I23O1_RAT
ID I23O1_RAT Reviewed; 407 AA.
AC Q9ERD9;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Indoleamine 2,3-dioxygenase 1;
DE Short=IDO-1;
DE EC=1.13.11.52 {ECO:0000250|UniProtKB:P14902};
DE AltName: Full=Indoleamine-pyrrole 2,3-dioxygenase;
GN Name=Ido1; Synonyms=Ido, Indo;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Lewis; TISSUE=Spleen;
RA Miki T., Stella A., Robbins P.D., Valdivia L.A., Gambotto A.;
RT "Cloning of rat indoleamine 2,3-dioxygenase mRNA.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the first and rate limiting step of the catabolism
CC of the essential amino acid tryptophan along the kynurenine pathway.
CC Involved in the peripheral immune tolerance, contributing to maintain
CC homeostasis by preventing autoimmunity or immunopathology that would
CC result from uncontrolled and overreacting immune responses. Tryptophan
CC shortage inhibits T lymphocytes division and accumulation of tryptophan
CC catabolites induces T-cell apoptosis and differentiation of regulatory
CC T-cells. Acts as a suppressor of anti-tumor immunity. Limits the growth
CC of intracellular pathogens by depriving tryptophan. Protects the fetus
CC from maternal immune rejection. {ECO:0000250|UniProtKB:P14902}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-tryptophan + O2 = N-formyl-D-kynurenine;
CC Xref=Rhea:RHEA:14189, ChEBI:CHEBI:15379, ChEBI:CHEBI:57719,
CC ChEBI:CHEBI:60051; EC=1.13.11.52;
CC Evidence={ECO:0000250|UniProtKB:P14902};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tryptophan + O2 = N-formyl-L-kynurenine;
CC Xref=Rhea:RHEA:24536, ChEBI:CHEBI:15379, ChEBI:CHEBI:57912,
CC ChEBI:CHEBI:58629; EC=1.13.11.52;
CC Evidence={ECO:0000250|UniProtKB:P14902};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Note=Binds 1 heme group per subunit. {ECO:0000250|UniProtKB:P14902};
CC -!- ACTIVITY REGULATION: Activity is inhibited by and MTH-trp
CC (methylthiohydantoin-DL-tryptophan), modestly inhibited by L-1MT (1-
CC methyl-L-tryptophan) but not D-1MT (1-methyl-D-tryptophan).
CC {ECO:0000250|UniProtKB:P14902}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P14902}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P28776}.
CC -!- INDUCTION: By IFNG/IFN-gamma in most cells.
CC {ECO:0000250|UniProtKB:P14902}.
CC -!- MISCELLANEOUS: Ido1 and Ido2 are 2 distinct enzymes which catalyze the
CC same reaction. Ido2 affinity for tryptophan is much lower than that of
CC Ido1. Ido2 may play a role as a negative regulator of Ido1 by competing
CC for heme-binding with Ido1. Low efficiency Ido2 enzymes have been
CC conserved throughout vertebrate evolution, whereas higher efficiency
CC Ido1 enzymes are dispensable in many lower vertebrate lineages. Ido1
CC may have arisen by gene duplication of a more ancient proto-IDO gene
CC before the divergence of marsupial and eutherian (placental) mammals.
CC {ECO:0000250|UniProtKB:P14902}.
CC -!- SIMILARITY: Belongs to the indoleamine 2,3-dioxygenase family.
CC {ECO:0000305}.
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DR EMBL; AF312699; AAG30573.1; -; mRNA.
DR RefSeq; NP_076463.1; NM_023973.1.
DR AlphaFoldDB; Q9ERD9; -.
DR SMR; Q9ERD9; -.
DR STRING; 10116.ENSRNOP00000050320; -.
DR BindingDB; Q9ERD9; -.
DR ChEMBL; CHEMBL4523451; -.
DR iPTMnet; Q9ERD9; -.
