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P78329

- CP4F2_HUMAN

UniProt

P78329 - CP4F2_HUMAN

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Protein
Leukotriene-B(4) omega-hydroxylase 1
Gene
CYP4F2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 activityi

(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.

Cofactori

Heme group By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei328 – 3281Heme (covalent; via 1 link) By similarity
Metal bindingi468 – 4681Iron (heme axial ligand) By similarity

GO - Molecular functioni

  1. alkane 1-monooxygenase activity Source: BHF-UCL
  2. alpha-tocopherol omega-hydroxylase activity Source: UniProtKB
  3. arachidonic acid epoxygenase activity Source: UniProtKB
  4. arachidonic acid omega-hydroxylase activity Source: UniProtKB
  5. heme binding Source: InterPro
  6. iron ion binding Source: InterPro
  7. leukotriene-B4 20-monooxygenase activity Source: UniProtKB
  8. protein binding Source: IntAct
  9. tocotrienol omega-hydroxylase activity Source: UniProtKB
  10. vitamin-K-epoxide reductase (warfarin-sensitive) activity Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. arachidonic acid metabolic process Source: UniProtKB
  2. drug metabolic process Source: UniProtKB
  3. epoxygenase P450 pathway Source: UniProtKB
  4. icosanoid metabolic process Source: Reactome
  5. leukotriene B4 catabolic process Source: UniProtKB
  6. leukotriene metabolic process Source: Reactome
  7. long-chain fatty acid metabolic process Source: BHF-UCL
  8. negative regulation of blood coagulation Source: UniProtKB
  9. negative regulation of icosanoid secretion Source: UniProtKB
  10. omega-hydroxylase P450 pathway Source: Reactome
  11. oxidation-reduction process Source: UniProtKB
  12. positive regulation of icosanoid secretion Source: UniProtKB
  13. pressure natriuresis Source: UniProtKB
  14. regulation of blood pressure Source: UniProtKB
  15. renal water homeostasis Source: UniProtKB
  16. small molecule metabolic process Source: Reactome
  17. sodium ion homeostasis Source: UniProtKB
  18. very long-chain fatty acid metabolic process Source: BHF-UCL
  19. vitamin E metabolic process Source: UniProtKB
  20. vitamin K biosynthetic process Source: UniProtKB
  21. xenobiotic metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS02675-MONOMER.
ReactomeiREACT_13425. Miscellaneous substrates.
REACT_13645. Eicosanoids.
REACT_13814. Fatty acids.
REACT_150134. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

Names & Taxonomyi

Protein namesi
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 namesi
Name:CYP4F2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:2645. CYP4F2.

Subcellular locationi

GO - Cellular componenti

  1. apical plasma membrane Source: UniProtKB
  2. cytoplasm Source: UniProtKB
  3. endoplasmic reticulum membrane Source: UniProtKB
  4. intracellular membrane-bounded organelle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

Orphaneti240997. Susceptibility to bleeding due to warfarine treatment.
240923. Warfarine toxicity.
PharmGKBiPA27121.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 520520Leukotriene-B(4) omega-hydroxylase 1
PRO_0000051850Add
BLAST

Proteomic databases

PaxDbiP78329.
PRIDEiP78329.

PTM databases

PhosphoSiteiP78329.

Expressioni

Tissue specificityi

Liver.

Gene expression databases

ArrayExpressiP78329.
BgeeiP78329.
CleanExiHS_CYP4F2.
GenevestigatoriP78329.

Organism-specific databases

HPAiHPA014048.
HPA017265.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
NCK1P163332EBI-1752413,EBI-389883

Protein-protein interaction databases

BioGridi114099. 3 interactions.
IntActiP78329. 5 interactions.
STRINGi9606.ENSP00000221700.

Structurei

3D structure databases

ProteinModelPortaliP78329.
SMRiP78329. Positions 71-520.

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.

Phylogenomic databases

eggNOGiCOG2124.
HOVERGENiHBG000182.
KOiK17726.
OMAiQGMVNPT.
OrthoDBiEOG7CNZFK.
PhylomeDBiP78329.
TreeFamiTF105088.

