CP4CB_MOUSE
ID CP4CB_MOUSE Reviewed; 508 AA.
AC A2A974;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Cytochrome P450 4A12B {ECO:0000303|PubMed:17112342};
DE EC=1.14.14.1 {ECO:0000269|PubMed:17112342};
DE Flags: Precursor;
GN Name=Cyp4a12b {ECO:0000303|PubMed:17112342, ECO:0000312|MGI:MGI:3611747};
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, TISSUE SPECIFICITY, PATHWAY, AND SUBCELLULAR LOCATION.
RX PubMed=17112342; DOI=10.1042/bj20061328;
RA Muller D.N., Schmidt C., Barbosa-Sicard E., Wellner M., Gross V.,
RA Hercule H., Markovic M., Honeck H., Luft F.C., Schunck W.H.;
RT "Mouse Cyp4a isoforms: enzymatic properties, gender- and strain-specific
RT expression, and role in renal 20-hydroxyeicosatetraenoic acid formation.";
RL Biochem. J. 403:109-118(2007).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC fatty acids and their oxygenated derivatives (oxylipins)
CC (PubMed:17112342). Mechanistically, uses molecular oxygen inserting one
CC oxygen atom into a substrate, and reducing the second into a water
CC molecule, with two electrons provided by NADPH via cytochrome P450
CC reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:17112342).
CC Catalyzes predominantly the oxidation of the terminal carbon (omega-
CC oxidation) of saturated and unsaturated fatty acids (PubMed:17112342).
CC May act as a major omega-hydroxylase for dodecanoic (lauric) acid in
CC kidney (PubMed:17112342). Participates in omega-hydroxylation of
CC (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to 20-
CC hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting
CC both as vasoconstrictive and natriuretic with overall effect on
CC arterial blood pressure (PubMed:17112342). Acts as an omega-hydroxylase
CC and epoxidase toward (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoc acid (EPA).
CC Catalyzes the epoxidation of the last double bond of EPA with no
CC preferred stereoselectivity, producing both (R,S) and (S,R)
CC stereoisomers (PubMed:17112342). Can also catalyze the omega-1 and
CC omega-2 oxidation of fatty acids with lower efficiency
CC (PubMed:17112342). {ECO:0000269|PubMed:17112342}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC Evidence={ECO:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000305|PubMed:17112342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 11-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39751, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18262, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76628; Evidence={ECO:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39752;
CC Evidence={ECO:0000305|PubMed:17112342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 12-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:38947, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18262, ChEBI:CHEBI:36204, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38948;
CC Evidence={ECO:0000305|PubMed:17112342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 18-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:39811, 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:63590; Evidence={ECO:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39812;
CC Evidence={ECO:0000305|PubMed:17112342};
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:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39760;
CC Evidence={ECO:0000305|PubMed:17112342};
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:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39756;
CC Evidence={ECO:0000305|PubMed:17112342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39787, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:76636; Evidence={ECO:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39788;
CC Evidence={ECO:0000305|PubMed:17112342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39791, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:76639; Evidence={ECO:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39792;
CC Evidence={ECO:0000305|PubMed:17112342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (17S,18R)-epoxy-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39783, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:76635; Evidence={ECO:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39784;
CC Evidence={ECO:0000305|PubMed:17112342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39779, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:76634; Evidence={ECO:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780;
CC Evidence={ECO:0000305|PubMed:17112342};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P20817};
CC -!- ACTIVITY REGULATION: Activated by cytochrome b5. The Vmax almost
CC doubles in the presence of cytochrome b5.
CC {ECO:0000269|PubMed:17112342}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2 uM for dodecanoic acid {ECO:0000269|PubMed:17112342};
CC KM=43 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (without
CC cytochrome b5) {ECO:0000269|PubMed:17112342};
CC KM=72 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (with cytochrome
CC b5) {ECO:0000269|PubMed:17112342};
CC KM=41 uM for (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid (without
CC cytochrome b5) {ECO:0000269|PubMed:17112342};
CC KM=62 uM for (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid (with
CC cytochrome b5) {ECO:0000269|PubMed:17112342};
CC Vmax=40 nmol/min/nmol enzyme toward dodecanoic acid
CC {ECO:0000269|PubMed:17112342};
CC Vmax=10 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z)-eicosatetraenoic
CC acid (without cytochrome b5) {ECO:0000269|PubMed:17112342};
CC Vmax=19 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z)-eicosatetraenoic
CC acid (with cytochrome b5) {ECO:0000269|PubMed:17112342};
CC Vmax=15 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoic acid (without cytochrome b5)
CC {ECO:0000269|PubMed:17112342};
CC Vmax=30 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoic acid (with cytochrome b5)
CC {ECO:0000269|PubMed:17112342};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000305|PubMed:17112342}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:17112342}; Peripheral membrane protein. Microsome
CC membrane {ECO:0000269|PubMed:17112342}; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in lung, but almost undetectable in the
CC kidneys of five different strains. {ECO:0000269|PubMed:17112342}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000255|RuleBase:RU000461}.
