ID   CP2U1_BOVIN             Reviewed;         543 AA.
AC   Q0IIF9;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 1.
DT   27-MAR-2024, entry version 101.
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   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Fetal liver;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
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   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; BC122663; AAI22664.1; -; mRNA.
DR   RefSeq; NP_001069518.1; NM_001076050.2.
DR   AlphaFoldDB; Q0IIF9; -.
DR   SMR; Q0IIF9; -.
DR   STRING; 9913.ENSBTAP00000017246; -.
DR   PaxDb; 9913-ENSBTAP00000017246; -.
DR   GeneID; 535227; -.
DR   KEGG; bta:535227; -.
DR   CTD; 113612; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   InParanoid; Q0IIF9; -.
DR   OrthoDB; 2900138at2759; -.
DR   Proteomes; UP000009136; Unplaced.
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: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:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
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.
PE   2: Evidence at transcript 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..543
FT                   /note="Cytochrome P450 2U1"
FT                   /id="PRO_0000291755"
FT   TRANSMEM        32..52
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        58..78
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        261..281
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        342..362
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        495..515
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         490
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   543 AA;  61997 MW;  00DEC2B84EC1D93C CRC64;
     MASPGLPQPP TEDAAWPLRL LHAPPGLLRL DPTGGALLLL VLAALLGWSW LWRLPERGIP
     PGPAPWPVVG NFGFVLLPRF LRRKSWPYRR ARNGGMNASG QGVQLLLADL GRVYGNIFSF
     LIGHYLVVVL NDFHSVREAL VQQAEVFSDR PRVPLTSIMT KGKGIVFAHY GPVWRQQRKF
     SHSTLRHFGL GKLSLEPKII EEFRYVKEEM QKHGDAPFNP FPIVNNAVSN IICSLCFGRR
     FDYTNSEFKQ MLNFMSRALE VCLNTQLLLV NICSWLYYLP FGPFKELRQI EKDLTLFLKK
     IIKDHRESLD VENPQDFIDM YLLHVEEEKK NNSNSGFDED YLFYIIGDLF IAGTDTTTNS
     LLWCLLYMSL HPNIQEKIHE EIARVIGADR APSLTDKAQM PYTEATIMEV QRLSTVVPLS
     IPHMTSEKTV LQGFTIPKGT IILPNLWSVH RDPAIWEKPN DFYPDRFLDD QGQLIKKETF
     IPFGIGKRVC MGEQLAKMEL FLMFVSLMQS FTFVLPKDSK PILTGKYGLT LAPHPFNIII
     SKR
//