CYP2D6
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Official Full Name
Cytochrome P450, Family 2, Subfamily D, Polypeptide 6 -
Overview
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize as many as 20% of commonly prescribed drugs. Its substrates include debrisoquine, an adrenergic-blocking drug; both anti-arrythmic drugs; and amitryptiline, an anti-depressant. The gene is highly polymorphic in the population; certain alleles result in the poor metabolizer phenotype, characterized by a decreased ability to metabolize the enzyme's substrates. The gene is located near two cytochrome P450 pseudogenes on chromosome 22q13.1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. -
Synonyms
CPD6;CYP2D;CYP2DL1;CYPIID6;P450C2D;P450DB1;CYP2D7AP;CYP2D7BP;CYP2D7P2;CYP2D8P2;P450-DB1;MGC120389;MGC120390;CYP2D6;cytochrome P450, family 2, subfamily D, polypeptide 6;cytochrome P450 2D6;OTTHUMP00000198705;OTTHUMP00000198706;cytochrome P450-DB1;microsomal monooxygenase;xenobiotic monooxygenase;debrisoquine 4-hydroxylase;flavoprotein-linked monooxygenase;cytochrome P450, family 2, subfamily D, polypeptide 7 pseudogene 2;cytochrome P450, family 2, subfamily D, polypeptide 8 pseudogene 2;cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolizing)-like 1;cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolizing), polypeptide 6;cytochrome P450, subfamily II (debrisoquine, sparteine, etc., -metabolising), polypeptide 7 pseudogene 2;cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolising), polypeptide 8 pseudogene 2;Debrisoquine 4 hydroxylase;EC 1.14.14.1;Flavoprotein linked monooxygenase;P450 DB1
Recombinant Proteins
- Human
- Rhesus macaque
- Chicken
- Pig
- E.coli
- Baculovirus
- Mammalian Cells
- Insect Cells
- P.pastoris
- HEK293
- Sf9 Cells
- GST
- Non
- His
- Flag
- Avi&Fc&His
Background
What is cyp2d6 protein?
The cytochrome P450 2D6 protein (CYP2D6) is an enzyme that is primarily involved in the metabolism of various drugs and xenobiotics in the body. It is part of the cytochrome P450 superfamily of enzymes, which are responsible for the oxidative metabolism of many compounds.
CYP2D6 is mainly expressed in the liver but is also present in other tissues such as the brain, gastrointestinal tract, and kidney. It plays a crucial role in drug metabolism by catalyzing the oxidation of a wide range of medications, including antidepressants, antipsychotics, antiarrhythmics, opioids, and beta-blockers.
The activity of CYP2D6 can vary among individuals due to genetic polymorphisms, leading to different metabolic phenotypes. These phenotypes are generally classified as poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM), and ultrarapid metabolizers (UM), based on their ability to metabolize CYP2D6 substrates.
What is the function of cyp2d6 protein?
The function of CYP2D6 is to oxidize or modify various drugs, converting them into metabolites that can be eliminated from the body. This process is essential for drug clearance and affects the efficacy and safety of many medications. CYP2D6 can also convert certain prodrugs into their active form, making them therapeutically effective.
However, it is important to note that the activity of CYP2D6 can vary significantly among individuals due to genetic variations. Some people have decreased or absent CYP2D6 activity, known as poor metabolizers, while others have increased activity, known as ultrarapid metabolizers. These differences in CYP2D6 activity can impact the effectiveness and side effects of drugs metabolized by this enzyme.
Cyp2d6 related signaling pathway
The signaling pathways related to Cyp2d6 are not well-defined. Its activity can be influenced by various factors, including genetic polymorphisms, drug interactions, and regulatory enzymes.
Cyp2d6 is involved in the metabolism of a wide range of drugs, including antidepressants, antipsychotics, beta-blockers, opioids, and antiarrhythmic agents. The phenotype of Cyp2d6 metabolizer status (such as poor metabolizer, intermediate metabolizer, extensive metabolizer, or ultra-rapid metabolizer) can affect drug response and the likelihood of experiencing adverse drug reactions.
Cyp2d6 Related Diseases
Poor Metabolizers: Individuals with reduced or no enzyme activity due to gene mutations are categorized as poor metabolizers. This can lead to increased drug concentrations and a higher risk of adverse drug reactions.
Ultrarapid Metabolizers: These individuals have multiple gene copies or gene duplications of CYP2D6, resulting in abnormally high enzyme activity. This can lead to rapid drug metabolism, potentially resulting in subtherapeutic drug levels and reduced drug efficacy.
Drug-Drug Interactions: The activity of CYP2D6 can be affected by the concomitant use of other drugs that inhibit or induce its function. These interactions can alter the metabolism and effectiveness of drugs metabolized by CYP2D6.
Psychiatric Disorders: CYP2D6 variations have been associated with the response to medications used for the treatment of psychiatric disorders such as depression and schizophrenia. Genetic testing for CYP2D6 variations may help personalize drug selection and dosing in these patients.
Biomedical Application of cyp2d6 Protein
The biomedical application of Cyp2d6 protein lies in the field of personalized medicine. Genetic testing for Cyp2d6 polymorphisms can help determine an individual's Cyp2d6 activity status, which can guide drug selection and dosage adjustments. For example, individuals with reduced Cyp2d6 activity may require lower doses of certain drugs to achieve the desired therapeutic effect, while individuals with ultra-rapid metabolizer status may require higher doses to reach therapeutic levels.
Case Study
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(Danxin Wang, 2015)
Fig2. 4C signals at chromosome 22. The X-axis represents relative distance from CYP2D6 promoter.
