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Overview

Uniprot IDP98187
Protein NameCytochrome P450 4F8
Gene NameCYP4F8
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
308 VLLLSEDKNGKELSD
452 FDPENAQKRSPMAFI

Function

A cytochrome P450 monooxygenase involved in the metabolism of endogenous polyunsaturated fatty acids (PUFAs) and their oxygenated derivatives (oxylipins). 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 (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon hydrogen bonds, with preference for omega-1 and omega-2 positions (PubMed:10791960, PubMed:15789615, PubMed:16112640). Hydroxylates (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) predominantly at omega-2 position to form (18R)-hydroxyeicosatetraenoic acid (18R-HETE) (PubMed:10791960). Exhibits omega-1 hydroxylase activity toward prostaglandin (PG) H1, PGH2 and PGI2 (PubMed:10791960, PubMed:15789615). Catalyzes the epoxidation of double bonds of PUFAs, including docosahexaenoic and docosapentaenoic acids (PubMed:16112640). Shows little activity against PGD2, PGE1, PGE2, PGF2alpha, and leukotriene B4

Protein Sequence

10 MSLLSLSWLG 20 LRPVAASPWL 30 LLLVVGASWL 40 LARILAWTYA 50 FYHNGRRLRC 60 FPQPRKQNWF 70 LGHLGLVTPT 80 EEGLRVLTQL 90 VATYPQGFVR 100 WLGPITPIIN 110 LCHPDIVRSV 120 INTSDAITDK 130 DIVFYKTLKP 140 WLGDGLLLSV 150 GDKWRHHRRL 160 LTPAFHFNIL 170 KPYIKIFSKS 180 ANIMHAKWQR 190 LAMEGSTCLD 200 VFEHISLMTL 210 DSLQKCIFSF 220 DSNCQEKPSE 230 YITAIMELSA 240 LVVKRNNQFF 250 RYKDFLYFLT 260 PCGRRFHRAC 270 RLVHDFTDAV 280 IQERRRTLTS 290 QGVDDFLQAK 300 AKSKTLDFID 310 VLLLSEDKNG 320 KELSDEDIRA 330 EADTFMFGGH 340 DTTASGLSWV 350 LYNLARHPEY 360 QERCRQEVQE 370 LLKDREPKEI 380 EWDDLAQLPF 390 LTMCLKESLR 400 LHPPIPTFAR 410 GCTQDVVLPD 420 SRVIPKGNVC 430 NINIFAIHHN 440 PSVWPDPEVY 450 DPFRFDPENA 460 QKRSPMAFIP 470 FSAGPRNCIG 480 QKFAMAEMKV 490 VLALTLLRFR 500 ILPDHREPRR 510 TPEIVLRAED 520 GLWLRVEPLG

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005789 endoplasmic reticulum membrane
Molecular Function GO:0018685 alkane 1-monooxygenase 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
Biological Process GO:0019369 arachidonate metabolic process
Biological Process GO:0006690 icosanoid metabolic process
Biological Process GO:0042361 menaquinone catabolic process
Biological Process GO:0042376 phylloquinone catabolic process
Biological Process GO:0006693 prostaglandin metabolic process

Reference

[1] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.