Target Information
Target General Information | Top | |||||
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Target ID |
T93480
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Target Name |
UDP-glucuronosyltransferase 1A1 (UGT1A1)
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Synonyms |
UGT1A1; Bilirubin-specific UDPGT isozyme 1; hUG-BR1; UDP-glucuronosyltransferase 1-1; UDPGT 1-1; UGT1*1; UGT1-01; UGT1.1; UDP-glucuronosyltransferase 1A isoform 1
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Gene Name |
UGT1A1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Inborn porphyrin/heme metabolism error [ICD-11: 5C58] | |||||
Function |
UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile. Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds. Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol. Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates. Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties. Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II. Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan.
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UniProt ID | ||||||
EC Number |
EC 2.4.1.17
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Sequence |
MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQLQQRGHEIVVL
APDASLYIRDGAFYTLKTYPVPFQREDVKESFVSLGHNVFENDSFLQRVIKTYKKIKKDS AMLLSGCSHLLHNKELMASLAESSFDVMLTDPFLPCSPIVAQYLSLPTVFFLHALPCSLE FEATQCPNPFSYVPRPLSSHSDHMTFLQRVKNMLIAFSQNFLCDVVYSPYATLASEFLQR EVTVQDLLSSASVWLFRSDFVKDYPRPIMPNMVFVGGINCLHQNPLSQEFEAYINASGEH GIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDL LGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTS EDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHD LTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
ADReCS ID | BADD_A01933 ; BADD_A02053 ; BADD_A05554 | |||||
HIT2.0 ID | T61OY3 |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | AT-342 | Drug Info | Phase 1/2 | Crigler-Najjar syndrome | [1] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Replacement | [+] 1 Replacement drugs | + | ||||
1 | AT-342 | 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).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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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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Pentose and glucuronate interconversions | hsa00040 | Affiliated Target |
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Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
Ascorbate and aldarate metabolism | hsa00053 | Affiliated Target |
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Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
Steroid hormone biosynthesis | hsa00140 | Affiliated Target |
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Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
Retinol metabolism | hsa00830 | Affiliated Target |
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Class: Metabolism => Metabolism of cofactors and vitamins | Pathway Hierarchy | ||
Porphyrin metabolism | hsa00860 | Affiliated Target |
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Class: Metabolism => Metabolism of cofactors and vitamins | Pathway Hierarchy | ||
Metabolism of xenobiotics by cytochrome P450 | hsa00980 | Affiliated Target |
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Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy | ||
Drug metabolism - cytochrome P450 | hsa00982 | Affiliated Target |
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Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy | ||
Drug metabolism - other enzymes | hsa00983 | Affiliated Target |
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Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy | ||
Bile secretion | hsa04976 | Affiliated Target |
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Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
Click to Show/Hide the Information of Affiliated Human Pathways |
Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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Closeness centrality | 1.60E-01 | Radiality | 1.24E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 2.00E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
References | Top | |||||
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REF 1 | ClinicalTrials.gov (NCT03223194) Gene Transfer Clinical Study in Crigler-Najjar Syndrome (VALENS). U.S. National Institutes of Health. |
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