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 27-MAR-2024, entry version 157. 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 CC [NADPH--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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 BioGRID; 221840; 1. DR STRING; 10090.ENSMUSP00000092966; -. DR GlyGen; Q9DBW0; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9DBW0; -. DR PhosphoSitePlus; Q9DBW0; -. DR SwissPalm; Q9DBW0; -. DR jPOST; Q9DBW0; -. DR MaxQB; Q9DBW0; -. DR PaxDb; 10090-ENSMUSP00000092966; -. DR ProteomicsDB; 285282; -. DR Pumba; Q9DBW0; -. DR DNASU; 102294; -. DR Ensembl; ENSMUST00000095328.6; ENSMUSP00000092966.5; ENSMUSG00000079057.5. DR GeneID; 102294; -. DR KEGG; mmu:102294; -. DR UCSC; uc009lou.1; mouse. DR AGR; MGI:2142763; -. 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; DIDHMPY; -. DR OrthoDB; 1611592at2759; -. 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 77 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 180 other cell types or tissues. DR ExpressionAtlas; Q9DBW0; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. 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 CDD; cd20680; CYP4V; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 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 PANTHER; PTHR24291:SF189; CYTOCHROME P450 4V2; 1. DR PANTHER; PTHR24291; CYTOCHROME P450 FAMILY 4; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; Q9DBW0; MM. 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 //