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Protein

Indoleamine 2,3-dioxygenase 2

Gene

IDO2

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 immune regulation. May not play a significant role in tryptophan-related tumoral resistance (PubMed:25691885).1 Publication1 Publication

Catalytic activityi

L-tryptophan + O2 = N-formyl-L-kynurenine.1 Publication

Cofactori

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

Enzyme regulationi

Activity is inhibited by D-1MT (1-methyl-D-tryptophan) and MTH-trp (methylthiohydantoin-DL-tryptophan) but not L-1MT (1-methyl-L-tryptophan).1 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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi360 – 3601Iron (heme proximal ligand)By similarity

GO - Molecular functioni

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

BRENDAi1.13.11.52. 2681.
ReactomeiR-HSA-71240. Tryptophan catabolism.
UniPathwayiUPA00333; UER00453.

Names & Taxonomyi

Protein namesi
Recommended name:
Indoleamine 2,3-dioxygenase 2 (EC:1.13.11.-1 Publication)
Short name:
IDO-2
Alternative name(s):
Indoleamine 2,3-dioxygenase-like protein 1
Indoleamine-pyrrole 2,3-dioxygenase-like protein 1
Gene namesi
Name:IDO2
Synonyms:INDOL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:27269. IDO2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA164720782.

Polymorphism and mutation databases

BioMutaiIDO2.
DMDMi215274147.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 420420Indoleamine 2,3-dioxygenase 2PRO_0000285262Add
BLAST

Proteomic databases

PaxDbiQ6ZQW0.
PRIDEiQ6ZQW0.

PTM databases

PhosphoSiteiQ6ZQW0.

Expressioni

Tissue specificityi

Detected in liver, small intestine, spleen, placenta, thymus, lung, brain, kidney, and colon (PubMed:17671174). Also expressed at low level in testis and thyroid. Not expressed in the majority of human tumor samples (>99%) (PubMed:25691885).1 Publication1 Publication

Gene expression databases

BgeeiQ6ZQW0.
ExpressionAtlasiQ6ZQW0. baseline and differential.

Interactioni

Protein-protein interaction databases

BioGridi127980. 9 interactions.
STRINGi9606.ENSP00000443432.

Structurei

3D structure databases

ProteinModelPortaliQ6ZQW0.
SMRiQ6ZQW0. Positions 30-416.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiENOG410IGEY. Eukaryota.
ENOG410XQHE. LUCA.
GeneTreeiENSGT00390000002154.
HOGENOMiHOG000190192.
InParanoidiQ6ZQW0.
KOiK00463.
OMAiPAGLMYE.
OrthoDBiEOG7NW695.
PhylomeDBiQ6ZQW0.
TreeFamiTF330978.

Family and domain databases

InterProiIPR000898. Indolamine_dOase.
[Graphical view]
PfamiPF01231. IDO. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms exist at least in placenta and brain.1 Publication

1 Publication

Isoform 1 (identifier: Q6ZQW0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLHFHYYDTS NKIMEPHRPN VKTAVPLSLE SYHISEEYGF LLPDSLKELP
60 70 80 90 100
DHYRPWMEIA NKLPQLIDAH QLQAHVDKMP LLSCQFLKGH REQRLAHLVL
110 120 130 140 150
SFLTMGYVWQ EGEAQPAEVL PRNLALPFVE VSRNLGLPPI LVHSDLVLTN
160 170 180 190 200
WTKKDPDGFL EIGNLETIIS FPGGESLHGF ILVTALVEKE AVPGIKALVQ
210 220 230 240 250
ATNAILQPNQ EALLQALQRL RLSIQDITKT LGQMHDYVDP DIFYAGIRIF
260 270 280 290 300
LSGWKDNPAM PAGLMYEGVS QEPLKYSGGS AAQSTVLHAF DEFLGIRHSK
310 320 330 340 350
ESGDFLYRMR DYMPPSHKAF IEDIHSAPSL RDYILSSGQD HLLTAYNQCV
360 370 380 390 400
QALAELRSYH ITMVTKYLIT AAAKAKHGKP NHLPGPPQAL KDRGTGGTAV
410 420
MSFLKSVRDK TLESILHPRG
Length:420
Mass (Da):47,075
Last modified:October 14, 2015 - v4
Checksum:i28C0CDCD10F933C4
GO
Isoform 2 (identifier: Q6ZQW0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     159-172: FLEIGNLETIISFP → DGVSLCLPGWSAVA
     173-420: Missing.

Show »
Length:172
Mass (Da):19,610
Checksum:iB5C794259EDE4DCC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1 – 1313Missing in ABM69260 (PubMed:14702039).CuratedAdd
BLAST

Polymorphismi

The variant Trp-248 (p.R248W) drastically reduces the enzymatic activity (PubMed:17671174, PubMed:18418598). The Del359-420 variant (p.Y359X) generates a truncated, enzymatically inactive protein (PubMed:17671174). The high prevalence of these polymorphic alleles results in a non-functional IDO2 enzyme in up to 50% of Caucasians (PubMed:18418598).1 Publication1 Publication

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti248 – 2481R → W Decreased indoleamine 2,3-dioxygenase activity. 1 Publication
Corresponds to variant rs10109853 [ dbSNP | Ensembl ].
VAR_032007
Natural varianti359 – 42062Missing Loss of indoleamine 2,3-dioxygenase activity. 1 Publication
VAR_073727Add
BLAST

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei159 – 17214FLEIG…IISFP → DGVSLCLPGWSAVA in isoform 2. 2 PublicationsVSP_024858Add
BLAST
Alternative sequencei173 – 420248Missing in isoform 2. 2 PublicationsVSP_024859Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EF052681 mRNA. Translation: ABM69260.1.
AK128691 mRNA. Translation: BAC87573.1.
AC007991 Genomic DNA. No translation available.
AC087518 Genomic DNA. No translation available.
BC113496 mRNA. Translation: AAI13497.1.
BC113498 mRNA. Translation: AAI13499.1.
RefSeqiNP_919270.2. NM_194294.2. [Q6ZQW0-1]
UniGeneiHs.676257.

