ID   PPO3_DROME              Reviewed;         683 AA.
AC   Q9W1V6; Q95R43; Q9BLD9;
DT   15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 143.
DE   RecName: Full=Phenoloxidase 3;
DE            EC=1.14.18.1;
DE   AltName: Full=Diphenol oxidase A3;
DE   AltName: Full=Diphenoloxidase subunit A3;
DE   AltName: Full=Prophenoloxidase 59;
DE   AltName: Full=Tyrosinase A3;
DE   Flags: Precursor;
GN   Name=PPO3; Synonyms=Dox-3, Dox-A3, proPO59; ORFNames=CG42640;
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 [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   [2]
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Embryo;
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   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-664, AND PROTEOLYTIC CLEAVAGE.
RC   STRAIN=Oregon-R; TISSUE=Larva, and Pupae;
RX   PubMed=12834045; DOI=10.1023/a:1023325610300;
RA   Asada N., Yokoyama G., Kawamoto N., Norioka S., Hatta T.;
RT   "Prophenol oxidase A3 in Drosophila melanogaster: activation and the PCR-
RT   based cDNA sequence.";
RL   Biochem. Genet. 41:151-163(2003).
RN   [5]
RP   SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX   PubMed=19141111; DOI=10.1111/j.1365-2583.2008.00858.x;
RA   Asano T., Takebuchi K.;
RT   "Identification of the gene encoding pro-phenoloxidase A(3) in the
RT   fruitfly, Drosophila melanogaster.";
RL   Insect Mol. Biol. 18:223-232(2009).
CC   -!- FUNCTION: This is a copper-containing oxidase that functions in the
CC       formation of pigments such as melanins and other polyphenolic
CC       compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA,
CC       DOPA to DOPA-quinone and possibly 5,6 dihydroxyindole to indole-5'6
CC       quinone (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 L-dopa + O2 = 2 H2O + 2 L-dopaquinone; Xref=Rhea:RHEA:34287,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57504,
CC         ChEBI:CHEBI:57924; EC=1.14.18.1;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-tyrosine + O2 = H2O + L-dopaquinone; Xref=Rhea:RHEA:18117,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57924,
CC         ChEBI:CHEBI:58315; EC=1.14.18.1;
CC   -!- COFACTOR:
CC       Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC         Evidence={ECO:0000250|UniProtKB:Q9ZP19};
CC       Note=Binds 2 copper ions per subunit. {ECO:0000250|UniProtKB:Q9ZP19};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Note=Expression not
CC       detected in larval hemolymph. {ECO:0000269|PubMed:19141111}.
CC   -!- DEVELOPMENTAL STAGE: Expression is very low during all stages of
CC       development. {ECO:0000269|PubMed:19141111}.
CC   -!- PTM: Upon activation, a trypsin type protease cleaves prophenol oxidase
CC       to yield the active enzyme. {ECO:0000269|PubMed:12834045}.
CC   -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB43866.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. It is a chimera between Dox-A3 and CG8193.; Evidence={ECO:0000305};
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DR   EMBL; AE013599; AAF46946.1; -; Genomic_DNA.
DR   EMBL; AY061624; AAL29172.1; -; mRNA.
DR   EMBL; AB055857; BAB43866.1; ALT_SEQ; Genomic_DNA.
DR   RefSeq; NP_524760.1; NM_080021.4.
DR   AlphaFoldDB; Q9W1V6; -.
DR   SMR; Q9W1V6; -.
DR   BioGRID; 69098; 1.
DR   STRING; 7227.FBpp0291496; -.
DR   GlyCosmos; Q9W1V6; 3 sites, No reported glycans.
DR   GlyGen; Q9W1V6; 3 sites.
DR   PaxDb; 7227-FBpp0291496; -.
DR   DNASU; 44513; -.
DR   EnsemblMetazoa; FBtr0302290; FBpp0291496; FBgn0261363.
DR   GeneID; 44513; -.
DR   KEGG; dme:Dmel_CG42640; -.
DR   AGR; FB:FBgn0261363; -.
DR   CTD; 44513; -.
DR   FlyBase; FBgn0261363; PPO3.
DR   VEuPathDB; VectorBase:FBgn0261363; -.
DR   eggNOG; ENOG502QQCG; Eukaryota.
DR   HOGENOM; CLU_012213_0_1_1; -.
DR   InParanoid; Q9W1V6; -.
DR   OMA; KSMGFPF; -.
DR   OrthoDB; 5406463at2759; -.
DR   PhylomeDB; Q9W1V6; -.
DR   BioGRID-ORCS; 44513; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 44513; -.
DR   PRO; PR:Q9W1V6; -.
DR   Proteomes; UP000000803; Chromosome 2R.
DR   Bgee; FBgn0261363; Expressed in embryonic/larval hemocyte (Drosophila) and 5 other cell types or tissues.
