Cytochrome P450 1A1

Function

A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins. 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 hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions. Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation. Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system. Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer. May play an important role in 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. May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent).

Classification

Family (Pfam)

PF00067 p450

InterPro

Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_E_grp-I_CYP1, Cyt_P450_sf

Functional cluster

Serine/Threonine Protein Kinases

Experimental structures · PDB · 6

• 4I8V X-ray 2.60A
• 6DWM X-ray 2.85A
• 6DWN X-ray 3.00A
• 6O5Y X-ray 3.17A
• 6UDL X-ray 2.85A
• 6UDM X-ray 3.08A

A predicted model is available from AlphaFold.

Gene Ontology · 68

• GO:0005789 endoplasmic reticulum membrane
• GO:0005743 mitochondrial inner membrane
• GO:0005739 mitochondrion
• GO:0008391 arachidonate monooxygenase activity
• GO:0032451 demethylase activity
• GO:0019899 enzyme binding
• GO:0101020 estrogen 16-alpha-hydroxylase activity
• GO:0101021 estrogen 2-hydroxylase activity
• GO:0016711 flavonoid 3'-monooxygenase activity
• GO:0020037 heme binding
• GO:0030544 Hsp70 protein binding
• GO:0051879 Hsp90 protein binding
• GO:0106256 hydroperoxy icosatetraenoate dehydratase activity
• GO:0005506 iron ion binding
• GO:0120319 long-chain fatty acid omega-1 hydroxylase activity
• GO:0102033 long-chain fatty acid omega-hydroxylase activity
• GO:0004497 monooxygenase activity
• GO:0016491 oxidoreductase activity
• GO:0016679 oxidoreductase activity, acting on diphenols and related substances as donors
• GO:0016712 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
• GO:0019825 oxygen binding
• GO:0008395 steroid hydroxylase activity
• GO:0070576 vitamin D 24-hydroxylase activity
• GO:0042904 9-cis-retinoic acid biosynthetic process
• GO:0043010 camera-type eye development
• GO:0071280 cellular response to copper ion
• GO:0009804 coumarin metabolic process
• GO:0019341 dibenzo-p-dioxin catabolic process
• GO:0048565 digestive tract development
• GO:0019373 epoxygenase P450 pathway
• GO:0008210 estrogen metabolic process
• GO:0009692 ethylene metabolic process
• GO:0006631 fatty acid metabolic process
• GO:0009812 flavonoid metabolic process
• GO:0070365 hepatocyte differentiation
• GO:0017143 insecticide metabolic process
• GO:0002933 lipid hydroxylation
• GO:0042759 long-chain fatty acid biosynthetic process
• GO:0001676 long-chain fatty acid metabolic process
• GO:0060137 maternal process involved in parturition
• GO:0046209 nitric oxide metabolic process
• GO:0097267 omega-hydroxylase P450 pathway
• GO:0006778 porphyrin-containing compound metabolic process
• GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
• GO:1904612 response to 2,3,7,8-tetrachlorodibenzodioxine
• GO:1904681 response to 3-methylcholanthrene
• GO:1904010 response to Aroclor 1254
• GO:0046685 response to arsenic-containing substance
• GO:1901497 response to diphenyl ether
• GO:0032094 response to food
• GO:0033595 response to genistein
• GO:0009635 response to herbicide
• GO:0055093 response to hyperoxia
• GO:0001666 response to hypoxia
• GO:0035902 response to immobilization stress
• GO:0010041 response to iron(III) ion
• GO:0032496 response to lipopolysaccharide
• GO:0009624 response to nematode
• GO:0033189 response to vitamin A
• GO:0042572 retinol metabolic process
• GO:0006694 steroid biosynthetic process
• GO:0006706 steroid catabolic process
• GO:0008202 steroid metabolic process
• GO:0048771 tissue remodeling
• GO:0009404 toxin metabolic process
• GO:0042359 vitamin D metabolic process
• GO:0042178 xenobiotic catabolic process
• GO:0006805 xenobiotic metabolic process

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Cytochrome P450 1A1 1.00
• Cytochrome P450 1A1 1.00
• Cytochrome P450 1A1 0.99
• Cytochrome P450 1A1 0.98
• Cytochrome P450 1A1 0.98
• Cytochrome P450 1A1 0.98
• Cytochrome P450 1A1 0.98
• Cytochrome P450 1A1 0.98
• Cytochrome P450 1A1 0.97
• Cytochrome P450 1A1 0.97
• Cytochrome P450 1A1 0.96
• Cytochrome P450 1A5 0.95

Co-cited proteins · studied together in the literature

• Cytochrome P450 1A2 9 shared papers
• Cytochrome P450 1B1 5 shared papers
• Cytochrome P450 2S1 1 shared papers
• Cytochrome P450 3A4 6 shared papers
• Aryl hydrocarbon receptor 1 shared papers
• Cytochrome P450 2D6 4 shared papers
• Cytochrome P450 2C19 4 shared papers
• Cytochrome P450 3A7 2 shared papers
• Cytochrome P450 2C8 3 shared papers
• Cytochrome P450 2E1 2 shared papers
• Cytochrome P450 3A5 3 shared papers
• Cytochrome P450 1B1 1 shared papers

Literature · 28 cited papers

• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Human cytochrome P450 1A1 structure and utility in understanding drug and xenobiotic metabolism. J. Biol. Chem. · 2013
• Human CYP2S1 metabolizes cyclooxygenase- and lipoxygenase-derived eicosanoids. Drug Metab. Dispos. · 2011
• Analysis of epoxyeicosatrienoic acids by chiral liquid chromatography/electron capture atmospheric pressure chemical ionization mass spectrometry using [13C]-analog internal standards. Rapid Commun. Mass Spectrom. · 2010
• Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450. J. Lipid Res. · 2010
• Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism. J. Lipid Res. · 2008
• The consensus coding sequences of human breast and colorectal cancers. Science · 2006
• Analysis of the DNA sequence and duplication history of human chromosome 15. Nature · 2006
• Association of CYP1A1 polymorphisms with differential metabolic activation of 17beta-estradiol and estrone. Cancer Res. · 2005
• Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus. Hum. Mutat. · 2005
• Novel nonsynonymous polymorphisms of the CYP1A1 Gene in Japanese. Drug Metab. Pharmacokinet. · 2003
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• … and 16 more in the literature graph