CP4AE_MOUSE
ID CP4AE_MOUSE Reviewed; 507 AA.
AC O35728; A2A975; Q3UER2; Q5EBH0;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Cytochrome P450 4A14 {ECO:0000303|PubMed:17112342};
DE AltName: Full=CYPIVA14;
DE AltName: Full=Lauric acid hydroxylase;
DE Flags: Precursor;
GN Name=Cyp4a14 {ECO:0000303|PubMed:17112342, ECO:0000312|MGI:MGI:1096550};
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 [GENOMIC DNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=C57BL/6 X CBA;
RX PubMed=9271096; DOI=10.1042/bj3250741;
RA Heng Y.M., Kuo C.-W.S., Jones P.S., Savory R., Shultz R.M., Tomlinson S.R.,
RA Gray T.J.B., Bell D.R.;
RT "A novel murine P-450 gene, Cyp4a14, is part of a cluster of Cyp4a and
RT Cyp4b, but not of CYP4F, genes in mouse and humans.";
RL Biochem. J. 325:741-749(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Liver;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND PATHWAY.
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).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC fatty acids (PubMed:17112342). Mechanistically, uses molecular oxygen
CC inserting one oxygen atom into a substrate, and reducing the second
CC into a water molecule, with two electrons provided by NADPH via
CC cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase)
CC (PubMed:17112342). Catalyzes the hydroxylation of saturated carbon
CC hydrogen bonds of fatty acids (PubMed:17112342). May act as a major
CC omega- and ommega-1 hydroxylase for dodecanoic (lauric) acid in kidney
CC (PubMed:17112342). Catalyzes with low efficiency the epoxidation of
CC 11,12-double bond of arachidonic acid (PubMed:17112342).
CC {ECO:0000269|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=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=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:51480, 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:76625; Evidence={ECO:0000269|PubMed:17112342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51481;
CC Evidence={ECO:0000305|PubMed:17112342};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P20817};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8 uM for dodecanoic acid {ECO:0000269|PubMed:17112342};
CC Vmax=40 nmol/min/nmol enzyme toward dodecanoic acid
CC {ECO:0000269|PubMed:17112342};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000305|PubMed:17112342}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Gender- and strain-specific expression in kidney
CC (at protein level). Predominantly expressed in females, the expression
CC among strains decreasing in the following order: FVB/N > NMRI > Balb/c
CC > 129 Sv/J > C57BL/6 (PubMed:17112342). Expressed at very low level in
CC liver, kidney and spleen of both male and female C57BL/6 X CBA hybrid
CC mice (PubMed:9271096). {ECO:0000269|PubMed:17112342,
CC ECO:0000269|PubMed:9271096}.
CC -!- INDUCTION: By peroxisome proliferator methylclofenapate; 1000-fold in
CC liver, 10-fold in kidney. {ECO:0000269|PubMed:9271096}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC089609; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; Y11638; CAA72345.1; -; Genomic_DNA.
DR EMBL; Y11639; CAA72345.1; JOINED; Genomic_DNA.
DR EMBL; Y11640; CAA72345.1; JOINED; Genomic_DNA.
DR EMBL; Y11641; CAA72345.1; JOINED; Genomic_DNA.
DR EMBL; Y11642; CAA72345.1; JOINED; Genomic_DNA.
DR EMBL; AK149392; BAE28849.1; -; mRNA.
DR EMBL; AK165452; BAE38193.1; -; mRNA.
DR EMBL; AL627182; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC089609; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS18491.1; -.
DR RefSeq; NP_031848.1; NM_007822.2.
DR AlphaFoldDB; O35728; -.
DR SMR; O35728; -.
DR IntAct; O35728; 1.
DR STRING; 10090.ENSMUSP00000030487; -.
DR SwissLipids; SLP:000000483; -.
DR CarbonylDB; O35728; -.
DR iPTMnet; O35728; -.
DR PhosphoSitePlus; O35728; -.
