Full text data of CYP4F3
CYP4F3
(LTB4H)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Leukotriene-B(4) omega-hydroxylase 2; 1.14.13.30 (CYPIVF3; Cytochrome P450 4F3; Cytochrome P450-LTB-omega; Leukotriene-B(4) 20-monooxygenase 2)
Leukotriene-B(4) omega-hydroxylase 2; 1.14.13.30 (CYPIVF3; Cytochrome P450 4F3; Cytochrome P450-LTB-omega; Leukotriene-B(4) 20-monooxygenase 2)
UniProt
Q08477
ID CP4F3_HUMAN Reviewed; 520 AA.
AC Q08477; B7Z8Z3; O60634; Q5U740;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-DEC-2004, sequence version 2.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Leukotriene-B(4) omega-hydroxylase 2;
DE EC=1.14.13.30;
DE AltName: Full=CYPIVF3;
DE AltName: Full=Cytochrome P450 4F3;
DE AltName: Full=Cytochrome P450-LTB-omega;
DE AltName: Full=Leukotriene-B(4) 20-monooxygenase 2;
GN Name=CYP4F3; Synonyms=LTB4H;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYP4F3A), AND VARIANT ASP-269.
RC TISSUE=Leukocyte;
RX PubMed=8486631;
RA Kikuta Y., Kusunose E., Endo K., Yamamoto S., Sogawa K.,
RA Fujii-Kuriyama Y., Kusunose M.;
RT "A novel form of cytochrome P-450 family 4 in human polymorphonuclear
RT leukocytes. cDNA cloning and expression of leukotriene B4 omega-
RT hydroxylase.";
RL J. Biol. Chem. 268:9376-9380(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM CYP4F3A), AND
RP VARIANT ASP-269.
RX PubMed=9539102; DOI=10.1089/dna.1998.17.221;
RA Kikuta Y., Kato M., Yamashita Y., Miyauchi Y., Tanaka K., Kamada N.,
RA Kusunose M.;
RT "Human leukotriene B4 omega-hydroxylase (CYP4F3) gene: molecular
RT cloning and chromosomal localization.";
RL DNA Cell Biol. 17:221-230(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYP4F3B).
RC TISSUE=Fetal liver;
RA Peng X., Morgan K., Morgan T.R.;
RT "A novel form of cytochrome P-450 family 4 in human fetal liver.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CYP4F3B).
RC TISSUE=Tongue, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-269; ILE-270 AND
RP THR-271.
RG SeattleSNPs variation discovery resource;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CYP4F3B).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP ALTERNATIVE SPLICING, AND ALTERNATIVE PROMOTER USAGE.
RX PubMed=10409674; DOI=10.1074/jbc.274.30.21191;
RA Christmas P., Ursino S.R., Fox J.W., Soberman R.J.;
RT "Expression of the CYP4F3 gene. tissue-specific splicing and
RT alternative promoters generate high and low K(m) forms of leukotriene
RT B(4) omega-hydroxylase.";
RL J. Biol. Chem. 274:21191-21199(1999).
RN [10]
RP ALTERNATIVE SPLICING, FUNCTION, SUBSTRATE SPECIFICITY, AND TISSUE
RP SPECIFICITY.
RX PubMed=11461919; DOI=10.1074/jbc.M104818200;
RA Christmas P., Jones J.P., Patten C.J., Rock D.A., Zheng Y.,
RA Cheng S.M., Weber B.M., Carlesso N., Scadden D.T., Rettie A.E.,
RA Soberman R.J.;
RT "Alternative splicing determines the function of CYP4F3 by switching
RT substrate specificity.";
RL J. Biol. Chem. 276:38166-38172(2001).
CC -!- FUNCTION: Cytochromes P450 are a group of heme-thiolate
CC monooxygenases. This enzyme requires molecular oxygen and NADPH.
CC Isoform CYP4F3A catalyzes the omega-hydroxylation of LTB4, a
CC potent chemoattractant for polymorphonuclear leukocytes, it has
CC low activity for arachidonic acid.
