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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Cytochrome P450 2J2''' (CYP2J2) is a [[protein]] that in humans is encoded by the ''CYP2J2'' [[gene]].<ref name="pmid9570962">{{cite journal | vauthors = Ma J, Ramachandran S, Fiedorek FT, Zeldin DC | title = Mapping of the CYP2J cytochrome P450 genes to human chromosome 1 and mouse chromosome 4 | journal = Genomics | volume = 49 | issue = 1 | pages = 152–5 | date = Apr 1998 | pmid = 9570962 | pmc =  | doi = 10.1006/geno.1998.5235 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CYP2J2 cytochrome P450, family 2, subfamily J, polypeptide 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1573| accessdate = }}</ref>  CYP2J2 is a member of the cytochrome P450 superfamily of [[enzymes]]. The enzymes are [[oxygenase]]s which catalyze many reactions involved in the metabolism of drugs and other [[xenobiotics]]) as well as in the synthesis of cholesterol, steroids and other lipids.
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| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Protein structure ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Cytochrome P450, family 2, subfamily J, polypeptide 2
| HGNCid = 2634
| Symbol = CYP2J2
| AltSymbols =; CPJ2
| OMIM = 601258
| ECnumber = 
| Homologene = 68091
| MGIid = 1270148
| GeneAtlas_image1 = PBB_GE_CYP2J2_205073_at_tn.png
| Function = {{GNF_GO|id=GO:0005506 |text = iron ion binding}} {{GNF_GO|id=GO:0008392 |text = arachidonic acid epoxygenase activity}} {{GNF_GO|id=GO:0020037 |text = heme binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}} {{GNF_GO|id=GO:0050381 |text = unspecific monooxygenase activity}}
| Component = {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}} {{GNF_GO|id=GO:0005792 |text = microsome}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0006118 |text = electron transport}} {{GNF_GO|id=GO:0006690 |text = icosanoid metabolic process}} {{GNF_GO|id=GO:0008016 |text = regulation of heart contraction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1573
    | Hs_Ensembl = ENSG00000134716
    | Hs_RefseqProtein = NP_000766
    | Hs_RefseqmRNA = NM_000775
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 60131568
    | Hs_GenLoc_end = 60165050
    | Hs_Uniprot = P51589
    | Mm_EntrezGene = 13110
    | Mm_Ensembl = ENSMUSG00000052914
    | Mm_RefseqmRNA = NM_010008
    | Mm_RefseqProtein = NP_034138
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 4
    | Mm_GenLoc_start = 96009175
    | Mm_GenLoc_end = 96045679
    | Mm_Uniprot = Q8BR78
  }}
}}
{{SI}}
{{EH}}


'''Cytochrome P450, family 2, subfamily J, polypeptide 2''', also known as '''CYP2J2''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CYP2J2 cytochrome P450, family 2, subfamily J, polypeptide 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1573| accessdate = }}</ref>
The CYP2J2 contains the following domains:<ref name="pmid26232558">{{cite journal | vauthors = McDougle DR, Baylon JL, Meling DD, Kambalyal A, Grinkova YV, Hammernik J, Tajkhorshid E, Das A | title = Incorporation of charged residues in the CYP2J2 F-G loop disrupts CYP2J2-lipid bilayer interactions | journal = Biochimica et Biophysica Acta | volume = 1848 | issue = 10 Pt A | pages = 2460–2470 | year = 2015 | pmid = 26232558 | pmc = 4559526 | doi = 10.1016/j.bbamem.2015.07.015 }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
• [[Hydrophobic]] binding domains
{{PBB_Summary
| section_title =
| summary_text = 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 thought to be the predominant enzyme responsible for epoxidation of endogenous arachidonic acid in cardiac tissue.<ref name="entrez">{{cite web | title = Entrez Gene: CYP2J2 cytochrome P450, family 2, subfamily J, polypeptide 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1573| accessdate = }}</ref>
}}


==References==
• F-G loop (containing non-conservative mutations) primary membrane binding motif
{{reflist}}
 
==Further reading==
The protein also contains an [[N-terminal]] anchor.
{{refbegin | 2}}
 