DR PhosphoSitePlus; Q9ERD9; -.
DR PaxDb; Q9ERD9; -.
DR GeneID; 66029; -.
DR KEGG; rno:66029; -.
DR UCSC; RGD:619989; rat.
DR CTD; 3620; -.
DR RGD; 619989; Ido1.
DR eggNOG; ENOG502RZ6X; Eukaryota.
DR InParanoid; Q9ERD9; -.
DR OrthoDB; 1206249at2759; -.
DR PhylomeDB; Q9ERD9; -.
DR BRENDA; 1.13.11.52; 5301.
DR Reactome; R-RNO-71240; Tryptophan catabolism.
DR PRO; PR:Q9ERD9; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0030485; C:smooth muscle contractile fiber; ISO:RGD.
DR GO; GO:0032421; C:stereocilium bundle; ISO:RGD.
DR GO; GO:0016597; F:amino acid binding; IDA:RGD.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0033754; F:indoleamine 2,3-dioxygenase activity; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019825; F:oxygen binding; IDA:RGD.
DR GO; GO:0004833; F:tryptophan 2,3-dioxygenase activity; ISO:RGD.
DR GO; GO:0034354; P:'de novo' NAD biosynthetic process from tryptophan; IBA:GO_Central.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0034276; P:kynurenic acid biosynthetic process; ISO:RGD.
DR GO; GO:0033555; P:multicellular organismal response to stress; ISO:RGD.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISO:RGD.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISO:RGD.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; ISO:RGD.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0002678; P:positive regulation of chronic inflammatory response; ISO:RGD.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:RGD.
DR GO; GO:0070234; P:positive regulation of T cell apoptotic process; ISO:RGD.
DR GO; GO:0002666; P:positive regulation of T cell tolerance induction; ISO:RGD.
DR GO; GO:0002830; P:positive regulation of type 2 immune response; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0036269; P:swimming behavior; ISO:RGD.
DR GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IDA:RGD.
DR InterPro; IPR000898; Indolamine_dOase.
DR InterPro; IPR037217; Trp/Indoleamine_2_3_dOase-like.
DR PANTHER; PTHR28657; PTHR28657; 1.
DR Pfam; PF01231; IDO; 1.
DR SUPFAM; SSF140959; SSF140959; 1.
DR PROSITE; PS00876; IDO_1; 1.
DR PROSITE; PS00877; IDO_2; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Dioxygenase; Heme; Immunity; Iron; Metal-binding;
KW Oxidoreductase; Reference proteome; Tryptophan catabolism.
FT CHAIN 1..407
FT /note="Indoleamine 2,3-dioxygenase 1"
FT /id="PRO_0000285261"
FT REGION 362..388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 350
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="proximal binding residue"
FT /evidence="ECO:0000250|UniProtKB:P14902"
SQ SEQUENCE 407 AA; 45831 MW; EDCA95EF25BDC81B CRC64;
MPHSQISPAE GSRRILEEYH IDEDVGFALP HPLEELPDTY RPWILVARNL PKLIENGKLR
EEVEKLPTLR TEELRGHRLQ RLAHLALGYI TMAYVWNRGD DDIRKVLPRN LAVPYCELSE
KLGLPPILSY ADCVLANWKK KDPNGPMTYE NMDILFSFPG GDCDKGFFLV SLMVEIAASP
AIKAIPTVSS AVEHQDPKAL EKALCSIAAS LEKAKEIFKR MRDFVDPDTF FHVLRIYLSG
WKGNPKLPEG LLYEGVWDTP KKFSGGSAGQ SSIFQSLDVL LGIKHDVGEG SAAEFLQEMR
EYMPPAHRNF LSSLESAPPV REFVILRRNE DLKEAYNECV NGLVSLRMFH LSIVDTYIVK
PSKQKPMGGH KSEEPSNTEN RGTGGTDVMN FLRSVKDTTK KALLSWP
