ID CP2U1_MOUSE Reviewed; 530 AA. AC Q9CX98; Q8BIM3; DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 26-JUN-2007, sequence version 2. DT 27-MAR-2024, entry version 166. DE RecName: Full=Cytochrome P450 2U1; DE AltName: Full=Long-chain fatty acid omega-monooxygenase; DE EC=1.14.14.80 {ECO:0000250|UniProtKB:Q7Z449}; GN Name=Cyp2u1 {ECO:0000312|MGI:MGI:1918769}; 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 [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC STRAIN=C57BL/6J; TISSUE=Heart, Lung, and Thymus; 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 [2] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=15752708; DOI=10.1016/j.abb.2005.02.001; RA Choudhary D., Jansson I., Stoilov I., Sarfarazi M., Schenkman J.B.; RT "Expression patterns of mouse and human CYP orthologs (families 1-4) during RT development and in different adult tissues."; RL Arch. Biochem. Biophys. 436:50-61(2005). RN [3] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=23176821; DOI=10.1016/j.ajhg.2012.11.001; RA Tesson C., Nawara M., Salih M.A., Rossignol R., Zaki M.S., Al Balwi M., RA Schule R., Mignot C., Obre E., Bouhouche A., Santorelli F.M., Durand C.M., RA Oteyza A.C., El-Hachimi K.H., Al Drees A., Bouslam N., Lamari F., RA Elmalik S.A., Kabiraj M.M., Seidahmed M.Z., Esteves T., Gaussen M., RA Monin M.L., Gyapay G., Lechner D., Gonzalez M., Depienne C., Mochel F., RA Lavie J., Schols L., Lacombe D., Yahyaoui M., Al Abdulkareem I., RA Zuchner S., Yamashita A., Benomar A., Goizet C., Durr A., Gleeson J.G., RA Darios F., Brice A., Stevanin G.; RT "Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form RT and function in hereditary spastic paraplegia."; RL Am. J. Hum. Genet. 91:1051-1064(2012). CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of CC arachidonic acid and its conjugates. Mechanistically, uses molecular CC oxygen inserting one oxygen atom into a substrate, and reducing the CC second into a water molecule, with two electrons provided by NADPH via CC cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Acts CC as an omega and omega-1 hydroxylase for arachidonic acid and possibly CC for other long chain fatty acids. May modulate the arachidonic acid CC signaling pathway and play a role in other fatty acid signaling CC processes. May down-regulate the biological activities of N- CC arachidonoyl-serotonin, an endocannabinoid that has anti-nociceptive CC effects through inhibition of fatty acid amide hydrolase FAAH, TRPV1 CC receptor and T-type calcium channels. Catalyzes C-2 oxidation of the CC indole ring of N-arachidonoyl-serotonin forming a less active product CC 2-oxo-N-arachidonoyl-serotonin. {ECO:0000250|UniProtKB:Q7Z449}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an omega-methyl-long-chain fatty acid + O2 + reduced CC [NADPH--hemoprotein reductase] = an omega-hydroxy-long-chain fatty CC acid + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; CC Xref=Rhea:RHEA:56748, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:140991, CC ChEBI:CHEBI:140992; EC=1.14.14.80; CC Evidence={ECO:0000250|UniProtKB:Q7Z449}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56749; CC Evidence={ECO:0000250|UniProtKB:Q7Z449}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:39759, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, CC ChEBI:CHEBI:76627; Evidence={ECO:0000250|UniProtKB:Q7Z449}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39760; CC Evidence={ECO:0000250|UniProtKB:Q7Z449}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:39755, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, CC ChEBI:CHEBI:76624; Evidence={ECO:0000250|UniProtKB:Q7Z449}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39756; CC Evidence={ECO:0000250|UniProtKB:Q7Z449}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-[(5Z,8Z,11Z,14Z)-eicosatetraenoyl]-serotonin + O2 + reduced CC [NADPH--hemoprotein reductase] = 2-oxo-N-[(5Z,8Z,11Z,14Z)- CC eicosatetraenoyl]-serotonin + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50296, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210, ChEBI:CHEBI:132255, ChEBI:CHEBI:132256; CC Evidence={ECO:0000250|UniProtKB:Q7Z449}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50297; CC Evidence={ECO:0000250|UniProtKB:Q7Z449}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC Evidence={ECO:0000250|UniProtKB:Q7Z449}; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q7Z449}; Multi-pass membrane protein CC {ECO:0000255}. Microsome membrane {ECO:0000250|UniProtKB:Q7Z449}; CC Multi-pass membrane protein {ECO:0000255}. Mitochondrion inner membrane CC {ECO:0000250|UniProtKB:Q7Z449}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9CX98-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9CX98-2; Sequence=VSP_026227, VSP_026228; CC Name=3; CC IsoId=Q9CX98-3; Sequence=VSP_026224, VSP_026225, VSP_026226; CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in heart, brain and CC liver. {ECO:0000269|PubMed:15752708, ECO:0000269|PubMed:23176821}. CC -!