We will be switching to the new UniProt website soon. Please explore and share your feedback.
Take me to the new website.
UniProtKB - P48775 (T23O_HUMAN)
Protein
Tryptophan 2,3-dioxygenase
Gene
TDO2
Organism
Homo sapiens (Human)
Status
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 PublicationsCatalytic activityi
- EC:1.13.11.11UniRule 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
- KM=0.135 mM for L-tryptophan1 Publication
- KM=0.132 mM for L-tryptophan1 Publication
: L-tryptophan degradation via kynurenine pathway Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes L-kynurenine from L-tryptophan.UniRule annotation2 Publications 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 144 | SubstrateUniRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 328 | Iron (heme axial ligand)UniRule annotationCombined sources1 Publication | 1 | |
Binding sitei | 342 | SubstrateUniRule annotationCombined sources1 Publication | 1 |
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
- protein homotetramerization Source: UniProtKB
- response to nitroglycerin Source: Ensembl
- tryptophan catabolic process to acetyl-CoA Source: GO_Central
- tryptophan catabolic process to kynurenine Source: UniProtKB
Keywordsi
Molecular function | Dioxygenase, Oxidoreductase |
Biological process | Tryptophan catabolism |
Ligand | Heme, Iron, Metal-binding |
Enzyme and pathway databases
BRENDAi | 1.13.11.11, 2681 1.13.11.52, 2681 |
PathwayCommonsi | P48775 |
Reactomei | R-HSA-71240, Tryptophan catabolism |
SABIO-RKi | P48775 |
SignaLinki | P48775 |
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 | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11708, TDO2 |
MIMi | 191070, gene |
neXtProti | NX_P48775 |
VEuPathDBi | HostDB:ENSG00000151790 |
Pathology & Biotechi
Involvement in diseasei
Hypertryptophanemia (HYPTRP)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive condition characterized by persistent hypertryptophanemia and hyperserotoninemia.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_080251 | 108 | M → I in HYPTRP; reduced tryptophan 2,3-dioxygenase activity; does not affect homotetramerization. 1 PublicationCorresponds to variant dbSNP:rs1553957997EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 42 | Y → A: Reduces enzyme activity by 99%. 1 Publication | 1 | |
Mutagenesisi | 45 | Y → A: Reduces enzyme activity by 99%. 1 Publication | 1 | |
Mutagenesisi | 72 | F → A: Abolishes enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 76 | H → A: Abolishes enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 140 | F → A: Reduces enzyme activity by 99%. 1 Publication | 1 | |
Mutagenesisi | 144 | R → A: Reduces enzyme activity by 99%. 1 Publication | 1 | |
Mutagenesisi | 151 | S → A: Reduces enzyme activity by 90%. 1 Publication | 1 | |
Mutagenesisi | 175 | Y → G: Reduces enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 328 | H → A: Abolishes enzyme activity. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 6999 |
MalaCardsi | TDO2 |
MIMi | 600627, phenotype |
OpenTargetsi | ENSG00000151790 |
Orphaneti | 2224, Hypertryptophanemia |
PharmGKBi | PA36427 |
Miscellaneous databases
Pharosi | P48775, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2140 |
DrugBanki | DB00779, Nalidixic acid DB00500, Tolmetin DB00150, Tryptophan |
GuidetoPHARMACOLOGYi | 2887 |
Genetic variation databases
BioMutai | TDO2 |
DMDMi | 1351188 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000072399 | 1 – 406 | Tryptophan 2,3-dioxygenaseAdd BLAST | 406 |
Proteomic databases
EPDi | P48775 |
MassIVEi | P48775 |
PaxDbi | P48775 |
PeptideAtlasi | P48775 |
PRIDEi | P48775 |
ProteomicsDBi | 55947 |
PTM databases
iPTMneti | P48775 |
PhosphoSitePlusi | P48775 |
Expressioni
Gene expression databases
Bgeei | ENSG00000151790, Expressed in liver and 137 other tissues |
ExpressionAtlasi | P48775, baseline and differential |
Genevisiblei | P48775, HS |
Organism-specific databases
HPAi | ENSG00000151790, Tissue enriched (liver) |
Interactioni
Subunit structurei
Homotetramer. Dimer of dimers.
