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P14902 (I23O1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Indoleamine 2,3-dioxygenase 1

Short name=IDO-1
EC=1.13.11.52
Alternative name(s):
Indoleamine-pyrrole 2,3-dioxygenase
Gene names
Name:IDO1
Synonyms:IDO, INDO
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length403 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen. Ref.7

Catalytic activity

D-tryptophan + O2 = N-formyl-D-kynurenine. Ref.7

L-tryptophan + O2 = N-formyl-L-kynurenine. Ref.7

Cofactor

Binds 1 heme group per subunit.

Enzyme regulation

Activity is inhibited by and MTH-trp (methylthiohydantoin-DL-tryptophan), modestly inhibited by L-1MT (1-methyl-L-tryptophan) but not D-1MT (1-methyl-D-tryptophan). Ref.7

Pathway

Amino-acid degradation; L-tryptophan degradation via kynurenine pathway; L-kynurenine from L-tryptophan: step 1/2.

Induction

By IFNG/IFN-gamma. Ref.1 Ref.7

Sequence similarities

Belongs to the indoleamine 2,3-dioxygenase family.

Biophysicochemical properties

Kinetic parameters:

Catalytic efficiency for L-tryptophan is 150 times higher than for D-tryptophan.

KM=21.23 µM for L-tryptophan Ref.8

KM=4.6 mM for D-tryptophan

Ontologies

Keywords
   Coding sequence diversityPolymorphism
   LigandHeme
Iron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

cytokine production involved in inflammatory response

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Traceable author statement PubMed 9712583. Source: ProtInc

kynurenic acid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

multicellular organismal response to stress

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of activated T cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-10 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell tolerance induction

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of chronic inflammatory response

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-12 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of type 2 immune response

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

swimming behavior

Inferred from electronic annotation. Source: Ensembl

tryptophan catabolic process

Traceable author statement. Source: Reactome

tryptophan catabolic process to kynurenine

Inferred from electronic annotation. Source: UniProtKB-UniPathway

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

smooth muscle contractile fiber

Inferred from electronic annotation. Source: Ensembl

stereocilium bundle

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionelectron carrier activity

Traceable author statement Ref.1. Source: UniProtKB

heme binding

Inferred from electronic annotation. Source: InterPro

indoleamine 2,3-dioxygenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

tryptophan 2,3-dioxygenase activity

Inferred from experiment. Source: Reactome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 403403Indoleamine 2,3-dioxygenase 1
PRO_0000215204

Sites

Metal binding3461Iron (heme proximal ligand)

Natural variations

Natural variant41A → T.
Corresponds to variant rs35059413 [ dbSNP | Ensembl ].
VAR_053368

Secondary structure

................................................................. 403
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P14902 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: E92CF57AD0D0BA8D

FASTA40345,326
        10         20         30         40         50         60 
MAHAMENSWT ISKEYHIDEE VGFALPNPQE NLPDFYNDWM FIAKHLPDLI ESGQLRERVE 

        70         80         90        100        110        120 
KLNMLSIDHL TDHKSQRLAR LVLGCITMAY VWGKGHGDVR KVLPRNIAVP YCQLSKKLEL 

       130        140        150        160        170        180 
PPILVYADCV LANWKKKDPN KPLTYENMDV LFSFRDGDCS KGFFLVSLLV EIAAASAIKV 

       190        200        210        220        230        240 
IPTVFKAMQM QERDTLLKAL LEIASCLEKA LQVFHQIHDH VNPKAFFSVL RIYLSGWKGN 

       250        260        270        280        290        300 
PQLSDGLVYE GFWEDPKEFA GGSAGQSSVF QCFDVLLGIQ QTAGGGHAAQ FLQDMRRYMP 

       310        320        330        340        350        360 
PAHRNFLCSL ESNPSVREFV LSKGDAGLRE AYDACVKALV SLRSYHLQIV TKYILIPASQ 

