P14902 (I23O1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Indoleamine 2,3-dioxygenase 1
Short name=IDO-1
EC=1.13.11.52

Alternative name(s):
Indoleamine-pyrrole 2,3-dioxygenase

Gene names

Name:	IDO1
Synonyms:	IDO, INDO

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	403 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen. Ref.7
Catalytic activity	D-tryptophan + O2 = N-formyl-D-kynurenine. Ref.7 L-tryptophan + O2 = N-formyl-L-kynurenine. Ref.7
Cofactor	Binds 1 heme group per subunit.
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). Ref.7
Pathway	Amino-acid degradation; L-tryptophan degradation via kynurenine pathway; L-kynurenine from L-tryptophan: step 1/2.
Induction	By IFNG/IFN-gamma. Ref.1 Ref.7
Sequence similarities	Belongs to the indoleamine 2,3-dioxygenase family.
Biophysicochemical properties	Kinetic parameters: Catalytic efficiency for L-tryptophan is 150 times higher than for D-tryptophan. KM=21.23 µM for L-tryptophan Ref.8 KM=4.6 mM for D-tryptophan

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	Heme Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	female pregnancy Traceable author statement. Source: ProtInc tryptophan catabolic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	electron carrier activity Traceable author statement Ref.1. Source: UniProtKB heme binding Inferred from electronic annotation. Source: InterPro indoleamine 2,3-dioxygenase activity Inferred from electronic annotation. Source: EC tryptophan 2,3-dioxygenase activity Inferred from experiment. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 403

403

Indoleamine 2,3-dioxygenase 1

PRO_0000215204

Sites

Metal binding

346

1

Iron (heme proximal ligand)

Natural variations

Natural variant

4

1

A → T.
Corresponds to variant rs35059413 [ dbSNP | Ensembl ].

VAR_053368

Secondary structure

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403

Helix Strand Turn

Details...

