Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0004)
DME Name UDP-glucuronosyltransferase 1A1 (UGT1A1), Homo sapiens DME Info
UniProt ID
UD11_HUMAN
EC Number    EC: 2.4.1.17     (Click to Show/Hide the Complete EC Tree)
Transferase
Glycosyltransferases
Hexosyltransferase
EC: 2.4.1.17
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Interactome
Disease Specific Interactions between Host Protein and DME (HOSPPI)
      ICD Disease Classification Healthy
               ICD-11: Healthy Click to Show/Hide the Full List of HOSPPI:        7 HOSPPI
                     Oligomerization
                            Cytochrome P450 1A1 (CYP1A1) Health Heterooligomer
Uniprot ID
CP1A1_HUMAN
Interaction Name CYP1A1-UGT1A1 heterooligomerization [1]
Studied Cell Lines liver microsomes
Description Cytochrome P450 1A1 (CYP1A1) is reported to heterooligomerize with the UGT1A1 protein, which leads to an increased activity of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between CYP1A1 and UGT1A1 can facilitate the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
                            Mutated UDPGT 1-1 (mUGT1A1) Health Homodimer
Uniprot ID
UD11_HUMAN
Interaction Name mUGT1A1-UGT1A1 homodimerization [4]
Studied Cell Lines Monkey kidney fibroblast-like cell line (COS)7
Description Mutated UDPGT 1-1 (mUGT1A1) is reported to homodimerize with the UGT1A1 protein, which leads to a markedly suppressed activity of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between mUGT1A1 and UGT1A1 can markedly inhibit the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
                            UDPGT 1-1 (UGT1A1) Health Homodimer
Uniprot ID
UD11_HUMAN
Interaction Name UGT1A1-UGT1A1 homodimerization [5]
Studied Cell Lines Monkey kidney fibroblast-like cell line (COS)
Affected Substrate(s): Octylgallate
Description UDPGT 1-1 (UGT1A1) is reported as a homodimer, which leads to a slight effect on the enzyme activity of drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the UGT1A1 homodimerization can slightly affect the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
                            UDPGT 1-9 (UGT1A9) Health Heterooligomer
Uniprot ID
UD19_HUMAN
Interaction Name UGT1A9-UGT1A1 heterooligomerization [6]
Studied Cell Lines Human embryonic kidney cell line (HEK293)
Affected Substrate(s): Estradiol (Metabolic product: Estradiol 3-O-glucuronide)
Activity Decreasing Vmax
Description UDPGT 1-9 (UGT1A9) is reported to heterooligomerize with the UGT1A1 protein, which leads to a suppressed activity of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between UGT1A9 and UGT1A1 can inhibit the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
                     Histone modification
                            Histone deacetylases (HDACs) Health Repression
Uniprot ID
HDAC1_HUMAN
Interaction Name HDACs-UGT1A1 interaction [2]
Studied Cell Lines Human kidney-derived HK-2 cells
Description Histone deacetylases (HDACs) are reported to deacetylate the UGT1A1 gene and thereby repress the transcriptional activity of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between HDACs and UGT1A1 can inhibit the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
                            Histone methyltransferases (HMTs) Health Repression
Uniprot ID
EHMT1_HUMAN
Interaction Name HMTs-UGT1A1 interaction [3]
Studied Cell Lines Fetal liver cells
Description The Histone 3 lysine 27 trimethylation of UGT1A1 gene is reported to repress the transcriptional activity of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between Histone methyltransferases (HMTs) and UGT1A1 can inhibit the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
                            Histone methyltransferases (HMTs) Health Activation
Uniprot ID
EHMT1_HUMAN
Interaction Name HMTs-UGT1A1 interaction [3]
Studied Cell Lines Adult liver cells
Description The Histone 3 lysine 4 dimethylation of UGT1A1 gene is reported to activate the transcriptional activity of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between Histone methyltransferases (HMTs) and UGT1A1 can enhance the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
      ICD Disease Classification 02 Neoplasms
               ICD-11: 2B90 Colorectal cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     DNA methylation
                            DNA methyltransferase (DNMT) Colorectal cancer Significant hypermethylation
Uniprot ID
DNMT1_HUMAN
Interaction Name DNMT-UGT1A1 interaction [7]
