CP2U1_RAT
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 03-AUG-2022, entry version 125.
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 [NADPH--
CC hemoprotein reductase] = an omega-hydroxy-long-chain fatty acid +
CC 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 [NADPH--
CC hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:39759, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC 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 [NADPH--
CC hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:39755, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC 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 [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:50296, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC 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}.
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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.ENSRNOP00000052433; -.
DR PaxDb; Q4V8D1; -.
DR Ensembl; ENSRNOT00000055570; ENSRNOP00000052433; ENSRNOG00000011053.
DR GeneID; 310848; -.
DR KEGG; rno:310848; -.
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; 702827at2759; -.
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 tissues.
DR Genevisible; Q4V8D1; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 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 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
