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Protein

Cytochrome P450 4F8

Gene

CYP4F8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Hydroxylates arachidonic acid (20:4n-6) to (18R)-hydroxyarachidonate. Shows little activity against prostaglandin (PG) D2, PGE1, PGE2, PGF2alpha, and leukotriene B4. Catalyzes omega-2 and omega-3-hydroxylation of PGH1 and PGH2. Catalyzes epoxidation of 4,7,10,13,16,19-(Z)-docosahexaenoic acid (22:6n-3) and 7,10,13,16,19-(Z)-docosapentaenoic acid (22:5n-3) and omega-3-hydroxylation of 4,7,10,13,16-(Z)-docosapentaenoic acid (22:5n-6). Catalyzes hydroxylation of PGI2 and carbaprostacyclin.3 Publications

Catalytic activityi

RH + [reduced NADPH--hemoprotein reductase] + O2 = ROH + [oxidized NADPH--hemoprotein reductase] + H2O.

Cofactori

hemeBy similarity

Kineticsi

The Vmax of the reaction with U-44069 as substrate is 260 pmol/min/pmol enzyme.
  1. KM=7 µM for 9-alpha,11-alpha-epoxymethano-PGH2 (U-44069)
  2. KM=40 µM for 6,9-alpha-methylene-PGI2

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi468Iron (heme axial ligand)By similarity1

    GO - Molecular functioni

    • alkane 1-monooxygenase activity Source: ProtInc
    • aromatase activity Source: UniProtKB-EC
    • heme binding Source: InterPro
    • iron ion binding Source: InterPro
    • monooxygenase activity Source: Reactome

    GO - Biological processi

    • icosanoid metabolic process Source: Reactome
    • prostaglandin metabolic process Source: ProtInc

    Keywordsi

    Molecular functionMonooxygenase, Oxidoreductase
    LigandHeme, Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiR-HSA-211935 Fatty acids
    R-HSA-211979 Eicosanoids
    R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX)
    SABIO-RKP98187

    Chemistry databases

    SwissLipidsiSLP:000001467

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 4F8 (EC:1.14.14.1)
    Alternative name(s):
    CYPIVF8
    Gene namesi
    Name:CYP4F8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 19

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000186526.12
    HGNCiHGNC:2648 CYP4F8
    MIMi611545 gene
    neXtProtiNX_P98187

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transmembranei15 – 37HelicalSequence analysisAdd BLAST23

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi328G → E: No effect on U-44069 and U-51605 hydroxylation. 20:4n-6 hydroxylation shifted from C-18 to C-19. 1 Publication1

    Organism-specific databases

    DisGeNETi11283
    OpenTargetsiENSG00000186526
    PharmGKBiPA405

    Polymorphism and mutation databases

    BioMutaiCYP4F8
    DMDMi10719963

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000518551 – 520Cytochrome P450 4F8Add BLAST520

    Proteomic databases

    EPDiP98187
    MaxQBiP98187
    PeptideAtlasiP98187
    PRIDEiP98187

    PTM databases

    iPTMnetiP98187
    PhosphoSitePlusiP98187

    Expressioni

    Tissue specificityi

    Expressed in the epithelium of seminal vesicles, in renal cortex, in adult and fetal liver, in epidermis, in corneal epithelium, in sweat glands, hair follicles, epithelial linings of the ampulla of vas deferens and of the stomach and small intestine, as well as in the transitional epithelium of the bladder and ureter (at protein level). In the epidermis, expressed from the basal cell to the granular cell layers. In the corneal epithelium, expressed in all cell layers. Also detected in prostate. Up-regulated in the epidermis of psoriatic lesions.3 Publications

    Gene expression databases

    BgeeiENSG00000186526
    CleanExiHS_CYP4F8
    ExpressionAtlasiP98187 baseline and differential
    GenevisibleiP98187 HS

    Organism-specific databases

    HPAiHPA058960

    Interactioni

    Protein-protein interaction databases

    BioGridi116439, 2 interactors

    Structurei

    3D structure databases

    ProteinModelPortaliP98187
    SMRiP98187
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    GeneTreeiENSGT00900000140829
    HOGENOMiHOG000233833
    HOVERGENiHBG000182
    InParanoidiP98187
    KOiK17728
    OMAiGCTQDVV
    OrthoDBiEOG091G06KN
    PhylomeDBiP98187

    Family and domain databases

    Gene3Di1.10.630.10, 1 hit
    InterProiView protein in InterPro
    IPR001128 Cyt_P450
    IPR017972 Cyt_P450_CS
    IPR002401 Cyt_P450_E_grp-I
    IPR036396 Cyt_P450_sf
    PfamiView protein in Pfam
    PF00067 p450, 1 hit
    PRINTSiPR00463 EP450I
    PR00385 P450
    SUPFAMiSSF48264 SSF48264, 1 hit
    PROSITEiView protein in PROSITE
    PS00086 CYTOCHROME_P450, 1 hit

    Sequencei

    Sequence statusi: Complete.

    P98187-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSLLSLSWLG LRPVAASPWL LLLVVGASWL LARILAWTYA FYHNGRRLRC
    60 70 80 90 100
    FPQPRKQNWF LGHLGLVTPT EEGLRVLTQL VATYPQGFVR WLGPITPIIN
    110 120 130 140 150
    LCHPDIVRSV INTSDAITDK DIVFYKTLKP WLGDGLLLSV GDKWRHHRRL
    160 170 180 190 200
    LTPAFHFNIL KPYIKIFSKS ANIMHAKWQR LAMEGSTCLD VFEHISLMTL
    210 220 230 240 250
    DSLQKCIFSF DSNCQEKPSE YITAIMELSA LVVKRNNQFF RYKDFLYFLT
    260 270 280 290 300
    PCGRRFHRAC RLVHDFTDAV IQERRRTLTS QGVDDFLQAK AKSKTLDFID
    310 320 330 340 350
    VLLLSEDKNG KELSDEDIRA EADTFMFGGH DTTASGLSWV LYNLARHPEY
    360 370 380 390 400
    QERCRQEVQE LLKDREPKEI EWDDLAQLPF LTMCLKESLR LHPPIPTFAR
    410 420 430 440 450
    GCTQDVVLPD SRVIPKGNVC NINIFAIHHN PSVWPDPEVY DPFRFDPENA
    460 470 480 490 500
    QKRSPMAFIP FSAGPRNCIG QKFAMAEMKV VLALTLLRFR ILPDHREPRR
    510 520
    TPEIVLRAED GLWLRVEPLG
    Length:520
    Mass (Da):59,995
    Last modified:May 1, 2000 - v1
    Checksum:i6839640CF4E9EB86
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_038347125Y → F No effect on U-44069 and 9,11-diazo-prostadienoic acid (U-51605) hydroxylation; loss of 20:4n-6 or 22:5n-6 oxidation. 1 PublicationCorresponds to variant dbSNP:rs2072600Ensembl.1
    Natural variantiVAR_038348447P → Q. Corresponds to variant dbSNP:rs2056822Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF133298 mRNA Translation: AAD49566.1
    CCDSiCCDS74303.1
    RefSeqiNP_009184.1, NM_007253.3
    UniGeneiHs.268554

    Genome annotation databases

    EnsembliENST00000612078; ENSP00000477567; ENSG00000186526
    GeneIDi11283
    KEGGihsa:11283
    UCSCiuc032hoh.2 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiCP4F8_HUMAN
    AccessioniPrimary (citable) accession number: P98187
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: May 1, 2000
    Last modified: May 23, 2018
    This is version 150 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

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