Overview
| Uniprot ID | P20815 |
|---|
| Protein Name | Cytochrome P450 3A5 |
|---|
| Gene Name | CYP3A5 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 34 |
TRTHGLFKRLGIPGP |
| 379 |
RLERTCKKDVEINGV |
Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). 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:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion 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 all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
Protein Sequence
10
MDLIPNLAVE
20
TWLLLAVSLV
30
LLYLYGTRTH
40
GLFKRLGIPG
50
PTPLPLLGNV
60
LSYRQGLWKF
70
DTECYKKYGK
80
MWGTYEGQLP
90
VLAITDPDVI
100
RTVLVKECYS
110
VFTNRRSLGP
120
VGFMKSAISL
130
AEDEEWKRIR
140
SLLSPTFTSG
150
KLKEMFPIIA
160
QYGDVLVRNL
170
RREAEKGKPV
180
TLKDIFGAYS
190
MDVITGTSFG
200
VNIDSLNNPQ
210
DPFVESTKKF
220
LKFGFLDPLF
230
LSIILFPFLT
240
PVFEALNVSL
250
FPKDTINFLS
260
KSVNRMKKSR
270
LNDKQKHRLD
280
FLQLMIDSQN
290
SKETESHKAL
300
SDLELAAQSI
310
IFIFAGYETT
320
SSVLSFTLYE
330
LATHPDVQQK
340
LQKEIDAVLP
350
NKAPPTYDAV
360
VQMEYLDMVV
370
NETLRLFPVA
380
IRLERTCKKD
390
VEINGVFIPK
400
GSMVVIPTYA
410
LHHDPKYWTE
420
PEEFRPERFS
430
KKKDSIDPYI
440
YTPFGTGPRN
450
CIGMRFALMN
460
MKLALIRVLQ
470
NFSFKPCKET
480
QIPLKLDTQG
490
LLQPEKPIVL
500
KVDSRDGTLS
GE
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005789 |
endoplasmic reticulum membrane |
| Cellular Component |
GO:0043231 |
intracellular membrane-bounded organelle |
| 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:0008401 |
retinoic acid 4-hydroxylase activity |
| Molecular Function |
GO:0050649 |
testosterone 6-beta-hydroxylase activity |
| Biological Process |
GO:0046222 |
aflatoxin metabolic process |
| Biological Process |
GO:0009822 |
alkaloid catabolic process |
| Biological Process |
GO:0008210 |
estrogen metabolic process |
| Biological Process |
GO:0002933 |
lipid hydroxylation |
| Biological Process |
GO:0070989 |
oxidative demethylation |
| Biological Process |
GO:0042573 |
retinoic acid metabolic process |
| Biological Process |
GO:0042572 |
retinol metabolic process |
| Biological Process |
GO:0008202 |
steroid 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.