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Protein

Indoleamine 2,3-dioxygenase 1

Gene

IDO1

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

Functioni

Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses (PubMed:25691885). Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells (PubMed:25691885). Acts as a suppressor of anti-tumor immunity (PubMed:23103127, PubMed:25157255, PubMed:14502282, PubMed:25691885). Limits the growth of intracellular pathogens by depriving tryptophan (PubMed:25691885). Protects the fetus from maternal immune rejection (PubMed:25691885).3 Publications2 Publications

Miscellaneous

IDO1 is the target for therapy in a range of clinical settings, including cancer, chronic infections, autoimmune and allergic syndromes, and transplantation.1 Publication
IDO1 and IDO2 are 2 distinct enzymes which catalyze the same reaction. IDO2 affinity for tryptophan is much lower than that of IDO1. 50% of Caucasians harbor polymorphisms which abolish IDO2 enzymatic activity. IDO2 is expressed in human tumors in an inactive form: tryptophan degradation is entirely provided by IDO1 in these cells (PubMed:18418598). IDO2 may play a role as a negative regulator of IDO1 by competing for heme-binding with IDO1 (PubMed:25394548). Low efficiency IDO2 enzymes have been conserved throughout vertebrate evolution, whereas higher efficiency IDO1 enzymes are dispensable in many lower vertebrate lineages (PubMed:25950090). IDO1 may have arisen by gene duplication of a more ancient proto-IDO gene before the divergence of marsupial and eutherian (placental) mammals.3 Publications
Elevated IDO1 expression is a hallmark of major viral infections including HIV, HBV, HCV or influenza and also of major bacteria infections, such as Tb, CAP, listeriosis and sepsis. Depletion of tryptophan and production of tryptophan metabolites with bactericidal activity are important as direct anti-pathogen mechanisms. Pathogens are able to highjack the immunosuppressive effects of IDO1 and make use of them to facilitate their own life cycle.1 Publication

Catalytic activityi

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

Cofactori

heme2 PublicationsNote: Binds 1 heme group per subunit (PubMed:16477023, PubMed:25313323). In the active form, the heme iron is in its ferrous state Fe(+2). The catalytic cycle does not alter the oxidation state of the heme, but IDO1 is prone to autoxidation (PubMed:16574111).3 Publications

Activity 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

    Pathwayi: L-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), Indoleamine 2,3-dioxygenase 2 (IDO2), Tryptophan 2,3-dioxygenase (TDO2)
    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)DescriptionActionsGraphical viewLength
    Metal bindingi346Iron (heme proximal ligand)Combined sources2 Publications1

    GO - Molecular functioni

    • electron transfer 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

    Keywordsi

    Molecular functionDioxygenase, Oxidoreductase
    Biological processImmunity, Tryptophan catabolism
    LigandHeme, Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05502-MONOMER
    BRENDAi1.13.11.11 2681
    1.13.11.52 2681
    ReactomeiR-HSA-71240 Tryptophan catabolism
    SABIO-RKiP14902
    UniPathwayi
    UPA00333;UER00453

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Indoleamine 2,3-dioxygenase 1 (EC:1.13.11.521 Publication)
    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
    Proteomesi
    • UP000005640 Componenti: Chromosome 8

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000131203.12
    HGNCiHGNC:6059 IDO1
    MIMi147435 gene
    neXtProtiNX_P14902

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi3620
    OpenTargetsiENSG00000131203
    PharmGKBiPA29869

    Chemistry databases

    ChEMBLiCHEMBL4685
    DrugBankiDB00150 L-Tryptophan
    DB01065 Melatonin
    GuidetoPHARMACOLOGYi2829

    Polymorphism and mutation databases

    BioMutaiIDO1
    DMDMi123948

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002152041 – 403Indoleamine 2,3-dioxygenase 1Add BLAST403

    Proteomic databases

    EPDiP14902
    PaxDbiP14902
    PeptideAtlasiP14902
    PRIDEiP14902
    ProteomicsDBi53093

