Overview
| Uniprot ID | P11712 |
|---|
| Protein Name | Cytochrome P450 2C9 |
|---|
| Gene Name | CYP2C9 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 118 |
GIVFSNGKKWKEIRR |
| 138 |
LRNFGMGKRSIEDRV |
| 247 |
MKSYILEKVKEHQES |
| 315 |
YALLLLLKHPEVTAK |
| 52 |
IGIKDISKSLTNLSK |
Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). 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) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Protein Sequence
10
MDSLVVLVLC
20
LSCLLLLSLW
30
RQSSGRGKLP
40
PGPTPLPVIG
50
NILQIGIKDI
60
SKSLTNLSKV
70
YGPVFTLYFG
80
LKPIVVLHGY
90
EAVKEALIDL
100
GEEFSGRGIF
110
PLAERANRGF
120
GIVFSNGKKW
130
KEIRRFSLMT
140
LRNFGMGKRS
150
IEDRVQEEAR
160
CLVEELRKTK
170
ASPCDPTFIL
180
GCAPCNVICS
190
IIFHKRFDYK
200
DQQFLNLMEK
210
LNENIKILSS
220
PWIQICNNFS
230
PIIDYFPGTH
240
NKLLKNVAFM
250
KSYILEKVKE
260
HQESMDMNNP
270
QDFIDCFLMK
280
MEKEKHNQPS
290
EFTIESLENT
300
AVDLFGAGTE
310
TTSTTLRYAL
320
LLLLKHPEVT
330
AKVQEEIERV
340
IGRNRSPCMQ
350
DRSHMPYTDA
360
VVHEVQRYID
370
LLPTSLPHAV
380
TCDIKFRNYL
390
IPKGTTILIS
400
LTSVLHDNKE
410
FPNPEMFDPH
420
HFLDEGGNFK
430
KSKYFMPFSA
440
GKRICVGEAL
450
AGMELFLFLT
460
SILQNFNLKS
470
LVDPKNLDTT
480
PVVNGFASVP
490
PFYQLCFIPV
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:0052741 |
(R)-limonene 6-monooxygenase activity |
| Molecular Function |
GO:0018675 |
(S)-limonene 6-monooxygenase activity |
| Molecular Function |
GO:0018676 |
(S)-limonene 7-monooxygenase activity |
| Molecular Function |
GO:0008405 |
arachidonate 11,12-epoxygenase activity |
| Molecular Function |
GO:0008404 |
arachidonate 14,15-epoxygenase activity |
| Molecular Function |
GO:0008392 |
arachidonate epoxygenase activity |
| Molecular Function |
GO:0034875 |
caffeine oxidase 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: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 |
| Molecular Function |
GO:0008395 |
steroid hydroxylase activity |
| Biological Process |
GO:0008203 |
cholesterol metabolic process |
| Biological Process |
GO:0019373 |
epoxygenase P450 pathway |
| Biological Process |
GO:0008210 |
estrogen metabolic process |
| Biological Process |
GO:0046456 |
icosanoid biosynthetic process |
| Biological Process |
GO:0042759 |
long-chain fatty acid biosynthetic process |
| Biological Process |
GO:0032787 |
monocarboxylic acid metabolic process |
| Biological Process |
GO:0016098 |
monoterpenoid metabolic process |
| Biological Process |
GO:0097267 |
omega-hydroxylase P450 pathway |
| Biological Process |
GO:0090346 |
organofluorine metabolic process |
| Biological Process |
GO:0070989 |
oxidative demethylation |
| Biological Process |
GO:0008202 |
steroid metabolic process |
| Biological Process |
GO:0019627 |
urea 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.