CC -!- FUNCTION: Isoform CYP4F3B: Has a 30-fold higher Km for LTB4
CC compared with CYP4F3A, but it utilizes arachidonic acid as a
CC substrate for omega-hydroxylation and generates 20-HETE, an
CC activator of kinases PKC and CK2.
CC -!- CATALYTIC ACTIVITY: (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-
CC 6,8,10,14-tetraenoate + NADPH + O(2) = (6Z,8E,10E,14Z)-(5S,12R)-
CC 5,12,20-trihydroxyicosa-6,8,10,14-tetraenoate + NADP(+) + H(2)O.
CC -!- COFACTOR: Heme group (By similarity).
CC -!- ENZYME REGULATION: Inhibited by carbon monoxide (CO).
CC -!- PATHWAY: Lipid metabolism; leukotriene B4 degradation.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein (By similarity). Microsome membrane; Single-pass
CC membrane protein (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=2;
CC Name=CYP4F3A;
CC IsoId=Q08477-1; Sequence=Displayed;
CC Name=CYP4F3B;
CC IsoId=Q08477-2; Sequence=VSP_047193;
CC -!- TISSUE SPECIFICITY: Isoform CYP4F3A is expressed in the
CC polymorphonuclear leukocytes as well as leukocytes and bone
CC marrow. Isoform CYP4F3B is selectively expressed in liver and
CC kidney and is also the predominant CYP4F isoform in trachea and
CC tissues of the gastrointestinal tract.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/cyp4f3/";
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DR EMBL; D12620; BAA02144.1; -; mRNA.
DR EMBL; D12621; BAA02145.1; -; mRNA.
DR EMBL; AB002454; BAA25990.1; -; mRNA.
DR EMBL; AB002461; BAA25991.1; -; Genomic_DNA.
DR EMBL; AF054821; AAC08589.1; -; mRNA.
DR EMBL; AK304200; BAH14129.1; -; mRNA.
DR EMBL; AK316136; BAH14507.1; -; mRNA.
DR EMBL; AY792513; AAV40834.1; -; Genomic_DNA.
DR EMBL; AD000685; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84489.1; -; Genomic_DNA.
DR EMBL; BC136299; AAI36300.1; -; mRNA.
DR PIR; A46661; A46661.
DR RefSeq; NP_000887.2; NM_000896.2.
DR RefSeq; NP_001186137.1; NM_001199208.1.
DR RefSeq; NP_001186138.1; NM_001199209.1.
DR UniGene; Hs.106242; -.
DR ProteinModelPortal; Q08477; -.
DR SMR; Q08477; 98-515.
DR IntAct; Q08477; 2.
DR PhosphoSite; Q08477; -.
DR DMDM; 56757430; -.
DR PaxDb; Q08477; -.
DR PRIDE; Q08477; -.
DR Ensembl; ENST00000221307; ENSP00000221307; ENSG00000186529.
DR Ensembl; ENST00000585846; ENSP00000468105; ENSG00000186529.
DR Ensembl; ENST00000586182; ENSP00000466395; ENSG00000186529.
DR Ensembl; ENST00000591058; ENSP00000466988; ENSG00000186529.
DR GeneID; 4051; -.
DR KEGG; hsa:4051; -.
DR UCSC; uc002nbk.3; human.
DR CTD; 4051; -.
DR GeneCards; GC19P015751; -.
DR H-InvDB; HIX0039919; -.
DR H-InvDB; HIX0169080; -.
DR H-InvDB; HIX0169326; -.
DR HGNC; HGNC:2646; CYP4F3.
DR MIM; 601270; gene.
DR neXtProt; NX_Q08477; -.
DR PharmGKB; PA234; -.
DR eggNOG; COG2124; -.
DR HOGENOM; HOG000233833; -.
DR HOVERGEN; HBG000182; -.
DR InParanoid; Q08477; -.
DR KO; K00490; -.
DR OMA; PVIRFCH; -.
DR OrthoDB; EOG7CNZFK; -.
DR PhylomeDB; Q08477; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; Q08477; -.
DR UniPathway; UPA00883; -.
DR GeneWiki; CYP4F3; -.
DR GenomeRNAi; 4051; -.
DR NextBio; 15870; -.
