ID CP2U1_RAT Reviewed; 530 AA. AC Q4V8D1; DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2005, sequence version 1. DT 27-MAR-2024, entry version 134. 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; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; 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 [2] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=14975754; DOI=10.1016/j.bbrc.2004.01.110; RA Karlgren M., Backlund M., Johansson I., Oscarson M., Ingelman-Sundberg M.; RT "Characterization and tissue distribution of a novel human cytochrome P450- RT CYP2U1."; RL Biochem. Biophys. Res. Commun. 315:679-685(2004). 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:0000269|PubMed:14975754}; Multi-pass membrane protein CC {ECO:0000255}. Microsome membrane {ECO:0000269|PubMed:14975754}; Multi- CC pass membrane protein {ECO:0000255}. Mitochondrion inner membrane CC {ECO:0000250|UniProtKB:Q7Z449}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Specifically expressed in thymus and brain. In CC brain, expressed in cortex, cerebellum, olfactory bulbs, pons and CC medulla and the limbic structures (at protein level). CC {ECO:0000269|PubMed:14975754}. 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; BC097442; AAH97442.1; -; mRNA. DR RefSeq; NP_001019950.1; NM_001024779.1. DR RefSeq; XP_006233372.1; XM_006233310.3. DR AlphaFoldDB; Q4V8D1; -. DR SMR; Q4V8D1; -. DR STRING; 10116.ENSRNOP00000069228; -. DR PhosphoSitePlus; Q4V8D1; -. DR PaxDb; 10116-ENSRNOP00000052433; -. DR Ensembl; ENSRNOT00000055570.4; ENSRNOP00000052433.2; ENSRNOG00000011053.8. DR Ensembl; ENSRNOT00055018264; ENSRNOP00055014673; ENSRNOG00055010802. DR Ensembl; ENSRNOT00060039804; ENSRNOP00060032901; ENSRNOG00060022963. DR Ensembl; ENSRNOT00065024060; ENSRNOP00065018762; ENSRNOG00065014561. DR KEGG; rno:310848; -. DR AGR; RGD:1309433; -. DR CTD; 113612; -. DR RGD; 1309433; Cyp2u1. DR eggNOG; KOG0156; Eukaryota. DR GeneTree; ENSGT00940000157714; -. DR HOGENOM; CLU_001570_22_0_1; -. DR InParanoid; Q4V8D1; -. DR OMA; EPCIQQG; -. DR OrthoDB; 2900138at2759; -. DR PhylomeDB; Q4V8D1; -. DR TreeFam; TF352043; -. DR Reactome; R-RNO-211958; Miscellaneous substrates. DR Reactome; R-RNO-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE). DR PRO; PR:Q4V8D1; -. DR Proteomes; UP000002494; Chromosome 2. DR Bgee; ENSRNOG00000011053; Expressed in thymus and 18 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:RGD. 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:RGD. 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; 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; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; Q4V8D1; RN. PE 1: Evidence at protein level; KW Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane; KW Metal-binding; Microsome; Mitochondrion; Mitochondrion inner membrane; KW Monooxygenase; Oxidoreductase; Reference proteome; Transmembrane; KW Transmembrane helix. FT CHAIN 1..530 FT /note="Cytochrome P450 2U1" FT /id="PRO_0000291758" 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" SQ SEQUENCE 530 AA; 60399 MW; 7BDF8BD34265801A CRC64; MSSIGGLRPA AGEQPGVGPH LQAVGGALLL CGLAVLLDWV WLQRQRAGGI PPGPKPRPLV GNFGYLLLPR FLRLHFWLGS GSQTDTVGRH VYLARLARVY GNIFSFFIGH RLVVVLSDFQ SVREALVQQA EVFSDRPRMP LISILTKEKG IVFAHYGPIW KQQRRFSHST LRHFGLGKLS LEPRIIEEFA YVKAEMQKHG EAPFSPFPVI SNAVSNIICS LCFGQRFDYT NKEFKKVLDF MSRGLEICLH SQLFLINLCP WFYYLPFGPF KELRQIERDI TCFLKNIIKE HQESLDANNP QDFIDMYLLH TQEEKDKCKG TNFDEDYLFY IIGDLFIAGT DTTTNSLLWC LLYMSLNPGV QKKVHEEIER VIGRDRAPSL TDKAQMPYTE ATIMEVQRLS MVVPLAIPHM TSEKTVLQGY SIPKGTVVLP NLWSIHRDPV IWEKPDDFCP HRFLDDQGQL LKRETFIPFG IGKRVCMGEQ LAKMELFLMF VSLMQSFTFA LPEGSEKPIM TGRFGLTLAP HPFNVTVSKR //