T23O_RAT
ID T23O_RAT Reviewed; 406 AA.
AC P21643; Q5EBC2; Q6LBW3;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 140.
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};
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=Tdo2 {ECO:0000255|HAMAP-Rule:MF_03020}; Synonyms=Tdo;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2372286; DOI=10.1016/0006-291x(90)91256-r;
RA Maezono K., Tashiro K., Nakamura T.;
RT "Deduced primary structure of rat tryptophan-2,3-dioxygenase.";
RL Biochem. Biophys. Res. Commun. 170:176-181(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-12, AND INDUCTION.
RX PubMed=3582368; DOI=10.1002/j.1460-2075.1987.tb04800.x;
RA Danesch U., Gloss B., Schmid W., Schuetz G., Schuele R., Renkawitz R.;
RT "Glucocorticoid induction of the rat tryptophan oxygenase gene is mediated
RT by two widely separated glucocorticoid-responsive elements.";
RL EMBO J. 6:625-630(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-12.
RC TISSUE=Liver;
RX PubMed=6327261; DOI=10.1002/j.1460-2075.1982.tb00026.x;
RA Schmid W., Scherer G., Danesch U., Zentgraf H., Matthias P., Strange C.M.,
RA Roewekamp W.G., Schuetz G.;
RT "Isolation and characterization of the rat tryptophan oxygenase gene.";
RL EMBO J. 1:1287-1293(1982).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 102-242.
RX PubMed=1511007; DOI=10.1016/0167-4781(92)90062-5;
RA Merkulov V.M., Merkulova T.I.;
RT "Nucleotide sequence of a fragment of the rat tryptophan oxygenase gene
RT showing high affinity to glucocorticoid receptor in vitro.";
RL Biochim. Biophys. Acta 1132:100-102(1992).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. {ECO:0000255|HAMAP-Rule:MF_03020}.
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};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03020};
CC Note=Binds 1 heme group per subunit. {ECO:0000255|HAMAP-Rule:MF_03020};
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}.
CC -!- SUBUNIT: Homotetramer. Dimer of dimers. {ECO:0000255|HAMAP-
CC Rule:MF_03020}.
CC -!- TISSUE SPECIFICITY: Liver.
CC -!- INDUCTION: By dexamethasone. {ECO:0000269|PubMed:3582368}.
CC -!- SIMILARITY: Belongs to the tryptophan 2,3-dioxygenase family.
CC {ECO:0000255|HAMAP-Rule:MF_03020}.
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DR EMBL; M55167; AAA63503.1; -; mRNA.
DR EMBL; BC089802; AAH89802.1; -; mRNA.
DR EMBL; X05145; CAA28794.1; -; Genomic_DNA.
DR EMBL; X01849; CAA25974.1; -; Genomic_DNA.
DR EMBL; X60833; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A35484; A35484.
DR RefSeq; NP_071798.1; NM_022403.2.
DR AlphaFoldDB; P21643; -.
DR SMR; P21643; -.
DR IntAct; P21643; 1.
DR STRING; 10116.ENSRNOP00000015732; -.
DR BindingDB; P21643; -.
DR ChEMBL; CHEMBL2686; -.
DR iPTMnet; P21643; -.
DR PhosphoSitePlus; P21643; -.
DR PaxDb; P21643; -.
DR PRIDE; P21643; -.
DR Ensembl; ENSRNOT00000015732; ENSRNOP00000015732; ENSRNOG00000011612.
DR GeneID; 64206; -.
DR KEGG; rno:64206; -.
DR UCSC; RGD:68370; rat.
DR CTD; 6999; -.
DR RGD; 68370; Tdo2.
DR eggNOG; KOG3906; Eukaryota.
DR GeneTree; ENSGT00390000008593; -.
DR HOGENOM; CLU_045599_1_1_1; -.
DR InParanoid; P21643; -.
DR OMA; WRWRNDH; -.
DR OrthoDB; 896211at2759; -.
DR PhylomeDB; P21643; -.
DR TreeFam; TF105827; -.
DR BRENDA; 1.13.11.11; 5301.
DR BRENDA; 1.13.11.52; 5301.
DR Reactome; R-RNO-71240; Tryptophan catabolism.
DR SABIO-RK; P21643; -.
DR UniPathway; UPA00333; UER00453.
DR PRO; PR:P21643; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000011612; Expressed in liver and 10 other tissues.
DR Genevisible; P21643; RN.
DR GO; GO:0016597; F:amino acid binding; IDA:RGD.
DR GO; GO:0020037; F:heme binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019825; F:oxygen binding; IDA:RGD.
DR GO; GO:0004833; F:tryptophan 2,3-dioxygenase activity; IDA:RGD.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:1904842; P:response to nitroglycerin; IEP:RGD.
DR GO; GO:0019442; P:tryptophan catabolic process to acetyl-CoA; IDA:RGD.
DR GO; GO:0019441; P:tryptophan catabolic process to kynurenine; ISS:UniProtKB.
DR GO; GO:0006568; P:tryptophan metabolic process; IDA:RGD.
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; PTHR10138; 1.
DR Pfam; PF03301; Trp_dioxygenase; 1.
DR SUPFAM; SSF140959; SSF140959; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Heme; Iron; Metal-binding; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Tryptophan catabolism.
FT CHAIN 1..406
FT /note="Tryptophan 2,3-dioxygenase"
FT /id="PRO_0000072401"
FT BINDING 72..76
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03020"
FT BINDING 144
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03020"
FT BINDING 328
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 BINDING 342
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03020"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 207
FT /note="Missing (in Ref. 5; X60833)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 406 AA; 47857 MW; 9C45973BEE3BF93A CRC64;
MSGCPFSGNS VGYTLKNLSM EDNEEDGAQT GVNRASKGGL IYGDYLQLEK ILNAQELQSE
IKGNKIHDEH LFIITHQAYE LWFKQILWEL DSVREIFQNG HVRDERNMLK VMTRMHRVVV
IFKLLVQQFS VLETMTALDF NDFREYLSPA SGFQSLQFRL LENKIGVLQS LRVPYNRKHY
RDNFEGDYNE LLLKSEQEQT LLQLVEAWLE RTPGLEPHGF NFWGKFEKNI LKGLEEEFLK
IQAKKDSEEK EEQMAEFRKQ KEVLLCLFDE KRHDYLLSKG ERRLSYRALQ GALMIYFYRE
EPRFQVPFQL LTSLMDIDTL MTKWRYNHVC MVHRMLGSKA GTGGSSGYYY LRSTVSDRYK
VFVDLFNLSS YLVPRHWIPK MNPIIHKFLY TAEYSDSSYF SSDESD