DR PRO; PR:Q08477; -.
DR ArrayExpress; Q08477; -.
DR Bgee; Q08477; -.
DR CleanEx; HS_CYP4F3; -.
DR Genevestigator; Q08477; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0052871; F:alpha-tocopherol omega-hydroxylase activity; IEA:UniProtKB-EC.
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; IEA:UniProtKB-EC.
DR GO; GO:0004497; F:monooxygenase activity; TAS:ProtInc.
DR GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
DR GO; GO:0036101; P:leukotriene B4 catabolic process; IEA:GOC.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Alternative promoter usage; Alternative splicing; Complete proteome;
KW Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome;
KW Monooxygenase; NADP; Oxidoreductase; Polymorphism; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1 520 Leukotriene-B(4) omega-hydroxylase 2.
FT /FTId=PRO_0000051851.
FT TRANSMEM 11 31 Helical; (Potential).
FT METAL 468 468 Iron (heme axial ligand) (By similarity).
FT BINDING 328 328 Heme (covalent; via 1 link) (By
FT similarity).
FT VAR_SEQ 67 114 IHSSEEGLLYTQSLACTFGDMCCWWVGPWHAIVRIFHPTYI
FT KPVLFAP -> VTPTEQGMRVLTQLVATYPQGFKVWMGPIF
FT PVIRFCHPNIIRSVINAS (in isoform CYP4F3B).
FT /FTId=VSP_047193.
FT VARIANT 96 96 H -> Q (in dbSNP:rs34923393).
FT /FTId=VAR_048457.
FT VARIANT 106 106 Y -> C (in dbSNP:rs35888783).
FT /FTId=VAR_048458.
FT VARIANT 269 269 A -> D (in dbSNP:rs1805040).
FT /FTId=VAR_001258.
FT VARIANT 270 270 V -> I (in dbSNP:rs28371536).
FT /FTId=VAR_020664.
FT VARIANT 271 271 I -> T (in dbSNP:rs28371479).
FT /FTId=VAR_020665.
FT CONFLICT 184 186 EGS -> KGY (in Ref. 3; AAC08589).
FT CONFLICT 488 488 R -> A (in Ref. 1; BAA02144 and 2;
FT BAA25990/BAA25991).
FT CONFLICT 512 512 L -> I (in Ref. 3; AAC08589).
SQ SEQUENCE 520 AA; 59847 MW; 2519D875280CF9DC CRC64;
MPQLSLSSLG LWPMAASPWL LLLLVGASWL LARILAWTYT FYDNCCRLRC FPQPPKRNWF
LGHLGLIHSS EEGLLYTQSL ACTFGDMCCW WVGPWHAIVR IFHPTYIKPV LFAPAAIVPK
DKVFYSFLKP WLGDGLLLSA GEKWSRHRRM LTPAFHFNIL KPYMKIFNES VNIMHAKWQL
LASEGSARLD MFEHISLMTL DSLQKCVFSF DSHCQEKPSE YIAAILELSA LVTKRHQQIL
LYIDFLYYLT PDGQRFRRAC RLVHDFTDAV IQERRRTLPS QGVDDFLQAK AKSKTLDFID
VLLLSKDEDG KKLSDEDIRA EADTFMFEGH DTTASGLSWV LYHLAKHPEY QERCRQEVQE
LLKDREPKEI EWDDLAQLPF LTMCIKESLR LHPPVPAVSR CCTQDIVLPD GRVIPKGIIC
LISVFGTHHN PAVWPDPEVY DPFRFDPKNI KERSPLAFIP FSAGPRNCIG QAFAMAEMKV
VLGLTLLRFR VLPDHTEPRR KPELVLRAEG GLWLRVEPLS
//
ID CP4F3_HUMAN Reviewed; 520 AA.
AC Q08477; B7Z8Z3; O60634; Q5U740;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-DEC-2004, sequence version 2.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Leukotriene-B(4) omega-hydroxylase 2;
DE EC=1.14.13.30;
DE AltName: Full=CYPIVF3;
DE AltName: Full=Cytochrome P450 4F3;
DE AltName: Full=Cytochrome P450-LTB-omega;
DE AltName: Full=Leukotriene-B(4) 20-monooxygenase 2;
GN Name=CYP4F3; Synonyms=LTB4H;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYP4F3A), AND VARIANT ASP-269.
