ID   T23O_DROME              Reviewed;         379 AA.
AC   P20351; Q9VZ50;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   27-MAR-2024, entry version 166.
DE   RecName: Full=Tryptophan 2,3-dioxygenase {ECO:0000255|HAMAP-Rule:MF_03020};
DE            Short=TDO {ECO:0000255|HAMAP-Rule:MF_03020};
DE            EC=1.13.11.11 {ECO:0000255|HAMAP-Rule:MF_03020, ECO:0000269|PubMed:23333332};
DE   AltName: Full=Protein vermilion {ECO:0000255|HAMAP-Rule:MF_03020, ECO:0000303|PubMed:2108317};
DE   AltName: Full=Tryptamin 2,3-dioxygenase {ECO:0000255|HAMAP-Rule:MF_03020};
DE   AltName: Full=Tryptophan oxygenase {ECO:0000255|HAMAP-Rule:MF_03020};
DE            Short=TO {ECO:0000255|HAMAP-Rule:MF_03020};
DE            Short=TRPO {ECO:0000255|HAMAP-Rule:MF_03020};
DE   AltName: Full=Tryptophan pyrrolase {ECO:0000255|HAMAP-Rule:MF_03020};
DE   AltName: Full=Tryptophanase {ECO:0000255|HAMAP-Rule:MF_03020};
GN   Name=v {ECO:0000255|HAMAP-Rule:MF_03020}; ORFNames=CG5163;
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], FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=2108317; DOI=10.1128/mcb.10.4.1423-1431.1990;
RA   Searles L.L., Ruth R.S., Pret A.-M., Fridell R.A., Ali A.J.;
RT   "Structure and transcription of the Drosophila melanogaster vermilion gene
RT   and several mutant alleles.";
RL   Mol. Cell. Biol. 10:1423-1431(1990).
RN   [2]
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   [3]
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   [4]
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   [5] {ECO:0007744|PDB:4HKA}
RP   X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 24-379 IN COMPLEX WITH HEME,
RP   CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF ASP-123; TYR-236; ARG-309
RP   AND TYR-335.
RX   PubMed=23333332; DOI=10.1016/j.jsb.2013.01.002;
RA   Huang W., Gong Z., Li J., Ding J.;
RT   "Crystal structure of Drosophila melanogaster tryptophan 2,3-dioxygenase
RT   reveals insights into substrate recognition and catalytic mechanism.";
RL   J. Struct. Biol. 181:291-299(2013).
CC   -!- FUNCTION: Heme-dependent dioxygenase that catalyzes the oxidative
CC       cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-
CC       tryptophan to N-formyl-L-kynurenine. Catalyzes the oxidative cleavage
CC       of the indole moiety (PubMed:23333332). Required during larval growth
CC       to control the level of potentially harmful free tryptophan in the
CC       hemolymph. In the adult the same reaction is the first step in the
CC       ommochrome biosynthetic pathway (PubMed:2108317). {ECO:0000255|HAMAP-
CC       Rule:MF_03020, ECO:0000269|PubMed:23333332,
CC       ECO:0000303|PubMed:2108317}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-tryptophan + O2 = N-formyl-L-kynurenine;
CC         Xref=Rhea:RHEA:24536, ChEBI:CHEBI:15379, ChEBI:CHEBI:57912,
CC         ChEBI:CHEBI:58629; EC=1.13.11.11; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03020, ECO:0000269|PubMed:23333332};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03020, ECO:0000269|PubMed:23333332};
CC       Note=Binds 1 heme group per subunit. {ECO:0000255|HAMAP-Rule:MF_03020,
CC       ECO:0000269|PubMed:23333332};
CC   -!- PATHWAY: Amino-acid degradation; L-tryptophan degradation via
CC       kynurenine pathway; L-kynurenine from L-tryptophan: step 1/2.
CC       {ECO:0000255|HAMAP-Rule:MF_03020, ECO:0000269|PubMed:23333332}.
CC   -!- PATHWAY: Pigment biosynthesis; ommochrome biosynthesis.
CC       {ECO:0000255|HAMAP-Rule:MF_03020}.
CC   -!- SUBUNIT: Homotetramer. Dimer of dimers. {ECO:0000255|HAMAP-
CC       Rule:MF_03020, ECO:0000269|PubMed:23333332}.
CC   -!- DEVELOPMENTAL STAGE: High in late larvae and in adult.
CC       {ECO:0000269|PubMed:2108317}.
CC   -!- SIMILARITY: Belongs to the tryptophan 2,3-dioxygenase family.
CC       {ECO:0000255|HAMAP-Rule:MF_03020}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M34147; AAA29014.1; -; Genomic_DNA.
DR   EMBL; AE014298; AAF47978.1; -; Genomic_DNA.
DR   EMBL; AY051478; AAK92902.1; -; mRNA.
DR   PIR; A34780; A34780.
DR   RefSeq; NP_511113.1; NM_078558.3.
DR   PDB; 4HKA; X-ray; 2.70 A; A=24-379.
DR   PDBsum; 4HKA; -.
DR   AlphaFoldDB; P20351; -.
DR   SMR; P20351; -.
DR   BioGRID; 58442; 2.
DR   IntAct; P20351; 1.
DR   STRING; 7227.FBpp0073242; -.
DR   PaxDb; 7227-FBpp0073242; -.
DR   DNASU; 32026; -.
