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P98187

- CP4F8_HUMAN

UniProt

P98187 - CP4F8_HUMAN

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Protein

Cytochrome P450 4F8

Gene

CYP4F8

Organism
Homo sapiens (Human)
Status
Reviewed - 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

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
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: 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
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.

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 52-518.
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.
GeneTreeiENSGT00760000118816.
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

        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:
EMBL
GenBank
DDBJ
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.

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 .
CCDSi CCDS74303.1.
RefSeqi NP_009184.1. NM_007253.3.
UniGenei Hs.268554.

3D structure databases

ProteinModelPortali P98187.
SMRi P98187. Positions 52-518.
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

Ensembli ENST00000612078 ; ENSP00000477567 ; ENSG00000186526 .
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.
GeneTreei ENSGT00760000118816.
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 29, 2014
This is version 122 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