UniRule annotation3 PublicationsBinary interactionsi
P48775
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 112858, 27 interactors |
IntActi | P48775, 24 interactors |
MINTi | P48775 |
STRINGi | 9606.ENSP00000444788 |
Chemistry databases
BindingDBi | P48775 |
Miscellaneous databases
RNActi | P48775, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P48775 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 72 – 76 | Substrate bindingUniRule annotationCombined sources1 Publication | 5 |
Sequence similaritiesi
Belongs to the tryptophan 2,3-dioxygenase family.UniRule annotation
Phylogenomic databases
eggNOGi | KOG3906, Eukaryota |
GeneTreei | ENSGT00390000008593 |
HOGENOMi | CLU_045599_1_1_1 |
InParanoidi | P48775 |
OMAi | MLVPHRG |
OrthoDBi | 497681at2759 |
PhylomeDBi | P48775 |
TreeFami | TF105827 |
Family and domain databases
HAMAPi | MF_01972, T23O, 1 hit |
InterProi | View protein in InterPro IPR037217, Trp/Indoleamine_2_3_dOase-like IPR004981, Trp_2_3_dOase |
PANTHERi | PTHR10138, PTHR10138, 1 hit |
Pfami | View protein in Pfam PF03301, Trp_dioxygenase, 1 hit |
SUPFAMi | SSF140959, SSF140959, 1 hit |
(1+)i Sequence
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
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD6RA50 | D6RA50_HUMAN | Tryptophan 2,3-dioxygenase | TDO2 | 65 | Annotation score: | ||
D6RB68 | D6RB68_HUMAN | Tryptophan 2,3-dioxygenase | TDO2 | 49 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_080251 | 108 | M → I in HYPTRP; reduced tryptophan 2,3-dioxygenase activity; does not affect homotetramerization. 1 PublicationCorresponds to variant dbSNP:rs1553957997EnsemblClinVar. | 1 |
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 |
CCDSi | CCDS34086.1 |
PIRi | G02022 |
RefSeqi | NP_005642.1, NM_005651.3 |
Genome annotation databases
Ensembli | ENST00000536354; ENSP00000444788; ENSG00000151790 ENST00000573403; ENSP00000460086; ENSG00000262635 |
GeneIDi | 6999 |
KEGGi | hsa:6999 |
MANE-Selecti | ENST00000536354.3; ENSP00000444788.2; NM_005651.4; NP_005642.1 |
UCSCi | uc003ipf.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 |
CCDSi | CCDS34086.1 |
PIRi | G02022 |
RefSeqi | NP_005642.1, NM_005651.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4PW8 | X-ray | 2.90 | A/B/C/D/E/F/G/H | 19-388 | [»] | |
5TI9 | X-ray | 2.50 | A/B/C/D | 18-389 | [»] | |
5TIA | X-ray | 2.44 | A/B/C/D | 18-389 | [»] | |
6A4I | X-ray | 2.65 | A/B/C/D | 19-388 | [»] | |
6PYY | X-ray | 2.40 | A/B/C/D | 18-389 | [»] | |
6PYZ | X-ray | 2.02 | A/B/C/D | 18-389 | [»] | |
6UD5 | X-ray | 2.05 | A/B/C/D | 18-389 | [»] | |
6VBN | X-ray | 3.18 | A/B/C/D | 18-388 | [»] | |
SMRi | P48775 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112858, 27 interactors |
IntActi | P48775, 24 interactors |
MINTi | P48775 |
STRINGi | 9606.ENSP00000444788 |
Chemistry databases
BindingDBi | P48775 |
ChEMBLi | CHEMBL2140 |
DrugBanki | DB00779, Nalidixic acid DB00500, Tolmetin DB00150, Tryptophan |
GuidetoPHARMACOLOGYi | 2887 |
PTM databases
iPTMneti | P48775 |
PhosphoSitePlusi | P48775 |
Genetic variation databases
BioMutai | TDO2 |
DMDMi | 1351188 |
Proteomic databases
EPDi | P48775 |
MassIVEi | P48775 |
PaxDbi | P48775 |
PeptideAtlasi | P48775 |
PRIDEi | P48775 |
ProteomicsDBi | 55947 |
Protocols and materials databases
Antibodypediai | 28079, 311 antibodies from 25 providers |
DNASUi | 6999 |
Genome annotation databases
Ensembli | ENST00000536354; ENSP00000444788; ENSG00000151790 ENST00000573403; ENSP00000460086; ENSG00000262635 |
GeneIDi | 6999 |
KEGGi | hsa:6999 |
MANE-Selecti | ENST00000536354.3; ENSP00000444788.2; NM_005651.4; NP_005642.1 |
UCSCi | uc003ipf.3, human |
Organism-specific databases
CTDi | 6999 |
DisGeNETi | 6999 |
GeneCardsi | TDO2 |
HGNCi | HGNC:11708, TDO2 |
HPAi | ENSG00000151790, Tissue enriched (liver) |
MalaCardsi | TDO2 |
MIMi | 191070, gene 600627, phenotype |
neXtProti | NX_P48775 |
OpenTargetsi | ENSG00000151790 |
Orphaneti | 2224, Hypertryptophanemia |
PharmGKBi | PA36427 |
VEuPathDBi | HostDB:ENSG00000151790 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3906, Eukaryota |
GeneTreei | ENSGT00390000008593 |
HOGENOMi | CLU_045599_1_1_1 |
InParanoidi | P48775 |
OMAi | MLVPHRG |
OrthoDBi | 497681at2759 |
PhylomeDBi | P48775 |
TreeFami | TF105827 |
Enzyme and pathway databases
UniPathwayi | UPA00333;UER00453 |
BRENDAi | 1.13.11.11, 2681 1.13.11.52, 2681 |
PathwayCommonsi | P48775 |
Reactomei | R-HSA-71240, Tryptophan catabolism |
SABIO-RKi | P48775 |
SignaLinki | P48775 |
Miscellaneous databases
BioGRID-ORCSi | 6999, 11 hits in 1035 CRISPR screens |
ChiTaRSi | TDO2, human |
GeneWikii | TDO2 |
GenomeRNAii | 6999 |
Pharosi | P48775, Tchem |
PROi | PR:P48775 |
RNActi | P48775, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000151790, Expressed in liver and 137 other tissues |
ExpressionAtlasi | P48775, baseline and differential |
Genevisiblei | P48775, HS |
Family and domain databases
HAMAPi | MF_01972, T23O, 1 hit |
InterProi | View protein in InterPro IPR037217, Trp/Indoleamine_2_3_dOase-like IPR004981, Trp_2_3_dOase |
PANTHERi | PTHR10138, PTHR10138, 1 hit |
Pfami | View protein in Pfam PF03301, Trp_dioxygenase, 1 hit |
SUPFAMi | SSF140959, SSF140959, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | T23O_HUMAN | |
Accessioni | P48775Primary (citable) accession number: P48775 Secondary accession number(s): A8K053 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1996 |
Last sequence update: | February 1, 1996 | |
Last modified: | February 23, 2022 | |
This is version 180 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families