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CP6D3_MUSDO
ID   CP6D3_MUSDO             Reviewed;         520 AA.
AC   Q964Q7; Q95NT8; Q964Q3; Q9BLF7; Q9GU30;
DT   24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   03-AUG-2022, entry version 92.
DE   RecName: Full=Cytochrome P450 6d3;
DE            EC=1.14.-.-;
DE   AltName: Full=CYPVID3;
DE   AltName: Full=Pyrethroid resistance cytochrome P450;
GN   Name=CYP6D3;
OS   Musca domestica (House fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Muscoidea;
OC   Muscidae; Musca.
OX   NCBI_TaxID=7370;
RN   [1]
RP   NUCLEOTIDE SEQUENCE, AND VARIANTS PHE-13; ASP-190; ARG-221; ASP-339;
RP   VAL-344; LEU-363 AND 519-ARG--ARG-520 DEL.
RC   STRAIN=CS, Edinburgh, and LPR;
RX   PubMed=11719063; DOI=10.1016/s0965-1748(01)00073-x;
RA   Kasai S., Scott J.G.;
RT   "Expression and regulation of CYP6D3 in the house fly, Musca domestica
RT   (L.).";
RL   Insect Biochem. Mol. Biol. 32:1-8(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE, AND VARIANTS PHE-13; ASP-190; ARG-221; ASP-339;
RP   VAL-344; LEU-363 AND 519-ARG--ARG-520 DEL.
RC   STRAIN=Edinburgh;
RX   PubMed=11437910; DOI=10.1046/j.1365-2583.2001.00256.x;
RA   Kasai S., Scott J.G.;
RT   "Cytochrome P450s CYP6D3 and CYP6D1 are part of a P450 gene cluster on
RT   autosome 1 in house fly.";
RL   Insect Mol. Biol. 10:191-196(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE, AND VARIANTS TYR-4; VAL-10; PHE-13; ALA-30; GLN-74;
RP   ARG-221 AND 519-ARG--ARG-520 DEL.
RC   STRAIN=YPER;
RA   Kamiya E., Yamakawa M., Shono T., Kono Y.;
RT   "Molecular cloning, nucleotide sequences and gene expression of new
RT   cytochrome P450s from the pyrethroid resistant housefly, Musca domestica L.
RT   (Diptera: Muscidae).";
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE OF 1-10.
RC   STRAIN=CS, and LPR;
RA   Kasai S., Scott J.G.;
RT   "5' flanking sequence of CYP6D3.";
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Metabolizes pyrethroid insecticides and other xenobiotics.
CC       {ECO:0000250}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC       Peripheral membrane protein {ECO:0000305}. Microsome membrane
CC       {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC   -!- DEVELOPMENTAL STAGE: No expression in eggs nor day 1 pupae, yet it is
CC       readily detectable in larvae and adults.
CC   -!- INDUCTION: By phenobarbital in susceptible CS (16-fold) and in the LPR
CC       (1.6-fold) strains.
CC   -!- POLYMORPHISM: Alleles from the pyrethroid-susceptible strains CS
CC       (CYP6D1v2) (shown here) and Edinburgh (CYP6D1v1), and two alleles from
CC       the pyrethroid-resistant strains LPR (CYP6D1v3) and YPER (CYP6D1v4) are
CC       described here.
CC   -!- MISCELLANEOUS: Expressed at higher levels in LPR compared to
CC       susceptible flies.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; AF283257; AAK69542.1; -; mRNA.
DR   EMBL; AF285767; AAK69552.1; -; mRNA.
DR   EMBL; AF200191; AAG28563.1; -; Genomic_DNA.
DR   EMBL; AB050702; BAB41135.1; -; mRNA.
DR   EMBL; AF283258; AAK69543.1; -; Genomic_DNA.
DR   EMBL; AF283259; AAK69544.1; -; Genomic_DNA.
DR   RefSeq; NP_001273810.1; NM_001286881.1.
DR   AlphaFoldDB; Q964Q7; -.
DR   SMR; Q964Q7; -.
DR   GeneID; 101899585; -.
DR   KEGG; mde:101899585; -.
DR   CTD; 101899585; -.