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(Edith Hintermann, 2013)
Fig3. Cell proliferation is induced variably by Ad-2D6 infection and CCl4 treatment. Sections from Ad-2D6-infected or CCl4-exposed livers were stained with an antibody to Ki67 as a marker for cell proliferation.
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(Niels Bjerre Holmn, 2015)
Fig4. EICs of AKB-48 hydroxy metabolites in HLM and recombinant CYP incubations. AKB-48 was incubated with a HLM, b rCYP3A4, c rCYP2C19, and d rCYP2D6. Aliquots of the incubations were quenched and analyzed by LC-HR-MS.
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(Huybrecht T'jollyn, 2015)
Fig5. Maturation of CYP2D6 tramadol clearance as a function of PMA (left) and body weight (right). PBPK predictions, represented as blue dots, are compared to in vivo maturation functions: Hill model (black), exponential model (red), and WinNonlin fits (light brown).
Quality Guarantee
High Purity
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Fig1. SDS-PAGE (CYP2D6-1918HFL)
Involved Pathway
CYP2D6 involved in several pathways and played different roles in them. We selected most pathways CYP2D6 participated on our site, such as Biological oxidations,CYP2E1 reactions,Cytochrome P450 - arranged by substrate type, which may be useful for your reference. Also, other proteins which involved in the same pathway with CYP2D6 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.
Pathway Name | Pathway Related Protein |
---|---|
Fatty acids | CYP2AD6,CYP2AD2,CYP2N13,CYP4T8,CYP2J2,CYP2V1,CYP4F12,CYP4A11,CYP4F22,CYP2F1 |
Metabolism | CHP,SLC6A12,DCK,APOC2,OXSR1,SULT4A1,CPT2,STARD5,PPM1K,CKMB |
Drug metabolism - cytochrome P450 | CYP2C8,CYP2E1,CYP2B6,CYP2A6,ADH1B,ADH7,GSTO2,CYP2C19,ADH2-1,ADH2-2 |
Biological oxidations | CYP2W1,CYP26A1,SLC35B3,CES1,CYP2AD2,CYP4A11,AHCY,CYP2C19,CYP1B1,CYP8B2 |
Cytochrome P450 - arranged by substrate type | CYP2C19,CYP2S1,CYP51A1,CYP3A7,CYP2K17,CYP2K19,CYP26A1,CYP2U1,CYP2AD6,CYP4F22 |
CYP2E1 reactions | CYP2S1,CYP2C9,CYP2F1,CYP2A13,CYP2C8,CYP2A6,CYP2Y3,CYP2B6,CYP2C19,CYP2A7 |
Fatty Acid Omega Oxidation | CYP4A11,ADH1A,ADH1B,CYP1A1,CYP2A6,ADH7,ADH1C,CYP2E1,ADH6,ADH4 |
Protein Function
CYP2D6 has several biochemical functions, for example, arachidonic acid epoxygenase activity,aromatase activity,drug binding. Some of the functions are cooperated with other proteins, some of the functions could acted by CYP2D6 itself. We selected most functions CYP2D6 had, and list some proteins which have the same functions with CYP2D6. You can find most of the proteins on our site.
Function | Related Protein |
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iron ion binding | CYP4X1,CYP2K16,CYP2X9,MSMO1,CYP2C55,CYP3A43,ALOX5,PPEF2,CYP2J5,CYP27C1 |
aromatase activity | CYP2F1,CYP2A13,CYP4Z1,CYP2C55,CYP1A2,CYP2C37,CYP4X1,CYP3A43,CYP2C18,CYP19A1 |
monooxygenase activity | FMO1,CYP2AA7,CYP2J6,CYP3C1L2,CYP2K6,CYP2F2,TPH1B,CYP3A4,CYP1A1,CYP2P7 |
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen | CYP2Y3,CYP2C50,CYP2C9,CYP2C70,CYP2D26,CYP2C19,CYP2D9,CYP2P7,CYP2F1,CYP2P8 |
steroid hydroxylase activity | FAM84B,CYP46A1.2,CYP2K19,CYP2A13,CYP2Y3,CYP2AA9,CYP2A7,CYP2K22,CYP2K17,CYP2B6 |
oxidoreductase activity | CYP1D1,CYP2P10,DHRS7,RYROXD1,FAXDC2,CYP2X10.2,AKR1CL1,RDH13,AOX4,OSGIN2 |
arachidonic acid epoxygenase activity | CYP2C39,CYP2AA8,CYP4F12,CYP2AA9,CYP2B6,CYP2P9,CYP2C38,CYP2AA2,CYP2B19,CYP2C8 |
oxygen binding | HBBE1.1,CYP2A4,CYP2U1,CYP2X7,MB,CYP2P6,CYP2Y3,CYP2AD3,HBE,HBBE2 |
heme binding | CYP2K16,CYCS,CYP2K22,CYP26A1,CBSA,MPX,HBE1,NOS3,CYP2F1,HBG2 |
Interacting Protein
CYP2D6 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CYP2D6 here. Most of them are supplied by our site. Hope this information will be useful for your research of CYP2D6.
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References
- Hintermann, E; Ehser, J; et al. Mechanism of autoimmune hepatic fibrogenesis induced by an adenovirus encoding the human liver autoantigen cytochrome P450 2D6. JOURNAL OF AUTOIMMUNITY 44:49-60(2013).
- Wang, DX; Papp, AC; et al. Functional characterization of CYP2D6 enhancer polymorphisms. HUMAN MOLECULAR GENETICS 24:1556-1562(2015).