ID   PPO2_DROME              Reviewed;         684 AA.
AC   Q9V521; Q9BLD9;
DT   15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   24-JAN-2024, entry version 147.
DE   RecName: Full=Phenoloxidase 2;
DE            Short=PO A3;
DE            EC=1.14.18.1;
DE   AltName: Full=Phenoloxidase subunit A3;
DE   AltName: Full=Processed phenoloxidase A3;
DE            Short=Pro-phenoloxidase A3;
DE   Flags: Precursor;
GN   Name=PPO2; Synonyms=proPo-A3, proPO45; ORFNames=CG8193;
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=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   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-670, PROTEOLYTIC CLEAVAGE, AND
RP   SUBCELLULAR LOCATION.
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       quinonee (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:0000269|PubMed:12834045,
CC       ECO:0000269|PubMed:19141111}. Note=Expressed in larval hemolymph.
CC   -!- DEVELOPMENTAL STAGE: Expression is high during the larval stage,
CC       predominantly in the feeding and wandering larvae.
CC       {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 PPO2.; Evidence={ECO:0000305};
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DR   EMBL; AE013599; AAF59001.1; -; Genomic_DNA.
DR   EMBL; AY060652; AAL28200.1; -; mRNA.
DR   EMBL; AB055857; BAB43866.1; ALT_SEQ; Genomic_DNA.
DR   RefSeq; NP_610443.1; NM_136599.4.
DR   AlphaFoldDB; Q9V521; -.
DR   SMR; Q9V521; -.
DR   BioGRID; 61748; 9.
DR   IntAct; Q9V521; 2.
DR   STRING; 7227.FBpp0087744; -.
DR   GlyCosmos; Q9V521; 4 sites, No reported glycans.
DR   GlyGen; Q9V521; 4 sites.
DR   PaxDb; 7227-FBpp0087744; -.
DR   EnsemblMetazoa; FBtr0088663; FBpp0087744; FBgn0033367.
DR   GeneID; 35910; -.
DR   KEGG; dme:Dmel_CG8193; -.
DR   UCSC; CG8193-RA; d. melanogaster.
DR   AGR; FB:FBgn0033367; -.
DR   CTD; 35910; -.
DR   FlyBase; FBgn0033367; PPO2.
DR   VEuPathDB; VectorBase:FBgn0033367; -.
DR   eggNOG; ENOG502QQCG; Eukaryota.
DR   GeneTree; ENSGT00940000165243; -.
DR   HOGENOM; CLU_012213_0_1_1; -.
DR   InParanoid; Q9V521; -.
DR   OMA; YYMHEQI; -.
DR   OrthoDB; 5406463at2759; -.
DR   PhylomeDB; Q9V521; -.
DR   SignaLink; Q9V521; -.
DR   BioGRID-ORCS; 35910; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 35910; -.
DR   PRO; PR:Q9V521; -.
DR   Proteomes; UP000000803; Chromosome 2R.
DR   Bgee; FBgn0033367; Expressed in insect adult head and 19 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IDA:FlyBase.
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:0050832; P:defense response to fungus; IMP:FlyBase.
DR   GO; GO:0050830; P:defense response to Gram-positive bacterium; IGI:FlyBase.
DR   GO; GO:0042417; P:dopamine metabolic process; IC:FlyBase.
DR   GO; GO:0042381; P:hemolymph coagulation; IDA:FlyBase.
DR   GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0035006; P:melanization defense response; IDA:FlyBase.
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; Q9V521; DM.
PE   1: Evidence at protein level;
KW   Copper; Disulfide bond; Glycoprotein; Melanin biosynthesis; Metal-binding;
KW   Monooxygenase; Oxidoreductase; Reference proteome; Secreted; Zymogen.
FT   PROPEP          1..50
FT                   /id="PRO_0000035907"
FT   CHAIN           51..684
FT                   /note="Phenoloxidase 2"
FT                   /id="PRO_0000035908"
FT   ACT_SITE        350
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q8MZM3"
FT   BINDING         208
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         212
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         238
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         365
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         369
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   BINDING         405
FT                   /ligand="Cu cation"
FT                   /ligand_id="ChEBI:CHEBI:23378"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   CARBOHYD        448
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        665
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        677
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        581..623
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT   DISULFID        583..630
FT                   /evidence="ECO:0000250|UniProtKB:Q9ZP19"
SQ   SEQUENCE   684 AA;  79285 MW;  16F946FFEEDB72EA CRC64;
     MADKKNLLLL FDHPTEPVFM DKGKRVTVFD VPDSFLTDRY RPISNEVQSR VGDKVEQRVP
     VREISIPDLR IPMSLGRDEQ FSLFLPKHRR IAGRLIDIFM NMRSVDDLQS VAVYARDRVN
     PVLFNYALSV ALLHRPDTQG LDLPSFSQTF PDRFIDSQVI RKMREESFVV QPGSRMPITI
     PRDYTASDLD PEHRLWYFRE DLGINLHHWH WHLVYPFEAS DRSIVAKDRR GELFYYMHQQ
     VIARYNAERF SNNLARVLPF NNLRDPIAEG YFPKMDSLVA SRAWPPRFES TRLSDLNRES
     DQLNVEIGDL ERWRDRIYEA IHQGFVMDER GNRVPLDEAT GIDTLGNMIE SSILSPNRVL
     YGDLHNNGHT FISYAHDPTS KHLESFGVMG DVSTAMRDPV FYKWHSYIDR IFQEHKSRLP
     AYTENQLNYP GVSIAGIQVD TNGGRPNNLT TFWQQSDVDM SRGFDFLPRG NVFARFTHLQ
     HLPFTYTISL NNDSGAQRFG YVRIFMAPKN DERGQPMLMR DQRSMMIELD KFVTSLNPGP
     NTIRRRSTES SVTIPFERTF RNLDANRPAA GTPEELEFNF CGCGWPNHML VPKGLPEGLQ
     CVLFIMVSNY ENDRIDQQLV GRCSDAASYC GVRDRLYPDR QSMGFPFDRL PRSGVDRLVN
     FLTPNMSIVD VNIRHENRTV QRPN
//