Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice.
Indoleamine 2,3-dioxygenase (INDO) and tryptophan 2,3-dioxygenase (TDO) each catalyze the first step in the kynurenine pathway of tryptophan metabolism. We describe the discovery of another enzyme with this activity, indoleamine 2,3-dioxygenase-like protein (INDOL1), which is closely related to INDO and is expressed in mice and humans. The corresponding genes have a similar genomic structure and are situated adjacent to each other on human and mouse chromosome 8. They are likely to have arisen by gene duplication before the origin of the tetrapods. The expression of INDOL1 is highest in the mouse kidney, followed by epididymis, and liver. Expression of mouse INDOL1 was further localized to the tubular cells in the kidney and the spermatozoa. INDOL1 was assigned its name because of its structural similarity to INDO. We demonstrate that INDOL1 catalyses the conversion of tryptophan to kynurenine therefore a more appropriate nomenclature for the enzymes might be INDO-1 and INDO-2, or the more commonly-used abbreviations, IDO-1 and IDO-2. Although the two proteins have similar enzymatic activities, their different expression patterns within tissues and during malaria infection, suggests a distinct role for each protein. This identification of INDOL1 may help to explain the regulation of the diversity of physiological and patho-physiological processes in which the kynurenine pathway is involved.
Ball
Helen J
HJ
Discipline of Pathology and Bosch Institute, University of Sydney, NSW 2006, Australia. helenb@med.usyd.edu.au
Sanchez-Perez
Angeles
A
Weiser
Silvia
S
Austin
Christopher J D
CJ
Astelbauer
Florian
F
Miu
Jenny
J
McQuillan
James A
JA
Stocker
Roland
R
Jermiin
Lars S
LS
Hunt
Nicholas H
NH
D000595:Amino Acid Sequence; D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger