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Protein

Tryptophan 2,3-dioxygenase

Gene

TDO2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-tryptophan to N-formyl-L-kynurenine. Catalyzes the oxidative cleavage of the indole moiety.UniRule annotation3 Publications

Catalytic activityi

L-tryptophan + O2 = N-formyl-L-kynurenine.UniRule annotation3 Publications

Cofactori

hemeUniRule annotation3 PublicationsNote: Binds 1 heme group per subunit.UniRule annotation1 Publication

Kineticsi

Kcat is 0.54 sec(-1) with L-tryptophan as substrate.1 Publication
  1. KM=0.135 mM for L-tryptophan1 Publication
  2. KM=0.132 mM for L-tryptophan1 Publication

    Pathwayi: L-tryptophan degradation via kynurenine pathway

    This protein is involved in step 1 of the subpathway that synthesizes L-kynurenine from L-tryptophan.UniRule annotation2 Publications
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Indoleamine 2,3-dioxygenase 1 (IDO1), Indoleamine 2,3-dioxygenase 2 (IDO2), Tryptophan 2,3-dioxygenase (TDO2)
    2. Kynurenine formamidase (AFMID)
    This subpathway is part of the pathway L-tryptophan degradation via kynurenine pathway, which is itself part of Amino-acid degradation.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-kynurenine from L-tryptophan, the pathway L-tryptophan degradation via kynurenine pathway and in Amino-acid degradation.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei144SubstrateUniRule annotationCombined sources1 Publication1
    Metal bindingi328Iron (heme axial ligand)UniRule annotationCombined sources1 Publication1
    Binding sitei342SubstrateUniRule annotationCombined sources1 Publication1

    GO - Molecular functioni

    • amino acid binding Source: Ensembl
    • heme binding Source: UniProtKB
    • identical protein binding Source: IntAct
    • metal ion binding Source: UniProtKB-KW
    • oxygen binding Source: Ensembl
    • tryptophan 2,3-dioxygenase activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionDioxygenase, Oxidoreductase
    Biological processTryptophan catabolism
    LigandHeme, Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS07771-MONOMER
    BRENDAi1.13.11.11 2681
    ReactomeiR-HSA-71240 Tryptophan catabolism
    UniPathwayi
    UPA00333;UER00453

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tryptophan 2,3-dioxygenaseUniRule annotation (EC:1.13.11.11UniRule annotation3 Publications)
    Short name:
    TDOUniRule annotation
    Alternative name(s):
    Tryptamin 2,3-dioxygenaseUniRule annotation
    Tryptophan oxygenaseUniRule annotation
    Short name:
    TOUniRule annotation
    Short name:
    TRPOUniRule annotation
    Tryptophan pyrrolaseUniRule annotation
    TryptophanaseUniRule annotation
    Gene namesi
    Name:TDO2UniRule annotation
    Synonyms:TDO
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 4

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000151790.8
    HGNCiHGNC:11708 TDO2
    MIMi191070 gene
    neXtProtiNX_P48775

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Pathology & Biotechi

    Involvement in diseasei

    Hypertryptophanemia (HYPTRP)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAn autosomal recessive condition characterized by persistent hypertryptophanemia and hyperserotoninemia.
    See also OMIM:600627
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_080251108M → I in HYPTRP; reduced tryptophan 2,3-dioxygenase activity; does not affect homotetramerization. 1 Publication1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi42Y → A: Reduces enzyme activity by 99%. 1 Publication1
    Mutagenesisi45Y → A: Reduces enzyme activity by 99%. 1 Publication1
    Mutagenesisi72F → A: Abolishes enzyme activity. 1 Publication1
    Mutagenesisi76H → A: Abolishes enzyme activity. 1 Publication1
    Mutagenesisi140F → A: Reduces enzyme activity by 99%. 1 Publication1
    Mutagenesisi144R → A: Reduces enzyme activity by 99%. 1 Publication1
    Mutagenesisi151S → A: Reduces enzyme activity by 90%. 1 Publication1
    Mutagenesisi175Y → G: Reduces enzyme activity. 1 Publication1
    Mutagenesisi328H → A: Abolishes enzyme activity. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi6999
    MalaCardsiTDO2
    MIMi600627 phenotype
    OpenTargetsiENSG00000151790
    Orphaneti2224 Hypertryptophanemia
    PharmGKBiPA36427