       370        380        390        400 
QPKENKTSED PSKLEAKGTG GTDLMNFLKT VRSTTEKSLL KEG 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA."
Dai W., Gupta S.L.
Biochem. Biophys. Res. Commun. 168:1-8(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION BY IFNG.
Tissue: Fibroblast.
[2]"Primary structure of human indoleamine 2,3-dioxygenase deduced from the nucleotide sequence of its cDNA."
Tone S., Takikawa O., Habara-Ohkubo A., Kadoya A., Yoshida R., Kido R.
Nucleic Acids Res. 18:367-367(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Lung.
[3]"Gene structure of human indoleamine 2,3-dioxygenase."
Kadoya A., Tone S., Maeda H., Minatogawa Y., Kido R.
Biochem. Biophys. Res. Commun. 189:530-536(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Human indoleamine 2,3-dioxygenase from peripheral blood."
He X., Xu L., Liu Y., Zeng Y.
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Peripheral blood.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[7]"Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan."
Metz R., Duhadaway J.B., Kamasani U., Laury-Kleintop L., Muller A.J., Prendergast G.C.
Cancer Res. 67:7082-7087(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, CATALYTIC ACTIVITY.
[8]"Evolution of vertebrate indoleamine 2,3-dioxygenases."
Yuasa H.J., Takubo M., Takahashi A., Hasegawa T., Noma H., Suzuki T.
J. Mol. Evol. 65:705-714(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[9]"Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase."
Sugimoto H., Oda S., Otsuki T., Hino T., Yoshida T., Shiro Y.
Proc. Natl. Acad. Sci. U.S.A. 103:2611-2616(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M34455 mRNA. Translation: AAA36081.1.
X17668 mRNA. Translation: CAA35663.1.
M86472 Genomic DNA. No translation available.
M86473 Genomic DNA. No translation available.
M86474 Genomic DNA. No translation available.
M86475 Genomic DNA. No translation available.
M86476 Genomic DNA. No translation available.
M86477 Genomic DNA. No translation available.
M86478 Genomic DNA. No translation available.
M86479 Genomic DNA. No translation available.
M86480 Genomic DNA. No translation available.
M86481 Genomic DNA. No translation available.
AY221100 mRNA. Translation: AAO34405.1.
AK313259 mRNA. Translation: BAG36069.1.
BC027882 mRNA. Translation: AAH27882.1.
CCDSCCDS47847.1.
PIRPC1161.
RefSeqNP_002155.1. NM_002164.5.
UniGeneHs.840.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2D0TX-ray2.30A/B1-403[»]
2D0UX-ray3.40A/B1-403[»]
ProteinModelPortalP14902.
SMRP14902. Positions 11-403.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109832. 4 interactions.
IntActP14902. 3 interactions.
MINTMINT-1414454.
STRING9606.ENSP00000253513.

Chemistry

BindingDBP14902.
ChEMBLCHEMBL4685.
DrugBankDB00150. L-Tryptophan.

PTM databases

PhosphoSiteP14902.

Polymorphism databases

DMDM123948.

Proteomic databases

PaxDbP14902.
PRIDEP14902.

Protocols and materials databases

DNASU3620.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000518237; ENSP00000430950; ENSG00000131203.
ENST00000522495; ENSP00000430505; ENSG00000131203.
GeneID3620.
KEGGhsa:3620.
UCSCuc003xnm.3. human.

Organism-specific databases

CTD3620.
GeneCardsGC08P039771.
HGNCHGNC:6059. IDO1.
HPAHPA023072.
HPA023149.
HPA027772.
MIM147435. gene.
neXtProtNX_P14902.
PharmGKBPA29869.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG73554.
HOGENOMHOG000203926.
HOVERGENHBG006100.
InParanoidP14902.
KOK00463.
OMAEAYDACV.
PhylomeDBP14902.
TreeFamTF330978.

Enzyme and pathway databases

BioCycMetaCyc:HS05502-MONOMER.
BRENDA1.13.11.11. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKP14902.
UniPathwayUPA00333; UER00453.

Gene expression databases

ArrayExpressP14902.
BgeeP14902.
GenevestigatorP14902.

Family and domain databases

InterProIPR000898. Indolamine_dOase.
[Graphical view]
PfamPF01231. IDO. 1 hit.
[Graphical view]
PROSITEPS00876. IDO_1. 1 hit.
PS00877. IDO_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIDO1. human.
EvolutionaryTraceP14902.
GeneWikiIndoleamine_2,3-dioxygenase.
GenomeRNAi3620.
NextBio14159.
PROP14902.
SOURCESearch...

Entry information

Entry nameI23O1_HUMAN
AccessionPrimary (citable) accession number: P14902
Secondary accession number(s): Q540B4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: July 9, 2014
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM