Q6ZQW0 (I23O2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Indoleamine 2,3-dioxygenase 2
Short name=IDO-2
EC=1.13.11.-

Alternative name(s):
Indoleamine 2,3-dioxygenase-like protein 1
Indoleamine-pyrrole 2,3-dioxygenase-like protein 1

Gene names

Name:	IDO2
Synonyms:	INDOL1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	407 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan catabolism. Ref.5
Catalytic activity	L-tryptophan + O2 = N-formyl-L-kynurenine. Ref.5
Cofactor	Binds 1 heme group per subunit By similarity.
Enzyme regulation	Activity is inhibited by D-1MT (1-methyl-D-tryptophan) and MTH-trp (methylthiohydantoin-DL-tryptophan) but not L-1MT (1-methyl-L-tryptophan). Ref.5
Pathway	Amino-acid degradation; L-tryptophan degradation via kynurenine pathway; L-kynurenine from L-tryptophan: step 1/2.
Tissue specificity	Detected in liver, small intestine, spleen, placenta, thymus, lung, brain, kidney, and colon. Ref.5
Sequence similarities	Belongs to the indoleamine 2,3-dioxygenase family.

Ontologies

Keywords
Biological process	Tryptophan catabolism
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Heme Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	tryptophan catabolic process to kynurenine Inferred from direct assay Ref.5. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	heme binding Inferred from electronic annotation. Source: InterPro indoleamine 2,3-dioxygenase activity Inferred from direct assay Ref.5. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW tryptophan 2,3-dioxygenase activity Inferred from experiment. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6ZQW0-1)

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.

Isoform 2 (identifier: Q6ZQW0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLHFHYYDTSNKIM
     146-159: FLEIGNLETIISFP → DGVSLCLPGWSAVA
     160-407: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 407	407	Indoleamine 2,3-dioxygenase 2		PRO_0000285262
Sites
	Metal binding	347	1	Iron (heme proximal ligand) By similarity
Natural variations
	Alternative sequence	1	1	M → MLHFHYYDTSNKIM in isoform 2.		VSP_024857
	Alternative sequence	146 – 159	14	FLEIG…IISFP → DGVSLCLPGWSAVA in isoform 2.		VSP_024858
	Alternative sequence	160 – 407	248	Missing in isoform 2.		VSP_024859
	Natural variant	235	1	R → W Reduced catalytic activity. Ref.5 Corresponds to variant rs10109853 [ dbSNP | Ensembl ].		VAR_032007

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2008. Version 3. Checksum: 975E8257B5EC3730	FASTA	407	45,424
	10 20 30 40 50 60 MEPHRPNVKT AVPLSLESYH ISEEYGFLLP DSLKELPDHY RPWMEIANKL PQLIDAHQLQ 70 80 90 100 110 120 AHVDKMPLLS CQFLKGHREQ RLAHLVLSFL TMGYVWQEGE AQPAEVLPRN LALPFVEVSR 130 140 150 160 170 180 NLGLPPILVH SDLVLTNWTK KDPDGFLEIG NLETIISFPG GESLHGFILV TALVEKEAVP 190 200 210 220 230 240 GIKALVQATN AILQPNQEAL LQALQRLRLS IQDITKTLGQ MHDYVDPDIF YAGIRIFLSG 250 260 270 280 290 300 WKDNPAMPAG LMYEGVSQEP LKYSGGSAAQ STVLHAFDEF LGIRHSKESG DFLYRMRDYM 310 320 330 340 350 360 PPSHKAFIED IHSAPSLRDY ILSSGQDHLL TAYNQCVQAL AELRSYHITM VTKYLITAAA 370 380 390 400 KAKHGKPNHL PGPPQALKDR GTGGTAVMSF LKSVRDKTLE SILHPRG
	Isoform 2 [UniParc]. Checksum: B5C794259EDE4DCC	FASTA	172	19,610
	10 20 30 40 50 60 MLHFHYYDTS NKIMEPHRPN VKTAVPLSLE SYHISEEYGF LLPDSLKELP DHYRPWMEIA 70 80 90 100 110 120 NKLPQLIDAH QLQAHVDKMP LLSCQFLKGH REQRLAHLVL SFLTMGYVWQ EGEAQPAEVL 130 140 150 160 170 PRNLALPFVE VSRNLGLPPI LVHSDLVLTN WTKKDPDGDG VSLCLPGWSA VA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM 1).
[2]	"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.
[3]	"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].
[4]	"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).
[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, ENZYME REGULATION, TISSUE SPECIFICITY, VARIANT TRP-235.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00375581. IPI00847197.
RefSeq	NP_919270.2. NM_194294.2.
UniGene	Hs.676257.
3D structure databases
HSSP	HSSP built from PDB template 2D0T based on UniProtKB P14902.
ProteinModelPortal	Q6ZQW0.
ModBase	Search...
PTM databases
PhosphoSite	Q6ZQW0.
Polymorphism databases
DMDM	215274147.
Proteomic databases
PRIDE	Q6ZQW0.
Protocols and materials databases
DNASU	169355.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000389060; ENSP00000426447; ENSG00000188676.
GeneID	169355.
KEGG	hsa:169355.
Organism-specific databases
CTD	169355.
GeneCards	GC08P039792.
H-InvDB	HIX0007468.
HGNC	HGNC:27269. IDO2.
MIM	612129. gene.
neXtProt	NX_Q6ZQW0.
PharmGKB	PA164720782.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HOG000190192.
InParanoid	Q6ZQW0.
KO	K00463.
OrthoDB	EOG4QNMX0.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00333; UER00453.
Gene expression databases
ArrayExpress	Q6ZQW0.
Bgee	Q6ZQW0.
Genevestigator	Q6ZQW0.
Family and domain databases
InterPro	IPR000898. Indolamine_dOase. [Graphical view]
Pfam	PF01231. IDO. 1 hit. [Graphical view]
PROSITE	PS00876. IDO_1. False negative. PS00877. IDO_2. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	IDO2. human.
GenomeRNAi	169355.
NextBio	88803.
SOURCE	Search...

Entry information

Entry name

I23O2_HUMAN

Accession

Primary (citable) accession number: Q6ZQW0
Secondary accession number(s): A4UD41

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 2007
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 68 of the entry and version 3 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.