RC TISSUE=Leukocyte;
RX PubMed=8486631;
RA Kikuta Y., Kusunose E., Endo K., Yamamoto S., Sogawa K.,
RA Fujii-Kuriyama Y., Kusunose M.;
RT "A novel form of cytochrome P-450 family 4 in human polymorphonuclear
RT leukocytes. cDNA cloning and expression of leukotriene B4 omega-
RT hydroxylase.";
RL J. Biol. Chem. 268:9376-9380(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM CYP4F3A), AND
RP VARIANT ASP-269.
RX PubMed=9539102; DOI=10.1089/dna.1998.17.221;
RA Kikuta Y., Kato M., Yamashita Y., Miyauchi Y., Tanaka K., Kamada N.,
RA Kusunose M.;
RT "Human leukotriene B4 omega-hydroxylase (CYP4F3) gene: molecular
RT cloning and chromosomal localization.";
RL DNA Cell Biol. 17:221-230(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYP4F3B).
RC TISSUE=Fetal liver;
RA Peng X., Morgan K., Morgan T.R.;
RT "A novel form of cytochrome P-450 family 4 in human fetal liver.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CYP4F3B).
RC TISSUE=Tongue, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-269; ILE-270 AND
RP THR-271.
RG SeattleSNPs variation discovery resource;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CYP4F3B).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP ALTERNATIVE SPLICING, AND ALTERNATIVE PROMOTER USAGE.
RX PubMed=10409674; DOI=10.1074/jbc.274.30.21191;
RA Christmas P., Ursino S.R., Fox J.W., Soberman R.J.;
RT "Expression of the CYP4F3 gene. tissue-specific splicing and
RT alternative promoters generate high and low K(m) forms of leukotriene
RT B(4) omega-hydroxylase.";
RL J. Biol. Chem. 274:21191-21199(1999).
RN [10]
RP ALTERNATIVE SPLICING, FUNCTION, SUBSTRATE SPECIFICITY, AND TISSUE
RP SPECIFICITY.
RX PubMed=11461919; DOI=10.1074/jbc.M104818200;
RA Christmas P., Jones J.P., Patten C.J., Rock D.A., Zheng Y.,
RA Cheng S.M., Weber B.M., Carlesso N., Scadden D.T., Rettie A.E.,
RA Soberman R.J.;
RT "Alternative splicing determines the function of CYP4F3 by switching
RT substrate specificity.";
RL J. Biol. Chem. 276:38166-38172(2001).
CC -!- FUNCTION: Cytochromes P450 are a group of heme-thiolate
CC monooxygenases. This enzyme requires molecular oxygen and NADPH.
CC Isoform CYP4F3A catalyzes the omega-hydroxylation of LTB4, a
CC potent chemoattractant for polymorphonuclear leukocytes, it has
CC low activity for arachidonic acid.
CC -!- FUNCTION: Isoform CYP4F3B: Has a 30-fold higher Km for LTB4
CC compared with CYP4F3A, but it utilizes arachidonic acid as a
CC substrate for omega-hydroxylation and generates 20-HETE, an
CC activator of kinases PKC and CK2.
CC -!- CATALYTIC ACTIVITY: (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-
CC 6,8,10,14-tetraenoate + NADPH + O(2) = (6Z,8E,10E,14Z)-(5S,12R)-
CC 5,12,20-trihydroxyicosa-6,8,10,14-tetraenoate + NADP(+) + H(2)O.
CC -!- COFACTOR: Heme group (By similarity).
CC -!- ENZYME REGULATION: Inhibited by carbon monoxide (CO).
