TDO2 tryptophan 2,3-dioxygenase [Homo sapiens (human)] - Gene

Summary

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Official Symbol: TDO2provided by HGNC
Official Full Name: tryptophan 2,3-dioxygenaseprovided by HGNC
Primary source: HGNC:11708
See related: Ensembl:ENSG00000151790; HPRD:01847; MIM:191070; Vega:OTTHUMG00000161838
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TO; TDO; TPH2; TRPO
Summary: This gene encodes a heme enzyme that plays a critical role in tryptophan metabolism by catalyzing the first and rate-limiting step of the kynurenine pathway. Increased activity of the encoded protein and subsequent kynurenine production may also play a role in cancer through the suppression of antitumor immune responses, and single nucleotide polymorphisms in this gene may be associated with autism. [provided by RefSeq, Feb 2012]

Genomic context

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Location :: 4q31-q32

Sequence :: Chromosome: 4; NC_000004.11 (156824845..156841558)

See TDO2 in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Data suggest that T342 in hTDO has critical role in controlling substrate binding, substrate stereoselectivity, H-bonding interaction between enzyme and intermediates, and regulating the dynamics of protein structure.
Title: Molecular basis for the substrate stereoselectivity in tryptophan dioxygenase.
The data suggest that TDO uses a ring-opening mechanism during N-formylkynurenine formation, rather than Criegee or dioxetane mechanisms as previously proposed.
Title: The mechanism of formation of N-formylkynurenine by heme dioxygenases.
Studies indicate that the heme dioxygenases are differentiated by their ability to catalyze the oxidation of l-tryptophan to N-formylkynurenine.
Title: Structure and reaction mechanism in the heme dioxygenases.
subtle differences between the TDO and IDO reactions
Title: The first step of the dioxygenation reaction carried out by tryptophan dioxygenase and indoleamine 2,3-dioxygenase as revealed by quantum mechanical/molecular mechanical studies.
TDO mediates antimicrobial and immunoregulatory effects. TDO-dependent inhibition of T-cell growth might be involved in the immunotolerance observed in vivo during allogeneic liver transplantation.
Title: Antimicrobial and immunoregulatory properties of human tryptophan 2,3-dioxygenase.
The tyrosine 42 of recombinant human TDO is responsible for the cooperative binding of l-Trp by participating in the active site of the adjacent subunit.
Title: Cooperative binding of L-trp to human tryptophan 2,3-dioxygenase: resonance Raman spectroscopic analysis.
significant mechanistic differences exist across the heme dioxygenase family, and the data are discussed within this broader framework
Title: A kinetic, spectroscopic, and redox study of human tryptophan 2,3-dioxygenase.
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder.
Polymorphism of tryptophan 2,3 dioxygenase gene is associated with autism.
Title: Association of tryptophan 2,3 dioxygenase gene polymorphism with autism.
We found that astrocytes, neurons, and microglia expressed IDO but only microglia were able to produce detectable amounts of quinolinic acid. However, astrocytes and neurons had the ability to catabolize quinolinic acid.
Title: Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons.

Submit: New GeneRIF Correction See all (11)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

First genome-wide association scan on neurophysiological endophenotypes points to trans-regulation effects on SLC2A3 in dyslexic children.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P48775	O95671	ASMTL	HPRD	PubMed
BioGRID:112858	BioGRID:114178	ASMTL	BioGRID	PubMed	Two-hybrid
BioGRID:112858	BioGRID:116982	SIRT3	BioGRID	PubMed	Positive Genetic

