Browse TDO2

Summary
SymbolTDO2
Nametryptophan 2,3-dioxygenase
Aliases TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location4q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location -
Domain PF03301 Tryptophan 2
Function

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.

> Gene Ontology
 
Biological Process GO:0006084 acetyl-CoA metabolic process
GO:0006568 tryptophan metabolic process
GO:0006569 tryptophan catabolic process
GO:0006576 cellular biogenic amine metabolic process
GO:0006586 indolalkylamine metabolic process
GO:0006637 acyl-CoA metabolic process
GO:0006732 coenzyme metabolic process
GO:0006790 sulfur compound metabolic process
GO:0009072 aromatic amino acid family metabolic process
GO:0009074 aromatic amino acid family catabolic process
GO:0009308 amine metabolic process
GO:0009310 amine catabolic process
GO:0016054 organic acid catabolic process
GO:0019439 aromatic compound catabolic process
GO:0019441 tryptophan catabolic process to kynurenine
GO:0019442 tryptophan catabolic process to acetyl-CoA
GO:0035383 thioester metabolic process
GO:0042180 cellular ketone metabolic process
GO:0042402 cellular biogenic amine catabolic process
GO:0042430 indole-containing compound metabolic process
GO:0042436 indole-containing compound catabolic process
GO:0042537 benzene-containing compound metabolic process
GO:0044106 cellular amine metabolic process
GO:0044270 cellular nitrogen compound catabolic process
GO:0044282 small molecule catabolic process
GO:0046218 indolalkylamine catabolic process
GO:0046700 heterocycle catabolic process
GO:0051186 cofactor metabolic process
GO:0070189 kynurenine metabolic process
GO:1901361 organic cyclic compound catabolic process
GO:1901565 organonitrogen compound catabolic process
GO:1901605 alpha-amino acid metabolic process
GO:1901606 alpha-amino acid catabolic process
Molecular Function GO:0004833 tryptophan 2,3-dioxygenase activity
GO:0016597 amino acid binding
GO:0016701 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen
GO:0016702 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
GO:0019825 oxygen binding
GO:0020037 heme binding
GO:0031406 carboxylic acid binding
GO:0043168 anion binding
GO:0046906 tetrapyrrole binding
GO:0051213 dioxygenase activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa00380 Tryptophan metabolism
hsa01100 Metabolic pathways
Reactome R-HSA-6788656: Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism
R-HSA-1430728: Metabolism
R-HSA-71291: Metabolism of amino acids and derivatives
R-HSA-71240: Tryptophan catabolism
Summary
SymbolTDO2
Nametryptophan 2,3-dioxygenase
Aliases TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location4q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TDO2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between TDO2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
23144293Brain neoplasmInhibit immunityFurther, it was also recently shown that TDO-2-dependent production of KYN by brain tumors might be a novel mechanism for suppressing antitumor immunity and supporting tumor growth through the activation of the Aryl hydrocarbon receptor (AhR).
25132599glioblastomaInhibit immunityAccordingly, gene expression profile analyses revealed negative correlation of FKBP52 and TDO in glial and neural tumors and in normal brain. Knockdown of FKBP52 and treatment with the FK-binding immunosuppressant FK506 enhanced TDO expression and activity in glioblastoma cells.
Summary
SymbolTDO2
Nametryptophan 2,3-dioxygenase
Aliases TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location4q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of TDO2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolTDO2
Nametryptophan 2,3-dioxygenase
Aliases TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location4q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of TDO2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0410.947
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.8920.529
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.5960.534
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-1.1340.0667
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.5370.629
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-1.8830.165
729033130MelanomaallAnti-PD-1 (nivolumab) 26231.1030.143
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.0070.379
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11121.1180.383
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.0190.989
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.190.5
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0510.793
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TDO2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.72.711
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.73.40.31
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolTDO2
Nametryptophan 2,3-dioxygenase
Aliases TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location4q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TDO2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolTDO2
Nametryptophan 2,3-dioxygenase
Aliases TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location4q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TDO2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TDO2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTDO2
Nametryptophan 2,3-dioxygenase
Aliases TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location4q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TDO2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTDO2
Nametryptophan 2,3-dioxygenase
Aliases TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location4q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TDO2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTDO2
Nametryptophan 2,3-dioxygenase
Aliases TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location4q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TDO2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTDO2
Nametryptophan 2,3-dioxygenase
Aliases TO; TRPO; tryptamin 2,3-dioxygenase; tryptophan oxygenase; tryptophan pyrrolase; tryptophanase
Chromosomal Location4q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TDO2 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.