{{PBB_Further_reading
=== F-G loop ===
| citations =
 
*{{cite journal  | author=Scarborough PE, Ma J, Qu W, Zeldin DC |title=P450 subfamily CYP2J and their role in the bioactivation of arachidonic acid in extrahepatic tissues. |journal=Drug Metab. Rev. |volume=31 |issue= 1 |pages= 205-34 |year= 1999 |pmid= 10065373 |doi= }}
The F-G loop mediates the binding and passage of substrates, and its hydrophobic region containing residues Trp-235, Phe-239 and Ille-236 allows the [[enzyme]] to interact with cellular membranes. Mutations to hydrophilic residues in the F-G loop alter the binding mechanism by changing insertion depth of the [[enzyme]] into the membrane.
*{{cite journal | author=Capdevila JH, Falck JR, Harris RC |title=Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase. |journal=J. Lipid Res. |volume=41 |issue= 2 |pages= 163-81 |year= 2000 |pmid= 10681399 |doi= }}
 
*{{cite journal | author=Wu S, Moomaw CR, Tomer KB, ''et al.'' |title=Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart. |journal=J. Biol. Chem. |volume=271 |issue= 7 |pages= 3460-8 |year= 1996 |pmid= 8631948 |doi= }}
== Tissue distribution ==
*{{cite journal | author=Zeldin DC, Foley J, Ma J, ''et al.'' |title=CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance. |journal=Mol. Pharmacol. |volume=50 |issue= 5 |pages= 1111-7 |year= 1996 |pmid= 8913342 |doi= }}
 
*{{cite journal  | author=Zeldin DC, Foley J, Boyle JE, ''et al.'' |title=Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas. |journal=Endocrinology |volume=138 |issue= 3 |pages= 1338-46 |year= 1997 |pmid= 9048644 |doi= }}
CYP2J2 is expressed predominately in the heart and, to a lesser extent, in other tissues such as the liver, gastrointestinal tract, pancreas, lung, and [[central nervous system]].<ref name="Karkhanis_2017" />
*{{cite journal  | author=Zeldin DC, Foley J, Goldsworthy SM, ''et al.'' |title=CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance. |journal=Mol. Pharmacol. |volume=51 |issue= 6 |pages= 931-43 |year= 1997 |pmid= 9187259 |doi= }}
 
*{{cite journal  | author=Ma J, Ramachandran S, Fiedorek FT, Zeldin DC |title=Mapping of the CYP2J cytochrome P450 genes to human chromosome 1 and mouse chromosome 4. |journal=Genomics |volume=49 |issue= 1 |pages= 152-5 |year= 1998 |pmid= 9570962 |doi= 10.1006/geno.1998.5235 }}
== Function ==
*{{cite journal  | author=Bylund J, Finnström N, Oliw EH |title=Gene expression of a novel cytochrome P450 of the CYP4F subfamily in human seminal vesicles. |journal=Biochem. Biophys. Res. Commun. |volume=261 |issue= 1 |pages= 169-74 |year= 1999 |pmid= 10405341 |doi= 10.1006/bbrc.1999.1011 }}
 
*{{cite journal  | author=Gu J, Su T, Chen Y, ''et al.'' |title=Expression of biotransformation enzymes in human fetal olfactory mucosa: potential roles in developmental toxicity. |journal=Toxicol. Appl. Pharmacol. |volume=165 |issue= 2 |pages= 158-62 |year= 2000 |pmid= 10828211 |doi= 10.1006/taap.2000.8923 }}
CYP2J2 localizes to the [[endoplasmic reticulum]] and is thought to be a prominent enzyme responsible for metabolizing endogenous [[polyunsaturated fatty acids]] to signaling molecules.<ref name="pmid23688135">{{cite journal | vauthors = Chen C, Wang DW | title = CYP epoxygenase derived EETs: from cardiovascular protection to human cancer therapy | journal = Current Topics in Medicinal Chemistry | volume = 13 | issue = 12 | pages = 1454–69 | year = 2013 | pmid = 23688135 | doi = 10.2174/1568026611313120007 }}</ref> It metabolizes [[arachidonic acid]] to the following eicosatrienoic acid [[epoxide]]s (termed EETs): 5,6-epoxy-8Z,11Z,14Z-EET, 8,9-epoxy-8Z,11Z,14Z-EET, 11,12-epoxy-5Z,8Z,14Z-EET, and 14,15-epoxy-5Z,8Z,11Z-EET.  CYP2J2 also metabolizes [[linoleic acid]] to 9,10-epoxy octadecaenoic acids (also termed [[vernolic acid]], linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecaenoic (also termed [[coronaric acid]], linoleic acid 12,13-oxide, or isoleukotoxin); [[docosahexaenoic acid]] to various [[epoxydocosapentaenoic acid]]s (also termed EDPs); and [[eicosapentaenoic acid]] to various epoxyeicosatetraenoic acids (also termed EEQs).<ref name="pmid21945326">{{cite journal | vauthors = Westphal C, Konkel A, Schunck WH | title = CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease? | journal = Prostaglandins & Other Lipid Mediators | volume = 96 | issue = 1-4 | pages = 99–108 | year = 2011 | pmid = 21945326 | doi = 10.1016/j.prostaglandins.2011.09.001 }}</ref>
*{{cite journal  | author=King LM, Ma J, Srettabunjong S, ''et al.'' |title=Cloning of CYP2J2 gene and identification of functional polymorphisms. |journal=Mol. Pharmacol. |volume=61 |issue= 4 |pages= 840-52 |year= 2002 |pmid= 11901223 |doi= }}
 