    PTM databases

    iPTMnetiP14902
    PhosphoSitePlusiP14902

    Expressioni

    Tissue specificityi

    Expressed in mature dendritic cells located in lymphoid organs (including lymph nodes, spleen, tonsils, Peyers's patches, the gut lamina propria, and the thymic medulla), in some epithelial cells of the female genital tract, as well as in endothelial cells of term placenta and in lung parenchyma (PubMed:25691885). Weakly or not expressed in most normal tissues, but mostly inducible in most tissues (PubMed:25691885). Expressed in more than 50% of tumors, either by tumoral, stromal, or endothelial cells (expression in tumor is associated with a worse clinical outcome) (PubMed:18418598). Not overexpressed in tumor-draining lymph nodes (PubMed:26155395, PubMed:25691885).3 Publications

    Inductioni

    By IFNG/IFN-gamma in most cells (PubMed:2109605, PubMed:1907934). Exogenous inflammatory stimuli induce the expression of IDO1 in antigen-presenting cells such as dendritic cells, macrophages and B-cells (PubMed:25157255).2 Publications1 Publication

    Gene expression databases

    BgeeiENSG00000131203 Expressed in 119 organ(s), highest expression level in epithelium of bronchus
    ExpressionAtlasiP14902 baseline and differential
    GenevisibleiP14902 HS

    Organism-specific databases

    HPAiCAB072820
    HPA023072
    HPA023149
    HPA027772

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi109832, 3 interactors
    IntActiP14902, 4 interactors
    STRINGi9606.ENSP00000430505

    Chemistry databases

    BindingDBiP14902

    Structurei

    Secondary structure

    1403
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliP14902
    SMRiP14902
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP14902

    Family & Domainsi

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiENOG410IGEY Eukaryota
    ENOG410XQHE LUCA
    GeneTreeiENSGT00390000002154
    HOGENOMiHOG000203926
    HOVERGENiHBG006100
    InParanoidiP14902
    KOiK00463
    OMAiYMPRHHR
    OrthoDBiEOG091G0DCU
    PhylomeDBiP14902
    TreeFamiTF330978

    Family and domain databases

    InterProiView protein in InterPro
    IPR000898 Indolamine_dOase
    IPR037217 Trp/Indoleamine_2_3_dOase-like
    PANTHERiPTHR28657 PTHR28657, 1 hit
    PfamiView protein in Pfam
    PF01231 IDO, 1 hit
    SUPFAMiSSF140959 SSF140959, 1 hit
    PROSITEiView protein in PROSITE
    PS00876 IDO_1, 1 hit
    PS00877 IDO_2, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    J3KN03J3KN03_HUMAN
    Indoleamine 2,3-dioxygenase 1
    IDO1
    170Annotation score:
    E5RIX2E5RIX2_HUMAN
    Indoleamine 2,3-dioxygenase 1
    IDO1
    78Annotation score:
    E5RH36E5RH36_HUMAN
    Indoleamine 2,3-dioxygenase 1
    IDO1
    47Annotation score:
    A0A140T9Z2A0A140T9Z2_HUMAN
    Indoleamine 2,3-dioxygenase 1
    IDO1
    180Annotation score:

    Sequence cautioni

    The sequence AC007991 differs from that shown. Reason: Erroneous gene model prediction.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti251G → R in AEF30540 (Ref. 5) Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0533684A → T. Corresponds to variant dbSNP:rs35059413Ensembl.1

