CP2K6_DANRE
ID CP2K6_DANRE Reviewed; 505 AA.
AC F1Q8C3; Q7SXK7; Q802U6; Q90Y45;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Cytochrome P450 2K6 {ECO:0000303|PubMed:15907766};
DE EC=1.14.14.- {ECO:0000269|PubMed:15907766};
GN Name=cyp2k6 {ECO:0000303|PubMed:15907766,
GN ECO:0000312|ZFIN:ZDB-GENE-040426-1571};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|Proteomes:UP000000437};
RN [1] {ECO:0000312|EMBL:AAK97022.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15907766; DOI=10.1016/j.cca.2005.02.002;
RA Wang-Buhler J.L., Lee S.J., Chung W.G., Stevens J.F., Tseng H.P.,
RA Hseu T.H., Hu C.H., Westerfield M., Yang Y.H., Miranda C.L., Buhler D.R.;
RT "CYP2K6 from zebrafish (Danio rerio): cloning, mapping,
RT developmental/tissue expression, and aflatoxin B1 activation by baculovirus
RT expressed enzyme.";
RL Comp. Biochem. Physiol. 140:207-219(2005).
RN [2] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3] {ECO:0000312|EMBL:AAH47194.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB {ECO:0000312|EMBL:AAH55556.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Metabolizes aflatoxin B1 (AFB1) to the cytotoxic derivative
CC AFB1 exo-8,9-epoxide. Does not show activity towards lauric acid.
CC {ECO:0000269|PubMed:15907766}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:15907766};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:15907766}; Single-pass membrane protein
CC {ECO:0000255}. Microsome membrane {ECO:0000269|PubMed:15907766};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Detected in liver and ovary.
CC {ECO:0000269|PubMed:15907766}.
CC -!- DEVELOPMENTAL STAGE: Expressed from 5 days post-fertilization onwards.
CC {ECO:0000269|PubMed:15907766}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000255|RuleBase:RU000461}.
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DR EMBL; AF283813; AAK97022.1; -; mRNA.
DR EMBL; AL929078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX511176; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC047194; AAH47194.2; -; mRNA.
DR EMBL; BC055556; AAH55556.1; -; mRNA.
DR EMBL; BC164859; AAI64859.1; -; mRNA.
DR RefSeq; NP_956803.1; NM_200509.1.
DR RefSeq; XP_009297487.1; XM_009299212.2.
DR AlphaFoldDB; F1Q8C3; -.
DR SMR; F1Q8C3; -.
DR STRING; 7955.ENSDARP00000092100; -.
DR PaxDb; F1Q8C3; -.
DR PRIDE; F1Q8C3; -.
DR Ensembl; ENSDART00000163743; ENSDARP00000134138; ENSDARG00000098995.
DR Ensembl; ENSDART00000170788; ENSDARP00000135007; ENSDARG00000098995.
DR GeneID; 393481; -.
DR KEGG; dre:393481; -.
DR CTD; 393481; -.
DR ZFIN; ZDB-GENE-040426-1571; cyp2k6.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000162649; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; F1Q8C3; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; F1Q8C3; -.
DR TreeFam; TF352043; -.
DR Reactome; R-DRE-211958; Miscellaneous substrates.
DR Reactome; R-DRE-211981; Xenobiotics.
DR PRO; PR:F1Q8C3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 3.
DR Bgee; ENSDARG00000098995; Expressed in intestine and 9 other tissues.
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:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
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:0046222; P:aflatoxin metabolic process; IDA:ZFIN.
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; Membrane; Metal-binding; Microsome;
KW Monooxygenase; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..505
FT /note="Cytochrome P450 2K6"
FT /id="PRO_0000442729"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 448
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:P33261"
FT CONFLICT 16
FT /note="T -> A (in Ref. 1; AAK97022 and 3; AAH47194/
FT AAH55556/AAI64859)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="K -> R (in Ref. 3; AAH47194/AAH55556/AAI64859)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="R -> K (in Ref. 3; AAH47194/AAH55556/AAI64859)"
FT /evidence="ECO:0000305"
FT CONFLICT 412
FT /note="N -> D (in Ref. 3; AAH55556)"
FT /evidence="ECO:0000305"
FT CONFLICT 416
FT /note="T -> M (in Ref. 3; AAH47194/AAH55556/AAI64859)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 505 AA; 57380 MW; A344168B9F9978F0 CRC64;
MALIEAFLLQ GSPTGTILGA LLLFLVIYLF SSSSSSQDKE KYPPGPKPLP LLGNLHILDL
KKTYLSLLEL SKKYGPIYTV YLGPKKVVIL SGYKIVKEAL VNLSEEFGDR DISPIFHDFN
RGYGIAFSNG ENWREMRRFA LSTLRDFGMG RKRSEELIIE EIKYVKEEFE KFGGNPFETK
LPLALAISNI IASIVFSVRF EYSNTKLHRM VGRAYENMKL TGSPSVQIYN MFPWLRPIVA
NRNQIVKNLR DTFKQNEELI NGVMKTLDPF NPRGIVDSFL IRQQKDEESG KTDSLYNSNN
LYCTVNNLFG AGTDTTVTTL RWGLLLMAKY PEIQAKVQDE IERVIGGRQP VVEDRKNLPY
TDAVIHEIQR FADISPIGAP RQTTCDVHLN GYFIKKGTPV FPLLVSVLRD ENEWETPDSF
NPKHFLNKQG QFVKKDAFMP FGAGRRVCIG ESLARMELFL FFTSLLQYFR FTPPPGVSED
DLDLTPVVGF TLNPKPHQLC AVKRS