DR   ExpressionAtlas; Q9W1V6; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; HDA:FlyBase.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0004097; F:catechol oxidase activity; IDA:FlyBase.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004503; F:tyrosinase activity; IDA:FlyBase.
DR   GO; GO:0042417; P:dopamine metabolic process; IC:FlyBase.
DR   GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0035011; P:melanotic encapsulation of foreign target; IGI:FlyBase.
DR   Gene3D; 1.10.1280.10; Di-copper center containing domain from catechol oxidase; 1.
DR   Gene3D; 2.60.40.1520; Hemocyanin, C-terminal domain; 1.
DR   Gene3D; 1.20.1370.10; Hemocyanin, N-terminal domain; 1.
DR   InterPro; IPR008922; Di-copper_centre_dom_sf.
DR   InterPro; IPR013788; Hemocyanin/hexamerin.
DR   InterPro; IPR000896; Hemocyanin/hexamerin_mid_dom.
DR   InterPro; IPR005203; Hemocyanin_C.
DR   InterPro; IPR037020; Hemocyanin_C_sf.
DR   InterPro; IPR005204; Hemocyanin_N.
DR   InterPro; IPR036697; Hemocyanin_N_sf.
DR   InterPro; IPR014756; Ig_E-set.
DR   InterPro; IPR002227; Tyrosinase_Cu-bd.
DR   PANTHER; PTHR11511; LARVAL STORAGE PROTEIN/PHENOLOXIDASE; 1.
DR   PANTHER; PTHR11511:SF4; PHENOLOXIDASE 2-RELATED; 1.
DR   Pfam; PF03723; Hemocyanin_C; 1.
DR   Pfam; PF00372; Hemocyanin_M; 1.
DR   Pfam; PF03722; Hemocyanin_N; 1.
DR   PRINTS; PR00187; HAEMOCYANIN.
DR   SUPFAM; SSF48056; Di-copper centre-containing domain; 1.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   SUPFAM; SSF48050; Hemocyanin, N-terminal domain; 1.
DR   PROSITE; PS00209; HEMOCYANIN_1; 1.
DR   PROSITE; PS00210; HEMOCYANIN_2; 1.
DR   PROSITE; PS00498; TYROSINASE_2; 1.
DR   Genevisible; Q9W1V6; DM.
PE   1: Evidence at protein level;
KW   Cleavage on pair of basic residues; Copper; Disulfide bond; Glycoprotein;
KW   Melanin biosynthesis; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Secreted; Zymogen.
FT   PROPEP          1..48
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000035905"
FT   CHAIN           51..683
FT                   /note="Phenoloxidase 3"
FT                   /id="PRO_0000035906"
FT   ACT_SITE        351
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q8MZM3"
FT   BINDING         209
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         213
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         239
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         366
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         370
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         406
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   CARBOHYD        358
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        492
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        546
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        574..617
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   DISULFID        576..624
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   CONFLICT        246
FT                   /note="Y -> N (in Ref. 3; AAL29172)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        491
FT                   /note="E -> D (in Ref. 3; AAL29172)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   683 AA;  79314 MW;  437CBDD9E8A278BF CRC64;
     MADKKNLLLL FDHPTEPVFM DKGGNGTVFD VPDSYVTDRY NQMCKKVQRR VSSASEKNVQ
     VKEIAIPDLS CSMRLGRSEQ FSIFLKSHRK MASHLIEIFT KMQTVDELQS VAVYARDRVN
     PVLFNYALSV ALLHRPDTKD LELPAFAQTF PDRFIDSKML RSMREESFVV ERSAARLPVV
     SSVKYTASDL DVEHRLWYFR EDLGVNLHHW HWHLVYPIEA PDRSIVDKDR RGELFYYMHQ
     QIIARYNAER LSNHMARVQP FNNLDEPIAE GYFPKMDSLV ASRAYPPRFD NTRLSDVDRP
     NNQLRVGIDD MKRWRERIYE AIHQGYVLDT NNEKIVLDDA KGIDILGNII EASDLTPNST
     LYGDFHNMGH ILIAYSHDPT NKHLEYAGVM GDASTAMRDP IFYKWHAFID NMFQEHKRLL
     SPYEKQELSF PDVRVESIQV ESQGQVNRLT TFWQESDVDM SRGLDFVPRG HVLARFTHLQ
     HHEFSYTIKV ENSSEATRYG YVRIFLAPKL DDRNAPMLLE QQRLMMVELD KFVVTMPPGS
     HTITRNSTES SVTIPFERTF RNLDKLEELQ NFLCGCGWPQ HMLIPKGRPE GLRFELFVMV
     SNYEEDKVDQ TVADCGCSIA ASYCGLRDRL YPDRKSMGFP FDRKPRRGSE ILENFLTPNM
     CAVEVIITHE DRTEKLREVP ARS
//