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Protein

Cytochrome P450 4F8

Gene

CYP4F8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
    • oxygen binding Source: Reactome

    GO - Biological processi

    • icosanoid metabolic process Source: Reactome
    • prostaglandin metabolic process Source: ProtInc
    Complete GO annotation...

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000171954-MONOMER.
    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

    HGNCiHGNC:2648. CYP4F8.

    Subcellular locationi

    Topology

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

    GO - Cellular componenti

    Complete GO annotation...

    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

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    GeneTreeiENSGT00760000118816.
    HOGENOMiHOG000233833.
    HOVERGENiHBG000182.
    InParanoidiP98187.
    KOiK17728.
    OMAiGCTQDVV.
    OrthoDBiEOG091G06KN.
    PhylomeDBiP98187.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]

    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 rs2072600dbSNPEnsembl.1
    Natural variantiVAR_038348447P → Q.Corresponds to variant rs2056822dbSNPEnsembl.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

    Cross-referencesi

    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.

    3D structure databases

    ProteinModelPortaliP98187.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116439. 2 interactors.

    Chemistry databases

    SwissLipidsiSLP:000001467.

    PTM databases

    iPTMnetiP98187.
    PhosphoSitePlusiP98187.

    Polymorphism and mutation databases

    BioMutaiCYP4F8.
    DMDMi10719963.

    Proteomic databases

    EPDiP98187.
    MaxQBiP98187.
    PeptideAtlasiP98187.
    PRIDEiP98187.

    Protocols and materials databases

    DNASUi11283.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi11283.
    DisGeNETi11283.
    GeneCardsiCYP4F8.
    HGNCiHGNC:2648. CYP4F8.
    HPAiHPA058960.
    MIMi611545. gene.
    neXtProtiNX_P98187.
    OpenTargetsiENSG00000186526.
    PharmGKBiPA405.
    GenAtlasiSearch...

    Phylogenomic databases

    GeneTreeiENSGT00760000118816.
    HOGENOMiHOG000233833.
    HOVERGENiHBG000182.
    InParanoidiP98187.
    KOiK17728.
    OMAiGCTQDVV.
    OrthoDBiEOG091G06KN.
    PhylomeDBiP98187.

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000171954-MONOMER.
    ReactomeiR-HSA-211935. Fatty acids.
    R-HSA-211979. Eicosanoids.
    R-HSA-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    SABIO-RKP98187.

    Miscellaneous databases

    ChiTaRSiCYP4F8. human.
    GeneWikiiCYP4F8.
    GenomeRNAii11283.
    PROiP98187.
    SOURCEiSearch...

    Gene expression databases

    CleanExiHS_CYP4F8.
    ExpressionAtlasiP98187. baseline and differential.
    GenevisibleiP98187. HS.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCP4F8_HUMAN
    AccessioniPrimary (citable) accession number: P98187
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: May 1, 2000
    Last modified: November 2, 2016
    This is version 141 of the entry and version 1 of the sequence. [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

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.