CC -!- PATHWAY: Lipid metabolism; leukotriene B4 degradation.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein (By similarity). Microsome membrane; Single-pass
CC membrane protein (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=2;
CC Name=CYP4F3A;
CC IsoId=Q08477-1; Sequence=Displayed;
CC Name=CYP4F3B;
CC IsoId=Q08477-2; Sequence=VSP_047193;
CC -!- TISSUE SPECIFICITY: Isoform CYP4F3A is expressed in the
CC polymorphonuclear leukocytes as well as leukocytes and bone
CC marrow. Isoform CYP4F3B is selectively expressed in liver and
CC kidney and is also the predominant CYP4F isoform in trachea and
CC tissues of the gastrointestinal tract.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/cyp4f3/";
CC -----------------------------------------------------------------------
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DR EMBL; D12620; BAA02144.1; -; mRNA.
DR EMBL; D12621; BAA02145.1; -; mRNA.
DR EMBL; AB002454; BAA25990.1; -; mRNA.
DR EMBL; AB002461; BAA25991.1; -; Genomic_DNA.
DR EMBL; AF054821; AAC08589.1; -; mRNA.
DR EMBL; AK304200; BAH14129.1; -; mRNA.
DR EMBL; AK316136; BAH14507.1; -; mRNA.
DR EMBL; AY792513; AAV40834.1; -; Genomic_DNA.
DR EMBL; AD000685; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84489.1; -; Genomic_DNA.
DR EMBL; BC136299; AAI36300.1; -; mRNA.
DR PIR; A46661; A46661.
DR RefSeq; NP_000887.2; NM_000896.2.
DR RefSeq; NP_001186137.1; NM_001199208.1.
DR RefSeq; NP_001186138.1; NM_001199209.1.
DR UniGene; Hs.106242; -.
DR ProteinModelPortal; Q08477; -.
DR SMR; Q08477; 98-515.
DR IntAct; Q08477; 2.
DR PhosphoSite; Q08477; -.
DR DMDM; 56757430; -.
DR PaxDb; Q08477; -.
DR PRIDE; Q08477; -.
DR Ensembl; ENST00000221307; ENSP00000221307; ENSG00000186529.
DR Ensembl; ENST00000585846; ENSP00000468105; ENSG00000186529.
DR Ensembl; ENST00000586182; ENSP00000466395; ENSG00000186529.
DR Ensembl; ENST00000591058; ENSP00000466988; ENSG00000186529.
DR GeneID; 4051; -.
DR KEGG; hsa:4051; -.
DR UCSC; uc002nbk.3; human.
DR CTD; 4051; -.
DR GeneCards; GC19P015751; -.
DR H-InvDB; HIX0039919; -.
DR H-InvDB; HIX0169080; -.
DR H-InvDB; HIX0169326; -.
DR HGNC; HGNC:2646; CYP4F3.
DR MIM; 601270; gene.
DR neXtProt; NX_Q08477; -.
DR PharmGKB; PA234; -.
DR eggNOG; COG2124; -.
DR HOGENOM; HOG000233833; -.
DR HOVERGEN; HBG000182; -.
DR InParanoid; Q08477; -.
DR KO; K00490; -.
DR OMA; PVIRFCH; -.
DR OrthoDB; EOG7CNZFK; -.
DR PhylomeDB; Q08477; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; Q08477; -.
DR UniPathway; UPA00883; -.
DR GeneWiki; CYP4F3; -.
DR GenomeRNAi; 4051; -.
DR NextBio; 15870; -.
DR PRO; PR:Q08477; -.
DR ArrayExpress; Q08477; -.
DR Bgee; Q08477; -.
DR CleanEx; HS_CYP4F3; -.
DR Genevestigator; Q08477; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0052871; F:alpha-tocopherol omega-hydroxylase activity; IEA:UniProtKB-EC.
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; IEA:UniProtKB-EC.
DR GO; GO:0004497; F:monooxygenase activity; TAS:ProtInc.
DR GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
DR GO; GO:0036101; P:leukotriene B4 catabolic process; IEA:GOC.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Alternative promoter usage; Alternative splicing; Complete proteome;
KW Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome;
KW Monooxygenase; NADP; Oxidoreductase; Polymorphism; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1 520 Leukotriene-B(4) omega-hydroxylase 2.
FT /FTId=PRO_0000051851.
FT TRANSMEM 11 31 Helical; (Potential).
