P78329 (CP4F2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leukotriene-B(4) omega-hydroxylase 1
EC=1.14.13.30

Alternative name(s):
CYPIVF2
Cytochrome P450 4F2
Cytochrome P450-LTB-omega
Leukotriene-B(4) 20-monooxygenase 1

Gene names

Name:

CYP4F2

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	Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Catalytic activity	(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate + NADPH + O2 = (6Z,8E,10E,14Z)-(5S,12R)-5,12,20-trihydroxyicosa-6,8,10,14-tetraenoate + NADP+ + H2O.
Cofactor	Heme group By similarity.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Tissue specificity	Liver.
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	drug metabolic process Inferred from mutant phenotype PubMed 21084764PubMed 21127708. Source: UniProtKB epoxygenase P450 pathway Inferred from direct assay PubMed 20861217PubMed 9618440. Source: UniProtKB negative regulation of blood coagulation Inferred from mutant phenotype PubMed 19297518. Source: UniProtKB negative regulation of icosanoid secretion Inferred from mutant phenotype PubMed 18391101. Source: UniProtKB positive regulation of icosanoid secretion Inferred from mutant phenotype PubMed 17341693. Source: UniProtKB pressure natriuresis Inferred from expression pattern PubMed 10660572. Source: UniProtKB renal water homeostasis Inferred from expression pattern PubMed 10660572. Source: UniProtKB sodium ion homeostasis Inferred from expression pattern PubMed 10660572. Source: UniProtKB very long-chain fatty acid metabolic process Inferred from direct assay PubMed 18433732. Source: BHF-UCL vitamin E metabolic process Inferred from direct assay PubMed 20861217. Source: UniProtKB vitamin K biosynthetic process Inferred from mutant phenotype PubMed 19297518. Source: UniProtKB xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	apical plasma membrane Inferred from direct assay PubMed 10660572. Source: UniProtKB endoplasmic reticulum membrane Traceable author statement PubMed 20861217. Source: UniProtKB
Molecular_function	alkane 1-monooxygenase activity Inferred from direct assay PubMed 18433732. Source: BHF-UCL alpha-tocopherol omega-hydroxylase activity Inferred from direct assay PubMed 20861217. Source: UniProtKB arachidonic acid epoxygenase activity Inferred from direct assay PubMed 20861217PubMed 9618440. Source: UniProtKB arachidonic acid omega-hydroxylase activity Inferred from direct assay PubMed 10660572PubMed 9618440. Source: UniProtKB 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 leukotriene-B4 20-monooxygenase activity Inferred from direct assay Ref.1PubMed 9799565. Source: UniProtKB tocotrienol omega-hydroxylase activity Inferred from direct assay PubMed 20861217. Source: UniProtKB vitamin-K-epoxide reductase (warfarin-sensitive) activity Inferred from mutant phenotype PubMed 19297518. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-1752413,EBI-389883

