General Information of Protein (ID: PRT01048)
Name Debrisoquine 4-hydroxylase (CYP2D6)
Synonyms   Click to Show/Hide Synonyms of This Protein
CYPIID6; Cholesterol 25-hydroxylase; Cytochrome P450-DB1; Debrisoquine 4-hydroxylase; CYP2D6; CYP2DL1
Gene Name CYP2D6 Gene ID
1565
UniProt ID
P10635
Family Oxidoreductases (EC 1)
EC Number   EC: 1.14.14.-  (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
Oxygen paired donor oxidoreductase
Flavin/flavoprotein donor oxidoreductase
EC: 1.14.14.-
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
Structure
2F9Q ; 3QM4 ; 3TBG ; 3TDA ; 4WNT ; 4WNU ; 4WNV ; 4WNW ; 4XRY ; 4XRZ ; 5TFT ; 5TFU ; 6CSB ; 6CSD
Function A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids. 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). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling. Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid. Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Regulatory Network
Full List of Metabolite(s) Regulating This Protein
      Organic acids and derivatives
            Glutamine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Glutamine absence (16 hours)
                      Induced Change CYP2D6 protein abundance levels: increase (FC = 8.32)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hepatocellular carcinoma [ICD-11: 2C12]
                      Details It is reported that glutamine absence causes the increase of CYP2D6 protein abundance compared with control group.
References
1 Quantitative proteomics analysis reveals glutamine deprivation activates fatty acid -oxidation pathway in HepG2 cells. Amino Acids. 2016 May;48(5):1297-307.

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