Beta strand

14 – 16

3

Turn

19 – 21

3

Helix

34 – 36

3

Helix

37 – 44

8

Helix

46 – 51

6

Helix

55 – 61

7

Helix

73 – 92

20

Beta strand

95 – 97

3

Beta strand

101 – 103

3

Helix

105 – 118

14

Helix

126 – 129

4

Beta strand

132 – 138

7

Helix

145 – 147

3

Beta strand

148 – 151

4

Helix

160 – 178

19

Helix

181 – 189

9

Helix

193 – 214

22

Helix

217 – 220

4

Helix

223 – 228

6

Helix

230 – 233

4

Beta strand

237 – 239

3

Helix

241 – 243

3

Beta strand

247 – 249

3

Turn

250 – 252

3

Helix

264 – 266

3

Helix

268 – 276

9

Beta strand

284 – 286

3

Helix

287 – 295

9

Helix

296 – 298

3

Helix

301 – 311

11

Helix

316 – 321

6

Helix

326 – 353

28

Helix

355 – 358

4

Helix

382 – 397

16

Sequences

	Sequence		Length	Mass (Da)
	P14902 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: E92CF57AD0D0BA8D	FASTA	403	45,326
	10 20 30 40 50 60 MAHAMENSWT ISKEYHIDEE VGFALPNPQE NLPDFYNDWM FIAKHLPDLI ESGQLRERVE 70 80 90 100 110 120 KLNMLSIDHL TDHKSQRLAR LVLGCITMAY VWGKGHGDVR KVLPRNIAVP YCQLSKKLEL 130 140 150 160 170 180 PPILVYADCV LANWKKKDPN KPLTYENMDV LFSFRDGDCS KGFFLVSLLV EIAAASAIKV 190 200 210 220 230 240 IPTVFKAMQM QERDTLLKAL LEIASCLEKA LQVFHQIHDH VNPKAFFSVL RIYLSGWKGN 250 260 270 280 290 300 PQLSDGLVYE GFWEDPKEFA GGSAGQSSVF QCFDVLLGIQ QTAGGGHAAQ FLQDMRRYMP 310 320 330 340 350 360 PAHRNFLCSL ESNPSVREFV LSKGDAGLRE AYDACVKALV SLRSYHLQIV TKYILIPASQ 370 380 390 400 QPKENKTSED PSKLEAKGTG GTDLMNFLKT VRSTTEKSLL KEG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA." Dai W., Gupta S.L. Biochem. Biophys. Res. Commun. 168:1-8(1990) [PubMed: 2109605] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION BY IFNG. Tissue: Fibroblast.
[2]	"Primary structure of human indoleamine 2,3-dioxygenase deduced from the nucleotide sequence of its cDNA." Tone S., Takikawa O., Habara-Ohkubo A., Kadoya A., Yoshida R., Kido R. Nucleic Acids Res. 18:367-367(1990) [PubMed: 2326172] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Lung.
[3]	"Gene structure of human indoleamine 2,3-dioxygenase." Kadoya A., Tone S., Maeda H., Minatogawa Y., Kido R. Biochem. Biophys. Res. Commun. 189:530-536(1992) [PubMed: 1449503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Human indoleamine 2,3-dioxygenase from peripheral blood." He X., Xu L., Liu Y., Zeng Y. Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Peripheral blood.
[5]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[7]	"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: 17671174] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, CATALYTIC ACTIVITY.
[8]	"Evolution of vertebrate indoleamine 2,3-dioxygenases." Yuasa H.J., Takubo M., Takahashi A., Hasegawa T., Noma H., Suzuki T. J. Mol. Evol. 65:705-714(2007) [PubMed: 18026683] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[9]	"Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase." Sugimoto H., Oda S., Otsuki T., Hino T., Yoshida T., Shiro Y. Proc. Natl. Acad. Sci. U.S.A. 103:2611-2616(2006) [PubMed: 16477023] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M34455 mRNA. Translation: AAA36081.1.
X17668 mRNA. Translation: CAA35663.1.
M86472 Genomic DNA. No translation available.
M86473 Genomic DNA. No translation available.
M86474 Genomic DNA. No translation available.
M86475 Genomic DNA. No translation available.
M86476 Genomic DNA. No translation available.
M86477 Genomic DNA. No translation available.
M86478 Genomic DNA. No translation available.
M86479 Genomic DNA. No translation available.
M86480 Genomic DNA. No translation available.
M86481 Genomic DNA. No translation available.
AY221100 mRNA. Translation: AAO34405.1.
AK313259 mRNA. Translation: BAG36069.1.
BC027882 mRNA. Translation: AAH27882.1.

IPI

IPI00028096.

PIR

PC1161.

RefSeq

NP_002155.1. NM_002164.5.

UniGene

Hs.840.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2D0T	X-ray	2.30	A/B	1-403	[»]
2D0U	X-ray	3.40	A/B	1-403	[»]

ProteinModelPortal

P14902.

SMR

P14902. Positions 11-403.

ModBase

Search...

Protein-protein interaction databases

IntAct

P14902. 3 interactions.

MINT

MINT-1414454.

STRING

P14902.

Polymorphism databases

DMDM

123948.

Proteomic databases

PRIDE

P14902.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000253513; ENSP00000253513; ENSG00000131203.

GeneID

3620.

KEGG

hsa:3620.

UCSC

uc003xnm.1. human.

Organism-specific databases

CTD

3620.

GeneCards

GC08P039771.

H-InvDB

HIX0007467.

HGNC

HGNC:6059. IDO1.

HPA

HPA023072.
HPA023149.
HPA027772.

MIM

147435. gene.

neXtProt

NX_P14902.

PharmGKB

PA164720757.
PA29869.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08850.

GeneTree

ENSGT00390000002154.

InParanoid

P14902.

OMA

FVLSKGD.

OrthoDB

EOG4B5P5C.

PhylomeDB

P14902.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-15002.

BRENDA

1.13.11.11. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P14902.

Bgee

P14902.

Genevestigator

P14902.

GermOnline

ENSG00000131203. Homo sapiens.

Family and domain databases

InterPro

IPR000898. Indolamine_dOase.
[Graphical view]

KO

K00463.

Pfam

PF01231. IDO. 1 hit.
[Graphical view]

PROSITE

PS00876. IDO_1. 1 hit.
PS00877. IDO_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P14902.

DrugBank

DB00150. L-Tryptophan.

NextBio

14159.

SOURCE

Search...

Entry information

Entry name

I23O1_HUMAN

Accession

Primary (citable) accession number: P14902
Secondary accession number(s): Q540B4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	January 25, 2012
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.