CP4V2_MOUSE
ID CP4V2_MOUSE Reviewed; 525 AA.
AC Q9DBW0;
DT 02-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Cytochrome P450 4V2;
DE AltName: Full=Docosahexaenoic acid omega-hydroxylase CYP4V2 {ECO:0000250|UniProtKB:Q6ZWL3};
DE EC=1.14.14.79 {ECO:0000250|UniProtKB:Q6ZWL3};
DE AltName: Full=Long-chain fatty acid omega-monooxygenase {ECO:0000250|UniProtKB:Q6ZWL3};
DE EC=1.14.14.80 {ECO:0000250|UniProtKB:Q6ZWL3};
GN Name=Cyp4v2; Synonyms=Cyp4v3;
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 STRAIN=C57BL/6J; TISSUE=Liver;
RA Fujita Y., Kase K., Ohi H.;
RT "Mouse mRNA for cytochrome P450, cDNA clone KK-1.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Lung;
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 PROTEIN SEQUENCE OF 472-478, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and Liver;
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).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in fatty acid
CC metabolism in the eye. Catalyzes the omega-hydroxylation of
CC polyunsaturated fatty acids (PUFAs) docosahexaenoate (DHA) and its
CC precursor eicosapentaenoate (EPA), and may contribute to the
CC homeostasis of these retinal PUFAs. Omega hydroxylates saturated fatty
CC acids such as laurate, myristate and palmitate, the catalytic
CC efficiency decreasing in the following order: myristate > laurate >
CC palmitate (C14>C12>C16). Mechanistically, uses molecular oxygen
CC inserting one oxygen atom into a substrate, and reducing the second
CC into a water molecule, with two electrons provided by NADPH via
CC cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).
CC {ECO:0000250|UniProtKB:Q6ZWL3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 12-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:38947, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18262, ChEBI:CHEBI:36204, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38948;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + tetradecanoate =
CC 14-hydroxytetradecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40203, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:77033; Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40204;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 16-hydroxyhexadecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40199, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:55329, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.80;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40200;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39791, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:76639; Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39792;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = 22-hydroxy-(4Z,7Z,10Z,13Z,16Z,19Z)-
CC docosahexaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40155, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77015,
CC ChEBI:CHEBI:77016; EC=1.14.14.79;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40156;
CC Evidence={ECO:0000250|UniProtKB:Q6ZWL3};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P51869};
CC -!- ACTIVITY REGULATION: Inhibited by N-hydroxy-N'-(4-n-butyl-2-
CC methylphenyl formamidine)(HET0016) with an IC(50) of 38 nM.
CC {ECO:0000250|UniProtKB:Q6ZWL3}.
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000250|UniProtKB:Q6ZWL3}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q6ZWL3}; Single-pass membrane protein
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AB056457; BAB33032.1; -; mRNA.
DR EMBL; AK004724; BAB23507.1; -; mRNA.
DR CCDS; CCDS22276.1; -.
DR RefSeq; NP_598730.1; NM_133969.2.
DR AlphaFoldDB; Q9DBW0; -.
DR SMR; Q9DBW0; -.
DR STRING; 10090.ENSMUSP00000092966; -.
DR iPTMnet; Q9DBW0; -.
DR PhosphoSitePlus; Q9DBW0; -.
DR SwissPalm; Q9DBW0; -.
DR jPOST; Q9DBW0; -.
DR MaxQB; Q9DBW0; -.
DR PaxDb; Q9DBW0; -.
DR PRIDE; Q9DBW0; -.
DR ProteomicsDB; 285282; -.
DR DNASU; 102294; -.
DR Ensembl; ENSMUST00000095328; ENSMUSP00000092966; ENSMUSG00000079057.
DR GeneID; 102294; -.
DR KEGG; mmu:102294; -.
DR UCSC; uc009lou.1; mouse.
DR CTD; 102294; -.
DR MGI; MGI:2142763; Cyp4v3.
DR VEuPathDB; HostDB:ENSMUSG00000079057; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000157278; -.
DR HOGENOM; CLU_001570_5_1_1; -.
DR InParanoid; Q9DBW0; -.
DR OMA; IFRRMKM; -.
DR OrthoDB; 1247045at2759; -.
DR PhylomeDB; Q9DBW0; -.
DR TreeFam; TF105088; -.
DR Reactome; R-MMU-211976; Endogenous sterols.
DR Reactome; R-MMU-2453902; The canonical retinoid cycle in rods (twilight vision).
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 102294; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Cyp4v3; mouse.
DR PRO; PR:Q9DBW0; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9DBW0; protein.
DR Bgee; ENSMUSG00000079057; Expressed in small intestine Peyer's patch and 179 other tissues.
DR ExpressionAtlas; Q9DBW0; baseline and differential.
DR Genevisible; Q9DBW0; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0102033; F:long-chain fatty acid omega-hydroxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0010430; P:fatty acid omega-oxidation; ISS:UniProtKB.
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 Direct protein sequencing; Endoplasmic reticulum; Heme; Iron;
KW Lipid metabolism; Membrane; Metal-binding; Monooxygenase; NADP;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..525
FT /note="Cytochrome P450 4V2"
FT /id="PRO_0000051861"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 329
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:P51869"
FT BINDING 467
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:P51869"
SQ SEQUENCE 525 AA; 60939 MW; 71BB341589BD10A6 CRC64;
MLWLWLGLSG QKLLLWGAAS AVSLAGATIL ISIFPMLVSY ARKWQQMRSI PSVARAYPLV
GHALYMKPNN AEFFQQLIYY TEEFRHLPII KLWIGPVPLV ALYKAENVEV ILTSSKQIDK
SFLYKFLQPW LGLGLLTSTG SKWRTRRKML TPTFHFTILE NFLDVMNEQA NILVNKLEKH
VNQEAFNCFF YITLCALDII CETAMGKNIG AQSNNDSEYV RTVYRMSDMI YRRMKMPWLW
FDLWYLVFKE GRDHKRGLKC LHTFTNNVIA ERVKERKAEE DWTGAGRGPI PSKNKRKAFL
DLLLSVTDEE GNRLSQEDIR EEVDTFMFEG HDTTAAAINW SLYLLGTNPE VQRKVDQELD
EVFGRSHRPV TLEDLKKLKY LDCVIKETLR VFPSVPLFAR SLSEDCEVGG YKVTKGTEAI
IIPYALHRDP RYFPDPEEFR PERFFPENSQ GRHPYAYVPF SAGPRNCIGQ KFAVMEEKTI
LACILRQFWV ESNQKREELG LAGDLILRPN NGIWIKLKRR HEDDP