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DR EMBL; AL627182; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS18490.1; -.
DR RefSeq; NP_758510.2; NM_172306.2.
DR AlphaFoldDB; A2A974; -.
DR SMR; A2A974; -.
DR STRING; 10090.ENSMUSP00000092487; -.
DR SwissLipids; SLP:000000506; -.
DR iPTMnet; A2A974; -.
DR PhosphoSitePlus; A2A974; -.
DR jPOST; A2A974; -.
DR MaxQB; A2A974; -.
DR PaxDb; A2A974; -.
DR PeptideAtlas; A2A974; -.
DR ProteomicsDB; 365309; -.
DR DNASU; 13118; -.
DR Ensembl; ENSMUST00000094887; ENSMUSP00000092487; ENSMUSG00000078597.
DR GeneID; 13118; -.
DR KEGG; mmu:13118; -.
DR UCSC; uc008ues.1; mouse.
DR CTD; 13118; -.
DR MGI; MGI:3611747; Cyp4a12b.
DR VEuPathDB; HostDB:ENSMUSG00000078597; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000155173; -.
DR HOGENOM; CLU_001570_5_1_1; -.
DR InParanoid; A2A974; -.
DR OMA; IAWNISG; -.
DR OrthoDB; 1247045at2759; -.
DR PhylomeDB; A2A974; -.
DR TreeFam; TF105088; -.
DR Reactome; R-MMU-211935; Fatty acids.
DR Reactome; R-MMU-211958; Miscellaneous substrates.
DR Reactome; R-MMU-211979; Eicosanoids.
DR Reactome; R-MMU-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-MMU-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 13118; 2 hits in 75 CRISPR screens.
DR PRO; PR:A2A974; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; A2A974; protein.
DR Bgee; ENSMUSG00000078597; Expressed in cortex of kidney and 24 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0103002; F:16-hydroxypalmitate dehydrogenase activity; ISO:MGI.
DR GO; GO:0018685; F:alkane 1-monooxygenase activity; ISO:MGI.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; ISO:MGI.
DR GO; GO:0008391; F:arachidonic acid monooxygenase activity; IBA:GO_Central.
DR GO; GO:0052869; F:arachidonic acid omega-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0120250; F:fatty acid omega-hydroxylase activity; ISO:MGI.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0102116; F:laurate hydroxylase activity; ISO:MGI.
DR GO; GO:0050051; F:leukotriene-B4 20-monooxygenase activity; ISO:MGI.
DR GO; GO:0102033; F:long-chain fatty acid omega-hydroxylase activity; ISO:MGI.
DR GO; GO:0004497; F:monooxygenase activity; ISO:MGI.
DR GO; GO:0019369; P:arachidonic acid metabolic process; ISO:MGI.
DR GO; GO:0006631; P:fatty acid metabolic process; ISO:MGI.
DR GO; GO:0046456; P:icosanoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0001822; P:kidney development; IBA:GO_Central.
DR GO; GO:0048252; P:lauric acid metabolic process; ISO:MGI.
DR GO; GO:0043651; P:linoleic acid metabolic process; IBA:GO_Central.
DR GO; GO:0097267; P:omega-hydroxylase P450 pathway; IDA:UniProtKB.
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; Membrane; Metal-binding; Microsome;
KW Monooxygenase; Oxidoreductase; Reference proteome; Signal.
FT SIGNAL 1..37
FT /evidence="ECO:0000255"
FT CHAIN 38..508
FT /note="Cytochrome P450 4A12B"
FT /evidence="ECO:0000255"
FT /id="PRO_0000448898"
FT BINDING 319
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:P51869"
FT BINDING 455
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|UniProtKB:P24464"
SQ SEQUENCE 508 AA; 58309 MW; FF77E39272F590C4 CRC64;
MSASALSSIR FPGSISEYLQ VASVLSLLLL LFKTAQLYLH RQWLLSSTQQ FPSPPSHWLF
GHKILKDQDL QDILTRIKNF PSACPQWLWG SKVRIQVYDP DYMKLILGRS DPKAHGSYRF
LAPWIGRGLL LLDGQTWFQH RRMLTPAFHY DILKPYTEIM ADSVHVMLDK WEQIVGQDST
LEIFQHITLM TLDTIMKCAF SHEGSVQLDR KYKSYIQAVE DLNNLFFLRV RNIFHQNDII
YRVSSNGCLA NSACQLAHDH TDQVIKSRRS QLQDEEELEK LKKKRRLDFL DILLFARMEN
GKSLSDKDLR AEVDTFMFEG HDTTASGISW IFYALATNPE HQQRCRKEIQ SLLGDGASIT
WNDLDKMPYT TMCIKEALRI YPPVPSVSRE LSSPVTFPDG RSLPKGIHVM LSFYGLHHNP
TVWPNPEVFD PSRFAPGSSR HSHSFLPFSG GARNCIGKQF AMNELKVAVA LTLLRFELLP
DPTRVPIPIP RIVLKSKNGI HLHLKKLQ