*{{cite journal  | author=Matsumoto S, Hirama T, Matsubara T, ''et al.'' |title=Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole. |journal=Drug Metab. Dispos. |volume=30 |issue= 11 |pages= 1240-5 |year= 2003 |pmid= 12386130 |doi= }}
CYP2J2, along with [[CYP219]], [[CYP2C8]], [[CYP2C9]], and possibly [[CYP2S1]] are the main producers of EETs and, very likely EEQs, EDPs, and the epoxides of linoleic acid.<ref name="pmid25240260">{{cite journal | vauthors = Wagner K, Vito S, Inceoglu B, Hammock BD | title = The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling | journal = Prostaglandins & Other Lipid Mediators | volume = 113-115 | issue = | pages = 2–12 | year = 2014 | pmid = 25240260 | pmc = 4254344 | doi = 10.1016/j.prostaglandins.2014.09.001 }}</ref><ref name="Spector_2015"/>
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
 
*{{cite journal  | author=Marden NY, Fiala-Beer E, Xiang SH, Murray M |title=Role of activator protein-1 in the down-regulation of the human CYP2J2 gene in hypoxia. |journal=Biochem. J. |volume=373 |issue= Pt 3 |pages= 669-80 |year= 2003 |pmid= 12737630 |doi= 10.1042/BJ20021903 }}
== Animal studies ==
*{{cite journal | author=Pucci L, Lucchesi D, Chirulli V, ''et al.'' |title=Cytochrome P450 2J2 polymorphism in healthy Caucasians and those with diabetes mellitus. |journal=American journal of pharmacogenomics : genomics-related research in drug development and clinical practice |volume=3 |issue= 5 |pages= 355-8 |year= 2004 |pmid= 14575523 |doi= }}
 
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
Animal model studies implicate the EETs, EDPs, and EEQs in regulating [[hypertension]], the development of [[myocardial infarction]] and other damage to the heart, the growth of various cancers, [[inflammation]], blood vessel formation, and pain perception; limited studies suggest but have not proven that these epoxides may function similarly in humans (see [[epoxyeicosatrienoic acid]], [[epoxydocosapentaenoic acid]], and [[epoxygenase]] pages).<ref name="Spector_2015">{{cite journal | vauthors = Spector AA, Kim HY | title = Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism | journal = Biochimica et Biophysica Acta | volume = 1851 | issue = 4 | pages = 356–65 | year = 2015 | pmid = 25093613 | doi = 10.1016/j.bbalip.2014.07.020 | pmc=4314516}}</ref> Vernolic and coronaric acids are potentially toxic, causing multiple organ failure and respiratory distress when injected into animals.<ref name="Spector_2015"/>
*{{cite journal | author=Seubert J, Yang B, Bradbury JA, ''et al.'' |title=Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway. |journal=Circ. Res. |volume=95 |issue= 5 |pages= 506-14 |year= 2005 |pmid= 15256482 |doi= 10.1161/01.RES.0000139436.89654.c8 }}
 
*{{cite journal | author=Xiao YF, Ke Q, Seubert JM, ''et al.'' |title=Enhancement of cardiac L-type Ca2+ currents in transgenic mice with cardiac-specific overexpression of CYP2J2. |journal=Mol. Pharmacol. |volume=66 |issue= 6 |pages= 1607-16 |year= 2005 |pmid= 15361551 |doi= 10.1124/mol.104.004150 }}
== Human studies ==
*{{cite journal | author=Spiecker M, Darius H, Hankeln T, ''et al.'' |title=Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2. |journal=Circulation |volume=110 |issue= 15 |pages= 2132-6 |year= 2005 |pmid= 15466638 |doi= 10.1161/01.CIR.0000143832.91812.60 }}
 