    Chemistry databases

    ChEMBLiCHEMBL2140
    DrugBankiDB00150 L-Tryptophan
    DB00779 Nalidixic Acid
    DB00500 Tolmetin
    GuidetoPHARMACOLOGYi2887

    Polymorphism and mutation databases

    BioMutaiTDO2
    DMDMi1351188

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000723991 – 406Tryptophan 2,3-dioxygenaseAdd BLAST406

    Proteomic databases

    EPDiP48775
    PaxDbiP48775
    PeptideAtlasiP48775
    PRIDEiP48775
    ProteomicsDBi55947

    PTM databases

    iPTMnetiP48775
    PhosphoSitePlusiP48775

    Expressioni

    Gene expression databases

    BgeeiENSG00000151790 Expressed in 118 organ(s), highest expression level in liver
    CleanExiHS_TDO2
    ExpressionAtlasiP48775 baseline and differential
    GenevisibleiP48775 HS

    Organism-specific databases

    HPAiHPA039611

    Interactioni

    Subunit structurei

    Homotetramer. Dimer of dimers.UniRule annotation3 Publications

    Binary interactionsi

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi112858, 23 interactors
    IntActiP48775, 19 interactors
    MINTiP48775
    STRINGi9606.ENSP00000444788

    Chemistry databases

    BindingDBiP48775

    Structurei

    Secondary structure

    1406
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliP48775
    SMRiP48775
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni72 – 76Substrate bindingUniRule annotationCombined sources1 Publication5

    Sequence similaritiesi

    Belongs to the tryptophan 2,3-dioxygenase family.UniRule annotation

    Phylogenomic databases

    eggNOGiKOG3906 Eukaryota
    COG3483 LUCA
    GeneTreeiENSGT00390000008593
    HOGENOMiHOG000221584
    HOVERGENiHBG003043
    InParanoidiP48775
    KOiK00453
    OMAiYWDLYQL
    OrthoDBiEOG091G080K
    PhylomeDBiP48775
    TreeFamiTF105827

    Family and domain databases

    HAMAPiMF_01972 T23O, 1 hit
    InterProiView protein in InterPro
    IPR037217 Trp/Indoleamine_2_3_dOase-like
    IPR004981 Trp_2_3_dOase
    PANTHERiPTHR10138 PTHR10138, 1 hit
    PfamiView protein in Pfam
    PF03301 Trp_dioxygenase, 1 hit
    SUPFAMiSSF140959 SSF140959, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

    P48775-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MSGCPFLGNN FGYTFKKLPV EGSEEDKSQT GVNRASKGGL IYGNYLHLEK
    60 70 80 90 100
    VLNAQELQSE TKGNKIHDEH LFIITHQAYE LWFKQILWEL DSVREIFQNG
    110 120 130 140 150
    HVRDERNMLK VVSRMHRVSV ILKLLVQQFS ILETMTALDF NDFREYLSPA
    160 170 180 190 200
    SGFQSLQFRL LENKIGVLQN MRVPYNRRHY RDNFKGEENE LLLKSEQEKT
    210 220 230 240 250
    LLELVEAWLE RTPGLEPHGF NFWGKLEKNI TRGLEEEFIR IQAKEESEEK
    260 270 280 290 300
    EEQVAEFQKQ KEVLLSLFDE KRHEHLLSKG ERRLSYRALQ GALMIYFYRE
    310 320 330 340 350
    EPRFQVPFQL LTSLMDIDSL MTKWRYNHVC MVHRMLGSKA GTGGSSGYHY
    360 370 380 390 400
    LRSTVSDRYK VFVDLFNLST YLIPRHWIPK MNPTIHKFLY TAEYCDSSYF

    SSDESD
    Length:406
    Mass (Da):47,872
    Last modified:February 1, 1996 - v1
    Checksum:i1B89901F445B79FE
    GO

    Computationally mapped potential isoform sequencesi

    There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    D6RA50D6RA50_HUMAN
    Tryptophan 2,3-dioxygenase
    TDO2
    65Annotation score:
    D6RB68D6RB68_HUMAN
    Tryptophan 2,3-dioxygenase
    TDO2
    49Annotation score:

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_080251108M → I in HYPTRP; reduced tryptophan 2,3-dioxygenase activity; does not affect homotetramerization. 1 Publication1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U32989 mRNA Translation: AAB08514.1
    AK289418 mRNA Translation: BAF82107.1
    CH471056 Genomic DNA Translation: EAX04885.1
    BC005355 mRNA Translation: AAH05355.1
    CCDSiCCDS34086.1
    PIRiG02022
    RefSeqiNP_005642.1, NM_005651.3
    UniGeneiHs.183671
    Hs.593955

