Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Indoleamine 2,3-dioxygenase 1

Gene

Ido1

Organism
Mus musculus (Mouse)
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. Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells. Acts as a suppressor of anti-tumor immunity (PubMed:25691885). Limits the growth of intracellular pathogens by depriving tryptophan. Protects the fetus from maternal immune rejection (PubMed:15063630).1 PublicationBy similarity1 Publication

Catalytic activityi

D-tryptophan + O2 = N-formyl-D-kynurenine.By similarity
L-tryptophan + O2 = N-formyl-L-kynurenine.By similarity

Cofactori

hemeBy similarityNote: Binds 1 heme group per subunit.By similarity

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).By similarity

Kineticsi

Catalytic efficiency for L-tryptophan is 90 times higher than for D-tryptophan.

  1. KM=28.1 µM for L-tryptophan1 Publication
  2. KM=2.87 mM for D-tryptophan1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi350 – 3501Iron (heme proximal ligand)By similarity

    GO - Molecular functioni

    GO - Biological processi

    • cytokine production involved in inflammatory response Source: MGI
    • defense response Source: MGI
    • immune system process Source: UniProtKB-KW
    • inflammatory response Source: MGI
    • kynurenic acid biosynthetic process Source: MGI
    • multicellular organismal response to stress Source: MGI
    • negative regulation of activated T cell proliferation Source: MGI
    • negative regulation of interleukin-10 production Source: MGI
    • negative regulation of T cell apoptotic process Source: MGI
    • negative regulation of T cell proliferation Source: MGI
    • positive regulation of apoptotic process Source: MGI
    • positive regulation of chronic inflammatory response Source: MGI
    • positive regulation of interleukin-12 production Source: MGI
    • positive regulation of T cell apoptotic process Source: MGI
    • positive regulation of T cell tolerance induction Source: MGI
    • positive regulation of type 2 immune response Source: MGI
    • response to lipopolysaccharide Source: MGI
    • swimming behavior Source: MGI
    • tryptophan catabolic process to kynurenine Source: MGI
    Complete GO annotation...

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    Immunity, Tryptophan catabolism

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    BRENDAi1.13.11.11. 3474.
    1.13.11.52. 3474.
    ReactomeiR-MMU-71240. Tryptophan catabolism.
    SABIO-RKP28776.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Indoleamine 2,3-dioxygenase 1 (EC:1.13.11.52By similarity)
    Short name:
    IDO-1
    Alternative name(s):
    Indoleamine-pyrrole 2,3-dioxygenase
    Gene namesi
    Name:Ido1
    Synonyms:Ido, Indo
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 8

    Organism-specific databases

    MGIiMGI:96416. Ido1.

    Subcellular locationi

    • Cytoplasmcytosol 1 Publication

    GO - Cellular componenti

    • cytoplasm Source: MGI
    • cytosol Source: UniProtKB-SubCell
    • smooth muscle contractile fiber Source: MGI
    • stereocilium bundle Source: MGI
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Knockout mice display normal development and function of dendritic cells, on T- or B-cells development (PubMed:18384884). They display increased sensitivity to the induction of inflammatory and autoimmune reactions (PubMed:22157149). They produce litters of normal sizes at normal rates, implying that compensatory or redundant immunosuppressive mechanisms protected allogeneic fetuses during gestation in knockout mice. Knockout mice display cardiac and gastrointestinal liabilities (PubMed:22157149).2 Publications

    Chemistry

    ChEMBLiCHEMBL1075294.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 407407Indoleamine 2,3-dioxygenase 1PRO_0000215205Add
    BLAST

    Proteomic databases

    MaxQBiP28776.
    PaxDbiP28776.
    PRIDEiP28776.

    PTM databases

    PhosphoSiteiP28776.

    Expressioni

    Tissue specificityi

    Highly expressed in epididymis, duodemum, jejunum, ileum, colon and spleen (PubMed:19741271). Highly expressed in epididymis, prostate, duodemum, jejunum, ileum, colon and spleen, not detected in the liver (at protein level) (PubMed:19741271). Expressed in tumors only upon exposure to IFN gamma (PubMed:25691885). Constitutively expressed in placenta in trophoblast cells (PubMed:15063630). Expression is restricted to perinuclear regions of primary trophoblast giant cells (TGCs) of fetal origin at mid-gestation (E10.5). After placentation (E14), no IDO expression was detected at the maternal-fetal interface (PubMed:15063630).1 Publication2 Publications

    Inductioni

    By IFNG/IFN-gamma in most cells.By similarity

    Gene expression databases

    BgeeiP28776.
    CleanExiMM_INDO.
    ExpressionAtlasiP28776. baseline and differential.
    GenevisibleiP28776. MM.

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Ptpn11P352355EBI-4410822,EBI-397236

    Protein-protein interaction databases

    BioGridi200512. 2 interactions.
    DIPiDIP-48663N.
    IntActiP28776. 2 interactions.
    STRINGi10090.ENSMUSP00000033956.

    Chemistry

    BindingDBiP28776.

    Structurei

    3D structure databases

    ProteinModelPortaliP28776.
    SMRiP28776. Positions 15-404.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiENOG410IGEY. Eukaryota.
    ENOG410XQHE. LUCA.
    GeneTreeiENSGT00390000002154.
    HOGENOMiHOG000190192.
    InParanoidiP28776.
    KOiK00463.
    OMAiAASAIKX.
    PhylomeDBiP28776.
    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.