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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P78329-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MSQLSLSWLG LWPVAASPWL LLLLVGASWL LAHVLAWTYA FYDNCRRLRC    50
FPQPPRRNWF WGHQGMVNPT EEGMRVLTQL VATYPQGFKV WMGPISPLLS 100
LCHPDIIRSV INASAAIAPK DKFFYSFLEP WLGDGLLLSA GDKWSRHRRM 150
LTPAFHFNIL KPYMKIFNES VNIMHAKWQL LASEGSACLD MFEHISLMTL 200
DSLQKCVFSF DSHCQEKPSE YIAAILELSA LVSKRHHEIL LHIDFLYYLT 250
PDGQRFRRAC RLVHDFTDAV IQERRRTLPS QGVDDFLQAK AKSKTLDFID 300
VLLLSKDEDG KKLSDEDIRA EADTFMFEGH DTTASGLSWV LYHLAKHPEY 350
QERCRQEVQE LLKDREPKEI EWDDLAHLPF LTMCMKESLR LHPPVPVISR 400
HVTQDIVLPD GRVIPKGIIC LISVFGTHHN PAVWPDPEVY DPFRFDPENI 450
KERSPLAFIP FSAGPRNCIG QTFAMAEMKV VLALTLLRFR VLPDHTEPRR 500
KPELVLRAEG GLWLRVEPLS 520
Length:520
Mass (Da):59,853
Last modified:May 1, 1997 - v1
Checksum:i1791F9E6EECB59B5
GO
Isoform 2 (identifier: P78329-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-149: Missing.
     307-339: DEDGKKLSDEDIRAEADTFMFEGHDTTASGLSW → AMTPRPVVSPGSCTTLQSTQNTRSAAGRRCKNF
     340-520: Missing.

Note: No experimental confirmation available.

Show »
Length:190
Mass (Da):21,709
Checksum:iE137B6FDB0B39573
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71S → Y.1 Publication
Corresponds to variant rs3093104 [ dbSNP | Ensembl ].
VAR_013116
Natural varianti12 – 121W → G.2 Publications
Corresponds to variant rs3093105 [ dbSNP | Ensembl ].
VAR_013117
Natural varianti185 – 1851G → V.2 Publications
Corresponds to variant rs3093153 [ dbSNP | Ensembl ].
VAR_013118
Natural varianti269 – 2691A → D.
Corresponds to variant rs1805040 [ dbSNP | Ensembl ].
VAR_020125
Natural varianti433 – 4331V → M.2 Publications
Corresponds to variant rs2108622 [ dbSNP | Ensembl ].
VAR_013119
Natural varianti519 – 5191L → M.1 Publication
Corresponds to variant rs3093200 [ dbSNP | Ensembl ].
VAR_013120

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 149149Missing in isoform 2.
VSP_055578Add
BLAST
Alternative sequencei307 – 33933DEDGK…SGLSW → AMTPRPVVSPGSCTTLQSTQ NTRSAAGRRCKNF in isoform 2.
VSP_055579Add
BLAST
Alternative sequencei340 – 520181Missing in isoform 2.
VSP_055580Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti12 – 132WP → CR in AAC50052. 1 Publication
Sequence conflicti12 – 132WP → CR in AAF86378. 1 Publication
Sequence conflicti25 – 251V → A in AAH67437. 1 Publication
Sequence conflicti169 – 1691E → D in AAH67440. 1 Publication
Sequence conflicti336 – 3361G → V in AAC50052. 1 Publication
Sequence conflicti391 – 3911L → V in AAC50052. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D26480 mRNA. Translation: BAA05490.1.
U02388 mRNA. Translation: AAC50052.2.
AB015306 Genomic DNA. Translation: BAA75823.1.
AK290790 mRNA. Translation: BAF83479.1.
AK300961 mRNA. Translation: BAG62587.1.
AF467894 Genomic DNA. Translation: AAL67578.1.
AC005336 Genomic DNA. Translation: AAC27730.1.
AC004791 Genomic DNA. No translation available.
BC067437 mRNA. Translation: AAH67437.1.
BC067439 mRNA. Translation: AAH67439.1.
BC067440 mRNA. Translation: AAH67440.1.
AF221943 Genomic DNA. Translation: AAF86378.1.
CCDSiCCDS12336.1.
PIRiS45702.
RefSeqiNP_001073.3. NM_001082.4.
UniGeneiHs.558423.

