Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0009)
DME Name	Cytochrome P450 2D6 (CYP2D6), Homo sapiens	DME Info
UniProt ID	CP2D6_HUMAN
EC Number	EC: 1.14.14.1 (Click to Show/Hide the Complete EC Tree) Oxidoreductase Oxygen paired donor oxidoreductase Flavin/flavoprotein donor oxidoreductase EC: 1.14.14.1
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: 4 HOSPPI
Oligomerization
Cytochrome b5 (CYB5A)		Health		Heterodimer
Uniprot ID	CYB5_HUMAN
Interaction Name	CYB5A-CYP2D6 heterodimerization				[1]
Studied Cell Lines	Transformed E. coli C41 (DE3) cell line
Affected Substrate(s):	Dextromethorphan
Description	Cytochrome b5 (CYB5A) is reported to heterodimerize with the CYP2D6 protein, which leads to an increased activity of the drug-metabolizing enzyme Cytochrome P450 2D6. As a result, the interaction between CYB5A and CYP2D6 can facilitate the drug-metabolizing process of Cytochrome P450 2D6.
Cytochrome P450 2C9 (CYP2C9)		Health		Heterooligomer
Uniprot ID	CP2C9_HUMAN
Interaction Name	CYP2C9-CYP2D6 heterooligomerization				[2]
Studied Cell Lines	DLPC vesicles
Affected Substrate(s):	Dextromethorphan (Metabolic product: Dextromethorphan O-demethylation)
Description	Cytochrome P450 2C9 (CYP2C9) is reported to heterooligomerize with the CYP2D6 protein, which has no effect on the enzyme activity of Cytochrome P450 2D6. As a result, the interaction between CYP2C9 and CYP2D6 can have no effect on the drug-metabolizing process of Cytochrome P450 2D6.
Cytochrome P450 2E1 (CYP2E1)		Health		Heterooligomer
Uniprot ID	CP2E1_HUMAN
Interaction Name	CYP2E1-CYP2D6 heterooligomerization				[3]
Studied Cell Lines	Insect cell microsomes
Affected Substrate(s):	AMMC (Metabolic product: AMMC O-demethylation)
Description	Cytochrome P450 2E1 (CYP2E1) is reported to heterooligomerize with the CYP2D6 protein, which leads to an altered activity of the drug-metabolizing enzyme Cytochrome P450 2D6. As a result, the interaction between CYP2E1 and CYP2D6 can alter the drug-metabolizing process of Cytochrome P450 2D6.
Cytochrome P450 3A4 (CYP3A4)		Health		Heterooligomer
Uniprot ID	CP3A4_HUMAN
Interaction Name	CYP3A4-CYP2D6 heterooligomerization				[4]
Studied Cell Lines	Living cells
Description	Cytochrome P450 3A4 (CYP3A4) is reported to heterooligomerize with the CYP2D6 protein, which leads to a suppressed activity of the drug-metabolizing enzyme Cytochrome P450 2D6. As a result, the interaction between CYP3A4 and CYP2D6 can inhibit the drug-metabolizing process of Cytochrome P450 2D6.
ICD Disease Classification 02 Neoplasms
ICD-11: 2A00 Brain cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Cerebellar liponeurocytoma		Significant hypomethylation
Interaction Name	DNMT-CYP2D6 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Significant hypomethylation p-value: 8.89E-03; delta-beta: -3.27E-01
Description	DNA methyltransferase (DNMT) is reported to significantly hypo-methylate the CYP2D6 gene, which leads to a significantly increased expression of the drug-metabolizing enzyme Cytochrome P450 2D6. As a result, the interaction between DNMT and CYP2D6 can significantly affect the drug-metabolizing process of Cytochrome P450 2D6.
DME methylation in the diseased tissue of patients DME methylation in the normal tissue of healthy individuals
Violin Diagram of DME Disease-specific Methylation Level			Click to View the Clearer Original Diagram
Download DME methylation barchart for all samples Download DME methylation data of patients in the disease section of the tissue Download DME methylation data in the tissue of healthy individual
ICD-11: 2C12 Liver cancer		Click to Show/Hide the Full List of HOSPPI: 2 HOSPPI
Transcription-factor regulation
Hepatocyte NF 4-alpha (HNF4A)		Liver cancer		Activation
Uniprot ID	HNF4A_HUMAN
Interaction Name	HNF4A-CYP2D6 interaction				[5]
Studied Cell Lines	HepG2 cell line
Ensembl ID	ENSG00000101076
Description	Hepatocyte NF 4-alpha (HNF4A) is reported to activate the transcription of CYP2D6 gene, which leads to an increased expression of the drug-metabolizing enzyme Cytochrome P450 2D6. As a result, the interaction between HNF4A and CYP2D6 can activate the drug-metabolizing process of Cytochrome P450 2D6.
Hepatocyte NF 4-gamma (HNF4G)		Liver cancer		Activation
Uniprot ID	HNF4G_HUMAN
Interaction Name	HNF4G-CYP2D6 interaction				[5]
Studied Cell Lines	HepG2 cell line
Ensembl ID	ENSG00000164749
Description	Hepatocyte NF 4-gamma (HNF4G) is reported to activate the transcription of CYP2D6 gene, which leads to an increased expression of the drug-metabolizing enzyme Cytochrome P450 2D6. As a result, the interaction between HNF4G and CYP2D6 can activate the drug-metabolizing process of Cytochrome P450 2D6.
ICD-11: 2D50 Brain cancer metastasis		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Posterior fossa ependymoma		Moderate hypomethylation
Interaction Name	DNMT-CYP2D6 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Moderate hypomethylation p-value: 1.34E-149; delta-beta: -2.14E-01
Description	DNA methyltransferase (DNMT) is reported to moderatly hypo-methylate the CYP2D6 gene, which leads to a moderatly increased expression of the drug-metabolizing enzyme Cytochrome P450 2D6. As a result, the interaction between DNMT and CYP2D6 can moderatly affect the drug-metabolizing process of Cytochrome P450 2D6.
DME methylation in the diseased tissue of patients DME methylation in the normal tissue of healthy individuals
Violin Diagram of DME Disease-specific Methylation Level			Click to View the Clearer Original Diagram
Download DME methylation barchart for all samples Download DME methylation data of patients in the disease section of the tissue Download DME methylation data in the tissue of healthy individual

References
1	Structural and functional effects of cytochrome b5 interactions with human cytochrome P450 enzymes. J Biol Chem. 2017 Dec 22;292(51):20818-20833.
2	CYP2D6-CYP2C9 protein-protein interactions and isoform-selective effects on substrate binding and catalysis. Drug Metab Dispos. 2009 Aug;37(8):1682-9.
3	Toward a systems approach to the human cytochrome P450 ensemble: interactions between CYP2D6 and CYP2E1 and their functional consequences. Biochem J. 2017 Oct 10;474(20):3523-3542.
4	Microsomal monooxygenase as a multienzyme system: the role of P450-P450 interactions. Expert Opin Drug Metab Toxicol. 2011 May;7(5):543-58.
5	Contribution of hepatocyte nuclear factor-4 to down-regulation of CYP2D6 gene expression by nitric oxide. Mol Pharmacol. 2002 Jan;61(1):194-200.

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