    P28776-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MALSKISPTE GSRRILEDHH IDEDVGFALP HPLVELPDAY SPWVLVARNL
    60 70 80 90 100
    PVLIENGQLR EEVEKLPTLS TDGLRGHRLQ RLAHLALGYI TMAYVWNRGD
    110 120 130 140 150
    DDVRKVLPRN IAVPYCELSE KLGLPPILSY ADCVLANWKK KDPNGPMTYE
    160 170 180 190 200
    NMDILFSFPG GDCDKGFFLV SLLVEIAASP AIKAIPTVSS AVERQDLKAL
    210 220 230 240 250
    EKALHDIATS LEKAKEIFKR MRDFVDPDTF FHVLRIYLSG WKCSSKLPEG
    260 270 280 290 300
    LLYEGVWDTP KMFSGGSAGQ SSIFQSLDVL LGIKHEAGKE SPAEFLQEMR
    310 320 330 340 350
    EYMPPAHRNF LFFLESAPPV REFVISRHNE DLTKAYNECV NGLVSVRKFH
    360 370 380 390 400
    LAIVDTYIMK PSKKKPTDGD KSEEPSNVES RGTGGTNPMT FLRSVKDTTE

    KALLSWP
    Length:407
    Mass (Da):45,641
    Last modified:December 1, 1992 - v1
    Checksum:i317681EABF96A727
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M69109 mRNA. Translation: AAA37872.1.
    BC049931 mRNA. Translation: AAH49931.1.
    CCDSiCCDS40299.1.
    PIRiJH0492.
    RefSeqiNP_001280619.1. NM_001293690.1.
    NP_032350.1. NM_008324.2.
    UniGeneiMm.392.

    Genome annotation databases

    EnsembliENSMUST00000033956; ENSMUSP00000033956; ENSMUSG00000031551.
    GeneIDi15930.
    KEGGimmu:15930.
    UCSCiuc009lfa.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M69109 mRNA. Translation: AAA37872.1.
    BC049931 mRNA. Translation: AAH49931.1.
    CCDSiCCDS40299.1.
    PIRiJH0492.
    RefSeqiNP_001280619.1. NM_001293690.1.
    NP_032350.1. NM_008324.2.
    UniGeneiMm.392.

    3D structure databases

    ProteinModelPortaliP28776.
    SMRiP28776. Positions 15-404.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi200512. 2 interactions.
    DIPiDIP-48663N.
    IntActiP28776. 2 interactions.
    STRINGi10090.ENSMUSP00000033956.

    Chemistry

    BindingDBiP28776.
    ChEMBLiCHEMBL1075294.

    PTM databases

    PhosphoSiteiP28776.

    Proteomic databases

    MaxQBiP28776.
    PaxDbiP28776.
    PRIDEiP28776.

    Protocols and materials databases

    DNASUi15930.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000033956; ENSMUSP00000033956; ENSMUSG00000031551.
    GeneIDi15930.
    KEGGimmu:15930.
    UCSCiuc009lfa.2. mouse.

    Organism-specific databases

    CTDi3620.
    MGIiMGI:96416. Ido1.

    Phylogenomic databases

    eggNOGiENOG410IGEY. Eukaryota.
    ENOG410XQHE. LUCA.
    GeneTreeiENSGT00390000002154.
    HOGENOMiHOG000190192.
    InParanoidiP28776.
    KOiK00463.
    OMAiAASAIKX.
    PhylomeDBiP28776.
    TreeFamiTF330978.

    Enzyme and pathway databases

    BRENDAi1.13.11.11. 3474.
    1.13.11.52. 3474.
    ReactomeiR-MMU-71240. Tryptophan catabolism.
    SABIO-RKP28776.

    Miscellaneous databases

    NextBioi288648.
    PROiP28776.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP28776.
    CleanExiMM_INDO.
    ExpressionAtlasiP28776. baseline and differential.
    GenevisibleiP28776. MM.

    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. "Cloning and expression of a cDNA encoding mouse indoleamine 2,3-dioxygenase."
      Habara-Ohkubo A., Takikawa O., Yoshida R.
      Gene 105:221-227(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
    2. "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].
      Strain: NMRI.
      Tissue: Mammary gland.
    3. "Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific."
      Baban B., Chandler P., McCool D., Marshall B., Munn D.H., Mellor A.L.
      J. Reprod. Immunol. 61:67-77(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    4. Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
    5. "Normal development and function of dendritic cells in mice lacking IDO-1 expression."
      de Faudeur G., de Trez C., Muraille E., Leo O.
      Immunol. Lett. 118:21-29(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    6. "Indoleamine 2,3-dioxygenase tissue distribution and cellular localization in mice: implications for its biological functions."
      Dai X., Zhu B.T.
      J. Histochem. Cytochem. 58:17-28(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    7. "Cardiac and gastrointestinal liabilities caused by deficiency in the immune modulatory enzyme indoleamine 2,3-dioxygenase."
      Chang M.Y., Smith C., DuHadaway J.B., Pyle J.R., Boulden J., Soler A.P., Muller A.J., Laury-Kleintop L.D., Prendergast G.C.
      Cancer Biol. Ther. 12:1050-1058(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    8. "Tryptophan-degrading enzymes in tumoral immune resistance."
      van Baren N., Van den Eynde B.J.
      Front. Immunol. 6:34-34(2015) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiI23O1_MOUSE
    AccessioniPrimary (citable) accession number: P28776
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: December 1, 1992
    Last modified: December 9, 2015
    This is version 126 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Ido1 and Ido2 are 2 distinct enzymes which catalyze the same reaction. Ido2 affinity for tryptophan is much lower than that of Ido1. Ido2 may play a role as a negative regulator of Ido1 by competing for heme-binding with Ido1. Low efficiency Ido2 enzymes have been conserved throughout vertebrate evolution, whereas higher efficiency Ido1 enzymes are dispensable in many lower vertebrate lineages. Ido1 may have arisen by gene duplication of a more ancient proto-IDO gene before the divergence of marsupial and eutherian (placental) mammals.By similarity

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. 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.