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Protein

Tryptophan 2,3-dioxygenase

Gene

TDO2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Incorporates oxygen into the indole moiety of tryptophan. Has a broad specificity towards tryptamine and derivatives including D- and L-tryptophan, 5-hydroxytryptophan and serotonin (By similarity).By similarity

Catalytic activityi

L-tryptophan + O2 = N-formyl-L-kynurenine.UniRule annotation

Cofactori

hemeUniRule annotationNote: Binds 2 heme groups per tetramer.UniRule annotation

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 annotation
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Indoleamine 2,3-dioxygenase 1 (IDO1), Tryptophan 2,3-dioxygenase (TDO2), Indoleamine 2,3-dioxygenase 2 (IDO2)
  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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei144 – 1441SubstrateUniRule annotation
Binding sitei151 – 1511HemeUniRule annotation
Metal bindingi328 – 3281Iron (heme axial ligand)UniRule annotation
Binding sitei342 – 3421SubstrateUniRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

Tryptophan catabolism

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS07771-MONOMER.
BRENDAi1.13.11.11. 2681.
ReactomeiR-HSA-71240. Tryptophan catabolism.
UniPathwayiUPA00333; UER00453.

Names & Taxonomyi

Protein namesi
Recommended name:
Tryptophan 2,3-dioxygenaseUniRule annotation (EC:1.13.11.11UniRule annotation)
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

HGNCiHGNC:11708. TDO2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA36427.

Chemistry

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

Polymorphism and mutation databases

BioMutaiTDO2.
DMDMi1351188.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 406406Tryptophan 2,3-dioxygenasePRO_0000072399Add
BLAST

Proteomic databases

PaxDbiP48775.
PeptideAtlasiP48775.
PRIDEiP48775.

PTM databases

iPTMnetiP48775.
PhosphoSiteiP48775.

Expressioni

Gene expression databases

BgeeiENSG00000151790.
CleanExiHS_TDO2.
ExpressionAtlasiP48775. baseline and differential.
GenevisibleiP48775. HS.

Organism-specific databases

HPAiHPA039611.

Interactioni

Subunit structurei

Homotetramer.UniRule annotation

Binary interactionsi

WithEntry#Exp.IntActNotes
ASMTLO956716EBI-743494,EBI-743231
DPM1O607623EBI-743494,EBI-719526
EIF4EP067303EBI-743494,EBI-73440
MOB1AQ9H8S93EBI-743494,EBI-748229
MOB3CQ70IA83EBI-743494,EBI-9679267
NGBQ9NPG23EBI-743494,EBI-10311409
SDCBPO005603EBI-743494,EBI-727004
SDCBP2Q9H1903EBI-743494,EBI-742426
ZFYVE26Q96H433EBI-743494,EBI-10286915

Protein-protein interaction databases

BioGridi112858. 16 interactions.
IntActiP48775. 12 interactions.
MINTiMINT-1446261.
STRINGi9606.ENSP00000444788.

Chemistry

BindingDBiP48775.

Structurei

Secondary structure

1
406
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi42 – 454Combined sources
Helixi48 – 514Combined sources
Helixi58 – 614Combined sources
Helixi68 – 9831Combined sources
Helixi105 – 12723Combined sources
Helixi129 – 1324Combined sources
Helixi137 – 14711Combined sources
Helixi150 – 1523Combined sources
Helixi156 – 16510Combined sources
Helixi189 – 1979Combined sources
Helixi201 – 21010Combined sources
Turni217 – 2204Combined sources
Helixi222 – 24120Combined sources
Beta strandi246 – 2483Combined sources
Helixi249 – 26618Combined sources
Helixi270 – 2789Combined sources
Helixi286 – 29712Combined sources
Turni298 – 3003Combined sources
Helixi302 – 3043Combined sources
Helixi305 – 33632Combined sources
Helixi363 – 3675Combined sources
Helixi368 – 3714Combined sources
Helixi375 – 3773Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4PW8X-ray2.90A/B/C/D/E/F/G/H19-388[»]
ProteinModelPortaliP48775.
SMRiP48775. Positions 41-382.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni42 – 465Substrate bindingUniRule annotation
Regioni72 – 765Substrate bindingUniRule annotation

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili239 – 27133UniRule annotationAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

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

Family and domain databases

HAMAPiMF_01972. T23O. 1 hit.
InterProiIPR004981. Trp_2_3_dOase.
[Graphical view]
PANTHERiPTHR10138. PTHR10138. 1 hit.
PfamiPF03301. Trp_dioxygenase. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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.

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
EntryMethodResolution (Å)ChainPositionsPDBsum
4PW8X-ray2.90A/B/C/D/E/F/G/H19-388[»]
ProteinModelPortaliP48775.
SMRiP48775. Positions 41-382.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112858. 16 interactions.
IntActiP48775. 12 interactions.
MINTiMINT-1446261.
STRINGi9606.ENSP00000444788.

Chemistry

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

PTM databases

iPTMnetiP48775.
PhosphoSiteiP48775.

Polymorphism and mutation databases

BioMutaiTDO2.
DMDMi1351188.

Proteomic databases

PaxDbiP48775.
PeptideAtlasiP48775.
PRIDEiP48775.

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.
GeneCardsiTDO2.
HGNCiHGNC:11708. TDO2.
HPAiHPA039611.
MIMi191070. gene.
neXtProtiNX_P48775.
PharmGKBiPA36427.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00333; UER00453.
BioCyciMetaCyc:HS07771-MONOMER.
BRENDAi1.13.11.11. 2681.
ReactomeiR-HSA-71240. Tryptophan catabolism.

Miscellaneous databases

ChiTaRSiTDO2. human.
GeneWikiiTDO2.
GenomeRNAii6999.
PROiP48775.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151790.
CleanExiHS_TDO2.
ExpressionAtlasiP48775. baseline and differential.
GenevisibleiP48775. HS.

Family and domain databases

HAMAPiMF_01972. T23O. 1 hit.
InterProiIPR004981. Trp_2_3_dOase.
[Graphical view]
PANTHERiPTHR10138. PTHR10138. 1 hit.
PfamiPF03301. Trp_dioxygenase. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiT23O_HUMAN
AccessioniPrimary (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: September 7, 2016
This is version 143 of the entry and version 1 of the sequence. [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. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.