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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 flavoprotein + O2 = ROH + oxidized flavoprotein + 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)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi468 – 4681Iron (heme axial ligand)By similarity

    GO - Molecular functioni

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

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_13645. Eicosanoids.
    REACT_13814. Fatty acids.
    REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    SABIO-RKP98187.

    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
    ProteomesiUP000005640 Componenti: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:2648. CYP4F8.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei15 – 3723HelicalSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi328 – 3281G → E: No effect on U-44069 and U-51605 hydroxylation. 20:4n-6 hydroxylation shifted from C-18 to C-19. 1 Publication

    Organism-specific databases

    PharmGKBiPA405.

    Polymorphism and mutation databases

    BioMutaiCYP4F8.
    DMDMi10719963.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 520520Cytochrome P450 4F8PRO_0000051855Add
    BLAST

    Proteomic databases

    PaxDbiP98187.
    PRIDEiP98187.

    PTM databases

    PhosphoSiteiP98187.

    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 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP98187.
    SMRiP98187. Positions 52-518.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG2124.
    GeneTreeiENSGT00760000118816.
    HOGENOMiHOG000233833.
    HOVERGENiHBG000182.
    InParanoidiP98187.
    KOiK17728.
    OMAiGCTQDVV.
    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)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti125 – 1251Y → 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 Publication
    Corresponds to variant rs2072600 [ dbSNP | Ensembl ].
    VAR_038347
    Natural varianti447 – 4471P → Q.
    Corresponds to variant rs2056822 [ dbSNP | Ensembl ].
    VAR_038348

    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.
    UCSCiuc002nbi.3. 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.
    SMRiP98187. Positions 52-518.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116439. 2 interactions.

    PTM databases

    PhosphoSiteiP98187.

    Polymorphism and mutation databases

    BioMutaiCYP4F8.
    DMDMi10719963.

    Proteomic databases

    PaxDbiP98187.
    PRIDEiP98187.

    Protocols and materials databases

    DNASUi11283.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000612078; ENSP00000477567; ENSG00000186526.
    GeneIDi11283.
    KEGGihsa:11283.
    UCSCiuc002nbi.3. human.

    Organism-specific databases

    CTDi11283.
    GeneCardsiGC19P015726.
    HGNCiHGNC:2648. CYP4F8.
    HPAiHPA058960.
    MIMi611545. gene.
    neXtProtiNX_P98187.
    PharmGKBiPA405.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG2124.
    GeneTreeiENSGT00760000118816.
    HOGENOMiHOG000233833.
    HOVERGENiHBG000182.
    InParanoidiP98187.
    KOiK17728.
    OMAiGCTQDVV.
    PhylomeDBiP98187.

    Enzyme and pathway databases

    ReactomeiREACT_13645. Eicosanoids.
    REACT_13814. Fatty acids.
    REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    SABIO-RKP98187.

    Miscellaneous databases

    ChiTaRSiCYP4F8. human.
    GeneWikiiCYP4F8.
    GenomeRNAii11283.
    NextBioi42955.
    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...

    Publicationsi

    1. "Gene expression of a novel cytochrome P450 of the CYP4F subfamily in human seminal vesicles."
      Bylund J., Finnstroem N., Oliw E.H.
      Biochem. Biophys. Res. Commun. 261:169-174(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Tissue: Seminal vesicle.
    2. "Identification of CYP4F8 in human seminal vesicles as a prominent 19-hydroxylase of prostaglandin endoperoxides."
      Bylund J., Hidestrand M., Ingelman-Sundberg M., Oliw E.H.
      J. Biol. Chem. 275:21844-21849(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    3. "Expression of CYP4F8 (prostaglandin H 19-hydroxylase) in human epithelia and prominent induction in epidermis of psoriatic lesions."
      Stark K., Toermae H., Cristea M., Oliw E.H.
      Arch. Biochem. Biophys. 409:188-196(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    4. "Oxygenation of polyunsaturated long chain fatty acids by recombinant CYP4F8 and CYP4F12 and catalytic importance of Tyr-125 and Gly-328 of CYP4F8."
      Stark K., Wongsud B., Burman R., Oliw E.H.
      Arch. Biochem. Biophys. 441:174-181(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, VARIANT PHE-125, MUTAGENESIS OF GLY-328.
    5. "On the mechanism of biosynthesis of 19-hydroxyprostaglandins of human seminal fluid and expression of cyclooxygenase-2, PGH 19-hydroxylase (CYP4F8) and microsomal PGE synthase-1 in seminal vesicles and vas deferens."
      Stark K., Bylund J., Toermae H., Sahlen G., Oliw E.H.
      Prostaglandins Other Lipid Mediat. 75:47-64(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.

    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: July 22, 2015
    This is version 129 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

    External Data

    Dasty 3

    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 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.