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P98187

- CP4F8_HUMAN

UniProt

P98187 - CP4F8_HUMAN

Protein

Cytochrome P450 4F8

Gene

CYP4F8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    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

    Heme group.By 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

    1. alkane 1-monooxygenase activity Source: ProtInc
    2. aromatase activity Source: UniProtKB-EC
    3. heme binding Source: InterPro
    4. iron ion binding Source: InterPro

    GO - Biological processi

    1. icosanoid metabolic process Source: Reactome
    2. prostaglandin metabolic process Source: ProtInc
    3. small molecule metabolic process Source: Reactome
    4. xenobiotic metabolic process Source: Reactome

    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: Unplaced

    Organism-specific databases

    HGNCiHGNC:2648. CYP4F8.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: Reactome
    2. integral component of membrane Source: UniProtKB-KW

    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.

    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.
    GenevestigatoriP98187.

    Interactioni

    Protein-protein interaction databases

    BioGridi116439. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliP98187.
    SMRiP98187. Positions 52-520.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

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

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG2124.
    HOGENOMiHOG000233833.
    HOVERGENiHBG000182.
    InParanoidiP98187.
    KOiK17728.
    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

    MSLLSLSWLG LRPVAASPWL LLLVVGASWL LARILAWTYA FYHNGRRLRC    50
    FPQPRKQNWF LGHLGLVTPT EEGLRVLTQL VATYPQGFVR WLGPITPIIN 100
    LCHPDIVRSV INTSDAITDK DIVFYKTLKP WLGDGLLLSV GDKWRHHRRL 150
    LTPAFHFNIL KPYIKIFSKS ANIMHAKWQR LAMEGSTCLD VFEHISLMTL 200
    DSLQKCIFSF DSNCQEKPSE YITAIMELSA LVVKRNNQFF RYKDFLYFLT 250
    PCGRRFHRAC RLVHDFTDAV IQERRRTLTS QGVDDFLQAK AKSKTLDFID 300
    VLLLSEDKNG KELSDEDIRA EADTFMFGGH DTTASGLSWV LYNLARHPEY 350
    QERCRQEVQE LLKDREPKEI EWDDLAQLPF LTMCLKESLR LHPPIPTFAR 400
    GCTQDVVLPD SRVIPKGNVC NINIFAIHHN PSVWPDPEVY DPFRFDPENA 450
    QKRSPMAFIP FSAGPRNCIG QKFAMAEMKV VLALTLLRFR ILPDHREPRR 500
    TPEIVLRAED GLWLRVEPLG 520
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF133298 mRNA. Translation: AAD49566.1.
    RefSeqiNP_009184.1. NM_007253.3.
    UniGeneiHs.268554.

    Genome annotation databases

    GeneIDi11283.
    KEGGihsa:11283.
    UCSCiuc002nbi.3. human.

    Polymorphism databases

    DMDMi10719963.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF133298 mRNA. Translation: AAD49566.1 .
    RefSeqi NP_009184.1. NM_007253.3.
    UniGenei Hs.268554.

    3D structure databases

    ProteinModelPortali P98187.
    SMRi P98187. Positions 52-520.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116439. 1 interaction.

    PTM databases

    PhosphoSitei P98187.

    Polymorphism databases

    DMDMi 10719963.

    Proteomic databases

    PaxDbi P98187.
    PRIDEi P98187.

    Protocols and materials databases

    DNASUi 11283.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 11283.
    KEGGi hsa:11283.
    UCSCi uc002nbi.3. human.

    Organism-specific databases

    CTDi 11283.
    GeneCardsi GC19P015726.
    HGNCi HGNC:2648. CYP4F8.
    MIMi 611545. gene.
    neXtProti NX_P98187.
    PharmGKBi PA405.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2124.
    HOGENOMi HOG000233833.
    HOVERGENi HBG000182.
    InParanoidi P98187.
    KOi K17728.
    PhylomeDBi P98187.

    Enzyme and pathway databases

    Reactomei REACT_13645. Eicosanoids.
    REACT_13814. Fatty acids.
    REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    SABIO-RK P98187.

    Miscellaneous databases

    ChiTaRSi CYP4F8. human.
    GeneWikii CYP4F8.
    GenomeRNAii 11283.
    NextBioi 42955.
    PROi P98187.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_CYP4F8.
    Genevestigatori P98187.

    Family and domain databases

    Gene3Di 1.10.630.10. 1 hit.
    InterProi IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    [Graphical view ]
    Pfami PF00067. p450. 1 hit.
    [Graphical view ]
    PRINTSi PR00463. EP450I.
    PR00385. P450.
    SUPFAMi SSF48264. SSF48264. 1 hit.
    PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    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: October 1, 2014
    This is version 121 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