Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0024)
DME Name Steroid 17-alpha-monooxygenase (CYP17A1), Homo sapiens DME Info
UniProt ID
CP17A_HUMAN
EC Number    EC: 1.14.99.9     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
Oxygen paired donor oxidoreductase
Oxygen paired donor oxidoreductase
EC: 1.14.99.9
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:        5 HOSPPI
                     Oligomerization
                            Cytochrome b5 (CYB5A) Health Heterooligomer
Uniprot ID
CYB5_HUMAN
Interaction Name CYB5A, POR and CYP17A1 heterooligomerization [1]
Studied Cell Lines Yeast cell line
Affected Substrate(s): Pregnenolone
Progesterone (Metabolic product: 17-Hydroxy pregnenolone)
Description Cytochrome b5 (CYB5A) and NADPH-CYP450 reductase (POR) are reported to heterooligomerize with the CYP17A1 protein, which leads to an increased activity of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction among CYB5A, POR and CYP17A1 can facilitate the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
                            NADPH-CYP450 reductase (POR) Health Heterooligomer
Uniprot ID
NCPR_HUMAN
Interaction Name POR, CYB5A and CYP17A1 heterooligomerization [1]
Studied Cell Lines Yeast cell line
Affected Substrate(s): Pregnenolone
Progesterone (Metabolic product: 17-Hydroxy pregnenolone)
Description NADPH-CYP450 reductase (POR) and Cytochrome b5 (CYB5A) are reported to heterooligomerize with the CYP17A1 protein, which leads to an increased activity of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction among POR, CYB5A and CYP17A1 can facilitate the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
                            Progesterone receptor 1 (PGRMC1) Health Heterooligomer
Uniprot ID
PGRC1_HUMAN
Interaction Name PGRMC1-CYP17A1 heterooligomerization [4]
Studied Cell Lines Monkey kidney fibroblast-like cell (COS)7
Affected Substrate(s): Progesterone (Metabolic product: Progesterone 17-hydroxylase)
17-Hydroxyprogesterone (Metabolic product: 17-Hydroxyprogesterone 1720 lyase)
Description Progesterone receptor 1 (PGRMC1) is reported to heterooligomerize with the CYP17A1 protein, which leads to a slight effect on the enzyme activity of Steroid 17-alpha-monooxygenase. As a result, the interaction between PGRMC1 and CYP17A1 can slightly affect on the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
                     Histone modification
                            Histone deacetylases (HDACs) Health Repression
Uniprot ID
HDAC1_HUMAN
Interaction Name HDACs-CYP17A1 interaction [2]
Studied Cell Lines Mouse adrenocortical Y1 cells
Description Histone deacetylases (HDACs) are reported to deacetylate the CYP17A1 gene and thereby repress the transcriptional activity of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction between HDACs and CYP17A1 can inhibit the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
                            Histone methyltransferases (HMTs) Health Repression
Uniprot ID
EHMT1_HUMAN
Interaction Name HMTs-CYP17A1 interaction [3]
Studied Cell Lines Rat testis
Description The Histone 3 lysine 9 trimethylation of CYP17A1 gene is reported to repress the transcriptional activity of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction between Histone methyltransferases (HMTs) and CYP17A1 can inhibit the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
      ICD Disease Classification 02 Neoplasms
               ICD-11: 2C12 Liver cancer Click to Show/Hide the Full List of HOSPPI:        1 HOSPPI
                     DNA methylation
                            DNA methyltransferase (DNMT) Liver cancer Significant hypermethylation
Uniprot ID
DNMT1_HUMAN
Interaction Name DNMT-CYP17A1 interaction [5]
Studied Cell Lines Live tissue
Description DNA methyltransferase (DNMT) is reported to significantly hyper-methylate the CYP17A1 gene, which leads to a significantly decreased expression of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction between DNMT and CYP17A1 can significantly affect the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
               ICD-11: 2D11 Adrenocortical carcinoma Click to Show/Hide the Full List of HOSPPI:        2 HOSPPI
                     Transcription-factor regulation
                            MAD homolog 3 (SMAD3) Adrenocortical carcinoma Repression
Uniprot ID
SMAD3_HUMAN
Interaction Name SMAD3-CYP17A1 interaction [6]
Studied Cell Lines H295R cell line
Ensembl ID
ENSG00000166949
Description MAD homolog 3 (SMAD3) is reported to repress the transcription of CYP17A1 gene, which leads to a decreased expression of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction between SMAD3 and CYP17A1 can repress the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