Pathways from BioSystems

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Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of amino acids and derivatives, organism-specific biosystem (from REACTOME)
Metabolism of amino acids and derivatives, organism-specific biosystemThis group of reactions is responsible for: 1) the breakdown of amino acids; 2) the synthesis of urea from ammonia and amino groups generated by amino acid breakdown; 3) the synthesis of the ten amin...
Monoamine Transport, organism-specific biosystem (from WikiPathways)
Monoamine Transport, organism-specific biosystem
Monoamine Transport
NAD biosynthesis II (from tryptophan), organism-specific biosystem (from BIOCYC)
NAD biosynthesis II (from tryptophan), organism-specific biosystem
NAD biosynthesis II (from tryptophan)
NAD biosynthesis II (from tryptophan), conserved biosystem (from BIOCYC)
NAD biosynthesis II (from tryptophan), conserved biosystemGeneral Background Nicotinamide adenine dinucleotide (NAD) and its phosphorylated derivative, nicotinamide adenine dinucleotide phosphate (NADP) are two of the most important coenzymes in redox reac...
Tryptophan catabolism, organism-specific biosystem (from REACTOME)
Tryptophan catabolism, organism-specific biosystemTryptophan is catabolized in seven steps to yield aminomuconate. Intermedistes in this process are used as well for the synthesis of serotonin and kynurenine (Peters 1991).
Tryptophan metabolism, organism-specific biosystem (from KEGG)
Tryptophan metabolism, organism-specific biosystem
Tryptophan metabolism
Tryptophan metabolism, organism-specific biosystem (from WikiPathways)
Tryptophan metabolism, organism-specific biosystem
Tryptophan metabolism
Tryptophan metabolism, conserved biosystem (from KEGG)
Tryptophan metabolism, conserved biosystem
Tryptophan metabolism
tryptophan degradation III (eukaryotic), organism-specific biosystem (from BIOCYC)
tryptophan degradation III (eukaryotic), organism-specific biosystem
tryptophan degradation III (eukaryotic)
tryptophan degradation III (eukaryotic), conserved biosystem (from BIOCYC)
tryptophan degradation III (eukaryotic), conserved biosystemAerobic |FRAME:TRP| degradation, also known as the |FRAME: CPD-14736| pathway, is the major route of L-tryptophan degradation in mammals. This complex network of biochemical transformations generates...
tryptophan degradation XI (mammalian, via kynurenine), conserved biosystem (from BIOCYC)
tryptophan degradation XI (mammalian, via kynurenine), conserved biosystemGeneral Background In mammals |FRAME: TRP| is an essential amino acid that must be obtained in the diet. It is utilized in protein synthesis and in biosynthesis of the neurotransmitter |FRAME: SERO...
tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde, organism-specific biosystem (from BIOCYC)
tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde, organism-specific biosystemThis upstream portion of tryptophan degradation is found in many eukaryotes (including all metazoa) and some prokaryotes. The compound : 2-AMINO-3-3-OXOPROP-2-ENYL-BUT-2-ENEDI, at which this pathway ...
tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde, conserved biosystem (from BIOCYC)
tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde, conserved biosystemThis upstream portion of tryptophan degradation is found in many eukaryotes (iincluding all metazoa) and some prokaryotes. The compound |FRAME: 2-AMINO-3-3-OXOPROP-2-ENYL-BUT-2-ENEDI|, at which this ...

General gene information

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Markers

A006M46 (e-PCR)
- UniSTS:1455

SHGC-50178 (e-PCR)
- UniSTS:16583

D4S3293 (e-PCR)
- UniSTS:759

Homology

Homologs of the TDO2 gene: The TDO2 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, and C.elegans.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
amino acid binding	IEA Inferred from Electronic Annotation more info
heme binding	IBA Inferred from Biological aspect of Ancestor more info
metal ion binding	IEA Inferred from Electronic Annotation more info
oxygen binding	IEA Inferred from Electronic Annotation more info
tryptophan 2,3-dioxygenase activity	IBA Inferred from Biological aspect of Ancestor more info
tryptophan 2,3-dioxygenase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
cellular nitrogen compound metabolic process	TAS Traceable Author Statement more info
small molecule metabolic process	TAS Traceable Author Statement more info
tryptophan catabolic process	TAS Traceable Author Statement more info
tryptophan catabolic process to acetyl-CoA	IBA Inferred from Biological aspect of Ancestor more info
tryptophan catabolic process to kynurenine	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: tryptophan 2,3-dioxygenase

Names: tryptophan 2,3-dioxygenase; tryptophanase; tryptophan oxygenase; tryptophan pyrrolase; tryptamin 2,3-dioxygenase

NP_005642.1

EC 1.13.11.11

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_005651.3 → NP_005642.1 tryptophan 2,3-dioxygenase

Status: REVIEWED

Source sequence(s)

AA705255, BG616664, U32989

Consensus CDS

CCDS34086.1

UniProtKB/Swiss-Prot

P48775

Related

ENSP00000444788, OTTHUMP00000220788, ENST00000536354, OTTHUMT00000366209

Conserved Domains (1) summary

pfam03301
Location:26 – 372
Blast Score: 1243

Trp_dioxygenase; Tryptophan 2,3-dioxygenase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 PATCHES

Genomic

NW_003315914.1 Reference GRCh37.p10 PATCHES

Range

68316..85029

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p10 Primary Assembly

Range

156824845..156841558

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

152563673..152580472

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018915.1 Alternate CHM1_1.0

Range

156616816..156633644

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01070177.1 (112129..118307)	None
genomic	ABBA01070178.1	None
genomic	AC093830.3 (68317..85020)	None
genomic	AMYH01014636.1 (404734..410950)	None
genomic	AMYH01014637.1	None
genomic	CH471056.2	EAX04884.1
		EAX04885.1
		EAX04886.1
mRNA	AA705255.1	None
mRNA	AK289418.1	BAF82107.1
mRNA	AK307741.1	None
mRNA	BC005355.1	AAH05355.1
mRNA	BG616664.1	None
mRNA	BX647341.1	None
mRNA	U32989.1	AAB08514.1
other-genetic	EU831460.1	ACE87147.1
other-genetic	EU831547.1	ACE86466.1
other-genetic	HQ447298.1	ADQ31785.1