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Protein

Indoleamine 2,3-dioxygenase 1

Gene

IDO1

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

Functioni

Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen.1 Publication

Catalytic activityi

D-tryptophan + O2 = N-formyl-D-kynurenine.1 Publication
L-tryptophan + O2 = N-formyl-L-kynurenine.1 Publication

Cofactori

hemeNote: Binds 1 heme group per subunit.

Enzyme regulationi

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).1 Publication

Kineticsi

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

  1. KM=21.23 µM for L-tryptophan1 Publication
  2. KM=4.6 mM for D-tryptophan1 Publication

    Pathway:iL-tryptophan degradation via kynurenine pathway

    This protein is involved in step 1 of the subpathway that synthesizes L-kynurenine from L-tryptophan.
    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
    Metal bindingi346 – 3461Iron (heme proximal ligand)

    GO - Molecular functioni

    • electron carrier activity Source: UniProtKB
    • heme binding Source: InterPro
    • indoleamine 2,3-dioxygenase activity Source: UniProtKB
    • metal ion binding Source: UniProtKB-KW
    • tryptophan 2,3-dioxygenase activity Source: Reactome

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05502-MONOMER.
    BRENDAi1.13.11.11. 2681.
    1.13.11.52. 2681.
    ReactomeiREACT_916. Tryptophan catabolism.
    SABIO-RKP14902.
    UniPathwayiUPA00333; UER00453.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Indoleamine 2,3-dioxygenase 1 (EC:1.13.11.52)
    Short name:
    IDO-1
    Alternative name(s):
    Indoleamine-pyrrole 2,3-dioxygenase
    Gene namesi
    Name:IDO1
    Synonyms:IDO, INDO
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:6059. IDO1.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29869.

    Chemistry

    DrugBankiDB00150. L-Tryptophan.
    DB01065. Melatonin.

    Polymorphism and mutation databases

    BioMutaiIDO1.
    DMDMi123948.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 403403Indoleamine 2,3-dioxygenase 1PRO_0000215204Add
    BLAST

    Proteomic databases

    PaxDbiP14902.
    PRIDEiP14902.

    PTM databases

    PhosphoSiteiP14902.

    Expressioni

    Inductioni

    By IFNG/IFN-gamma.1 Publication

    Gene expression databases

    BgeeiP14902.
    ExpressionAtlasiP14902. baseline and differential.
    GenevisibleiP14902. HS.

    Organism-specific databases

    HPAiHPA023072.
    HPA023149.
    HPA027772.

    Interactioni

    Protein-protein interaction databases

    BioGridi109832. 3 interactions.
    IntActiP14902. 3 interactions.
    MINTiMINT-1414454.
    STRINGi9606.ENSP00000430505.

    Structurei

    Secondary structure

    1
    403
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi14 – 163Combined sources
    Turni19 – 213Combined sources
    Helixi34 – 363Combined sources
    Helixi37 – 448Combined sources
    Helixi46 – 516Combined sources
    Helixi55 – 617Combined sources
    Helixi67 – 693Combined sources
    Helixi73 – 9220Combined sources
    Beta strandi95 – 973Combined sources
    Beta strandi101 – 1033Combined sources
    Helixi105 – 11814Combined sources
    Helixi126 – 1294Combined sources
    Beta strandi132 – 1387Combined sources
    Helixi145 – 1473Combined sources
    Beta strandi148 – 1514Combined sources
    Helixi160 – 17819Combined sources
    Helixi181 – 1899Combined sources
    Helixi193 – 21422Combined sources
    Helixi217 – 2204Combined sources
    Helixi223 – 2286Combined sources
    Helixi230 – 2334Combined sources
    Beta strandi237 – 2393Combined sources
    Helixi241 – 2433Combined sources
    Beta strandi247 – 2493Combined sources
    Turni250 – 2523Combined sources
    Beta strandi254 – 2574Combined sources
    Helixi264 – 2663Combined sources
    Helixi268 – 2769Combined sources
    Beta strandi284 – 2863Combined sources
    Helixi287 – 2959Combined sources
    Helixi296 – 2983Combined sources
    Helixi301 – 31111Combined sources
    Helixi316 – 3216Combined sources
    Turni322 – 3243Combined sources
    Helixi326 – 35328Combined sources
    Helixi355 – 3584Combined sources
    Helixi382 – 39716Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2D0TX-ray2.30A/B1-403[»]
    2D0UX-ray3.40A/B1-403[»]
    4PK5X-ray2.79A/B1-403[»]
    4PK6X-ray3.45A/B1-403[»]
    ProteinModelPortaliP14902.
    SMRiP14902. Positions 11-403.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP14902.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the indoleamine 2,3-dioxygenase family.Curated

    Phylogenomic databases

    eggNOGiNOG73554.
    GeneTreeiENSGT00390000002154.
    HOGENOMiHOG000203926.
    HOVERGENiHBG006100.
    InParanoidiP14902.
    KOiK00463.
    OMAiEAYDACV.
    PhylomeDBiP14902.
    TreeFamiTF330978.

