CP4F3_MOUSE
ID CP4F3_MOUSE Reviewed; 524 AA.
AC Q99N16; E9QLZ3; Q9D8N4;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Cytochrome P450 4F3 {ECO:0000303|PubMed:16380383};
DE AltName: Full=CYPIVF3;
DE AltName: Full=Leukotriene-B(4) omega-1/omega-2 hydroxylase {ECO:0000303|PubMed:16380383};
GN Name=Cyp4f3 {ECO:0000250|UniProtKB:Q08477};
GN Synonyms=Cyp4f18 {ECO:0000303|PubMed:24632148,
GN ECO:0000312|MGI:MGI:1919304};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RA Antonovic L., Kawashima H., Strobel H.;
RT "Protein expression and catalytic activity assessment of mouse 4F clones.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INDUCTION.
RX PubMed=16380383; DOI=10.1074/jbc.m513101200;
RA Christmas P., Tolentino K., Primo V., Berry K.Z., Murphy R.C., Chen M.,
RA Lee D.M., Soberman R.J.;
RT "Cytochrome P-450 4F18 is the leukotriene B4 omega-1/omega-2 hydroxylase in
RT mouse polymorphonuclear leukocytes: identification as the functional
RT orthologue of human polymorphonuclear leukocyte CYP4F3A in the down-
RT regulation of responses to LTB4.";
RL J. Biol. Chem. 281:7189-7196(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24632148; DOI=10.1016/j.bbalip.2014.03.002;
RA Winslow V., Vaivoda R., Vasilyev A., Dombkowski D., Douaidy K., Stark C.,
RA Drake J., Guilliams E., Choudhary D., Preffer F., Stoilov I., Christmas P.;
RT "Altered leukotriene B4 metabolism in CYP4F18-deficient mice does not
RT impact inflammation following renal ischemia.";
RL Biochim. Biophys. Acta 1841:868-879(2014).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC the pro-inflammatory lipid mediator leukotriene B4 (LTB4)
CC (PubMed:16380383, PubMed:24632148). Hydroxylates at the omega-1 and
CC omega-2 positions LTB4. This oxidation step leads to LTB4 inactivation,
CC which is postulated to be a crucial part of the resolution of
CC inflammation (PubMed:16380383, PubMed:24632148). Mechanistically, uses
CC molecular oxygen inserting one oxygen atom into a substrate, and
CC reducing the second into a water molecule, with two electrons provided
CC by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein
CC reductase) (PubMed:16380383, PubMed:24632148).
CC {ECO:0000269|PubMed:16380383, ECO:0000269|PubMed:24632148}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=leukotriene B4 + O2 + reduced [NADPH--hemoprotein reductase] =
CC 18-hydroxy-leukotriene B4 + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:53440, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57461, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:137391; Evidence={ECO:0000269|PubMed:16380383,
CC ECO:0000269|PubMed:24632148};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53441;
CC Evidence={ECO:0000305|PubMed:16380383, ECO:0000305|PubMed:24632148};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=leukotriene B4 + O2 + reduced [NADPH--hemoprotein reductase] =
CC 19-hydroxy-leukotriene B4 + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:53436, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57461, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:137390; Evidence={ECO:0000269|PubMed:16380383,
CC ECO:0000269|PubMed:24632148};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53437;
CC Evidence={ECO:0000305|PubMed:16380383, ECO:0000305|PubMed:24632148};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P51869};
CC -!- PATHWAY: Lipid metabolism; leukotriene B4 degradation.
CC {ECO:0000269|PubMed:16380383, ECO:0000269|PubMed:24632148}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:16380383}; Single-pass membrane protein
CC {ECO:0000305}. Microsome membrane {ECO:0000305|PubMed:16380383};
CC Single-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highest level in polymorphonuclear leukocytes and
CC dendritic cells. Detectable in lymph nodes, spleen, bone marrow and
CC peripheral blood. Highly expressed in ovary. Very low level in liver,
CC kidney, and smooth muscle. Expressed in neutrophils (at protein level).
CC {ECO:0000269|PubMed:16380383, ECO:0000269|PubMed:24632148}.
CC -!- INDUCTION: Up-regulated in bone marrow-derived dendritic cells by
CC bacterial lipopolysaccharide (LPS), a ligand for toll-like receptor 4
CC (TLR4), and by poly(I:C), a ligand for TLR3.
CC {ECO:0000269|PubMed:16380383}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate. No
CC visible phenotype. {ECO:0000269|PubMed:24632148}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000255}.
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DR EMBL; AF233647; AAK15013.1; -; mRNA.
DR EMBL; AK007863; BAB25315.1; -; mRNA.
DR EMBL; AC162522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013494; AAH13494.1; -; mRNA.
DR CCDS; CCDS22406.1; -.
DR RefSeq; NP_077764.2; NM_024444.2.
DR RefSeq; XP_006509811.1; XM_006509748.2.
DR AlphaFoldDB; Q99N16; -.
DR SMR; Q99N16; -.
DR BioGRID; 215120; 29.
DR STRING; 10090.ENSMUSP00000003574; -.
DR SwissLipids; SLP:000001724; -.
DR iPTMnet; Q99N16; -.
