D. A. Fisher, and P. R. Larsen
Maternal and Fetal Thyroid Function
N. Engl. J. Med., October 20, 1994; 331(16): 1072 - 1078.
[Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1992 by The Endocrine Society