Biomarker: CYP1B1

Histology type: endometrial carcinoma

Country: Greece

Region: Athens

Followed up time :

Subgroup 1 name : overexpressed CYP1B1 mRNA

Subgroup 1 number: 6

Subgroup 2 name: downregulated CYP1B1 mRNA

Subgroup 2 number: 8

Conclusion: Overexpression of active CYP1 enzymes in 21 % of the tumors highlights the potential use of the latter enzymes as chemotherapeutic targets in endometrial cancer.

Sample type : tissue

Sample method: qRT-PCR/Western blotting,enzyme activity assays,HPLC and mass spectrometry analysis

Expression pattern : overexpression

Statictics: Mean ;Range

Cohort age: 63.7;46–72

Funtion Uniprot: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:20972997, PubMed:11555828, PubMed:12865317, PubMed:10681376, PubMed:15258110). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:20972997, PubMed:11555828, PubMed:12865317, PubMed:10681376, PubMed:15258110). Exhibits catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2- and 4-hydroxy E1 and E2. Displays a predominant hydroxylase activity toward E2 at the C-4 position (PubMed:11555828, PubMed:12865317). Metabolizes testosterone and progesterone to B or D ring hydroxylated metabolites (PubMed:10426814). May act as a major enzyme for all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376, PubMed:15258110). Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and 14,15- EpETrE, that function as lipid mediators in the vascular system (PubMed:20972997). Additionally, displays dehydratase activity toward oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This activity is independent of cytochrome P450 reductase, NADPH, and O2 (PubMed:21068195). Also involved in the oxidative metabolism of xenobiotics, particularly converting polycyclic aromatic hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-damaging products (PubMed:10426814). Plays an important role in retinal vascular development. Under hyperoxic O2 conditions, promotes retinal angiogenesis and capillary morphogenesis, likely by metabolizing the oxygenated products generated during the oxidative stress. Also, contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression (By similarity).

UniProt ID: Q16678

UniProt Link: https://www.uniprot.org/uniprotkb/Q16678/entry

Biological function from UniProt: #Fatty acid metabolism #Lipid metabolism #Steroid metabolism

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed in heart, brain, lung, skeletal muscle, kidney, spleen, thymus, prostate, testis, ovary, small intestine, colon, and peripheral blood leukocytes (PubMed:8175734). Expressed in retinal endothelial cells and umbilical vein endothelial cells (at protein level) (PubMed:19005183).

Subcellular UniProt: #Endoplasmic reticulum #Membrane #Microsome #Mitochondrion

Alternative name from UniProt:

Catalytic activity: https://www.uniprot.org/uniprotkb/Q16678/entry

Activity regulation: Enzyme activity is increased by liposomes containing anionic phospholipids, phosphatidic acid and cardiolipin. Inhibited by naringenin with an IC50 of 5 uM (PubMed:22888116, PubMed:22935222). Enzyme activity is increased by cytochrome b5

Recommended name: Cytochrome P450 1B1

Gene name from HGNC: CYP1B1 (CP1B, GLC3A)

HPA class: Disease related genes Enzymes Human disease related genes Metabolic proteins Potential drug targets

AlphaFold DB: Q16678

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q16678

Induction: By polycyclic aromatic hydrocarbons (PAH) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

HPA link: https://www.proteinatlas.org/ENSG00000138061-CYP1B1

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Mainly cytoplasmic expression in most tissues.

Single cell type specificity Cell type enhanced (Prostatic glandular cells, Urothelial cells, Peritubular cells)

Immune cell specificity: Immune cell enriched (classical monocyte)

Subcellular summary HPA Located in Mitochondria

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable) and urothelial cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000138061-CYP1B1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000138061-CYP1B1/pathology/endometrial+cancer

Phenotype ID: 617315;231300;137750

Disease: Anterior segment dysgenesis 6 (ASGD6);Glaucoma 3, primary congenital, A (GLC3A);Glaucoma 1, open angle, A (GLC1A)

Note1: The disease is caused by variants affecting the gene represented in this entry;The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry;The gene represented in this entry acts as a disease modifier. Digenic mutations in CYP1B1 and MYOC have been found in a family segregating both primary adult-onset and juvenile forms of open angle glaucoma (PubMed:11774072). All affected family members with mutations in both MYOC and CYP1B1 had juvenile glaucoma, whereas those with only the MYOC mutation had the adult-onset form (PubMed:11774072)

OMIM: 601771

OMIM link1: https://www.omim.org/entry/617315;https://www.omim.org/entry/231300;https://www.omim.org/entry/137750;

OMIM link2: https://www.omim.org/entry/601771

HGNC ID: HGNC:2597

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2597