DR SwissPalm; O35728; -.
DR EPD; O35728; -.
DR jPOST; O35728; -.
DR MaxQB; O35728; -.
DR PaxDb; O35728; -.
DR PeptideAtlas; O35728; -.
DR PRIDE; O35728; -.
DR ProteomicsDB; 283932; -.
DR DNASU; 13119; -.
DR Ensembl; ENSMUST00000030487; ENSMUSP00000030487; ENSMUSG00000028715.
DR GeneID; 13119; -.
DR KEGG; mmu:13119; -.
DR UCSC; uc008uev.2; mouse.
DR CTD; 13119; -.
DR MGI; MGI:1096550; Cyp4a14.
DR VEuPathDB; HostDB:ENSMUSG00000028715; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000155173; -.
DR HOGENOM; CLU_001570_5_1_1; -.
DR InParanoid; O35728; -.
DR OMA; NWAGRFA; -.
DR OrthoDB; 1247045at2759; -.
DR PhylomeDB; O35728; -.
DR TreeFam; TF105088; -.
DR BRENDA; 1.14.14.80; 3474.
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 UniPathway; UPA00199; -.
DR BioGRID-ORCS; 13119; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Cyp4a14; mouse.
DR PRO; PR:O35728; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; O35728; protein.
DR Bgee; ENSMUSG00000028715; Expressed in left lobe of liver and 20 other tissues.
DR Genevisible; O35728; MM.
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; IEA:UniProtKB-SubCell.
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:0050544; F:arachidonic acid binding; ISO:MGI.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; ISO:MGI.
DR GO; GO:0008391; F:arachidonic acid monooxygenase activity; ISO:MGI.
DR GO; GO:0005504; F:fatty acid binding; 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:0019369; P:arachidonic acid metabolic process; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0043651; P:linoleic acid 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; Membrane; Metal-binding; Microsome;
KW Monooxygenase; NADP; Oxidoreductase; Phosphoprotein; Reference proteome.
FT PROPEP 1..4
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P20817"
FT /id="PRO_0000046058"
FT CHAIN 5..507
FT /note="Cytochrome P450 4A14"
FT /evidence="ECO:0000250|UniProtKB:P20817"
FT /id="PRO_0000046059"
FT BINDING 318
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:P20817"
FT BINDING 454
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:P20817"
FT MOD_RES 437
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20817"
FT CONFLICT 231
FT /note="N -> D (in Ref. 2; BAE28849)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="Q -> R (in Ref. 4; BC089609)"
FT /evidence="ECO:0000305"
FT CONFLICT 401
FT /note="S -> F (in Ref. 4; BC089609)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 507 AA; 58720 MW; EB46205838D4549C CRC64;
MGFFLFSPTR YLDGISGFFQ WAFLLSLFLV LFKAVQFYLR RQWLLKTLQH FPCMPSHWLW
GHHLKDKELQ QILIWVEKFP SACLQCLSGS NIRVLLYDPD YVKVVLGRSD PKASGIYQFF
APWIGYGLLL LNGKKWFQHR RMLTPAFHYD ILKPYVKIMA DSVNIMLDKW EKLDGQDHPL
EIFHCVSLMT LDTVMKCAFS YQGSVQLDEN SKLYTKAVED LNNLTFFRLR NAFYKYNIIY
NMSSDGRLSH HACQIAHEHT DGVIKMRKSQ LQNEEELQKA RKKRHLDFLD ILLFARMEDR
NSLSDEDLRA EVDTFMFEGH DTTASGISWI FYALATHPEH QQRCREEVQS ILGDGTSVTW
DHLGQMPYTT MCIKEALRLY PPVISVSREL SSPVTFPDGR SIPKGITATI SIYGLHHNPR
FWPNPKVFDP SRFAPDSSHH SHAYLPFSGG SRNCIGKQFA MNELKVAVAL TLLRFELLPD
PTRIPVPIAR LVLKSKNGIH LCLKKLR