DR PhosphoSitePlus; Q99N16; -.
DR jPOST; Q99N16; -.
DR MaxQB; Q99N16; -.
DR PaxDb; Q99N16; -.
DR PeptideAtlas; Q99N16; -.
DR PRIDE; Q99N16; -.
DR ProteomicsDB; 285281; -.
DR Antibodypedia; 27108; 138 antibodies from 27 providers.
DR Ensembl; ENSMUST00000003574; ENSMUSP00000003574; ENSMUSG00000003484.
DR GeneID; 72054; -.
DR KEGG; mmu:72054; -.
DR UCSC; uc009mfe.2; mouse.
DR CTD; 72054; -.
DR MGI; MGI:1919304; Cyp4f18.
DR VEuPathDB; HostDB:ENSMUSG00000003484; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000163407; -.
DR HOGENOM; CLU_001570_5_1_1; -.
DR InParanoid; Q99N16; -.
DR OMA; GRSCIGY; -.
DR OrthoDB; 1247045at2759; -.
DR PhylomeDB; Q99N16; -.
DR TreeFam; TF105088; -.
DR Reactome; R-MMU-211935; Fatty acids.
DR Reactome; R-MMU-211958; Miscellaneous substrates.
DR Reactome; R-MMU-211979; Eicosanoids.
DR Reactome; R-MMU-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-MMU-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
DR UniPathway; UPA00883; -.
DR BioGRID-ORCS; 72054; 2 hits in 74 CRISPR screens.
DR PRO; PR:Q99N16; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q99N16; protein.
DR Bgee; ENSMUSG00000003484; Expressed in granulocyte and 56 other tissues.
DR ExpressionAtlas; Q99N16; baseline and differential.
DR Genevisible; Q99N16; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0097259; F:20-aldehyde-leukotriene B4 20-monooxygenase activity; ISO:MGI.
DR GO; GO:0097258; F:20-hydroxy-leukotriene B4 omega oxidase activity; ISO:MGI.
DR GO; GO:0008391; F:arachidonic acid monooxygenase activity; IBA:GO_Central.
DR GO; GO:0102207; F:docosanoate omega-hydroxylase activity; ISO:MGI.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0050051; F:leukotriene-B4 20-monooxygenase activity; ISO:MGI.
DR GO; GO:0120319; F:long-chain fatty acid omega-1 hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0102033; F:long-chain fatty acid omega-hydroxylase activity; ISO:MGI.
DR GO; GO:0140692; F:very long-chain fatty acid omega-hydroxylase activity; ISO:MGI.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IBA:GO_Central.
DR GO; GO:0010430; P:fatty acid omega-oxidation; ISO:MGI.
DR GO; GO:0036101; P:leukotriene B4 catabolic process; ISO:MGI.
DR GO; GO:0036102; P:leukotriene B4 metabolic process; IDA:UniProtKB.
DR GO; GO:2001302; P:lipoxin A4 metabolic process; ISO:MGI.
DR GO; GO:2001304; P:lipoxin B4 metabolic process; ISO:MGI.
DR GO; GO:0042361; P:menaquinone catabolic process; IBA:GO_Central.
DR GO; GO:0097267; P:omega-hydroxylase P450 pathway; ISO:MGI.
DR GO; GO:0042376; P:phylloquinone catabolic process; IBA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..524
FT /note="Cytochrome P450 4F3"
FT /id="PRO_0000238924"
FT TRANSMEM 19..39
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 468
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P33274"
FT CONFLICT 6
FT /note="M -> L (in Ref. 1; AAK15013 and 4; AAH13494)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="P -> Q (in Ref. 1; AAK15013 and 4; AAH13494)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="D -> G (in Ref. 2; BAB25315)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="T -> A (in Ref. 1; AAK15013 and 4; AAH13494)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="V -> D (in Ref. 1; AAK15013 and 4; AAH13494)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 524 AA; 59843 MW; E97FACEB00CFD7CB CRC64;
MSQLSMSWMG LGHTAASPWL LLLLAGASCL LAYILTPIYG VFENSLRLRC FPQPPKRNWI
LGHLGLIQSS EEGLLYIQSL VRTFRDACCW WVGPLHPVIR IFHPAFIKPV VLAPALVAPK
DTVFYRFLKP WLGDGLLMST GDKWSRHRRM LTPAFHFNIL KPYVKVFNDS TNIMHAKWQR
LASKGSAYLN MFEHISLMTL DSLQKCVFSF DSNCQEKPSE YITAILELST LVARRHQRLL
LHVDLFYYLT HDGMRFRKAC RLVHDFTDAV IRERRRTLLD QGGVDVLKAK AKAKTLDFID
VLLLSKDEHG KALSDEDIRA EADTFMFGGH DTTASGLSWI LYNLARHPEY QERCRQEVRE
LLRDREPEEI EWDDLAQLPF LTMCIKESLR LHPPVTAISR CCTQDIVLPD GRVIPKGVIS
RISIFGTHHN PAVWPDPEVY DPFRFDADNV KGRSPLAFIP FSAGPRNCIG QTFAMSEMKV
ALALTLLRFR VLPDDKEPRR KPELILRAEG GLWLKVEPLS AGAQ