}}
Tissue samples containing carcinomas were obtained from 130 subjects and analyzed for expression of CYP2J2. Increased detection of CYP2J2 mRNA and protein were evident in 77% of patient carcinoma cell lines. Cell proliferation was positively regulated by CYP2J2 and furthermore CYP2J2 was shown to promote tumor progression.<ref name="ReferenceA">{{cite journal|last1=Jiang|first1=Jian-Gang|last2=Chen|first2=Chun-Lian|last3=Card|first3=Jeffrey W|last4=Yang|first4=Shilin|last5=Chen|first5=Ji-Xiong|last6=Fu|first6=Xiang-Ning|last7=Ning|first7=Yao-Gui|last8=Zeldin|first8=Darryl C|last9=Wang|first9=Dao Wen|title=Cytochrome P450 Promotes the neoplastic phenotype of carcinoma cells and is Up-regulated in Human Tumors|journal=Cancer Research|date=2005|volume=65|issue=11|pages=4707–4715}}</ref> There was also a greater amount of CYP2J2 mRNA in various tumor types, including esophageal [[adenocarcinoma]], [[breast carcinoma]], and [[stomach carcinoma]] compared to that of surrounding normal tissue.
 
The overexpression of CYP2J2 and its effects on carcinoma cells are also evident when EETs are administered exogenously, suggesting a link between the production of EETs and cancer progression. Furthermore, tumor progression increases at a faster rate in cell lines with over-expression of CYP2J2 compared to control cancer cell lines.<ref name="ReferenceA"/>
 
== Clinical significance ==
 
CYP2J2 is over-expressed in a number of cancers, and forced over-expression of CYP2J2 in human cancer cells lines accelerates proliferation and protects cells against [[apoptosis]].<ref name="Karkhanis_2017">{{cite journal | vauthors = Karkhanis A, Hong Y, Chan EC | title = Inhibition and inactivation of human CYP2J2: Implications in cardiac pathophysiology and opportunities in cancer therapy | journal = Biochemical Pharmacology | volume = 135 | issue = | pages = 12–21 | year = 2017 | pmid = 28237650 | doi = 10.1016/j.bcp.2017.02.017 }}</ref>
 
HETEs and EETs derived from CYP2J2 have also been shown to contribute to the proper functioning of the cardiovascular system and the regulation of the renal and pulmonary systems in humans.{{citation needed|date=April 2018}} CYP2J2 is readily expressed in the [[cardiac myocytes]] and [[endothelial cells]] of the coronary artery where various EETs are produced. The presence of EETs relaxes vascular smooth muscle cells by hyperpolarizing the cell membrane, thus highlighting the protective anti-inflammatory function of CYP2J2 in the circulatory system.<ref name="Karkhanis_2017" /> There is still conflict in studies on the effects of EETs in relation to the cardiovascular system.<ref name="Xu_2013">{{cite journal | vauthors = Xu M, Ju W, Hao H, Wang G, Li P | title = Cytochrome P450 2J2: distribution, function, regulation, genetic polymorphisms and clinical significance | journal = Drug Metabolism Reviews | volume = 45 | issue = 3 | pages = 311–52 | year = 2013 | pmid = 23865864 | doi = 10.3109/03602532.2013.806537 }}</ref><ref name="Askari_2013">{{cite journal | vauthors = Askari A, Thomson SJ, Edin ML, Zeldin DC, Bishop-Bailey D | title = Roles of the epoxygenase CYP2J2 in the endothelium | journal = Prostaglandins & Other Lipid Mediators | volume = 107 | issue = | pages = 56–63 | year = 2013 | pmid = 23474289 | pmc = 3711961 | doi = 10.1016/j.prostaglandins.2013.02.003 }}</ref> P450 enzymes have shown both positive and negative effects in the heart, and the production of EETs has been shown to produce vascular protective and vascular depressive mechanisms.<ref name="Karkhanis_2017" /> The over-expression of CYP2J2 enhances the activation of [[mitoKATP]], and is believed to confer a physiological benefit by altering the production of [[reactive oxygen species]].<ref name="Karkhanis_2017" />
{{-}}
 