FT METAL 468 468 Iron (heme axial ligand) (By similarity).
FT BINDING 328 328 Heme (covalent; via 1 link) (By
FT similarity).
FT VAR_SEQ 67 114 IHSSEEGLLYTQSLACTFGDMCCWWVGPWHAIVRIFHPTYI
FT KPVLFAP -> VTPTEQGMRVLTQLVATYPQGFKVWMGPIF
FT PVIRFCHPNIIRSVINAS (in isoform CYP4F3B).
FT /FTId=VSP_047193.
FT VARIANT 96 96 H -> Q (in dbSNP:rs34923393).
FT /FTId=VAR_048457.
FT VARIANT 106 106 Y -> C (in dbSNP:rs35888783).
FT /FTId=VAR_048458.
FT VARIANT 269 269 A -> D (in dbSNP:rs1805040).
FT /FTId=VAR_001258.
FT VARIANT 270 270 V -> I (in dbSNP:rs28371536).
FT /FTId=VAR_020664.
FT VARIANT 271 271 I -> T (in dbSNP:rs28371479).
FT /FTId=VAR_020665.
FT CONFLICT 184 186 EGS -> KGY (in Ref. 3; AAC08589).
FT CONFLICT 488 488 R -> A (in Ref. 1; BAA02144 and 2;
FT BAA25990/BAA25991).
FT CONFLICT 512 512 L -> I (in Ref. 3; AAC08589).
SQ SEQUENCE 520 AA; 59847 MW; 2519D875280CF9DC CRC64;
MPQLSLSSLG LWPMAASPWL LLLLVGASWL LARILAWTYT FYDNCCRLRC FPQPPKRNWF
LGHLGLIHSS EEGLLYTQSL ACTFGDMCCW WVGPWHAIVR IFHPTYIKPV LFAPAAIVPK
DKVFYSFLKP WLGDGLLLSA GEKWSRHRRM LTPAFHFNIL KPYMKIFNES VNIMHAKWQL
LASEGSARLD MFEHISLMTL DSLQKCVFSF DSHCQEKPSE YIAAILELSA LVTKRHQQIL
LYIDFLYYLT PDGQRFRRAC RLVHDFTDAV IQERRRTLPS QGVDDFLQAK AKSKTLDFID
VLLLSKDEDG KKLSDEDIRA EADTFMFEGH DTTASGLSWV LYHLAKHPEY QERCRQEVQE
LLKDREPKEI EWDDLAQLPF LTMCIKESLR LHPPVPAVSR CCTQDIVLPD GRVIPKGIIC
LISVFGTHHN PAVWPDPEVY DPFRFDPKNI KERSPLAFIP FSAGPRNCIG QAFAMAEMKV
VLGLTLLRFR VLPDHTEPRR KPELVLRAEG GLWLRVEPLS
//
MIM
601270
*RECORD*
*FIELD* NO
601270
*FIELD* TI
*601270 CYTOCHROME P450, FAMILY 4, SUBFAMILY F, POLYPEPTIDE 3; CYP4F3
;;CYTOCHROME P450, SUBFAMILY IVF, POLYPEPTIDE 3;;
read moreLEUKOTRIENE B4 OMEGA-HYDROXYLASE; LTB4H;;
LTB4 OMEGA-HYDROXYLASE
*FIELD* TX
CLONING
Leukotrienes are a group of bioactive compounds that play important
roles in such processes as inflammation. Kikuta et al. (1993) isolated a
cDNA for human leukotriene B4 omega-hydroxylase (LTB4H), an enzyme that
catalyzes the omega-hydroxylation of leukotriene B4. The deduced
520-amino acid LTB4H protein has a predicted molecular mass of 59,805
Da. It contains a cysteine in the conserved heme-binding domain near the
C-terminus, which is a characteristic feature of the cytochrome P450
superfamily; the protein shares 31 to 44% similarity with CYP4A, CYP4B
(124075), and CYP4C. Kikuta et al. (1993) detected transcript from the
LTB4H gene in polymorphonuclear leukocytes and leukocytes.
GENE STRUCTURE
Kikuta et al. (1998) determined that the CYP4F3 gene contains 13 exons
and spans approximately 22.2 kb.