                            Steroidogenic factor 1 (NR5A1) Adrenocortical carcinoma Activation
Uniprot ID
STF1_HUMAN
Interaction Name NR5A1-CYP17A1 interaction [6]
Studied Cell Lines H295R cell line
Ensembl ID
ENSG00000136931
Description Steroidogenic factor 1 (NR5A1) is reported to activate the transcription of CYP17A1 gene, which leads to an increased expression of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction between NR5A1 and CYP17A1 can activate the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
               ICD-11: 2F37 Endocrine gland cancer Click to Show/Hide the Full List of HOSPPI:        2 HOSPPI
                     Transcription-factor regulation
                            COUP TF factor 1 (NR2F1) Pituitary adenoma Repression
Uniprot ID
COT1_HUMAN
Interaction Name NR2F1-CYP17A1 interaction [7]
Studied Cell Lines Human adrenal gland and adrenocortical tumor cells
Ensembl ID
ENSG00000175745
Description COUP TF factor 1 (NR2F1) is reported to repress the transcription of CYP17A1 gene, which leads to a decreased expression of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction between NR2F1 and CYP17A1 can repress the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
                            Nuclear receptor family 0 B1 (NR0B1) Pituitary adenoma Repression
Uniprot ID
NR0B1_HUMAN
Interaction Name NR0B1-CYP17A1 interaction [7]
Studied Cell Lines Human adrenal gland and adrenocortical tumor cells
Ensembl ID
ENSG00000169297
Description Nuclear receptor family 0 B1 (NR0B1) is reported to repress the transcription of CYP17A1 gene, which leads to a decreased expression of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction between NR0B1 and CYP17A1 can repress the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
      ICD Disease Classification 05 Endocrine/nutritional/metabolic diseases
               ICD-11: 5A80 Polycystic ovary syndrome Click to Show/Hide the Full List of HOSPPI:        2 HOSPPI
                     Transcription-factor regulation
                            Nuclear factor 1 C-type (NFIC) Polycystic ovary syndrome Activation
Uniprot ID
NFIC_HUMAN
Interaction Name NFIC-CYP17A1 interaction [8]
Studied Cell Lines PCOS theca cell line
Ensembl ID
ENSG00000141905
Description Nuclear factor 1 C-type (NFIC) is reported to activate the transcription of CYP17A1 gene, which leads to an increased expression of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction between NFIC and CYP17A1 can activate the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
                            TF factor GATA-6 (GATA6) Polycystic ovary syndrome Activation
Uniprot ID
GATA6_HUMAN
Interaction Name GATA6-CYP17A1 interaction [9]
Studied Cell Lines PCOS theca cell line
Ensembl ID
ENSG00000141448
Description TF factor GATA-6 (GATA6) is reported to activate the transcription of CYP17A1 gene, which leads to an increased expression of the drug-metabolizing enzyme Steroid 17-alpha-monooxygenase. As a result, the interaction between GATA6 and CYP17A1 can activate the drug-metabolizing process of Steroid 17-alpha-monooxygenase.
References
1 Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer. J Biol Chem. 1998 Feb 6;273(6):3158-65.
2 Role of DNA methylation in the tissue-specific expression of the CYP17A1 gene for steroidogenesis in rodents. J Endocrinol. 2009 Jul;202(1):99-109.
3 Enhanced histone H3K9 tri-methylation suppresses steroidogenesis in rat testis chronically exposed to arsenic. Ecotoxicol Environ Saf. 2019 Apr 15;170:513-520.
4 Molecular identification of adrenal inner zone antigen as a heme-binding protein. FEBS J. 2005 Nov;272(22):5832-43.
5 Epigenetics of gene expression in human hepatoma cells: expression profiling the response to inhibition of DNA methylation and histone deacetylation. BMC Genomics. 2006 Jul 19;7:181.
6 SMAD3 inhibits SF-1-dependent activation of the CYP17 promoter in H295R cells. Mol Cell Biochem. 2008 Jan;307(1-2):65-71.
7 Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors: possible implications in steroidogenesis. Mol Genet Metab. 2001 Sep-Oct;74(1-2):206-16.
8 Increased cytochrome P450 17alpha-hydroxylase promoter function in theca cells isolated from patients with polycystic ovary syndrome involves nuclear factor-1. Mol Endocrinol. 2004 Mar;18(3):588-605.
9 The molecular signature of polycystic ovary syndrome (PCOS) theca cells defined by gene expression profiling. J Reprod Immunol. 2004 Aug;63(1):51-60.

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