Studied Cell Lines Colon tissue
Description DNA methyltransferase (DNMT) is reported to significantly hyper-methylate the UGT1A1 gene, which leads to a significantly decreased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between DNMT and UGT1A1 can significantly affect the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
               ICD-11: 2C12 Liver cancer Click to Show/Hide the Full List of HOSPPI:        5 HOSPPI
                     Transcription-factor regulation
                            Aryl hydrocarbon receptor (AHR) Liver cancer Activation
Uniprot ID
AHR_HUMAN
Interaction Name AHR-UGT1A1 interaction [8]
Studied Cell Lines HepG2 cell line
Ensembl ID
ENSG00000106546
Description Aryl hydrocarbon receptor (AHR) is reported to activate the transcription of UGT1A1 gene, which leads to an increased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between AHR and UGT1A1 can activate the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
                            Glucocorticoid receptor (NR3C1) Liver cancer Activation
Uniprot ID
GCR_HUMAN
Interaction Name NR3C1-UGT1A1 interaction [8]
Studied Cell Lines HepG2 cell line
Ensembl ID
ENSG00000113580
Description Glucocorticoid receptor (NR3C1) is reported to activate the transcription of UGT1A1 gene, which leads to an increased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between NR3C1 and UGT1A1 can activate the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
                            Hepatocyte NF 1-alpha (HNF1A) Liver cancer Activation
Uniprot ID
HNF1A_HUMAN
Interaction Name HNF1A-UGT1A1 interaction [8]
Studied Cell Lines HepG2 cell line
Ensembl ID
ENSG00000135100
Description Hepatocyte NF 1-alpha (HNF1A) is reported to activate the transcription of UGT1A1 gene, which leads to an increased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between HNF1A and UGT1A1 can activate the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
                            Nuclear receptor family 0 I3 (NR1I3) Liver cancer Activation
Uniprot ID
NR1I3_HUMAN
Interaction Name NR1I3-UGT1A1 interaction [8]
Studied Cell Lines HepG2 cell line
Ensembl ID
ENSG00000143257
Description Nuclear receptor family 0 I3 (NR1I3) is reported to activate the transcription of UGT1A1 gene, which leads to an increased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between NR1I3 and UGT1A1 can activate the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
                            Pregnane X receptor (PXR) Liver cancer Activation
Uniprot ID
NR1I2_HUMAN
Interaction Name PXR-UGT1A1 interaction [8]
Studied Cell Lines HepG2 cell line
Ensembl ID
ENSG00000144852
Description Pregnane X receptor (PXR) is reported to activate the transcription of UGT1A1 gene, which leads to an increased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 1A1. As a result, the interaction between PXR and UGT1A1 can activate the drug-metabolizing process of UDP-glucuronosyltransferase 1A1.
References
1 Interaction between cytochrome P450 and other drug-metabolizing enzymes: evidence for an association of CYP1A1 with microsomal epoxide hydrolase and UDP-glucuronosyltransferase. Biochem Biophys Res Commun. 2000 Jul 14;273(3):1048-52.
2 Epigenetic regulation is a crucial factor in the repression of UGT1A1 expression in the human kidney. Drug Metab Dispos. 2013 Oct;41(10):1738-43.
3 Histone Modifications Regulate the Developmental Expression of Human Hepatic UDP-Glucuronosyltransferase 1A1. Drug Metab Dispos. 2017 Dec;45(12):1372-1378.
4 Homodimerization of human bilirubin-uridine-diphosphoglucuronate glucuronosyltransferase-1 (UGT1A1) and its functional implications. J Biol Chem. 2001 Nov 9;276(45):42108-15.
5 Oligomerization of the UDP-glucuronosyltransferase 1A proteins: homo- and heterodimerization analysis by fluorescence resonance energy transfer and co-immunoprecipitation. J Biol Chem. 2007 Feb 16;282(7):4821-9.
6 Effects of coexpression of UGT1A9 on enzymatic activities of human UGT1A isoforms. Drug Metab Dispos. 2007 May;35(5):747-57.
7 Regulation of UGT1A1 and HNF1 transcription factor gene expression by DNA methylation in colon cancer cells. BMC Mol Biol. 2010 Jan 22;11:9.
8 Transcriptional regulation of human UGT1A1 gene expression through distal and proximal promoter motifs: implication of defects in the UGT1A1 gene promoter. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):597-605.

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