Genome annotation databases

EnsembliENST00000502986; ENSP00000443432; ENSG00000188676. [Q6ZQW0-1]
GeneIDi169355.
KEGGihsa:169355.

Keywords - Coding sequence diversityi

Alternative splicing, 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
EF052681 mRNA. Translation: ABM69260.1.
AK128691 mRNA. Translation: BAC87573.1.
AC007991 Genomic DNA. No translation available.
AC087518 Genomic DNA. No translation available.
BC113496 mRNA. Translation: AAI13497.1.
BC113498 mRNA. Translation: AAI13499.1.
RefSeqiNP_919270.2. NM_194294.2. [Q6ZQW0-1]
UniGeneiHs.676257.

3D structure databases

ProteinModelPortaliQ6ZQW0.
SMRiQ6ZQW0. Positions 30-416.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127980. 9 interactions.
STRINGi9606.ENSP00000443432.

PTM databases

PhosphoSiteiQ6ZQW0.

Polymorphism and mutation databases

BioMutaiIDO2.
DMDMi215274147.

Proteomic databases

PaxDbiQ6ZQW0.
PRIDEiQ6ZQW0.

Protocols and materials databases

DNASUi169355.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000502986; ENSP00000443432; ENSG00000188676. [Q6ZQW0-1]
GeneIDi169355.
KEGGihsa:169355.

Organism-specific databases

CTDi169355.
GeneCardsiIDO2.
H-InvDBHIX0007468.
HGNCiHGNC:27269. IDO2.
MIMi612129. gene.
neXtProtiNX_Q6ZQW0.
PharmGKBiPA164720782.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGEY. Eukaryota.
ENOG410XQHE. LUCA.
GeneTreeiENSGT00390000002154.
HOGENOMiHOG000190192.
InParanoidiQ6ZQW0.
KOiK00463.
OMAiPAGLMYE.
OrthoDBiEOG7NW695.
PhylomeDBiQ6ZQW0.
TreeFamiTF330978.

Enzyme and pathway databases

UniPathwayiUPA00333; UER00453.
BRENDAi1.13.11.52. 2681.
ReactomeiR-HSA-71240. Tryptophan catabolism.

Miscellaneous databases

ChiTaRSiIDO2. human.
GenomeRNAii169355.
NextBioi88803.
PROiQ6ZQW0.
SOURCEiSearch...

Gene expression databases

BgeeiQ6ZQW0.
ExpressionAtlasiQ6ZQW0. baseline and differential.

Family and domain databases

InterProiIPR000898. Indolamine_dOase.
[Graphical view]
PfamiPF01231. IDO. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Uterus.
  2. "DNA sequence and analysis of human chromosome 8."
    Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T.
    , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
    Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "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] (ISOFORM 2).
  4. "Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice."
    Ball H.J., Sanchez-Perez A., Weiser S., Austin C.J.D., Astelbauer F., Miu J., McQuillan J.A., Stocker R., Jermiin L.S., Hunt N.H.
    Gene 396:203-213(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 13-420 (ISOFORM 1).
  5. "Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan."
    Metz R., Duhadaway J.B., Kamasani U., Laury-Kleintop L., Muller A.J., Prendergast G.C.
    Cancer Res. 67:7082-7087(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, ENZYME REGULATION, TISSUE SPECIFICITY, VARIANTS TRP-248 AND 359-TYR--GLY-420 DEL.
  6. "IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism."
    Loeb S., Koenigsrainer A., Zieker D., Bruecher B.L., Rammensee H.G., Opelz G., Terness P.
    Cancer Immunol. Immunother. 58:153-157(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: MISCELLANEOUS, DIFFERENCE BETWEEN IDO1 AND IDO2.
  7. "Heme-binding-mediated negative regulation of the tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) by IDO2."
    Lee Y.K., Lee H.B., Shin D.M., Kang M.J., Yi E.C., Noh S., Lee J., Lee C., Min C.K., Choi E.Y.
    Exp. Mol. Med. 46:E121-E121(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: POLYMORPHISM, DIFFERENCE BETWEEN IDO1 AND IDO2.
  8. "Low efficiency IDO2 enzymes are conserved in lower vertebrates, whereas higher efficiency IDO1 enzymes are dispensable."
    Yuasa H.J., Mizuno K., Ball H.J.
    FEBS J. 282:2735-2745(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: DIFFERENCE BETWEEN IDO1 AND IDO2.
  9. Cited for: REVIEW.
  10. "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 nameiI23O2_HUMAN
AccessioniPrimary (citable) accession number: Q6ZQW0
Secondary accession number(s): A4UD41, F5H5G0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: October 14, 2015
Last modified: January 20, 2016
This is version 90 of the entry and version 4 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 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

Keywords - Technical termi

Complete proteome, 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. 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.