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Q08477 (CP4F3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leukotriene-B(4) omega-hydroxylase 2

EC=1.14.13.30
Alternative name(s):
CYPIVF3
Cytochrome P450 4F3
Cytochrome P450-LTB-omega
Leukotriene-B(4) 20-monooxygenase 2
Gene names
Name:CYP4F3
Synonyms:LTB4H
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

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

General annotation (Comments)

Function

Cytochromes P450 are a group of heme-thiolate monooxygenases. This enzyme requires molecular oxygen and NADPH. Isoform CYP4F3A catalyzes the omega-hydroxylation of LTB4, a potent chemoattractant for polymorphonuclear leukocytes, it has low activity for arachidonic acid. Ref.10

Isoform CYP4F3B:Has a 30-fold higher Km for LTB4 compared with CYP4F3A, but it utilizes arachidonic acid as a substrate for omega-hydroxylation and generates 20-HETE, an activator of kinases PKC and CK2. Ref.10

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.

Enzyme regulation

Inhibited by carbon monoxide (CO).

Pathway

Lipid metabolism; leukotriene B4 degradation.

Subcellular location

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

Tissue specificity

Isoform CYP4F3A is expressed in the polymorphonuclear leukocytes as well as leukocytes and bone marrow. Isoform CYP4F3B is selectively expressed in liver and kidney and is also the predominant CYP4F isoform intrachea and tissues of the gastrointestinal tract. Ref.10

Sequence similarities

Belongs to the cytochrome P450 family.

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]
Isoform CYP4F3A (identifier: Q08477-1)

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.
Isoform CYP4F3B (identifier: Q08477-2)

The sequence of this isoform differs from the canonical sequence as follows:
     67-114: IHSSEEGLLY...TYIKPVLFAP → VTPTEQGMRV...NIIRSVINAS

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 520520Leukotriene-B(4) omega-hydroxylase 2
PRO_0000051851

Regions

Transmembrane11 – 3121Helical; Potential

Sites

Metal binding4681Iron (heme axial ligand) By similarity
Binding site3281Heme (covalent; via 1 link) By similarity

Natural variations

Alternative sequence67 – 11448IHSSE…VLFAP → VTPTEQGMRVLTQLVATYPQ GFKVWMGPIFPVIRFCHPNI IRSVINAS in isoform CYP4F3B.
VSP_047193
Natural variant961H → Q.
Corresponds to variant rs34923393 [ dbSNP | Ensembl ].
VAR_048457
Natural variant1061Y → C.
Corresponds to variant rs35888783 [ dbSNP | Ensembl ].
VAR_048458
Natural variant2691A → D. Ref.1 Ref.2 Ref.5
Corresponds to variant rs1805040 [ dbSNP | Ensembl ].
VAR_001258
Natural variant2701V → I. Ref.5
Corresponds to variant rs28371536 [ dbSNP | Ensembl ].
VAR_020664
Natural variant2711I → T. Ref.5
Corresponds to variant rs28371479 [ dbSNP | Ensembl ].
VAR_020665

Experimental info

Sequence conflict184 – 1863EGS → KGY in AAC08589. Ref.3
Sequence conflict4881R → A in BAA02144. Ref.1
Sequence conflict4881R → A in BAA25990. Ref.2
Sequence conflict4881R → A in BAA25991. Ref.2
Sequence conflict5121L → I in AAC08589. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform CYP4F3A [UniParc].

Last modified December 21, 2004. Version 2.
Checksum: 2519D875280CF9DC

FASTA52059,847
        10         20         30         40         50         60 
MPQLSLSSLG LWPMAASPWL LLLLVGASWL LARILAWTYT FYDNCCRLRC FPQPPKRNWF 

        70         80         90        100        110        120 
LGHLGLIHSS EEGLLYTQSL ACTFGDMCCW WVGPWHAIVR IFHPTYIKPV LFAPAAIVPK 

       130        140        150        160        170        180 
DKVFYSFLKP WLGDGLLLSA GEKWSRHRRM LTPAFHFNIL KPYMKIFNES VNIMHAKWQL 

       190        200        210        220        230        240 
LASEGSARLD MFEHISLMTL DSLQKCVFSF DSHCQEKPSE YIAAILELSA LVTKRHQQIL 

       250        260        270        280        290        300 
LYIDFLYYLT PDGQRFRRAC RLVHDFTDAV IQERRRTLPS QGVDDFLQAK AKSKTLDFID 

       310        320        330        340        350        360 
VLLLSKDEDG KKLSDEDIRA EADTFMFEGH DTTASGLSWV LYHLAKHPEY QERCRQEVQE 

       370        380        390        400        410        420 
LLKDREPKEI EWDDLAQLPF LTMCIKESLR LHPPVPAVSR CCTQDIVLPD GRVIPKGIIC 

       430        440        450        460        470        480 
LISVFGTHHN PAVWPDPEVY DPFRFDPKNI KERSPLAFIP FSAGPRNCIG QAFAMAEMKV 

       490        500        510        520 
VLGLTLLRFR VLPDHTEPRR KPELVLRAEG GLWLRVEPLS 

« Hide

Isoform CYP4F3B [UniParc].

