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8  structures 411  species 1  interaction 1055  sequences 21  architectures

Family: IDO (PF01231)

Summary: Indoleamine 2,3-dioxygenase

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This is the Wikipedia entry entitled "Indoleamine 2,3-dioxygenase". More...

Indoleamine 2,3-dioxygenase Edit Wikipedia article

Indoleamine 2,3-dioxygenase 1
PBB Protein INDO image.jpg
PDB rendering based on 2d0t.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols IDO1 ; IDO; IDO-1; INDO
External IDs OMIM147435 MGI96416 HomoloGene48082 ChEMBL: 4685 GeneCards: IDO1 Gene
EC number
RNA expression pattern
PBB GE INDO 210029 at tn.png
More reference expression data
Species Human Mouse
Entrez 3620 15930
Ensembl ENSG00000131203 ENSMUSG00000031551
UniProt P14902 P28776
RefSeq (mRNA) NM_002164 NM_001293690
RefSeq (protein) NP_002155 NP_001280619
Location (UCSC) Chr 8:
39.9 – 39.93 Mb
Chr 8:
24.58 – 24.6 Mb
PubMed search [1] [2]

Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO EC is an enzyme that in humans is encoded by the IDO1 gene.[1][2] This enzyme catalyzes the degradation of the essential amino acid L-tryptophan to N-formylkynurenine.[3]


Indoleamine 2,3-dioxygenase is the first and rate-limiting enzyme of tryptophan catabolism through kynurenine pathway, thus causing depletion of tryptophan which can cause halted growth of microbes as well as T cells.

IDO is an immunomodulatory enzyme produced by some alternatively activated macrophages and other immunoregulatory cells (also used as an immune subversion strategy by many tumors). Interferon-gamma has an antiproliferative effect on many tumor cells and inhibits intracellular pathogens such as Toxoplasma and chlamydia, at least partly because of the induction of indoleamine 2,3-dioxygenase.

Clinical significance

It has been shown that IDO permits tumor cells to escape the immune system by depletion of L-Trp in the microenvironment of cells. A wide range of human cancers such as prostatic, colorectal, pancreatic, cervical, gastric, ovarian, head, lung, etc. overexpress human IDO (hIDO).[4][5]


Norharmane, via inhibition of indoleamine 2,3-dioxygenase exerts neuroprotective properties by suppressing kynurenine neurotoxic metabolites such as quinolinic acid, 3-hydroxy-kynurenine and nitric oxide synthase.[6] Rosmarinic acid inhibits the expression of indoleamine 2,3-dioxygenase via its cyclooxygenase-inhibiting properties.[7] COX-2 inhibitors down-regulate indoleamine 2,3-dioxygenase, leading to a reduction in kynurenine levels as well as reducing proinflammatory cytokine activity.[8] Alpha-Methyl-Tryptophan also inhibits indoleamine dioxygenase.[9]

Indoleamine 2,3-dioxygenase
PDB 2d0t EBI.jpg
crystal structure of 4-phenylimidazole bound form of human indoleamine 2,3-dioxygenase
Symbol IDO
Pfam PF01231
Pfam clan CL0380
InterPro IPR000898
Indoleamine 2,3-dioxygenase
EC number
CAS number 9014-51-1
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

