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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 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

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

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

    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), 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)DescriptionActionsGraphical viewLength
    Metal bindingi346Iron (heme proximal ligand)Combined sources2 Publications1

    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 - Biological processi

    Immunity, Tryptophan catabolism

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05502-MONOMER.
    ZFISH:HS05502-MONOMER.
    BRENDAi1.13.11.11. 2681.
    1.13.11.52. 2681.
    ReactomeiR-HSA-71240. Tryptophan catabolism.
    SABIO-RKP14902.
    UniPathwayiUPA00333; 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

    HGNCiHGNC:6059. IDO1.

    Subcellular locationi

    • Cytoplasmcytosol 1 PublicationBy similarity

    GO - Cellular componenti

    Complete GO annotation...

    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.

    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.
    ExpressionAtlasiP14902. baseline and differential.
    GenevisibleiP14902. HS.

    Organism-specific databases

    HPAiHPA023072.
    HPA023149.
    HPA027772.

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi109832. 3 interactors.
    IntActiP14902. 4 interactors.
    MINTiMINT-1414454.
    STRINGi9606.ENSP00000430505.

    Chemistry databases

    BindingDBiP14902.

    Structurei

    Secondary structure

    1403
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi13 – 15Combined sources3
    Turni19 – 21Combined sources3
    Helixi34 – 36Combined sources3
    Helixi37 – 44Combined sources8
    Helixi46 – 51Combined sources6
    Helixi55 – 61Combined sources7
    Helixi67 – 69Combined sources3
    Helixi73 – 92Combined sources20
    Beta strandi95 – 97Combined sources3
    Beta strandi101 – 103Combined sources3
    Helixi105 – 118Combined sources14
    Helixi126 – 129Combined sources4
    Turni130 – 132Combined sources3
    Beta strandi135 – 138Combined sources4
    Helixi145 – 147Combined sources3
    Beta strandi148 – 151Combined sources4
    Helixi160 – 178Combined sources19
    Helixi181 – 189Combined sources9
    Helixi193 – 214Combined sources22
    Helixi217 – 220Combined sources4
    Helixi223 – 228Combined sources6
    Helixi230 – 233Combined sources4
    Beta strandi237 – 239Combined sources3
    Helixi241 – 243Combined sources3
    Beta strandi247 – 249Combined sources3
    Turni250 – 252Combined sources3
    Beta strandi254 – 257Combined sources4
    Helixi264 – 266Combined sources3
    Helixi268 – 276Combined sources9
    Beta strandi284 – 286Combined sources3
    Helixi287 – 295Combined sources9
    Helixi296 – 298Combined sources3
    Helixi301 – 311Combined sources11
    Helixi316 – 321Combined sources6
    Turni322 – 324Combined sources3
    Helixi326 – 353Combined sources28
    Helixi355 – 360Combined sources6
    Helixi381 – 397Combined sources17

    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[»]
    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.
    OMAiEAYDACV.
    OrthoDBiEOG091G0DCU.
    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

    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 rs35059413dbSNPEnsembl.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

    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[»]
    ProteinModelPortaliP14902.
    SMRiP14902.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi109832. 3 interactors.
    IntActiP14902. 4 interactors.
    MINTiMINT-1414454.
    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.

    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.
    GeneCardsiIDO1.
    HGNCiHGNC:6059. IDO1.
    HPAiHPA023072.
    HPA023149.
    HPA027772.
    MIMi147435. gene.
    neXtProtiNX_P14902.
    OpenTargetsiENSG00000131203.
    PharmGKBiPA29869.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    UniPathwayiUPA00333; UER00453.
    BioCyciMetaCyc:HS05502-MONOMER.
    ZFISH:HS05502-MONOMER.
    BRENDAi1.13.11.11. 2681.
    1.13.11.52. 2681.
    ReactomeiR-HSA-71240. Tryptophan catabolism.
    SABIO-RKP14902.

    Miscellaneous databases

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

    Gene expression databases

    BgeeiENSG00000131203.
    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...

    Entry informationi

    Entry nameiI23O1_HUMAN
    AccessioniPrimary (citable) accession number: P14902
    Secondary accession number(s): E5RGR8, F6M9T7, Q540B4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: April 1, 1990
    Last modified: November 2, 2016
    This is version 158 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

    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

    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

    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.