Checksum: EA737D889AD662C2
Show »

FASTA52059,739

References

« Hide 'large scale' references
[1]"A novel form of cytochrome P-450 family 4 in human polymorphonuclear leukocytes. cDNA cloning and expression of leukotriene B4 omega-hydroxylase."
Kikuta Y., Kusunose E., Endo K., Yamamoto S., Sogawa K., Fujii-Kuriyama Y., Kusunose M.
J. Biol. Chem. 268:9376-9380(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYP4F3A), VARIANT ASP-269.
Tissue: Leukocyte.
[2]"Human leukotriene B4 omega-hydroxylase (CYP4F3) gene: molecular cloning and chromosomal localization."
Kikuta Y., Kato M., Yamashita Y., Miyauchi Y., Tanaka K., Kamada N., Kusunose M.
DNA Cell Biol. 17:221-230(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM CYP4F3A), VARIANT ASP-269.
[3]"A novel form of cytochrome P-450 family 4 in human fetal liver."
Peng X., Morgan K., Morgan T.R.
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYP4F3B).
Tissue: Fetal liver.
[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. expand/collapse author list , 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] (ISOFORM CYP4F3B).
Tissue: Tongue and Trachea.
[5]SeattleSNPs variation discovery resource
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASP-269; ILE-270 AND THR-271.
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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 CYP4F3B).
[9]"Expression of the CYP4F3 gene. tissue-specific splicing and alternative promoters generate high and low K(m) forms of leukotriene B(4) omega-hydroxylase."
Christmas P., Ursino S.R., Fox J.W., Soberman R.J.
J. Biol. Chem. 274:21191-21199(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, ALTERNATIVE PROMOTER USAGE.
[10]"Alternative splicing determines the function of CYP4F3 by switching substrate specificity."
Christmas P., Jones J.P., Patten C.J., Rock D.A., Zheng Y., Cheng S.M., Weber B.M., Carlesso N., Scadden D.T., Rettie A.E., Soberman R.J.
J. Biol. Chem. 276:38166-38172(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, FUNCTION, SUBSTRATE SPECIFICITY, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D12620 mRNA. Translation: BAA02144.1.
D12621 mRNA. Translation: BAA02145.1.
AB002454 mRNA. Translation: BAA25990.1.
AB002461 Genomic DNA. Translation: BAA25991.1.
AF054821 mRNA. Translation: AAC08589.1.
AK304200 mRNA. Translation: BAH14129.1.
AK316136 mRNA. Translation: BAH14507.1.
AY792513 Genomic DNA. Translation: AAV40834.1.
AD000685 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84489.1.
BC136299 mRNA. Translation: AAI36300.1.
PIRA46661.
RefSeqNP_000887.2. NM_000896.2.
NP_001186137.1. NM_001199208.1.
NP_001186138.1. NM_001199209.1.
UniGeneHs.106242.

3D structure databases

ProteinModelPortalQ08477.
SMRQ08477. Positions 98-510.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110229. 1 interaction.
IntActQ08477. 2 interactions.

PTM databases

PhosphoSiteQ08477.

Polymorphism databases

DMDM56757430.

Proteomic databases

PaxDbQ08477.
PRIDEQ08477.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000221307; ENSP00000221307; ENSG00000186529. [Q08477-1]
ENST00000585846; ENSP00000468105; ENSG00000186529. [Q08477-2]
ENST00000586182; ENSP00000466395; ENSG00000186529. [Q08477-2]
ENST00000591058; ENSP00000466988; ENSG00000186529. [Q08477-2]
GeneID4051.
KEGGhsa:4051.
UCSCuc002nbj.3. human. [Q08477-1]
uc002nbk.3. human.

Organism-specific databases

CTD4051.
GeneCardsGC19P015751.
H-InvDBHIX0039919.
HIX0169080.
HIX0169326.
HGNCHGNC:2646. CYP4F3.
MIM601270. gene.
neXtProtNX_Q08477.
PharmGKBPA234.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000233833.
HOVERGENHBG000182.
InParanoidQ08477.
KOK17726.
OMAPVIRFCH.
OrthoDBEOG7CNZFK.
PhylomeDBQ08477.
TreeFamTF105088.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKQ08477.
UniPathwayUPA00883.

Gene expression databases

ArrayExpressQ08477.
BgeeQ08477.
CleanExHS_CYP4F3.
GenevestigatorQ08477.

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

GeneWikiCYP4F3.
GenomeRNAi4051.
NextBio15870.
PROQ08477.
SOURCESearch...

Entry information

Entry nameCP4F3_HUMAN
AccessionPrimary (citable) accession number: Q08477
Secondary accession number(s): B7Z8Z3, O60634, Q5U740
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: December 21, 2004
Last modified: April 16, 2014
This is version 142 of the entry and version 2 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

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