CP2U1_MOUSE
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 03-AUG-2022, entry version 157.
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 [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: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};
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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; Q9CX98; -.
DR PRIDE; Q9CX98; -.
DR ProteomicsDB; 278008; -. [Q9CX98-1]
DR ProteomicsDB; 278009; -. [Q9CX98-2]
DR ProteomicsDB; 278010; -. [Q9CX98-3]
DR Antibodypedia; 26251; 149 antibodies from 25 providers.
DR DNASU; 71519; -.
DR Ensembl; ENSMUST00000106337; ENSMUSP00000101944; ENSMUSG00000027983. [Q9CX98-1]
DR Ensembl; ENSMUST00000200236; ENSMUSP00000142519; ENSMUSG00000027983. [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 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; 702827at2759; -.
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 74 CRISPR screens.
DR PRO; PR:Q9CX98; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9CX98; protein.
DR Bgee; ENSMUSG00000027983; Expressed in hepatobiliary system and 54 other tissues.
DR Genevisible; Q9CX98; MM.
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: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 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; IPR008069; Cyt_P450_E_grp-I_CYP2D-like.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01686; EP450ICYP2D.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
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