== References ==
{{reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Scarborough PE, Ma J, Qu W, Zeldin DC | title = P450 subfamily CYP2J and their role in the bioactivation of arachidonic acid in extrahepatic tissues | journal = Drug Metabolism Reviews | volume = 31 | issue = 1 | pages = 205–34 | date = Feb 1999 | pmid = 10065373 | doi = 10.1081/DMR-100101915 }}
* {{cite journal | vauthors = Capdevila JH, Falck JR, Harris RC | title = Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase | journal = Journal of Lipid Research | volume = 41 | issue = 2 | pages = 163–81 | date = Feb 2000 | pmid = 10681399 | doi = }}
* {{cite journal | vauthors = Wu S, Moomaw CR, Tomer KB, Falck JR, Zeldin DC | title = Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart | journal = The Journal of Biological Chemistry | volume = 271 | issue = 7 | pages = 3460–8 | date = Feb 1996 | pmid = 8631948 | doi = 10.1074/jbc.271.7.3460 }}
* {{cite journal | vauthors = Zeldin DC, Foley J, Ma J, Boyle JE, Pascual JM, Moomaw CR, Tomer KB, Steenbergen C, Wu S | title = CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance | journal = Molecular Pharmacology | volume = 50 | issue = 5 | pages = 1111–7 | date = Nov 1996 | pmid = 8913342 | doi = }}
* {{cite journal | vauthors = Zeldin DC, Foley J, Boyle JE, Moomaw CR, Tomer KB, Parker C, Steenbergen C, Wu S | title = Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas | journal = Endocrinology | volume = 138 | issue = 3 | pages = 1338–46 | date = Mar 1997 | pmid = 9048644 | doi = 10.1210/en.138.3.1338 }}
* {{cite journal | vauthors = Zeldin DC, Foley J, Goldsworthy SM, Cook ME, Boyle JE, Ma J, Moomaw CR, Tomer KB, Steenbergen C, Wu S | title = CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance | journal = Molecular Pharmacology | volume = 51 | issue = 6 | pages = 931–43 | date = Jun 1997 | pmid = 9187259 | doi =  }}
* {{cite journal | vauthors = Bylund J, Finnström N, Oliw EH | title = Gene expression of a novel cytochrome P450 of the CYP4F subfamily in human seminal vesicles | journal = Biochemical and Biophysical Research Communications | volume = 261 | issue = 1 | pages = 169–74 | date = Jul 1999 | pmid = 10405341 | doi = 10.1006/bbrc.1999.1011 }}
* {{cite journal | vauthors = Gu J, Su T, Chen Y, Zhang QY, Ding X | title = Expression of biotransformation enzymes in human fetal olfactory mucosa: potential roles in developmental toxicity | journal = Toxicology and Applied Pharmacology | volume = 165 | issue = 2 | pages = 158–62 | date = Jun 2000 | pmid = 10828211 | doi = 10.1006/taap.2000.8923 }}
* {{cite journal | vauthors = King LM, Ma J, Srettabunjong S, Graves J, Bradbury JA, Li L, Spiecker M, Liao JK, Mohrenweiser H, Zeldin DC | title = Cloning of CYP2J2 gene and identification of functional polymorphisms | journal = Molecular Pharmacology | volume = 61 | issue = 4 | pages = 840–52 | date = Apr 2002 | pmid = 11901223 | doi = 10.1124/mol.61.4.840 }}
* {{cite journal | vauthors = Matsumoto S, Hirama T, Matsubara T, Nagata K, Yamazoe Y | title = Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole | journal = Drug Metabolism and Disposition | volume = 30 | issue = 11 | pages = 1240–5 | date = Nov 2002 | pmid = 12386130 | doi = 10.1124/dmd.30.11.1240 }}
* {{cite journal | vauthors = Marden NY, Fiala-Beer E, Xiang SH, Murray M | title = Role of activator protein-1 in the down-regulation of the human CYP2J2 gene in hypoxia | journal = The Biochemical Journal | volume = 373 | issue = Pt 3 | pages = 669–80 | date = Aug 2003 | pmid = 12737630 | pmc = 1223548 | doi = 10.1042/BJ20021903 }}
* {{cite journal | vauthors = Pucci L, Lucchesi D, Chirulli V, Penno G, Johansson I, Gervasi P, Del Prato S, Longo V | title = Cytochrome P450 2J2 polymorphism in healthy Caucasians and those with diabetes mellitus | journal = American Journal of Pharmacogenomics | volume = 3 | issue = 5 | pages = 355–8 | year = 2004 | pmid = 14575523 | doi = 10.2165/00129785-200303050-00006 }}
* {{cite journal | vauthors = Seubert J, Yang B, Bradbury JA, Graves J, Degraff LM, Gabel S, Gooch R, Foley J, Newman J, Mao L, Rockman HA, Hammock BD, Murphy E, Zeldin DC | title = Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway | journal = Circulation Research | volume = 95 | issue = 5 | pages = 506–14 | date = Sep 2004 | pmid = 15256482 | doi = 10.1161/01.RES.0000139436.89654.c8 }}
* {{cite journal | vauthors = Xiao YF, Ke Q, Seubert JM, Bradbury JA, Graves J, Degraff LM, Falck JR, Krausz K, Gelboin HV, Morgan JP, Zeldin DC | title = Enhancement of cardiac L-type Ca2+ currents in transgenic mice with cardiac-specific overexpression of CYP2J2 | journal = Molecular Pharmacology | volume = 66 | issue = 6 | pages = 1607–16 | date = Dec 2004 | pmid = 15361551 | doi = 10.1124/mol.104.004150 }}
* {{cite journal | vauthors = Spiecker M, Darius H, Hankeln T, Soufi M, Sattler AM, Schaefer JR, Node K, Börgel J, Mügge A, Lindpaintner K, Huesing A, Maisch B, Zeldin DC, Liao JK | title = Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2 | journal = Circulation | volume = 110 | issue = 15 | pages = 2132–6 | date = Oct 2004 | pmid = 15466638 | pmc = 2633457 | doi = 10.1161/01.CIR.0000143832.91812.60 }}
{{refend}}
{{refend}}


