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P98187 (CP4F8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome P450 4F8

EC=1.14.14.1
Alternative name(s):
CYPIVF8
Gene names
Name:CYP4F8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length520 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.4 Ref.5

Catalytic activity

RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.

Cofactor

Heme group By similarity.

Subcellular location

Endoplasmic reticulum membrane; Single-pass membrane protein By similarity. Microsome membrane By similarity.

Tissue specificity

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. Ref.1 Ref.3 Ref.5

Sequence similarities

Belongs to the cytochrome P450 family.

Biophysicochemical properties

Kinetic parameters:

The Vmax of the reaction with U-44069 as substrate is 260 pmol/min/pmol enzyme.

KM=7 µM for 9-alpha,11-alpha-epoxymethano-PGH2 (U-44069)

KM=40 µM for 6,9-alpha-methylene-PGI2

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 520520Cytochrome P450 4F8
PRO_0000051855

Regions

Transmembrane15 – 3723Helical; Potential

Sites

Metal binding4681Iron (heme axial ligand) By similarity

Natural variations

Natural variant1251Y → 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. Ref.4
Corresponds to variant rs2072600 [ dbSNP | Ensembl ].
VAR_038347
Natural variant4471P → Q.
Corresponds to variant rs2056822 [ dbSNP | Ensembl ].
VAR_038348

Experimental info

Mutagenesis3281G → E: No effect on U-44069 and U-51605 hydroxylation. 20:4n-6 hydroxylation shifted from C-18 to C-19. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P98187 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 6839640CF4E9EB86

FASTA52059,995
        10         20         30         40         50         60 
MSLLSLSWLG LRPVAASPWL LLLVVGASWL LARILAWTYA FYHNGRRLRC FPQPRKQNWF 

        70         80         90        100        110        120 
LGHLGLVTPT EEGLRVLTQL VATYPQGFVR WLGPITPIIN LCHPDIVRSV INTSDAITDK 

       130        140        150        160        170        180 
DIVFYKTLKP WLGDGLLLSV GDKWRHHRRL LTPAFHFNIL KPYIKIFSKS ANIMHAKWQR 

       190        200        210        220        230        240 
LAMEGSTCLD VFEHISLMTL DSLQKCIFSF DSNCQEKPSE YITAIMELSA LVVKRNNQFF 

       250        260        270        280        290        300 
RYKDFLYFLT PCGRRFHRAC RLVHDFTDAV IQERRRTLTS QGVDDFLQAK AKSKTLDFID 

       310        320        330        340        350        360 
VLLLSEDKNG KELSDEDIRA EADTFMFGGH DTTASGLSWV LYNLARHPEY QERCRQEVQE 

       370        380        390        400        410        420 
LLKDREPKEI EWDDLAQLPF LTMCLKESLR LHPPIPTFAR GCTQDVVLPD SRVIPKGNVC 

       430        440        450        460        470        480 
NINIFAIHHN PSVWPDPEVY DPFRFDPENA QKRSPMAFIP FSAGPRNCIG QKFAMAEMKV 

       490        500        510        520 
VLALTLLRFR ILPDHREPRR TPEIVLRAED GLWLRVEPLG 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF133298 mRNA. Translation: AAD49566.1.
RefSeqNP_009184.1. NM_007253.3.
UniGeneHs.268554.

3D structure databases

ProteinModelPortalP98187.
SMRP98187. Positions 48-519.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116439. 1 interaction.

PTM databases

PhosphoSiteP98187.

Polymorphism databases

DMDM10719963.

Proteomic databases

PaxDbP98187.
PRIDEP98187.

Protocols and materials databases

DNASU11283.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID11283.
KEGGhsa:11283.
UCSCuc002nbi.3. human.

Organism-specific databases

CTD11283.
GeneCardsGC19P015726.
HGNCHGNC:2648. CYP4F8.
MIM611545. gene.
neXtProtNX_P98187.
PharmGKBPA405.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000233833.
HOVERGENHBG000182.
InParanoidP98187.
KOK17728.
PhylomeDBP98187.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKP98187.

Gene expression databases

CleanExHS_CYP4F8.
GenevestigatorP98187.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCYP4F8. human.
GeneWikiCYP4F8.
GenomeRNAi11283.
NextBio42955.
PROP98187.
SOURCESearch...

Entry information

Entry nameCP4F8_HUMAN
AccessionPrimary (citable) accession number: P98187
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM