Overview
| Uniprot ID | P10632 |
|---|
| Protein Name | Cytochrome P450 2C8 |
|---|
| Gene Name | CYP2C8 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 249 |
SYIREKVKEHQASLD |
| 375 |
HAVTTDTKFRNYLIP |
Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). 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:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Protein Sequence
10
MEPFVVLVLC
20
LSFMLLFSLW
30
RQSCRRRKLP
40
PGPTPLPIIG
50
NMLQIDVKDI
60
CKSFTNFSKV
70
YGPVFTVYFG
80
MNPIVVFHGY
90
EAVKEALIDN
100
GEEFSGRGNS
110
PISQRITKGL
120
GIISSNGKRW
130
KEIRRFSLTT
140
LRNFGMGKRS
150
IEDRVQEEAH
160
CLVEELRKTK
170
ASPCDPTFIL
180
GCAPCNVICS
190
VVFQKRFDYK
200
DQNFLTLMKR
210
FNENFRILNS
220
PWIQVCNNFP
230
LLIDCFPGTH
240
NKVLKNVALT
250
RSYIREKVKE
260
HQASLDVNNP
270
RDFIDCFLIK
280
MEQEKDNQKS
290
EFNIENLVGT
300
VADLFVAGTE
310
TTSTTLRYGL
320
LLLLKHPEVT
330
AKVQEEIDHV
340
IGRHRSPCMQ
350
DRSHMPYTDA
360
VVHEIQRYSD
370
LVPTGVPHAV
380
TTDTKFRNYL
390
IPKGTTIMAL
400
LTSVLHDDKE
410
FPNPNIFDPG
420
HFLDKNGNFK
430
KSDYFMPFSA
440
GKRICAGEGL
450
ARMELFLFLT
460
TILQNFNLKS
470
VDDLKNLNTT
480
AVTKGIVSLP
490
PSYQICFIPV
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005789 |
endoplasmic reticulum membrane |
| Molecular Function |
GO:0008392 |
arachidonate epoxygenase activity |
| Molecular Function |
GO:0034875 |
caffeine oxidase activity |
| Molecular Function |
GO:0101020 |
estrogen 16-alpha-hydroxylase activity |
| Molecular Function |
GO:0020037 |
heme binding |
| Molecular Function |
GO:0005506 |
iron ion binding |
| Molecular Function |
GO:0004497 |
monooxygenase 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:0008401 |
retinoic acid 4-hydroxylase activity |
| Biological Process |
GO:0019373 |
epoxygenase P450 pathway |
| Biological Process |
GO:0008210 |
estrogen metabolic process |
| Biological Process |
GO:0046456 |
icosanoid biosynthetic process |
| Biological Process |
GO:0002933 |
lipid hydroxylation |
| Biological Process |
GO:0042759 |
long-chain fatty acid biosynthetic process |
| Biological Process |
GO:0097267 |
omega-hydroxylase P450 pathway |
| Biological Process |
GO:0006082 |
organic acid 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: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.