{{SIB}}
==External links==
* {{UCSC gene info|CYP2J2}}


{{WH}}
{{Cytochrome P450}}
{{WikiDoc Sources}}

Latest revision as of 00:45, 30 April 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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Wikidata
View/Edit Human

Cytochrome P450 2J2 (CYP2J2) is a protein that in humans is encoded by the CYP2J2 gene.[1][2] CYP2J2 is a member of the cytochrome P450 superfamily of enzymes. The enzymes are oxygenases which catalyze many reactions involved in the metabolism of drugs and other xenobiotics) as well as in the synthesis of cholesterol, steroids and other lipids.

Protein structure

The CYP2J2 contains the following domains:[3]

• Hydrophobic binding domains

• F-G loop (containing non-conservative mutations) primary membrane binding motif

The protein also contains an N-terminal anchor.

F-G loop

The F-G loop mediates the binding and passage of substrates, and its hydrophobic region containing residues Trp-235, Phe-239 and Ille-236 allows the enzyme to interact with cellular membranes. Mutations to hydrophilic residues in the F-G loop alter the binding mechanism by changing insertion depth of the enzyme into the membrane.

Tissue distribution

CYP2J2 is expressed predominately in the heart and, to a lesser extent, in other tissues such as the liver, gastrointestinal tract, pancreas, lung, and central nervous system.[4]

Function

CYP2J2 localizes to the endoplasmic reticulum and is thought to be a prominent enzyme responsible for metabolizing endogenous polyunsaturated fatty acids to signaling molecules.[5] It metabolizes arachidonic acid to the following eicosatrienoic acid epoxides (termed EETs): 5,6-epoxy-8Z,11Z,14Z-EET, 8,9-epoxy-8Z,11Z,14Z-EET, 11,12-epoxy-5Z,8Z,14Z-EET, and 14,15-epoxy-5Z,8Z,11Z-EET. CYP2J2 also metabolizes linoleic acid to 9,10-epoxy octadecaenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecaenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); docosahexaenoic acid to various epoxydocosapentaenoic acids (also termed EDPs); and eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed EEQs).[6]

CYP2J2, along with CYP219, CYP2C8, CYP2C9, and possibly CYP2S1 are the main producers of EETs and, very likely EEQs, EDPs, and the epoxides of linoleic acid.[7][8]

Animal studies

Animal model studies implicate the EETs, EDPs, and EEQs in regulating hypertension, the development of myocardial infarction and other damage to the heart, the growth of various cancers, inflammation, blood vessel formation, and pain perception; limited studies suggest but have not proven that these epoxides may function similarly in humans (see epoxyeicosatrienoic acid, epoxydocosapentaenoic acid, and epoxygenase pages).[8] Vernolic and coronaric acids are potentially toxic, causing multiple organ failure and respiratory distress when injected into animals.[8]

Human studies

Tissue samples containing carcinomas were obtained from 130 subjects and analyzed for expression of CYP2J2. Increased detection of CYP2J2 mRNA and protein were evident in 77% of patient carcinoma cell lines. Cell proliferation was positively regulated by CYP2J2 and furthermore CYP2J2 was shown to promote tumor progression.[9] There was also a greater amount of CYP2J2 mRNA in various tumor types, including esophageal adenocarcinoma, breast carcinoma, and stomach carcinoma compared to that of surrounding normal tissue.

