Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0037)
DME Name Steroid 21-hydroxylase (CYP21A2), Homo sapiens DME Info
UniProt ID
CP21A_HUMAN
EC Number    EC: 1.14.14.16     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
Oxygen paired donor oxidoreductase
Flavin/flavoprotein donor oxidoreductase
EC: 1.14.14.16
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 b5 (CYB5A) Health Heterodimer
Uniprot ID
CYB5_HUMAN
Interaction Name CYB5A-CYP21A2 heterodimerization [1]
Studied Cell Lines Escherichia coli cell line
Description Cytochrome b5 (CYB5A) is reported to heterodimerize with the CYP21A2 protein, which leads to an altered activity of the drug-metabolizing enzyme Steroid 21-hydroxylase. As a result, the interaction between CYB5A and CYP21A2 can modulate the drug-metabolizing process of Steroid 21-hydroxylase.
                            Cytochrome P450-C17 (CYP17A1) Health Heterooligomer
Uniprot ID
CP17A_HUMAN
Interaction Name CYP17A1-CYP21A2 heterooligomerization [2]
Studied Cell Lines Escherichia coli JM109 competent cell line
Affected Substrate(s): 17-Hydroxyprogesterone (Metabolic product: 11-Deoxycortisol)
Description Cytochrome P450-C17 (CYP17A1) is reported to heterooligomerize with the CYP21A2 protein, which leads to a decreased activity of the drug-metabolizing enzyme Steroid 21-hydroxylase. As a result, the interaction between CYP17A1 and CYP21A2 can decrease the drug-metabolizing process of Steroid 21-hydroxylase.
                            Progesterone receptor 1 (PGRMC1) Health Heterooligomer
Uniprot ID
PGRC1_HUMAN
Interaction Name PGRMC1-CYP21A2 heterooligomerization [3]
Studied Cell Lines Monkey kidney fibroblast-like cell (COS)7
Affected Substrate(s): Progesterone (Metabolic product: Progesterone 21-hydroxylase)
Description Progesterone receptor 1 (PGRMC1) is reported to heterooligomerize with the CYP21A2 protein, which leads to activation of the drug-metabolizing enzyme Steroid 21-hydroxylase. As a result, the interaction between PGRMC1 and CYP21A2 can activate the drug-metabolizing process of Steroid 21-hydroxylase.
      ICD Disease Classification 02 Neoplasms
               ICD-11: 2A00 Brain cancer Click to Show/Hide the Full List of HOSPPI:        2 HOSPPI
                     DNA methylation
                            DNA methyltransferase (DNMT) Brain neuroblastoma Significant hypomethylation
Interaction Name DNMT-CYP21A2 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue Significant hypomethylation
p-value: 1.60E-17; delta-beta: -5.84E-01
Description DNA methyltransferase (DNMT) is reported to significantly hypo-methylate the CYP21A2 gene, which leads to a significantly increased expression of the drug-metabolizing enzyme Steroid 21-hydroxylase. As a result, the interaction between DNMT and CYP21A2 can significantly affect the drug-metabolizing process of Steroid 21-hydroxylase.
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
                            DNA methyltransferase (DNMT) Multilayered rosettes embryonal tumour Significant hypomethylation
Interaction Name DNMT-CYP21A2 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue Significant hypomethylation
p-value: 1.31E-10; delta-beta: -4.00E-01
Description DNA methyltransferase (DNMT) is reported to significantly hypo-methylate the CYP21A2 gene, which leads to a significantly increased expression of the drug-metabolizing enzyme Steroid 21-hydroxylase. As a result, the interaction between DNMT and CYP21A2 can significantly affect the drug-metabolizing process of Steroid 21-hydroxylase.
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: 2B30 Lymphoma Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     DNA methylation
                            DNA methyltransferase (DNMT) Lymphoma Moderate hypomethylation
Interaction Name DNMT-CYP21A2 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue Moderate hypomethylation
p-value: 3.74E-08; delta-beta: -2.13E-01
Description DNA methyltransferase (DNMT) is reported to moderatly hypo-methylate the CYP21A2 gene, which leads to a moderatly increased expression of the drug-metabolizing enzyme Steroid 21-hydroxylase. As a result, the interaction between DNMT and CYP21A2 can moderatly affect the drug-metabolizing process of Steroid 21-hydroxylase.
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:        1 HOSPPI
                     Oligomerization
                            Progesterone receptor 1 (PGRMC1) Liver cancer Heterooligomer
Uniprot ID
PGRC1_HUMAN
Interaction Name PGRMC1-CYP21A2 heterooligomerization [4]
Studied Cell Lines Human embryonic kidney cells (HEK293) and Human liver cancer cell lines (HepG2)
Description Progesterone receptor 1 (PGRMC1) is reported to heterooligomerize with the CYP21A2 protein, which leads to a slight effect on the enzyme activity of Steroid 21-hydroxylase. As a result, the interaction between PGRMC1 and CYP21A2 can slightly affect the drug-metabolizing process of Steroid 21-hydroxylase.
References
1 SPR-Based study of affinity of cytochrome P450s / redox partners interactions modulated by steroidal substrates. J Steroid Biochem Mol Biol. 2019 Mar;187:124-129.
2 Mechanism of intermolecular interactions of microsomal cytochrome P450s CYP17 and CYP21 involved in steroid hormone biosynthesis. Biochemistry (Mosc). 2012 Jun;77(6):585-92.
3 Characterization of the adrenal-specific antigen IZA (inner zone antigen) and its role in the steroidogenesis. Mol Cell Endocrinol. 2004 Feb 27;215(1-2):143-8.
4 Progesterone receptor membrane component 1 inhibits the activity of drug-metabolizing cytochromes P450 and binds to cytochrome P450 reductase. Mol Pharmacol. 2011 Mar;79(3):340-50.

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