Names & Taxonomy

Uniprot ID:
P14902
Entry Name:
I23O1_HUMAN
Status:
reviewed
Protein Names:
Indoleamine 2,3-dioxygenase 1 (IDO-1) (EC 1.13.11.52) (Indoleamine-pyrrole 2,3-dioxygenase)
Gene Names:
IDO1 IDO INDO
Gene Names Primary:
IDO1
Organism:
Homo sapiens (Human)

Structure

Length:
403
Sequence:
MAHAMENSWTISKEYHIDEEVGFALPNPQENLPDFYNDWMFIAKHLPDLIESGQLRERVEKLNMLSIDHLTDHKSQRLARLVLGCITMAYVWGKGHGDVRKVLPRNIAVPYCQLSKKLELPPILVYADCVLANWKKKDPNKPLTYENMDVLFSFRDGDCSKGFFLVSLLVEIAAASAIKVIPTVFKAMQMQERDTLLKALLEIASCLEKALQVFHQIHDHVNPKAFFSVLRIYLSGWKGNPQLSDGLVYEGFWEDPKEFAGGSAGQSSVFQCFDVLLGIQQTAGGGHAAQFLQDMRRYMPPAHRNFLCSLESNPSVREFVLSKGDAGLREAYDACVKALVSLRSYHLQIVTKYILIPASQQPKENKTSEDPSKLEAKGTGGTDLMNFLKTVRSTTEKSLLKEG
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm, cytosol

Function

Function:
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).
Pathway:
Amino-acid degradation; L-tryptophan degradation via kynurenine pathway; L-kynurenine from L-tryptophan: step 1/2.
Catalytic Activity:
D-tryptophan + O(2) = N-formyl-D-kynurenine.
Cofactor:
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413;
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: ; Kinetic parameters: KM=21.23 uM for L-tryptophan
Enzyme Regulation:
ENZYME REGULATION: 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).
Cross Reference Drug Bank:
DB00150 DB01065
Gene Ontology Go:
cytosol
smooth muscle contractile fiber
stereocilium bundle
electron carrier activity
heme binding
indoleamine 2,3-dioxygenase activity
metal ion binding
tryptophan 2,3-dioxygenase activity
cellular nitrogen compound metabolic process
cytokine production involved in inflammatory response
female pregnancy
immune system process
kynurenic acid biosynthetic process
multicellular organismal response to stress
negative regulation of interleukin-10 production
negative regulation of T cell apoptotic process
negative regulation of T cell proliferation
positive regulation of chronic inflammatory response
positive regulation of interleukin-12 production
positive regulation of T cell apoptotic process
positive regulation of T cell tolerance induction
positive regulation of type 2 immune response
response to lipopolysaccharide
small molecule metabolic process
swimming behavior
tryptophan catabolic process
tryptophan catabolic process to kynurenine
Gene Ontology Biological Process:
cellular nitrogen compound metabolic process
cytokine production involved in inflammatory response
female pregnancy
immune system process
kynurenic acid biosynthetic process
multicellular organismal response to stress
negative regulation of interleukin-10 production
negative regulation of T cell apoptotic process
negative regulation of T cell proliferation
positive regulation of chronic inflammatory response
positive regulation of interleukin-12 production
positive regulation of T cell apoptotic process
positive regulation of T cell tolerance induction
positive regulation of type 2 immune response
response to lipopolysaccharide
small molecule metabolic process
swimming behavior
tryptophan catabolic process
tryptophan catabolic process to kynurenine
Gene Ontology Molecular Function:
electron carrier activity
heme binding
indoleamine 2,3-dioxygenase activity
metal ion binding
tryptophan 2,3-dioxygenase activity
Gene Ontology Cellular Component:
cytosol
smooth muscle contractile fiber
stereocilium bundle
Keywords:
3D-structure
Complete proteome
Cytoplasm
Dioxygenase
Direct protein sequencing
Heme
Immunity
Iron
Metal-binding
Oxidoreductase
Polymorphism
Reference proteome
Tryptophan catabolism

Publication

PubMed ID:
2109605 2326172 1449503 14702039 16421571 15489334 1907934 14502282 16574111 17671174 18026683 18418598 25394548 25950090 26155395 23103127 25157255 25691885 25970480 16477023 25313323