MAPPING
By fluorescence in situ hybridization, Kikuta et al. (1998) mapped the
CYP4F3 gene to chromosome 19p13.2.
*FIELD* RF
1. Kikuta, Y.; Kato, M.; Yamashita, Y.; Miyauchi, Y.; Tanaka, K.;
Kamada, N.; Kusunose, M.: Human leukotriene B4 omega-hydroxylase
(CYP4F3) gene: molecular cloning and chromosomal localization. DNA
Cell Biol. 17: 221-230, 1998.
2. Kikuta, Y.; Kusunose, E.; Endo, K.; Yamamoto, S.; Sogawa, K.; Fujii-Kuriyama,
Y.; Kusunose, M.: A novel form of cytochrome P-450 family 4 in human
polymorphonuclear leukocytes: cDNA cloning and expression of leukotriene
B4 omega-hydroxylase. J. Biol. Chem. 268: 9376-9380, 1993.
*FIELD* CN
Carol A. Bocchini - updated: 3/7/1999
*FIELD* CD
Mark H. Paalman: 5/21/1996
*FIELD* ED
carol: 09/29/2007
mgross: 1/13/2000
carol: 9/30/1999
terry: 3/9/1999
carol: 3/7/1999
mark: 5/21/1996
terry: 5/21/1996
mark: 5/21/1996
terry: 5/21/1996
*RECORD*
*FIELD* NO
601270
*FIELD* TI
*601270 CYTOCHROME P450, FAMILY 4, SUBFAMILY F, POLYPEPTIDE 3; CYP4F3
;;CYTOCHROME P450, SUBFAMILY IVF, POLYPEPTIDE 3;;
read moreLEUKOTRIENE B4 OMEGA-HYDROXYLASE; LTB4H;;
LTB4 OMEGA-HYDROXYLASE
*FIELD* TX
CLONING
Leukotrienes are a group of bioactive compounds that play important
roles in such processes as inflammation. Kikuta et al. (1993) isolated a
cDNA for human leukotriene B4 omega-hydroxylase (LTB4H), an enzyme that
catalyzes the omega-hydroxylation of leukotriene B4. The deduced
520-amino acid LTB4H protein has a predicted molecular mass of 59,805
Da. It contains a cysteine in the conserved heme-binding domain near the
C-terminus, which is a characteristic feature of the cytochrome P450
superfamily; the protein shares 31 to 44% similarity with CYP4A, CYP4B
(124075), and CYP4C. Kikuta et al. (1993) detected transcript from the
LTB4H gene in polymorphonuclear leukocytes and leukocytes.
GENE STRUCTURE
Kikuta et al. (1998) determined that the CYP4F3 gene contains 13 exons
and spans approximately 22.2 kb.
MAPPING
By fluorescence in situ hybridization, Kikuta et al. (1998) mapped the
CYP4F3 gene to chromosome 19p13.2.
*FIELD* RF
1. Kikuta, Y.; Kato, M.; Yamashita, Y.; Miyauchi, Y.; Tanaka, K.;
Kamada, N.; Kusunose, M.: Human leukotriene B4 omega-hydroxylase
(CYP4F3) gene: molecular cloning and chromosomal localization. DNA
Cell Biol. 17: 221-230, 1998.
2. Kikuta, Y.; Kusunose, E.; Endo, K.; Yamamoto, S.; Sogawa, K.; Fujii-Kuriyama,
Y.; Kusunose, M.: A novel form of cytochrome P-450 family 4 in human
polymorphonuclear leukocytes: cDNA cloning and expression of leukotriene
B4 omega-hydroxylase. J. Biol. Chem. 268: 9376-9380, 1993.
*FIELD* CN
Carol A. Bocchini - updated: 3/7/1999
*FIELD* CD
Mark H. Paalman: 5/21/1996
*FIELD* ED
carol: 09/29/2007
mgross: 1/13/2000
carol: 9/30/1999
terry: 3/9/1999
carol: 3/7/1999
mark: 5/21/1996
terry: 5/21/1996
mark: 5/21/1996
terry: 5/21/1996