DR   VEuPathDB; VectorBase:MDOA002847; -.
DR   eggNOG; KOG0158; Eukaryota.
DR   Proteomes; UP000095301; Whole Genome Shotgun Assembly.
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:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
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   2: Evidence at transcript level;
KW   Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome;
KW   Monooxygenase; Oxidoreductase.
FT   CHAIN           1..520
FT                   /note="Cytochrome P450 6d3"
FT                   /id="PRO_0000051879"
FT   BINDING         461
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   VARIANT         4
FT                   /note="F -> Y (in allele CYP6D3v4)"
FT                   /evidence="ECO:0000269|Ref.3"
FT   VARIANT         10
FT                   /note="L -> V (in allele CYP6D3v4)"
FT                   /evidence="ECO:0000269|Ref.3"
FT   VARIANT         13
FT                   /note="I -> F (in allele CYP6D3v1, allele CYP6D3v3 and
FT                   allele CYP6D3v4)"
FT                   /evidence="ECO:0000269|PubMed:11437910,
FT                   ECO:0000269|PubMed:11719063, ECO:0000269|Ref.3"
FT   VARIANT         30
FT                   /note="V -> A (in allele CYP6D3v4)"
FT                   /evidence="ECO:0000269|Ref.3"
FT   VARIANT         74
FT                   /note="K -> Q (in allele CYP6D3v4)"
FT                   /evidence="ECO:0000269|Ref.3"
FT   VARIANT         190
FT                   /note="E -> D (in allele CYP6D3v1)"
FT                   /evidence="ECO:0000269|PubMed:11437910,
FT                   ECO:0000269|PubMed:11719063"
FT   VARIANT         221
FT                   /note="Q -> R (in allele CYP6D3v1, allele CYP6D3v3 and
FT                   allele CYP6D3v4)"
FT                   /evidence="ECO:0000269|PubMed:11437910,
FT                   ECO:0000269|PubMed:11719063, ECO:0000269|Ref.3"
FT   VARIANT         339
FT                   /note="E -> D (in allele CYP6D3v1)"
FT                   /evidence="ECO:0000269|PubMed:11437910,
FT                   ECO:0000269|PubMed:11719063"
FT   VARIANT         344
FT                   /note="A -> V (in allele CYP6D3v1)"
FT                   /evidence="ECO:0000269|PubMed:11437910,
FT                   ECO:0000269|PubMed:11719063"
FT   VARIANT         363
FT                   /note="I -> L (in allele CYP6D3v1)"
FT                   /evidence="ECO:0000269|PubMed:11437910,
FT                   ECO:0000269|PubMed:11719063"
FT   VARIANT         519..520
FT                   /note="Missing (in allele CYP6D3v1, allele CYP6D3v3 and
FT                   allele CYP6D3v4)"
SQ   SEQUENCE   520 AA;  59525 MW;  176DDC951A67B910 CRC64;
     MLLFLLITLL SAIFIFAKRH YTQWQRLGLV SDEAVIPFGS LAKVFRKERP FGLVMYDLYE
     KFQEQVVGIY LFFKPALLIR DAELARQILT SDFNSFHDRG IYVDEKNDPM SANLFALEGQ
     SWRTLRMKLT PSFSSGKLKG MFETVDDVGN KLLEYLNNQL KDGQTHVLDI KSILTTYAID
     IIGSVIFGLE IDSFTNPDNE FRVLSDRSFD NESRSFLSKL QNLTNFVCPP IAKLLTRLGT
     KEPVVYRLRD IVKRTIEFRE ENNVVRKDLL HLLIQLRNTG KISDDNDNLW NKVESTATNL
     KAMSIDMIAS NSFLFYIAGS ETTASSTSFT IYELAMNPEA LKKAQNEVDE CLKKHGIKPD
     GRITYEAIQD MKYLDLCVKE TTRKYPGLPF LNRQCTQDFK VPNSKFTIKK DTNVIISLLG
     LHRDAKYFPE PLAYKPERFA DETKDYDAAA YMPFGEGPRH CIAQRMGVMN TKVALAKILA
     NFNIEPMPHK EAEFQFNTAP VLVPVNGLRV GLSKRSFNRR
 
 
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