Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0040)
DME Name UDP-glucuronosyltransferase 2B7 (UGT2B7), Homo sapiens DME Info
UniProt ID
UD2B7_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:        3 HOSPPI
                     Oligomerization
                            Cytochrome P450 1A2 (CYP1A2) Health Heterooligomer
Uniprot ID
CP1A2_HUMAN
Interaction Name CYP1A2-UGT2B7 heterooligomerization [1]
Studied Cell Lines Monkey kidney fibroblast-like cell line (COS)
Affected Substrate(s): Morphine (Metabolic product: Glucuronidation of the morphine 3-hydroxyl group)
Description Cytochrome P450 1A2 (CYP1A2) is reported to heterooligomerize with the UGT2B7 protein, which leads to an altered activity of the drug-metabolizing enzyme UDP-glucuronosyltransferase 2B7. As a result, the interaction between CYP1A2 and UGT2B7 can modulate the drug-metabolizing process of UDP-glucuronosyltransferase 2B7.
                            Cytochrome P450 2C9 (CYP2C9) Health Heterooligomer
Uniprot ID
CP2C9_HUMAN
Interaction Name CYP2C9-UGT2B7 heterooligomerization [1]
Studied Cell Lines Monkey kidney fibroblast-like cell line (COS)
Affected Substrate(s): Morphine (Metabolic product: Glucuronidation of the morphine 3-hydroxyl group)
Description Cytochrome P450 2C9 (CYP2C9) is reported to heterooligomerize with the UGT2B7 protein, which leads to an altered activity of the drug-metabolizing enzyme UDP-glucuronosyltransferase 2B7. As a result, the interaction between CYP2C9 and UGT2B7 can modulate the drug-metabolizing process of UDP-glucuronosyltransferase 2B7.
                            Cytochrome P450 3A4 (CYP3A4) Health Heterooligomer
Uniprot ID
CP3A4_HUMAN
Interaction Name CYP3A4-UGT2B7 heterooligomerization [1], [2]
Studied Cell Lines Monkey kidney fibroblast-like cell line (COS)
Affected Substrate(s): Morphine (Metabolic product: Glucuronidation of the morphine 3-hydroxyl group)
Azidothymidine
Activity Increasing Km by about 9.8-fold
Description Cytochrome P450 3A4 (CYP3A4) is reported to heterooligomerize with the UGT2B7 protein, which leads to an altered activity of the drug-metabolizing enzyme UDP-glucuronosyltransferase 2B7. As a result, the interaction between CYP3A4 and UGT2B7 can modulate the drug-metabolizing process of UDP-glucuronosyltransferase 2B7.
      ICD Disease Classification 02 Neoplasms
               ICD-11: 2B90 Colorectal cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Transcription-factor regulation
                            NFE2-related factor 2 (NFE2L2) Colorectal cancer Activation
Uniprot ID
NF2L2_HUMAN
Interaction Name NFE2L2-UGT2B7 interaction [3]
Studied Cell Lines Caco-2 cell line
Ensembl ID
ENSG00000116044
Description NFE2-related factor 2 (NFE2L2) is reported to activate the transcription of UGT2B7 gene, which leads to an increased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 2B7. As a result, the interaction between NFE2L2 and UGT2B7 can activate the drug-metabolizing process of UDP-glucuronosyltransferase 2B7.
               ICD-11: 2C12 Liver cancer Click to Show/Hide the Full List of HOSPPI:        4 HOSPPI
                     Transcription-factor regulation
                            Hepatocyte NF 1-alpha (HNF1A) Liver cancer Activation
Uniprot ID
HNF1A_HUMAN
Interaction Name HNF1A-UGT2B7 interaction [4]
Studied Cell Lines HepG2 cell line
Ensembl ID
ENSG00000135100
Description Hepatocyte NF 1-alpha (HNF1A) is reported to activate the transcription of UGT2B7 gene, which leads to an increased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 2B7. As a result, the interaction between HNF1A and UGT2B7 can activate the drug-metabolizing process of UDP-glucuronosyltransferase 2B7.
                            NFE2-related factor 2 (NFE2L2) Liver cancer Activation
Uniprot ID
NF2L2_HUMAN
Interaction Name NFE2L2-UGT2B7 interaction [3]
Studied Cell Lines HepG2, HuH7 and HLE cell lines
Ensembl ID
ENSG00000116044
Description NFE2-related factor 2 (NFE2L2) is reported to activate the transcription of UGT2B7 gene, which leads to an increased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 2B7. As a result, the interaction between NFE2L2 and UGT2B7 can activate the drug-metabolizing process of UDP-glucuronosyltransferase 2B7.
                            Octamer-binding protein 1 (POU2F1) Liver cancer Activation
Uniprot ID
PO2F1_HUMAN
Interaction Name POU2F1-UGT2B7 interaction [4]
Studied Cell Lines HepG2 cell line
Ensembl ID
ENSG00000143190
Description Octamer-binding protein 1 (POU2F1) is reported to activate the transcription of UGT2B7 gene, which leads to an increased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 2B7. As a result, the interaction between POU2F1 and UGT2B7 can activate the drug-metabolizing process of UDP-glucuronosyltransferase 2B7.
                     Non-coding RNA regulation
                            hsa-miR-216b-5p Liver cancer Suppression
miRBase ID
MIMAT0004959
Interaction Name hsa-miR-216b-5p--UGT2B7 regulation [5]
Studied Cell Lines HuH7 and Hep3B cell lines
Description hsa-miR-216b-5p is reported to suppress UGT2B7 mRNA translation by binding to the 3' untranslated region (3'UTR) of UGT2B7 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme UDP-glucuronosyltransferase 2B7.
               ICD-11: 2C82 Prostate cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     Histone modification
                            Histone deacetylases (HDACs) Prostate cancer Repression
Uniprot ID
HDAC1_HUMAN
Interaction Name HDACs-UGT2B7 interaction [6]
Studied Cell Lines LNCaP cell line
Description Histone deacetylases (HDACs) are reported to deacetylate the UGT2B7 gene and thereby repress the transcriptional activity of the drug-metabolizing enzyme UDP-glucuronosyltransferase 2B7. As a result, the interaction between HDACs and UGT2B7 can inhibit the drug-metabolizing process of UDP-glucuronosyltransferase 2B7.
References
1 Modulation of UDP-glucuronosyltransferase function by cytochrome P450: evidence for the alteration of UGT2B7-catalyzed glucuronidation of morphine by CYP3A4. Mol Pharmacol. 2005 Mar;67(3):665-72.
2 Altered CYP2C9 activity following modulation of CYP3A4 levels in human hepatocytes: an example of protein-protein interactions. Drug Metab Dispos. 2014 Nov;42(11):1940-6.
3 Genetic polymorphisms in the 5'-flanking region of human UDP-glucuronosyltransferase 2B7 affect the Nrf2-dependent transcriptional regulation. Pharmacogenet Genomics. 2008 Aug;18(8):709-20.
4 Octamer transcription factor-1 enhances hepatic nuclear factor-1alpha-mediated activation of the human UDP glucuronosyltransferase 2B7 promoter. Mol Pharmacol. 2000 May;57(5):940-7.
5 Regulation of UGT2B Expression and Activity by miR-216b-5p in Liver Cancer Cell Lines. J Pharmacol Exp Ther. 2016 Oct;359(1):182-93.
6 Valproic acid induces neuroendocrine differentiation and UGT2B7 up-regulation in human prostate carcinoma cell line. Drug Metab Dispos. 2007 Jun;35(6):968-72.

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