CP4A6_RABIT
ID CP4A6_RABIT Reviewed; 510 AA.
AC P14580;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Cytochrome P450 4A6;
DE AltName: Full=CYPIVA6;
DE AltName: Full=Cytochrome P450-KA-1;
DE AltName: Full=Lauric acid omega-hydroxylase;
DE AltName: Full=Long-chain fatty acid omega-monooxygenase;
DE EC=1.14.14.80 {ECO:0000250|UniProtKB:Q02928};
DE Flags: Precursor;
GN Name=CYP4A6;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=2340280; DOI=10.1021/bi00456a004;
RA Johnson E.F., Walker D.L., Griffin K.J., Clark J.E., Okita R.T.,
RA Meurhoff A.S., Masters B.S.S.;
RT "Cloning and expression of three rabbit kidney cDNAs encoding lauric acid
RT omega-hydroxylases.";
RL Biochemistry 29:873-879(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 5-24.
RC TISSUE=Kidney;
RX PubMed=2600085; DOI=10.1016/s0021-9258(20)88237-4;
RA Yokotani N., Bernhardt R., Sogawa K., Kusunose E., Gotoh O., Kusunose M.,
RA Fujii-Kuriyama Y.;
RT "Two forms of omega-hydroxylase toward prostaglandin A and laurate. cDNA
RT cloning and their expression.";
RL J. Biol. Chem. 264:21665-21669(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1605646; DOI=10.1016/0003-9861(92)90545-8;
RA Muerhoff A.S., Griffin K.J., Johnson E.F.;
RT "Characterization of a rabbit gene encoding a clofibrate-inducible fatty
RT acid omega-hydroxylase: CYP4A6.";
RL Arch. Biochem. Biophys. 296:66-72(1992).
RN [4]
RP PROTEIN SEQUENCE OF 5-24.
RX PubMed=2361958; DOI=10.1093/oxfordjournals.jbchem.a123039;
RA Kikuta Y., Kusunose E., Okumoto T., Kubota I., Kusunose M.;
RT "Purification and characterization of two forms of cytochrome P-450 with
RT omega-hydroxylase activities toward prostaglandin A and fatty acids from
RT rabbit liver microsomes.";
RL J. Biochem. 107:280-286(1990).
CC -!- FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases.
CC In liver microsomes, this enzyme is involved in an NADPH-dependent
CC electron transport pathway. It oxidizes a variety of structurally
CC unrelated compounds, including steroids, fatty acids, and xenobiotics.
CC -!- FUNCTION: The kidney P-450 system is rather specialized for the omega-
CC hydroxylation of fatty acids. Both P450-KA1 and P450-KA2 catalyze the
CC omega- and (omega-1)-hydroxylation of various fatty acids with no drug-
CC metabolizing activity, and hydroxylate prostaglandin A1 and A2 solely
CC at the omega-position.
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:Q02928};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P51869};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Liver; kidney.
CC -!- INDUCTION: P450 can be induced to high levels in liver and other
CC tissues by various foreign compounds, including drugs, pesticides, and
CC carcinogens.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; M28656; AAA31230.1; -; mRNA.
DR EMBL; M29531; AAA31234.1; -; mRNA.
DR PIR; A34160; A34160.
DR RefSeq; NP_001164542.1; NM_001171071.1.
DR RefSeq; NP_001164599.1; NM_001171128.1.
DR AlphaFoldDB; P14580; -.
DR SMR; P14580; -.
DR STRING; 9986.ENSOCUP00000004037; -.
DR GeneID; 100328612; -.
DR GeneID; 100328946; -.
DR KEGG; ocu:100328612; -.
DR KEGG; ocu:100328946; -.
DR CTD; 100328946; -.
DR eggNOG; KOG0157; Eukaryota.
DR InParanoid; P14580; -.
DR OrthoDB; 1247045at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
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 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 Direct protein sequencing; Endoplasmic reticulum; Heme; Iron; Membrane;
KW Metal-binding; Microsome; Monooxygenase; NADP; Oxidoreductase;
KW Reference proteome.
FT PROPEP 1..4
FT /evidence="ECO:0000269|PubMed:2361958,
FT ECO:0000269|PubMed:2600085"
FT /id="PRO_0000003575"
FT CHAIN 5..510
FT /note="Cytochrome P450 4A6"
FT /id="PRO_0000003576"
FT BINDING 321
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:P51869"
FT BINDING 457
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:P51869"
FT CONFLICT 27
FT /note="L -> C (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 380
FT /note="L -> M (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 424..425
FT /note="VW -> CG (in Ref. 2; AAA31234)"
FT /evidence="ECO:0000305"
FT CONFLICT 434..435
FT /note="FP -> SR (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="F -> S (in Ref. 2; AAA31234)"
FT /evidence="ECO:0000305"
FT CONFLICT 476
FT /note="V -> L (in Ref. 2; AAA31234)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 510 AA; 58300 MW; B7A85E1208A2B9E1 CRC64;
MSVSALNPTR LPGSLSGLLQ VAGLLGLLLL LLKAAQLYLH RQWLLRALQQ FPCPPFHWLL
GHSREFQNGH ELQVMLKWVE KFPSACPRWL WGSRAHLLIY DPDYMKVILG RSDPKAQGSY
RFLAPWIGYG LLLLNGQTWF QHRRMLTPAF HYDILKPYVG LMADSVQIML DKWEQLVSQD
SSLEVFQDIS LMTLDTIMKC AFSHQGSVQL DRNSQSYIQA VGDLNNLFFS RVRNVFHQSD
TIYRLSPEGR LSHRACQLAH EHTDRVIQQR KAQLQQEGEL EKVRRKRRLD FLDVLLFAKM
ENGSSLSDQD LRAEVDTFMF EGHDTTASGI SWIFYALATH PEHQHRCREE IQGLLGDGAS
ITWEHLDQMP YTTMCIKEAL RLYPPVPGVG RQLSSPVTFP DGRSLPKGVI VTLSIYALHH
NPKVWPNPEV FDPFPFAPGS ARHSHAFLPF SGGPRNCIGK QFAMNELKVA VALTLVRFEL
LPDPKRVPDQ KPRLVLKSSN GIHLRLRKLR