The overexpression of CYP2J2 and its effects on carcinoma cells are also evident when EETs are administered exogenously, suggesting a link between the production of EETs and cancer progression. Furthermore, tumor progression increases at a faster rate in cell lines with over-expression of CYP2J2 compared to control cancer cell lines.[9]

Clinical significance

CYP2J2 is over-expressed in a number of cancers, and forced over-expression of CYP2J2 in human cancer cells lines accelerates proliferation and protects cells against apoptosis.[4]

HETEs and EETs derived from CYP2J2 have also been shown to contribute to the proper functioning of the cardiovascular system and the regulation of the renal and pulmonary systems in humans.[citation needed] CYP2J2 is readily expressed in the cardiac myocytes and endothelial cells of the coronary artery where various EETs are produced. The presence of EETs relaxes vascular smooth muscle cells by hyperpolarizing the cell membrane, thus highlighting the protective anti-inflammatory function of CYP2J2 in the circulatory system.[4] There is still conflict in studies on the effects of EETs in relation to the cardiovascular system.[10][11] P450 enzymes have shown both positive and negative effects in the heart, and the production of EETs has been shown to produce vascular protective and vascular depressive mechanisms.[4] The over-expression of CYP2J2 enhances the activation of mitoKATP, and is believed to confer a physiological benefit by altering the production of reactive oxygen species.[4]

References

  1. ↑ Ma J, Ramachandran S, Fiedorek FT, Zeldin DC (Apr 1998). "Mapping of the CYP2J cytochrome P450 genes to human chromosome 1 and mouse chromosome 4". Genomics. 49 (1): 152–5. doi:10.1006/geno.1998.5235. PMID 9570962.
  2. ↑ "Entrez Gene: CYP2J2 cytochrome P450, family 2, subfamily J, polypeptide 2".
  3. ↑ McDougle DR, Baylon JL, Meling DD, Kambalyal A, Grinkova YV, Hammernik J, Tajkhorshid E, Das A (2015). "Incorporation of charged residues in the CYP2J2 F-G loop disrupts CYP2J2-lipid bilayer interactions". Biochimica et Biophysica Acta. 1848 (10 Pt A): 2460–2470. doi:10.1016/j.bbamem.2015.07.015. PMC 4559526. PMID 26232558.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Karkhanis A, Hong Y, Chan EC (2017). "Inhibition and inactivation of human CYP2J2: Implications in cardiac pathophysiology and opportunities in cancer therapy". Biochemical Pharmacology. 135: 12–21. doi:10.1016/j.bcp.2017.02.017. PMID 28237650.
  5. ↑ Chen C, Wang DW (2013). "CYP epoxygenase derived EETs: from cardiovascular protection to human cancer therapy". Current Topics in Medicinal Chemistry. 13 (12): 1454–69. doi:10.2174/1568026611313120007. PMID 23688135.
  6. ↑ Westphal C, Konkel A, Schunck WH (2011). "CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?". Prostaglandins & Other Lipid Mediators. 96 (1–4): 99–108. doi:10.1016/j.prostaglandins.2011.09.001. PMID 21945326.
  7. ↑ Wagner K, Vito S, Inceoglu B, Hammock BD (2014). "The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling". Prostaglandins & Other Lipid Mediators. 113-115: 2–12. doi:10.1016/j.prostaglandins.2014.09.001. PMC 4254344. PMID 25240260.
  8. ↑ 8.0 8.1 8.2 Spector AA, Kim HY (2015). "Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism". Biochimica et Biophysica Acta. 1851 (4): 356–65. doi:10.1016/j.bbalip.2014.07.020. PMC 4314516. PMID 25093613.
  9. ↑ 9.0 9.1 Jiang, Jian-Gang; Chen, Chun-Lian; Card, Jeffrey W; Yang, Shilin; Chen, Ji-Xiong; Fu, Xiang-Ning; Ning, Yao-Gui; Zeldin, Darryl C; Wang, Dao Wen (2005). "Cytochrome P450 Promotes the neoplastic phenotype of carcinoma cells and is Up-regulated in Human Tumors". Cancer Research. 65 (11): 4707–4715.
  10. ↑ Xu M, Ju W, Hao H, Wang G, Li P (2013). "Cytochrome P450 2J2: distribution, function, regulation, genetic polymorphisms and clinical significance". Drug Metabolism Reviews. 45 (3): 311–52. doi:10.3109/03602532.2013.806537. PMID 23865864.
  11. ↑ Askari A, Thomson SJ, Edin ML, Zeldin DC, Bishop-Bailey D (2013). "Roles of the epoxygenase CYP2J2 in the endothelium". Prostaglandins & Other Lipid Mediators. 107: 56–63. doi:10.1016/j.prostaglandins.2013.02.003. PMC 3711961. PMID 23474289.

