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

Help top of page

Summary

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]

Help top of page

Genomic context

Location :: 4q31-q32

Sequence :: Chromosome: 4; NC_000004.11 (156824847..156841550)

See TDO2 in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

Help top of page

Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Help top of page

Bibliography

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)

Help top of page

Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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

Help top of page

Products	Interactant	Other Gene	Complex	Source	Pubs	Description
P48775	O95671	ASMTL		HPRD	PubMed
BioGRID:112858	BioGRID:114178	ASMTL		BioGRID	PubMed	Two-hybrid

Function	Evidence Code	Pubs
amino acid binding	IEA Inferred from Electronic Annotation more info
heme binding	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
oxidoreductase activity	IEA Inferred from Electronic Annotation more info
oxygen binding	IEA Inferred from Electronic Annotation 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	IEA Inferred from Electronic Annotation 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
soluble fraction	IEA Inferred from Electronic Annotation more info

General protein information

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

Help top of page

NCBI Reference Sequences (RefSeq)

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

cl03994
Location:26 – 372
Blast Score: 1243

Trp_dioxygenase; Tryptophan 2,3-dioxygenase

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p5 Primary Assembly

Range

156824847..156841550

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 PATCHES

Genomic

NW_003315914.1 Reference GRCh37.p5 PATCHES

Range

68318..85021

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

152563675..152580464

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Help top of page

Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC093830.3 (68316..85019)	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