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 520	520	Leukotriene-B(4) omega-hydroxylase 1		PRO_0000051850
Sites
	Metal binding	468	1	Iron (heme axial ligand) By similarity
	Binding site	328	1	Heme (covalent; via 1 link) By similarity
Natural variations
	Natural variant	7	1	S → Y. Ref.5 Corresponds to variant rs3093104 [ dbSNP | Ensembl ].		VAR_013116
	Natural variant	12	1	W → G. Ref.5 Ref.7 Corresponds to variant rs3093105 [ dbSNP | Ensembl ].		VAR_013117
	Natural variant	185	1	G → V. Ref.4 Ref.5 Corresponds to variant rs3093153 [ dbSNP | Ensembl ].		VAR_013118
	Natural variant	269	1	A → D. Corresponds to variant rs1805040 [ dbSNP | Ensembl ].		VAR_020125
	Natural variant	433	1	V → M. Ref.5 Ref.7 Corresponds to variant rs2108622 [ dbSNP | Ensembl ].		VAR_013119
	Natural variant	519	1	L → M. Ref.5 Corresponds to variant rs3093200 [ dbSNP | Ensembl ].		VAR_013120
Experimental info
	Sequence conflict	12 – 13	2	WP → CR in AAC50052. Ref.2
	Sequence conflict	12 – 13	2	WP → CR in AAF86378. Ref.8
	Sequence conflict	25	1	V → A in AAH67437. Ref.7
	Sequence conflict	169	1	E → D in AAH67440. Ref.7
	Sequence conflict	336	1	G → V in AAC50052. Ref.2
	Sequence conflict	391	1	L → V in AAC50052. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P78329 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 1791F9E6EECB59B5	FASTA	520	59,853
	10 20 30 40 50 60 MSQLSLSWLG LWPVAASPWL LLLLVGASWL LAHVLAWTYA FYDNCRRLRC FPQPPRRNWF 70 80 90 100 110 120 WGHQGMVNPT EEGMRVLTQL VATYPQGFKV WMGPISPLLS LCHPDIIRSV INASAAIAPK 130 140 150 160 170 180 DKFFYSFLEP WLGDGLLLSA GDKWSRHRRM LTPAFHFNIL KPYMKIFNES VNIMHAKWQL 190 200 210 220 230 240 LASEGSACLD MFEHISLMTL DSLQKCVFSF DSHCQEKPSE YIAAILELSA LVSKRHHEIL 250 260 270 280 290 300 LHIDFLYYLT PDGQRFRRAC RLVHDFTDAV IQERRRTLPS QGVDDFLQAK AKSKTLDFID 310 320 330 340 350 360 VLLLSKDEDG KKLSDEDIRA EADTFMFEGH DTTASGLSWV LYHLAKHPEY QERCRQEVQE 370 380 390 400 410 420 LLKDREPKEI EWDDLAHLPF LTMCMKESLR LHPPVPVISR HVTQDIVLPD GRVIPKGIIC 430 440 450 460 470 480 LISVFGTHHN PAVWPDPEVY DPFRFDPENI KERSPLAFIP FSAGPRNCIG QTFAMAEMKV 490 500 510 520 VLALTLLRFR VLPDHTEPRR KPELVLRAEG GLWLRVEPLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of a novel form of leukotriene B4 omega-hydroxylase from human liver." Kikuta Y., Kusunose E., Kondo T., Yamamoto S., Kinoshita H., Kusunose M. FEBS Lett. 348:70-74(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"The human liver CYP4F2 cDNA sequence and expression in baculovirus-infected insect cells." Chen L., Hardwick J.P. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene." Kikuta Y., Miyauchi Y., Kusunose E., Kusunose M. DNA Cell Biol. 18:723-730(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-185. Tissue: Kidney.
[5]	SeattleSNPs variation discovery resource Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-7; GLY-12; VAL-185; MET-433 AND MET-519.
[6]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS GLY-12 AND MET-433.
[8]	"Promoter activity and regulation of the CYP4F2 leukotriene B4 omega hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells." Zhang X., Chen L., Hardwick J.P. Arch. Biochem. Biophys. 378:364-376(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-175. Tissue: Liver.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	D26480 mRNA. Translation: BAA05490.1. U02388 mRNA. Translation: AAC50052.2. AB015306 Genomic DNA. Translation: BAA75823.1. AK290790 mRNA. Translation: BAF83479.1. AF467894 Genomic DNA. Translation: AAL67578.1. AC005336 Genomic DNA. Translation: AAC27730.1. BC067437 mRNA. Translation: AAH67437.1. BC067439 mRNA. Translation: AAH67439.1. BC067440 mRNA. Translation: AAH67440.1. AF221943 Genomic DNA. Translation: AAF86378.1.
IPI	IPI01018663.
PIR	S45702.
RefSeq	NP_001073.3. NM_001082.3.
UniGene	Hs.558423.
3D structure databases
ProteinModelPortal	P78329.
ModBase	Search...
Protein-protein interaction databases
IntAct	P78329. 5 interactions.
MINT	MINT-2804703.
STRING	9606.ENSP00000221700.
PTM databases
PhosphoSite	P78329.
Polymorphism databases
DMDM	6166044.
Proteomic databases
PaxDb	P78329.
PRIDE	P78329.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000221700; ENSP00000221700; ENSG00000186115.
GeneID	8529.
KEGG	hsa:8529.
UCSC	uc002nbs.1. human.
Organism-specific databases
CTD	8529.
GeneCards	GC19M015988.
HGNC	HGNC:2645. CYP4F2.
HPA	HPA014048. HPA017265.
MIM	604426. gene.
neXtProt	NX_P78329.
Orphanet	240997. Susceptibility to bleeding due to warfarine treatment. 240923. Warfarine toxicity.
PharmGKB	PA27121.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2124.
HOVERGEN	HBG000182.
KO	K00490.
OMA	HFRIERA.
PhylomeDB	P78329.
Enzyme and pathway databases
BioCyc	MetaCyc:HS02675-MONOMER.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P78329.
Bgee	P78329.
CleanEx	HS_CYP4F2.
Genevestigator	P78329.
GermOnline	ENSG00000186115. 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
BindingDB	P78329.
ChEMBL	CHEMBL3379.
GenomeRNAi	8529.
NextBio	31940.
SOURCE	Search...

Entry information

Entry name

CP4F2_HUMAN

Accession

Primary (citable) accession number: P78329
Secondary accession number(s): A8K425 , Q16677, Q6NWT4, Q6NWT6, Q9NNZ0, Q9UIU8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 128 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.