Genome annotation databases

EnsembliENST00000011989; ENSP00000011989; ENSG00000186115.
ENST00000221700; ENSP00000221700; ENSG00000186115.
GeneIDi8529.
KEGGihsa:8529.
UCSCiuc002nbs.1. human.

Polymorphism databases

DMDMi6166044.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D26480 mRNA. Translation: BAA05490.1 .
U02388 mRNA. Translation: AAC50052.2 .
AB015306 Genomic DNA. Translation: BAA75823.1 .
AK290790 mRNA. Translation: BAF83479.1 .
AK300961 mRNA. Translation: BAG62587.1 .
AF467894 Genomic DNA. Translation: AAL67578.1 .
AC005336 Genomic DNA. Translation: AAC27730.1 .
AC004791 Genomic DNA. No translation available.
BC067437 mRNA. Translation: AAH67437.1 .
BC067439 mRNA. Translation: AAH67439.1 .
BC067440 mRNA. Translation: AAH67440.1 .
AF221943 Genomic DNA. Translation: AAF86378.1 .
CCDSi CCDS12336.1.
PIRi S45702.
RefSeqi NP_001073.3. NM_001082.4.
UniGenei Hs.558423.

3D structure databases

ProteinModelPortali P78329.
SMRi P78329. Positions 71-520.
ModBasei Search...

Protein-protein interaction databases

BioGridi 114099. 3 interactions.
IntActi P78329. 5 interactions.
STRINGi 9606.ENSP00000221700.

Chemistry

BindingDBi P78329.
ChEMBLi CHEMBL3379.

PTM databases

PhosphoSitei P78329.

Polymorphism databases

DMDMi 6166044.

Proteomic databases

PaxDbi P78329.
PRIDEi P78329.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000011989 ; ENSP00000011989 ; ENSG00000186115 .
ENST00000221700 ; ENSP00000221700 ; ENSG00000186115 .
GeneIDi 8529.
KEGGi hsa:8529.
UCSCi uc002nbs.1. human.

Organism-specific databases

CTDi 8529.
GeneCardsi GC19M015988.
HGNCi HGNC:2645. CYP4F2.
HPAi HPA014048.
HPA017265.
MIMi 604426. gene.
neXtProti NX_P78329.
Orphaneti 240997. Susceptibility to bleeding due to warfarine treatment.
240923. Warfarine toxicity.
PharmGKBi PA27121.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2124.
HOVERGENi HBG000182.
KOi K17726.
OMAi QGMVNPT.
OrthoDBi EOG7CNZFK.
PhylomeDBi P78329.
TreeFami TF105088.

Enzyme and pathway databases

BioCyci MetaCyc:HS02675-MONOMER.
Reactomei REACT_13425. Miscellaneous substrates.
REACT_13645. Eicosanoids.
REACT_13814. Fatty acids.
REACT_150134. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

Miscellaneous databases

GeneWikii CYP4F2.
GenomeRNAii 8529.
NextBioi 31940.
PROi P78329.
SOURCEi Search...

Gene expression databases

ArrayExpressi P78329.
Bgeei P78329.
CleanExi HS_CYP4F2.
Genevestigatori P78329.

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

« Hide 'large scale' publications
  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] (ISOFORM 1).
    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] (ISOFORM 1).
    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] (ISOFORMS 1 AND 2), VARIANT VAL-185.
    Tissue: Kidney and Small intestine.
  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] (ISOFORM 1), 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.

Entry informationi

Entry nameiCP4F2_HUMAN
AccessioniPrimary (citable) accession number: P78329
Secondary accession number(s): A8K425
, B4DV75, Q16677, Q6NWT4, Q6NWT6, Q9NNZ0, Q9UIU8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: May 1, 1997
Last modified: September 3, 2014
This is version 141 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

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