    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.
    JF772862 mRNA Translation: AEF30540.1
    AY221100 mRNA Translation: AAO34405.1
    AK313259 mRNA Translation: BAG36069.1
    AC007991 Genomic DNA No translation available.
    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.5 human
    uc064mfy.1 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    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.
    JF772862 mRNA Translation: AEF30540.1
    AY221100 mRNA Translation: AAO34405.1
    AK313259 mRNA Translation: BAG36069.1
    AC007991 Genomic DNA No translation available.
    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
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2D0TX-ray2.30A/B1-403[»]
    2D0UX-ray3.40A/B1-403[»]
    4PK5X-ray2.79A/B1-403[»]
    4PK6X-ray3.45A/B1-403[»]
    4U72X-ray2.00A/B1-403[»]
    4U74X-ray2.31A/B1-403[»]
    5EK2X-ray2.68A/B1-403[»]
    5EK3X-ray2.21A/B1-403[»]
    5EK4X-ray2.64A/B1-403[»]
    5ETWX-ray2.70A/B1-403[»]
    5WHRX-ray2.28A/B12-403[»]
    5WMUX-ray2.40A/B11-403[»]
    5WMVX-ray2.60A/B11-403[»]
    5WMWX-ray3.03A/B11-403[»]
    5WMXX-ray2.69A/B11-403[»]
    5WN8X-ray2.50A/B12-403[»]
    5XE1X-ray3.20A/B1-403[»]
    6AZUX-ray2.82A/B/C/D5-403[»]
    6AZVX-ray2.75A/B/C/D5-403[»]
    6AZWX-ray2.78A/B11-403[»]
    6CXUX-ray2.49A/B11-403[»]
    6CXVX-ray2.60A/B11-403[»]
    6E35X-ray2.41A/B11-403[»]
    6F0AX-ray2.26A/C11-403[»]
    ProteinModelPortaliP14902
    SMRiP14902
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi109832, 3 interactors
    IntActiP14902, 4 interactors
    STRINGi9606.ENSP00000430505

    Chemistry databases

    BindingDBiP14902
    ChEMBLiCHEMBL4685
    DrugBankiDB00150 L-Tryptophan
    DB01065 Melatonin
    GuidetoPHARMACOLOGYi2829

    PTM databases

    iPTMnetiP14902
    PhosphoSitePlusiP14902

    Polymorphism and mutation databases

    BioMutaiIDO1
    DMDMi123948

    Proteomic databases

    EPDiP14902
    PaxDbiP14902
    PeptideAtlasiP14902
    PRIDEiP14902
    ProteomicsDBi53093

    Protocols and materials databases

    DNASUi3620
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000518237; ENSP00000430950; ENSG00000131203
    ENST00000522495; ENSP00000430505; ENSG00000131203
    GeneIDi3620
    KEGGihsa:3620
    UCSCiuc003xnm.5 human
    uc064mfy.1 human

    Organism-specific databases

    CTDi3620
    DisGeNETi3620
    EuPathDBiHostDB:ENSG00000131203.12
    GeneCardsiIDO1
    HGNCiHGNC:6059 IDO1
    HPAiCAB072820
    HPA023072
    HPA023149
    HPA027772
    MIMi147435 gene
    neXtProtiNX_P14902
    OpenTargetsiENSG00000131203
    PharmGKBiPA29869
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiENOG410IGEY Eukaryota
    ENOG410XQHE LUCA
    GeneTreeiENSGT00390000002154
    HOGENOMiHOG000203926
    HOVERGENiHBG006100
    InParanoidiP14902
    KOiK00463
    OMAiYMPRHHR
    OrthoDBiEOG091G0DCU
    PhylomeDBiP14902
    TreeFamiTF330978

    Enzyme and pathway databases

    UniPathwayi
    UPA00333;UER00453

    BioCyciMetaCyc:HS05502-MONOMER
    BRENDAi1.13.11.11 2681
    1.13.11.52 2681
    ReactomeiR-HSA-71240 Tryptophan catabolism
    SABIO-RKiP14902

    Miscellaneous databases

    ChiTaRSiIDO1 human
    EvolutionaryTraceiP14902
    GeneWikiiIndoleamine_2,3-dioxygenase
    GenomeRNAii3620
    PROiPR:P14902
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000131203 Expressed in 119 organ(s), highest expression level in epithelium of bronchus
    ExpressionAtlasiP14902 baseline and differential
    GenevisibleiP14902 HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR000898 Indolamine_dOase
    IPR037217 Trp/Indoleamine_2_3_dOase-like
    PANTHERiPTHR28657 PTHR28657, 1 hit
    PfamiView protein in Pfam
    PF01231 IDO, 1 hit
    SUPFAMiSSF140959 SSF140959, 1 hit
    PROSITEiView protein in PROSITE
    PS00876 IDO_1, 1 hit
    PS00877 IDO_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiI23O1_HUMAN
    AccessioniPrimary (citable) accession number: P14902
    Secondary accession number(s): E5RGR8, F6M9T7, Q540B4
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: April 1, 1990
    Last modified: November 7, 2018
    This is version 173 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
      Index of protein domains and families
    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. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
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