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C12A4_DROME
ID   C12A4_DROME             Reviewed;         536 AA.
AC   Q9VE00; B8A3W5; Q461P8; Q5CAL0; Q6A1J1; Q6A1J2; Q8SZL9;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 2.
DT   03-AUG-2022, entry version 154.
DE   RecName: Full=Probable cytochrome P450 12a4, mitochondrial;
DE            EC=1.14.-.-;
DE   AltName: Full=CYPXIIA4;
DE   Flags: Precursor;
GN   Name=Cyp12a4; ORFNames=CG6042;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS VAL-208; THR-252;
RP   GLY-289; GLY-295; ALA-417 AND PRO-499.
RC   STRAIN=Subline 5, Subline 7, and Subline 8;
RX   PubMed=16076534; DOI=10.1016/j.gene.2005.06.005;
RA   Marsano R.M., Caizzi R., Moschetti R., Junakovic N.;
RT   "Evidence for a functional interaction between the Bari1 transposable
RT   element and the cytochrome P450 cyp12a4 gene in Drosophila melanogaster.";
RL   Gene 357:122-128(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND TISSUE SPECIFICITY.
RC   STRAIN=NB16;
RX   PubMed=16120680; DOI=10.1073/pnas.0503709102;
RA   Bogwitz M.R., Chung H., Magoc L., Rigby S., Wong W., O'Keefe M.,
RA   McKenzie J.A., Batterham P., Daborn P.J.;
RT   "Cyp12a4 confers lufenuron resistance in a natural population of Drosophila
RT   melanogaster.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:12807-12812(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [4]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Head;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley;
RA   Carlson J.W., Booth B., Frise E., Park S., Wan K.H., Yu C., Celniker S.E.;
RL   Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Has a role in resistance to insecticide lufenuron, but no
CC       other insecticides. {ECO:0000269|PubMed:16120680}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Mitochondrion membrane {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expression in third-instar larvae is detected in
CC       the midgut and Malpighian tubules of both lufenuron-resistant and wild-
CC       type strains, higher expression level is seen in lufenuron-resistant
CC       strains. {ECO:0000269|PubMed:16120680}.
CC   -!- MISCELLANEOUS: Bari1 transposable element insertion in the 3' end of
CC       the gene leads to ten-fold more abundant expression than in flies
CC       lacking the insert.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; AJ748833; CAG38967.1; -; Genomic_DNA.
DR   EMBL; AJ748834; CAG38968.1; -; Genomic_DNA.
DR   EMBL; AJ890254; CAI64834.1; -; mRNA.
DR   EMBL; DQ026292; AAY89653.1; -; Genomic_DNA.
DR   EMBL; AE014297; AAF55636.2; -; Genomic_DNA.
DR   EMBL; AY070663; AAL48134.1; -; mRNA.
DR   EMBL; BT056257; ACL68704.1; -; mRNA.
DR   RefSeq; NP_650783.2; NM_142526.4.
DR   AlphaFoldDB; Q9VE00; -.
DR   SMR; Q9VE00; -.
DR   BioGRID; 67292; 2.
DR   DIP; DIP-23927N; -.
DR   IntAct; Q9VE00; 4.
DR   STRING; 7227.FBpp0083145; -.
DR   PaxDb; Q9VE00; -.
DR   PRIDE; Q9VE00; -.
DR   DNASU; 42294; -.
DR   EnsemblMetazoa; FBtr0083731; FBpp0083145; FBgn0038681.
DR   GeneID; 42294; -.
DR   KEGG; dme:Dmel_CG6042; -.
DR   CTD; 42294; -.
DR   FlyBase; FBgn0038681; Cyp12a4.
DR   VEuPathDB; VectorBase:FBgn0038681; -.
DR   eggNOG; KOG0159; Eukaryota.
DR   GeneTree; ENSGT00940000165868; -.
DR   HOGENOM; CLU_001570_28_0_1; -.
DR   InParanoid; Q9VE00; -.
DR   OMA; MWALSMK; -.
DR   OrthoDB; 574756at2759; -.
DR   PhylomeDB; Q9VE00; -.
DR   BioGRID-ORCS; 42294; 0 hits in 3 CRISPR screens.
DR   ChiTaRS; Cyp12a4; fly.
DR   GenomeRNAi; 42294; -.
DR   PRO; PR:Q9VE00; -.
DR   Proteomes; UP000000803; Chromosome 3R.
DR   Bgee; FBgn0038681; Expressed in adult Malpighian tubule (Drosophila) and 26 other tissues.
DR   Genevisible; Q9VE00; DM.
DR   GO; GO:0031966; C:mitochondrial 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   GO; GO:0017085; P:response to insecticide; IMP:FlyBase.
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   Heme; Iron; Membrane; Metal-binding; Mitochondrion; Monooxygenase;
KW   Oxidoreductase; Reference proteome; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..536
FT                   /note="Probable cytochrome P450 12a4, mitochondrial"
FT                   /id="PRO_0000003608"
FT   BINDING         482
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         208
FT                   /note="I -> V (in strain: Subline 5)"
FT                   /evidence="ECO:0000269|PubMed:16076534"
FT   VARIANT         252
FT                   /note="I -> T (in strain: Subline 5 and Subline 7)"
FT                   /evidence="ECO:0000269|PubMed:16076534"
FT   VARIANT         289
FT                   /note="E -> G (in strain: Subline 5)"
FT                   /evidence="ECO:0000269|PubMed:16076534"
FT   VARIANT         295
FT                   /note="D -> G (in strain: Subline 8)"
FT                   /evidence="ECO:0000269|PubMed:16076534"
FT   VARIANT         417
FT                   /note="V -> A (in strain: Subline 8)"
FT                   /evidence="ECO:0000269|PubMed:16076534"
FT   VARIANT         499
FT                   /note="L -> P (in strain: Subline 7)"
FT                   /evidence="ECO:0000269|PubMed:16076534"
FT   CONFLICT        203
FT                   /note="D -> H (in Ref. 5; AAL48134)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   536 AA;  61777 MW;  DDE51C7726A8805E CRC64;
     MLKVRSALSL IQSQKATLSL ATQKRWQTNV ATAEAREDSE WLQAKPFEQI PRLNMWALSM
     KMSMPGGKYK NMELMEMFEA MRQDYGDIFF MPGIMGNPPF LSTHNPQDFE VVFRNEGVWP
     NRPGNYTLLY HREEYRKDFY QGVMGVIPTQ GKPWGDFRTV VNPVLMQPKN VRLYYKKMSQ
     VNQEFVQRIL ELRDPDTLEA PDDFIDTINR WTLESVSVVA LDKQLGLLKN SNKESEALKL
     FHYLDEFFIV SIDLEMKPSP WRYIKTPKLK RLMRALDGIQ EVTLAYVDEA IERLDKEAKE
     GVVRPENEQS VLEKLLKVDR KVATVMAMDM LMAGVDTTSS TFTALLLCLA KNPEKQARLR
     EEVMKVLPNK NSEFTEASMK NVPYLRACIK ESQRLHPLIV GNARVLARDA VLSGYRVPAG
     TYVNIVPLNA LTRDEYFPQA SEFLPERWLR SPKDSESKCP ANELKSTNPF VFLPFGFGPR
     MCVGKRIVEM ELELGTARLI RNFNVEFNYP TENAFRSALI NLPNIPLKFK FIDLPN
 
 
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