- DEVELOPMENTAL STAGE: Expressed at all stages after 7 dpc. Expressed in CC brain structures including cortex, diencephalon, medulla oblongata, CC spine and cerebellum at 12 dpc. Expression in embryonic nervous system CC increases during development, as measured at 15 dpc and 18 dpc CC timepoints. {ECO:0000269|PubMed:15752708, ECO:0000269|PubMed:23176821}. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AK142740; Type=Frameshift; Evidence={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; AK018458; BAB31223.1; -; mRNA. DR EMBL; AK041477; BAC30954.1; -; mRNA. DR EMBL; AK142740; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS51069.1; -. [Q9CX98-1] DR RefSeq; NP_082092.2; NM_027816.3. [Q9CX98-1] DR AlphaFoldDB; Q9CX98; -. DR SMR; Q9CX98; -. DR BioGRID; 214754; 43. DR STRING; 10090.ENSMUSP00000101944; -. DR iPTMnet; Q9CX98; -. DR PhosphoSitePlus; Q9CX98; -. DR MaxQB; Q9CX98; -. DR PaxDb; 10090-ENSMUSP00000101944; -. DR ProteomicsDB; 278008; -. [Q9CX98-1] DR ProteomicsDB; 278009; -. [Q9CX98-2] DR ProteomicsDB; 278010; -. [Q9CX98-3] DR Antibodypedia; 26251; 171 antibodies from 25 providers. DR DNASU; 71519; -. DR Ensembl; ENSMUST00000106337.7; ENSMUSP00000101944.3; ENSMUSG00000027983.14. [Q9CX98-1] DR Ensembl; ENSMUST00000200236.2; ENSMUSP00000142519.2; ENSMUSG00000027983.14. [Q9CX98-2] DR GeneID; 71519; -. DR KEGG; mmu:71519; -. DR UCSC; uc008rjn.1; mouse. [Q9CX98-1] DR UCSC; uc008rjo.1; mouse. [Q9CX98-2] DR UCSC; uc008rjp.1; mouse. [Q9CX98-3] DR AGR; MGI:1918769; -. DR CTD; 113612; -. DR MGI; MGI:1918769; Cyp2u1. DR VEuPathDB; HostDB:ENSMUSG00000027983; -. DR eggNOG; KOG0156; Eukaryota. DR GeneTree; ENSGT00940000157714; -. DR HOGENOM; CLU_001570_22_3_1; -. DR InParanoid; Q9CX98; -. DR OMA; EPCIQQG; -. DR OrthoDB; 2900138at2759; -. DR PhylomeDB; Q9CX98; -. DR TreeFam; TF352043; -. DR Reactome; R-MMU-211958; Miscellaneous substrates. DR Reactome; R-MMU-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE). DR BioGRID-ORCS; 71519; 4 hits in 79 CRISPR screens. DR PRO; PR:Q9CX98; -. DR Proteomes; UP000000589; Chromosome 3. DR RNAct; Q9CX98; Protein. DR Bgee; ENSMUSG00000027983; Expressed in hepatobiliary system and 55 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central. DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell. DR GO; GO:0052869; F:arachidonic acid omega-hydroxylase activity; ISO:MGI. DR GO; GO:0020037; F:heme binding; IBA:GO_Central. 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:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IBA:GO_Central. DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central. DR GO; GO:0097267; P:omega-hydroxylase P450 pathway; ISO:MGI. DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central. DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central. DR CDD; cd20666; CYP2U1; 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; IPR008069; Cyt_P450_E_grp-I_CYP2D-like. DR InterPro; IPR036396; Cyt_P450_sf. DR PANTHER; PTHR24300:SF281; CYTOCHROME P450 2U1; 1. DR PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR01686; EP450ICYP2D. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; Q9CX98; MM. PE 2: Evidence at transcript level; KW Alternative splicing; Endoplasmic reticulum; Heme; Iron; Lipid metabolism; KW Membrane; Metal-binding; Microsome; Mitochondrion; KW Mitochondrion inner membrane; Monooxygenase; Oxidoreductase; KW Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1..530 FT /note="Cytochrome P450 2U1" FT /id="PRO_0000291757" FT TRANSMEM 21..41 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 99..119 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 247..267 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 328..348 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 481..501 FT /note="Helical" FT /evidence="ECO:0000255" FT BINDING 476 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" FT VAR_SEQ 236..270 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_026224" FT VAR_SEQ 416 FT /note="V -> A (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_026225" FT VAR_SEQ 417..530 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_026226" FT VAR_SEQ 473..501 FT /note="KRVCMGEQLAKMELFLMFVSLMQTFTFAL -> QLKLGFNLFFTLSLVCVCV FT CVCVCVYRHV (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_026227" FT VAR_SEQ 502..530 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_026228" SQ SEQUENCE 530 AA; 60578 MW; FCB595EADA88A213 CRC64; MSSLGDQRPA AGEQPGARLH VRATGGALLL CLLAVLLGWV WLRRQRACGI PPGPKPRPLV GNFGHLLVPR FLRPQFWLGS GSQTDTVGQH VYLARMARVY GNIFSFFIGH RLVVVLSDFH SVREALVQQA EVFSDRPRMP LISIMTKEKG IVFAHYGPIW KQQRRFSHST LRHFGLGKLS LEPRIIEEFA YVKEAMQKHG EAPFSPFPII SNAVSNIICS LCFGQRFDYT NKEFKKVLDF MSRGLEICLH SQLFLINICP WFYYLPFGPF KELRQIERDI SCFLKNIIRE HQESLDASNP QDFIDMYLLH MEEEQGASRR SSFDEDYLFY IIGDLFIAGT DTTTNSLLWC LLYMSLNPDV QKKVHEEIER VIGCDRAPSL TDKAQMPYTE ATIMEVQRLS MVVPLAIPHM TSEKTVLQGF TIPKGTVVLI NLWSVHRDPA IWEKPDDFCP HRFLDDQGQL LKRETFIPFG IGKRVCMGEQ LAKMELFLMF VSLMQTFTFA LPEGSEKPVM TGRFGLTLAP HPFNVTISKR //