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