    Family and domain databases

    InterProiIPR000898. Indolamine_dOase.
    [Graphical view]
    PfamiPF01231. IDO. 1 hit.
    [Graphical view]
    PROSITEiPS00876. IDO_1. 1 hit.
    PS00877. IDO_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P14902-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAHAMENSWT ISKEYHIDEE VGFALPNPQE NLPDFYNDWM FIAKHLPDLI
    60 70 80 90 100
    ESGQLRERVE KLNMLSIDHL TDHKSQRLAR LVLGCITMAY VWGKGHGDVR
    110 120 130 140 150
    KVLPRNIAVP YCQLSKKLEL PPILVYADCV LANWKKKDPN KPLTYENMDV
    160 170 180 190 200
    LFSFRDGDCS KGFFLVSLLV EIAAASAIKV IPTVFKAMQM QERDTLLKAL
    210 220 230 240 250
    LEIASCLEKA LQVFHQIHDH VNPKAFFSVL RIYLSGWKGN PQLSDGLVYE
    260 270 280 290 300
    GFWEDPKEFA GGSAGQSSVF QCFDVLLGIQ QTAGGGHAAQ FLQDMRRYMP
    310 320 330 340 350
    PAHRNFLCSL ESNPSVREFV LSKGDAGLRE AYDACVKALV SLRSYHLQIV
    360 370 380 390 400
    TKYILIPASQ QPKENKTSED PSKLEAKGTG GTDLMNFLKT VRSTTEKSLL

    KEG
    Length:403
    Mass (Da):45,326
    Last modified:April 1, 1990 - v1
    Checksum:iE92CF57AD0D0BA8D
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti4 – 41A → T.
    Corresponds to variant rs35059413 [ dbSNP | Ensembl ].
    VAR_053368

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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.
    CCDSiCCDS47847.1.
    PIRiPC1161.
    RefSeqiNP_002155.1. NM_002164.5.
    UniGeneiHs.840.

    Genome annotation databases

    EnsembliENST00000518237; ENSP00000430950; ENSG00000131203.
    ENST00000522495; ENSP00000430505; ENSG00000131203.
    GeneIDi3620.
    KEGGihsa:3620.
    UCSCiuc003xnm.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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.
    CCDSiCCDS47847.1.
    PIRiPC1161.
    RefSeqiNP_002155.1. NM_002164.5.
    UniGeneiHs.840.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2D0TX-ray2.30A/B1-403[»]
    2D0UX-ray3.40A/B1-403[»]
    4PK5X-ray2.79A/B1-403[»]
    4PK6X-ray3.45A/B1-403[»]
    ProteinModelPortaliP14902.
    SMRiP14902. Positions 11-403.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi109832. 3 interactions.
    IntActiP14902. 3 interactions.
    MINTiMINT-1414454.
    STRINGi9606.ENSP00000430505.

    Chemistry

    BindingDBiP14902.
    ChEMBLiCHEMBL4685.
    DrugBankiDB00150. L-Tryptophan.
    DB01065. Melatonin.
    GuidetoPHARMACOLOGYi2829.

    PTM databases

    PhosphoSiteiP14902.

    Polymorphism and mutation databases

    BioMutaiIDO1.
    DMDMi123948.

    Proteomic databases

    PaxDbiP14902.
    PRIDEiP14902.

    Protocols and materials databases

    DNASUi3620.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000518237; ENSP00000430950; ENSG00000131203.
    ENST00000522495; ENSP00000430505; ENSG00000131203.
    GeneIDi3620.
    KEGGihsa:3620.
    UCSCiuc003xnm.3. human.

    Organism-specific databases

    CTDi3620.
    GeneCardsiGC08P039771.
    HGNCiHGNC:6059. IDO1.
    HPAiHPA023072.
    HPA023149.
    HPA027772.
    MIMi147435. gene.
    neXtProtiNX_P14902.
    PharmGKBiPA29869.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiNOG73554.
    GeneTreeiENSGT00390000002154.
    HOGENOMiHOG000203926.
    HOVERGENiHBG006100.
    InParanoidiP14902.
    KOiK00463.
    OMAiEAYDACV.
    PhylomeDBiP14902.
    TreeFamiTF330978.

    Enzyme and pathway databases

    UniPathwayiUPA00333; UER00453.
    BioCyciMetaCyc:HS05502-MONOMER.
    BRENDAi1.13.11.11. 2681.
    1.13.11.52. 2681.
    ReactomeiREACT_916. Tryptophan catabolism.
    SABIO-RKP14902.

    Miscellaneous databases

    ChiTaRSiIDO1. human.
    EvolutionaryTraceiP14902.
    GeneWikiiIndoleamine_2,3-dioxygenase.
    GenomeRNAii3620.
    NextBioi14159.
    PROiP14902.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP14902.
    ExpressionAtlasiP14902. baseline and differential.
    GenevisibleiP14902. HS.

    Family and domain databases

    InterProiIPR000898. Indolamine_dOase.
    [Graphical view]
    PfamiPF01231. IDO. 1 hit.
    [Graphical view]
    PROSITEiPS00876. IDO_1. 1 hit.
    PS00877. IDO_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    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. 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.
      , 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. 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).

    Entry informationi

    Entry nameiI23O1_HUMAN
    AccessioniPrimary (citable) accession number: P14902
    Secondary accession number(s): Q540B4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: April 1, 1990
    Last modified: July 22, 2015
    This is version 145 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, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.