Further reading

  • Scarborough PE, Ma J, Qu W, Zeldin DC (Feb 1999). "P450 subfamily CYP2J and their role in the bioactivation of arachidonic acid in extrahepatic tissues". Drug Metabolism Reviews. 31 (1): 205–34. doi:10.1081/DMR-100101915. PMID 10065373.
  • Capdevila JH, Falck JR, Harris RC (Feb 2000). "Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase". Journal of Lipid Research. 41 (2): 163–81. PMID 10681399.
  • Wu S, Moomaw CR, Tomer KB, Falck JR, Zeldin DC (Feb 1996). "Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart". The Journal of Biological Chemistry. 271 (7): 3460–8. doi:10.1074/jbc.271.7.3460. PMID 8631948.
  • Zeldin DC, Foley J, Ma J, Boyle JE, Pascual JM, Moomaw CR, Tomer KB, Steenbergen C, Wu S (Nov 1996). "CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance". Molecular Pharmacology. 50 (5): 1111–7. PMID 8913342.
  • Zeldin DC, Foley J, Boyle JE, Moomaw CR, Tomer KB, Parker C, Steenbergen C, Wu S (Mar 1997). "Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas". Endocrinology. 138 (3): 1338–46. doi:10.1210/en.138.3.1338. PMID 9048644.
  • Zeldin DC, Foley J, Goldsworthy SM, Cook ME, Boyle JE, Ma J, Moomaw CR, Tomer KB, Steenbergen C, Wu S (Jun 1997). "CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance". Molecular Pharmacology. 51 (6): 931–43. PMID 9187259.
  • Bylund J, Finnström N, Oliw EH (Jul 1999). "Gene expression of a novel cytochrome P450 of the CYP4F subfamily in human seminal vesicles". Biochemical and Biophysical Research Communications. 261 (1): 169–74. doi:10.1006/bbrc.1999.1011. PMID 10405341.
  • Gu J, Su T, Chen Y, Zhang QY, Ding X (Jun 2000). "Expression of biotransformation enzymes in human fetal olfactory mucosa: potential roles in developmental toxicity". Toxicology and Applied Pharmacology. 165 (2): 158–62. doi:10.1006/taap.2000.8923. PMID 10828211.
  • King LM, Ma J, Srettabunjong S, Graves J, Bradbury JA, Li L, Spiecker M, Liao JK, Mohrenweiser H, Zeldin DC (Apr 2002). "Cloning of CYP2J2 gene and identification of functional polymorphisms". Molecular Pharmacology. 61 (4): 840–52. doi:10.1124/mol.61.4.840. PMID 11901223.
  • Matsumoto S, Hirama T, Matsubara T, Nagata K, Yamazoe Y (Nov 2002). "Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole". Drug Metabolism and Disposition. 30 (11): 1240–5. doi:10.1124/dmd.30.11.1240. PMID 12386130.
  • Marden NY, Fiala-Beer E, Xiang SH, Murray M (Aug 2003). "Role of activator protein-1 in the down-regulation of the human CYP2J2 gene in hypoxia". The Biochemical Journal. 373 (Pt 3): 669–80. doi:10.1042/BJ20021903. PMC 1223548. PMID 12737630.
  • Pucci L, Lucchesi D, Chirulli V, Penno G, Johansson I, Gervasi P, Del Prato S, Longo V (2004). "Cytochrome P450 2J2 polymorphism in healthy Caucasians and those with diabetes mellitus". American Journal of Pharmacogenomics. 3 (5): 355–8. doi:10.2165/00129785-200303050-00006. PMID 14575523.
  • Seubert J, Yang B, Bradbury JA, Graves J, Degraff LM, Gabel S, Gooch R, Foley J, Newman J, Mao L, Rockman HA, Hammock BD, Murphy E, Zeldin DC (Sep 2004). "Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway". Circulation Research. 95 (5): 506–14. doi:10.1161/01.RES.0000139436.89654.c8. PMID 15256482.
  • Xiao YF, Ke Q, Seubert JM, Bradbury JA, Graves J, Degraff LM, Falck JR, Krausz K, Gelboin HV, Morgan JP, Zeldin DC (Dec 2004). "Enhancement of cardiac L-type Ca2+ currents in transgenic mice with cardiac-specific overexpression of CYP2J2". Molecular Pharmacology. 66 (6): 1607–16. doi:10.1124/mol.104.004150. PMID 15361551.
  • Spiecker M, Darius H, Hankeln T, Soufi M, Sattler AM, Schaefer JR, Node K, Börgel J, Mügge A, Lindpaintner K, Huesing A, Maisch B, Zeldin DC, Liao JK (Oct 2004). "Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2". Circulation. 110 (15): 2132–6. doi:10.1161/01.CIR.0000143832.91812.60. PMC 2633457. PMID 15466638.

External links

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