    Genome annotation databases

    EnsembliENST00000536354; ENSP00000444788; ENSG00000151790
    ENST00000573403; ENSP00000460086; ENSG00000262635
    GeneIDi6999
    KEGGihsa:6999
    UCSCiuc003ipf.3 human

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U32989 mRNA Translation: AAB08514.1
    AK289418 mRNA Translation: BAF82107.1
    CH471056 Genomic DNA Translation: EAX04885.1
    BC005355 mRNA Translation: AAH05355.1
    CCDSiCCDS34086.1
    PIRiG02022
    RefSeqiNP_005642.1, NM_005651.3
    UniGeneiHs.183671
    Hs.593955

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4PW8X-ray2.90A/B/C/D/E/F/G/H19-388[»]
    5TI9X-ray2.50A/B/C/D18-389[»]
    5TIAX-ray2.44A/B/C/D18-389[»]
    6A4IX-ray2.65A/B/C/D19-388[»]
    ProteinModelPortaliP48775
    SMRiP48775
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi112858, 23 interactors
    IntActiP48775, 19 interactors
    MINTiP48775
    STRINGi9606.ENSP00000444788

    Chemistry databases

    BindingDBiP48775
    ChEMBLiCHEMBL2140
    DrugBankiDB00150 L-Tryptophan
    DB00779 Nalidixic Acid
    DB00500 Tolmetin
    GuidetoPHARMACOLOGYi2887

    PTM databases

    iPTMnetiP48775
    PhosphoSitePlusiP48775

    Polymorphism and mutation databases

    BioMutaiTDO2
    DMDMi1351188

    Proteomic databases

    EPDiP48775
    PaxDbiP48775
    PeptideAtlasiP48775
    PRIDEiP48775
    ProteomicsDBi55947

    Protocols and materials databases

    DNASUi6999
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000536354; ENSP00000444788; ENSG00000151790
    ENST00000573403; ENSP00000460086; ENSG00000262635
    GeneIDi6999
    KEGGihsa:6999
    UCSCiuc003ipf.3 human

    Organism-specific databases

    CTDi6999
    DisGeNETi6999
    EuPathDBiHostDB:ENSG00000151790.8
    GeneCardsiTDO2
    HGNCiHGNC:11708 TDO2
    HPAiHPA039611
    MalaCardsiTDO2
    MIMi191070 gene
    600627 phenotype
    neXtProtiNX_P48775
    OpenTargetsiENSG00000151790
    Orphaneti2224 Hypertryptophanemia
    PharmGKBiPA36427
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3906 Eukaryota
    COG3483 LUCA
    GeneTreeiENSGT00390000008593
    HOGENOMiHOG000221584
    HOVERGENiHBG003043
    InParanoidiP48775
    KOiK00453
    OMAiYWDLYQL
    OrthoDBiEOG091G080K
    PhylomeDBiP48775
    TreeFamiTF105827

    Enzyme and pathway databases

    UniPathwayi
    UPA00333;UER00453

    BioCyciMetaCyc:HS07771-MONOMER
    BRENDAi1.13.11.11 2681
    ReactomeiR-HSA-71240 Tryptophan catabolism

    Miscellaneous databases

    ChiTaRSiTDO2 human
    GeneWikiiTDO2
    GenomeRNAii6999
    PROiPR:P48775
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000151790 Expressed in 118 organ(s), highest expression level in liver
    CleanExiHS_TDO2
    ExpressionAtlasiP48775 baseline and differential
    GenevisibleiP48775 HS

    Family and domain databases

    HAMAPiMF_01972 T23O, 1 hit
    InterProiView protein in InterPro
    IPR037217 Trp/Indoleamine_2_3_dOase-like
    IPR004981 Trp_2_3_dOase
    PANTHERiPTHR10138 PTHR10138, 1 hit
    PfamiView protein in Pfam
    PF03301 Trp_dioxygenase, 1 hit
    SUPFAMiSSF140959 SSF140959, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiT23O_HUMAN
    AccessioniPrimary (citable) accession number: P48775
    Secondary accession number(s): A8K053
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 1996
    Last modified: November 7, 2018
    This is version 161 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    7. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
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