Target Information
Target General Information | Top | |||||
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Target ID |
T16792
(Former ID: TTDS00426)
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Target Name |
Iodothyronine deiodinase type I (DIO1)
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Synonyms |
Type-I 5'-deiodinase; Type I iodothyronine deiodinase; Type 1 DI; TXDI1; ITDI1; DIOI; 5DI
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Gene Name |
DIO1
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Thyrotoxicosis [ICD-11: 5A02] | |||||
Function |
Plays a role in providing a source of plasma T3 by deiodination of T4 in peripheral tissues such as liver and kidney. Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into T3 (3,5,3'-triiodothyronine) and of T3 into T2 (3,3'-diiodothyronine).
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UniProt ID | ||||||
EC Number |
EC 1.21.99.4
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Sequence |
MGLPQPGLWLKRLWVLLEVAVHVVVGKVLLILFPDRVKRNILAMGEKTGMTRNPHFSHDN
WIPTFFSTQYFWFVLKVRWQRLEDTTELGGLAPNCPVVRLSGQRCNIWEFMQGNRPLVLN FGSCTUPSFMFKFDQFKRLIEDFSSIADFLVIYIEEAHASDGWAFKNNMDIRNHQNLQDR LQAAHLLLARSPQCPVVVDTMQNQSSQLYAALPERLYIIQEGRILYKGKSGPWNYNPEEV RAVLEKLHS Click to Show/Hide
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HIT2.0 ID | T92Q77 |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Propylthiouracil | Drug Info | Approved | Hyperthyroidism | [2], [3], [4] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | Propylthiouracil | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Thyroid hormone signaling pathway | hsa04919 | Affiliated Target |
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Class: Organismal Systems => Endocrine system | Pathway Hierarchy |
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target Affiliated Biological Pathways | Top | |||||
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BioCyc | [+] 3 BioCyc Pathways | + | ||||
1 | Thyronamine and iodothyronamine metabolism | |||||
2 | Thyroid hormone metabolism II (via conjugation and/or degradation) | |||||
3 | Thyroid hormone metabolism I (via deiodination) | |||||
KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | Thyroid hormone signaling pathway | |||||
WikiPathways | [+] 3 WikiPathways | + | ||||
1 | Selenium Metabolism and Selenoproteins | |||||
2 | Metabolism of amino acids and derivatives | |||||
3 | Selenium Micronutrient Network |
References | Top | |||||
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REF 1 | Type 1 iodothyronine deiodinase is the major source of circulating T3 in hyperthyroidism: implications for therapy. Nat Clin Pract Endocrinol Metab. 2007 Nov;3(11):740-1. | |||||
REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6650). | |||||
REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 006188. | |||||
REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 |
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