See also


  1. ^ Dai W, Gupta SL (Apr 1990). "Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA". Biochemical and Biophysical Research Communications 168 (1): 1–8. doi:10.1016/0006-291X(90)91666-G. PMID 2109605. 
  2. ^ Najfeld V, Menninger J, Muhleman D, Comings DE, Gupta SL (1993). "Localization of indoleamine 2,3-dioxygenase gene (INDO) to chromosome 8p12-->p11 by fluorescent in situ hybridization". Cytogenetics and Cell Genetics 64 (3-4): 231–2. doi:10.1159/000133584. PMID 8404046. 
  3. ^ "Entrez Gene: INDO indoleamine-pyrrole 2,3 dioxygenase". 
  4. ^ Uyttenhove C, Pilotte L, Théate I, Stroobant V, Colau D, Parmentier N, et al. (2003). "Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase". Nat. Med. 9 (10): 1269–74. doi:10.1038/nm934. PMID 14502282. 
  5. ^ Jiang T, Sun Y, Yin Z, Feng S, Sun L, Li Z (2015). "Research progress of indoleamine 2,3-dioxygenase inhibitors". Future Med Chem 7 (2): 185–201. doi:10.4155/fmc.14.151. PMID 25686005. 
  6. ^ Chiarugi A, Dello Sbarba P, Paccagnini A, Donnini S, Filippi S, Moroni F (Aug 2000). "Combined inhibition of indoleamine 2,3-dioxygenase and nitric oxide synthase modulates neurotoxin release by interferon-gamma-activated macrophages". Journal of Leukocyte Biology 68 (2): 260–6. PMID 10947071. 
  7. ^ Lee HJ, Jeong YI, Lee TH, Jung ID, Lee JS, Lee CM, et al. (May 2007). "Rosmarinic acid inhibits indoleamine 2,3-dioxygenase expression in murine dendritic cells". Biochemical Pharmacology 73 (9): 1412–21. doi:10.1016/j.bcp.2006.12.018. PMID 17229401. 
  8. ^ Cesario A, Rocca B, Rutella S (2011). "The interplay between indoleamine 2,3-dioxygenase 1 (IDO1) and cyclooxygenase (COX)-2 in chronic inflammation and cancer". Current Medicinal Chemistry 18 (15): 2263–71. doi:10.2174/092986711795656063. PMID 21517752. 
  9. ^ Hou DY, Muller AJ, Sharma MD, DuHadaway J, Banerjee T, Johnson M, et al. (2007). "Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses". Cancer Res. 67 (2): 792–801. doi:10.1158/0008-5472.CAN-06-2925. PMID 17234791. 

Further reading

External links

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Internal database links

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This tab holds annotation information from the InterPro database.

InterPro entry IPR000898

Indoleamine 2,3-dioxgyenase (IDO, EC) [PUBMED:1907934] is a cytosolic haem protein which, together with the hepatic enzyme tryptophan 2,3-dioxygenase, catalyzes the conversion of tryptophan and other indole derivatives to kynurenines. The physiological role of IDO is not fully understood but is of great interest, because IDO is widely distributed in human tissues, can be up-regulated via cytokines such as interferon-gamma, and can thereby modulate the levels of tryptophan, which is vital for cell growth. The degradative action of IDO on tryptophan leads to cell death by starvation of this essential and relatively scarce amino acid. IDO is a haem-containing enzyme of about 400 amino acids. Site-directed mutagenesis showed His346 (SWISSPROT) to be essential for haem binding, indicating that this histidine residue may be the proximal ligand. Mutation of Asp274 also compromised the ability of IDO to bind haem, suggesting that Asp274 may coordinate to haem directly as the distal ligand or is essential in maintaining the conformation of the haem pocket [PUBMED:12766158].

Other proteins that are evolutionarily related to IDO include yeast hypothetical protein YJR078w; and myoglobin from the red muscle of the archaeogastropodic molluscs, Nordotis madaka (Giant abalone) and Sulculus diversicolor [PUBMED:8011076, PUBMED:12711393]. These unusual globins lack enzymatic activity but have kept the haem group.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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Pfam Clan

This family is a member of clan IDO-like (CL0380), which has the following description:

Superfamily contains bacterial tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase-like families.

The clan contains the following 3 members:

DUF1864 IDO Trp_dioxygenase


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Seed source: Prosite
Previous IDs: none
Type: Family
Author: Finn RD, Bateman A
Number in seed: 192
Number in full: 1055
Average length of the domain: 369.40 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 72.46 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.8 20.8
Trusted cut-off 21.7 20.8
Noise cut-off 20.6 20.1
Model length: 408
Family (HMM) version: 14
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Species distribution

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Archea Archea Eukaryota Eukaryota
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Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IDO domain has been found. There are 8 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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