Search Results

Overview

Uniprot ID	P08684
Protein Name	Cytochrome P450 3A4
Gene Name	CYP3A4
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
141	SPTFTSGKLKEMVPI
143	TFTSGKLKEMVPIIA
168	RREAETGKPVTLKDV
266	SRLEDTQKHRVDFLQ
379	RLERVCKKDVEINGM
413	KYWTEPEKFLPERFS
466	VLQNFSFKPCKETQI
469	NFSFKPCKETQIPLK
66	MFDMECHKKYGKVWG
96	MIKTVLVKECYSVFT

Function

A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). 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 (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). 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 C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)

Protein Sequence

10 MALIPDLAME 20 TWLLLAVSLV 30 LLYLYGTHSH 40 GLFKKLGIPG 50 PTPLPFLGNI 60 LSYHKGFCMF 70 DMECHKKYGK 80 VWGFYDGQQP 90 VLAITDPDMI 100 KTVLVKECYS 110 VFTNRRPFGP 120 VGFMKSAISI 130 AEDEEWKRLR 140 SLLSPTFTSG 150 KLKEMVPIIA 160 QYGDVLVRNL 170 RREAETGKPV 180 TLKDVFGAYS 190 MDVITSTSFG 200 VNIDSLNNPQ 210 DPFVENTKKL 220 LRFDFLDPFF 230 LSITVFPFLI 240 PILEVLNICV 250 FPREVTNFLR 260 KSVKRMKESR 270 LEDTQKHRVD 280 FLQLMIDSQN 290 SKETESHKAL 300 SDLELVAQSI 310 IFIFAGYETT 320 SSVLSFIMYE 330 LATHPDVQQK 340 LQEEIDAVLP 350 NKAPPTYDTV 360 LQMEYLDMVV 370 NETLRLFPIA 380 MRLERVCKKD 390 VEINGMFIPK 400 GVVVMIPSYA 410 LHRDPKYWTE 420 PEKFLPERFS 430 KKNKDNIDPY 440 IYTPFGSGPR 450 NCIGMRFALM 460 NMKLALIRVL 470 QNFSFKPCKE 480 TQIPLKLSLG 490 GLLQPEKPVV 500 LKVESRDGTV SGA

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005789	endoplasmic reticulum membrane
Cellular Component	GO:0043231	intracellular membrane-bounded organelle
Molecular Function	GO:0102320	1,8-cineole 2-exo-monooxygenase activity
Molecular Function	GO:0062181	1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity
Molecular Function	GO:0062188	anandamide 11,12 epoxidase activity
Molecular Function	GO:0062189	anandamide 14,15 epoxidase activity
Molecular Function	GO:0062187	anandamide 8,9 epoxidase activity
Molecular Function	GO:0034875	caffeine oxidase activity
Molecular Function	GO:0019899	enzyme binding
Molecular Function	GO:0101020	estrogen 16-alpha-hydroxylase activity
Molecular Function	GO:0101021	estrogen 2-hydroxylase activity
Molecular Function	GO:0020037	heme binding
Molecular Function	GO:0005506	iron ion binding
Molecular Function	GO:0004497	monooxygenase activity
Molecular Function	GO:0016491	oxidoreductase activity
Molecular Function	GO:0019825	oxygen binding
Molecular Function	GO:0050591	quinine 3-monooxygenase activity
Molecular Function	GO:0008401	retinoic acid 4-hydroxylase activity
Molecular Function	GO:0005496	steroid binding
Molecular Function	GO:0008395	steroid hydroxylase activity
Molecular Function	GO:0050649	testosterone 6-beta-hydroxylase activity
Molecular Function	GO:0070576	vitamin D 24-hydroxylase activity
Molecular Function	GO:0030343	vitamin D3 25-hydroxylase activity
Biological Process	GO:0046222	aflatoxin metabolic process
Biological Process	GO:0009822	alkaloid catabolic process
Biological Process	GO:0008209	androgen metabolic process
Biological Process	GO:0008203	cholesterol metabolic process
Biological Process	GO:0008210	estrogen metabolic process
Biological Process	GO:0002933	lipid hydroxylation
Biological Process	GO:0006629	lipid metabolic process
Biological Process	GO:0042759	long-chain fatty acid biosynthetic process
Biological Process	GO:0016098	monoterpenoid metabolic process
Biological Process	GO:0070989	oxidative demethylation
Biological Process	GO:0042573	retinoic acid metabolic process
Biological Process	GO:0042572	retinol metabolic process
Biological Process	GO:0006706	steroid catabolic process
Biological Process	GO:0008202	steroid metabolic process
Biological Process	GO:0042369	vitamin D catabolic process
Biological Process	GO:0042359	vitamin D metabolic process
Biological Process	GO:0042178	xenobiotic catabolic process
Biological Process	GO:0006805	xenobiotic metabolic process

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.