P98187 (CP4F8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 4F8
EC=1.14.14.1

Alternative name(s):
CYPIVF8

Gene names

Name:

CYP4F8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	520 AA.
Sequence status	Complete.
Protein existence	Evidence 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

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	prostaglandin metabolic process Traceable author statement Ref.1. Source: ProtInc xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	alkane 1-monooxygenase activity Traceable author statement Ref.1. Source: ProtInc aromatase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 520	520	Cytochrome P450 4F8		PRO_0000051855
Regions
	Transmembrane	15 – 37	23	Helical; Potential
Sites
	Metal binding	468	1	Iron (heme axial ligand) By similarity
Natural variations
	Natural variant	125	1	Y → 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 variant	447	1	P → Q. Corresponds to variant rs2056822 [ dbSNP | Ensembl ].		VAR_038348
Experimental info
	Mutagenesis	328	1	G → 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		Length	Mass (Da)
	P98187 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 6839640CF4E9EB86	FASTA	520	59,995
	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

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.
IPI	IPI00024332.
RefSeq	NP_009184.1. NM_007253.3.
UniGene	Hs.268554.
3D structure databases
ProteinModelPortal	P98187.
ModBase	Search...
PTM databases
PhosphoSite	P98187.
Polymorphism databases
DMDM	10719963.
Proteomic databases
PaxDb	P98187.
PRIDE	P98187.
Protocols and materials databases
DNASU	11283.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	11283.
KEGG	hsa:11283.
UCSC	uc002nbi.3. human.
Organism-specific databases
CTD	11283.
GeneCards	GC19P015726.
HGNC	HGNC:2648. CYP4F8.
MIM	611545. gene.
neXtProt	NX_P98187.
PharmGKB	PA405.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2124.
HOGENOM	HOG000233833.
HOVERGEN	HBG000182.
InParanoid	P98187.
KO	K00490.
OrthoDB	EOG40CHGX.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
CleanEx	HS_CYP4F8.
Genevestigator	P98187.
GermOnline	ENSG00000186526. Homo sapiens.
Family and domain databases
Gene3D	1.10.630.10. 1 hit.
InterPro	IPR001128. Cyt_P450. IPR017972. Cyt_P450_CS. IPR002401. Cyt_P450_E_grp-I. [Graphical view]
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00463. EP450I. PR00385. P450.
SUPFAM	SSF48264. Cytochrome_P450. 1 hit.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CYP4F8. human.
GenomeRNAi	11283.
NextBio	42955.
SOURCE	Search...

Entry information

Entry name

CP4F8_HUMAN

Accession

Primary (citable) accession number: P98187

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.