DR   EnsemblMetazoa; FBtr0073386; FBpp0073242; FBgn0003965.
DR   GeneID; 32026; -.
DR   KEGG; dme:Dmel_CG2155; -.
DR   UCSC; CG2155-RA; d. melanogaster.
DR   AGR; FB:FBgn0003965; -.
DR   CTD; 32026; -.
DR   FlyBase; FBgn0003965; v.
DR   VEuPathDB; VectorBase:FBgn0003965; -.
DR   eggNOG; KOG3906; Eukaryota.
DR   HOGENOM; CLU_045599_1_1_1; -.
DR   InParanoid; P20351; -.
DR   OMA; WRWRNDH; -.
DR   OrthoDB; 5488022at2759; -.
DR   PhylomeDB; P20351; -.
DR   BRENDA; 1.13.11.11; 1994.
DR   BRENDA; 1.13.11.52; 1994.
DR   Reactome; R-DME-71240; Tryptophan catabolism.
DR   UniPathway; UPA00271; -.
DR   UniPathway; UPA00333; UER00453.
DR   BioGRID-ORCS; 32026; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 32026; -.
DR   PRO; PR:P20351; -.
DR   Proteomes; UP000000803; Chromosome X.
DR   Bgee; FBgn0003965; Expressed in insect adult head and 11 other cell types or tissues.
DR   ExpressionAtlas; P20351; baseline and differential.
DR   GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004833; F:tryptophan 2,3-dioxygenase activity; IDA:UniProtKB.
DR   GO; GO:0048072; P:compound eye pigmentation; TAS:FlyBase.
DR   GO; GO:0070189; P:kynurenine metabolic process; IMP:FlyBase.
DR   GO; GO:0006727; P:ommochrome biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR   GO; GO:0006569; P:tryptophan catabolic process; TAS:FlyBase.
DR   GO; GO:0019442; P:tryptophan catabolic process to acetyl-CoA; IBA:GO_Central.
DR   GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IDA:UniProtKB.
DR   Gene3D; 1.10.287.3810; -; 1.
DR   Gene3D; 1.20.58.480; -; 1.
DR   HAMAP; MF_01972; T23O; 1.
DR   InterPro; IPR037217; Trp/Indoleamine_2_3_dOase-like.
DR   InterPro; IPR004981; Trp_2_3_dOase.
DR   PANTHER; PTHR10138; TRYPTOPHAN 2,3-DIOXYGENASE; 1.
DR   PANTHER; PTHR10138:SF0; TRYPTOPHAN 2,3-DIOXYGENASE; 1.
DR   Pfam; PF03301; Trp_dioxygenase; 1.
DR   SUPFAM; SSF140959; Indolic compounds 2,3-dioxygenase-like; 1.
DR   Genevisible; P20351; DM.
PE   1: Evidence at protein level;
KW   3D-structure; Dioxygenase; Heme; Iron; Metal-binding; Oxidoreductase;
KW   Reference proteome; Tryptophan catabolism.
FT   CHAIN           1..379
FT                   /note="Tryptophan 2,3-dioxygenase"
FT                   /id="PRO_0000065780"
FT   BINDING         57..61
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03020"
FT   BINDING         128
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03020"
FT   BINDING         312
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:0000255|HAMAP-Rule:MF_03020,
FT                   ECO:0000269|PubMed:23333332, ECO:0007744|PDB:4HKA"
FT   BINDING         327
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03020"
FT   MUTAGEN         123
FT                   /note="D->A: Strongly reduced enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:23333332"
FT   MUTAGEN         236
FT                   /note="Y->F: Strongly reduced enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:23333332"
FT   MUTAGEN         309
FT                   /note="R->A: Strongly reduced enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:23333332"
FT   MUTAGEN         335
FT                   /note="Y->F: Strongly reduced enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:23333332"
FT   HELIX           27..30
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           33..36
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           43..46
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           54..82
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   STRAND          83..85
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           89..116
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           121..125
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           128..130
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           135..137
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           140..149
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           153..155
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           163..166
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           170..181
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           185..194
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   TURN            201..204
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           206..226
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           231..252
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           254..262
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           270..281
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           286..320
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           331..338
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           348..351
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           352..356
FT                   /evidence="ECO:0007829|PDB:4HKA"
FT   HELIX           360..362
FT                   /evidence="ECO:0007829|PDB:4HKA"
SQ   SEQUENCE   379 AA;  44421 MW;  E9E4C1B1C86D687F CRC64;
     MSCPYAGNGN DHDDSAVPLT TEVGKIYGEY LMLDKLLDAQ CMLSEEDKRP VHDEHLFIIT
     HQAYELWFKQ IIFEFDSIRD MLDAEVIDET KTLEIVKRLN RVVLILKLLV DQVPILETMT
     PLDFMDFRKY LAPASGFQSL QFRLIENKLG VLTEQRVRYN QKYSDVFSDE EARNSIRNSE
     KDPSLLELVQ RWLERTPGLE ESGFNFWAKF QESVDRFLEA QVQSAMEEPV EKAKNYRLMD
     IEKRREVYRS IFDPAVHDAL VRRGDRRFSH RALQGAIMIT FYRDEPRFSQ PHQLLTLLMD
     IDSLITKWRY NHVIMVQRMI GSQQLGTGGS SGYQYLRSTL SDRYKVFLDL FNLSTFLIPR
     EAIPPLDETI RKKLINKSV
//