TY - JOUR
T1 - Cloning and characterization of a human β,β-carotene-15, 15′-dioxygenase that is highly expressed in the retinal pigment epithelium
AU - Yan, Weiming
AU - Jang, Geeng Fu
AU - Haeseleer, Françoise
AU - Esumi, Noriko
AU - Chang, Jinghua
AU - Kerrigan, Michelle
AU - Campochiaro, Michael
AU - Campochiaro, Peter
AU - Palczewski, Krzysztof
AU - Zack, Donald J.
N1 - Funding Information:
This research was supported, in part, by funds from The Foundation Fighting Blindness (Wilmer AMD Center Grant), NIH vision training grants (J.K.M. and J.C.), NIH (EY08061 and Core Grant EY01765), unrestricted grants from Research to Prevent Blindness, Inc. (RPB), and grants from the Ruth and Milton Steinbach Fund, the E. K. Bishop Foundation, and the Macula Vision Foundation. W.Y. is a recipient of fellowship from Fight-For-Sight, and D.J.Z. is a recipient of a Career Development Award from RPB.
PY - 2001/3/1
Y1 - 2001/3/1
N2 - Retinoids play a critical role in vision, as well as in development and cellular differentiation. β,β-Carotene-15,15′-dioxygenase (Bcdo), the enzyme that catalyzes the oxidative cleavage of β,β-carotene into two retinal molecules, plays an important role in retinoid synthesis. We report here the first cloning of a mammalian Bcdo. Human BCDO encodes a protein of 547 amino acid residues that demonstrates 68% identity with chicken Bcdo. It is expressed highly in the retinal pigment epithelium (RPE) and also in kidney, intestine, liver, brain, stomach, and testis. The gene spans approximately 20 kb, is composed of 11 exons and 10 introns, and maps to chromosome 16q21-q23. A mouse orthologue was also identified, and its predicted amino acid sequence is 83% identical with human BCDO. Biochemical analysis of baculovirus expressed human BCDO demonstrates the predicted β,β-carotene-15,15′-dioxygenase activity. The expression pattern of BCDO suggests that it may provide a local supplement to the retinoids available to photoreceptors, as well as a supplement to the retinoid pools utilized elsewhere in the body. In addition, the finding that many of the enzymes involved in retinoid metabolism are mutated in retinal degenerations suggests that BCDO may also be a candidate gene for retinal degenerative disease.
AB - Retinoids play a critical role in vision, as well as in development and cellular differentiation. β,β-Carotene-15,15′-dioxygenase (Bcdo), the enzyme that catalyzes the oxidative cleavage of β,β-carotene into two retinal molecules, plays an important role in retinoid synthesis. We report here the first cloning of a mammalian Bcdo. Human BCDO encodes a protein of 547 amino acid residues that demonstrates 68% identity with chicken Bcdo. It is expressed highly in the retinal pigment epithelium (RPE) and also in kidney, intestine, liver, brain, stomach, and testis. The gene spans approximately 20 kb, is composed of 11 exons and 10 introns, and maps to chromosome 16q21-q23. A mouse orthologue was also identified, and its predicted amino acid sequence is 83% identical with human BCDO. Biochemical analysis of baculovirus expressed human BCDO demonstrates the predicted β,β-carotene-15,15′-dioxygenase activity. The expression pattern of BCDO suggests that it may provide a local supplement to the retinoids available to photoreceptors, as well as a supplement to the retinoid pools utilized elsewhere in the body. In addition, the finding that many of the enzymes involved in retinoid metabolism are mutated in retinal degenerations suggests that BCDO may also be a candidate gene for retinal degenerative disease.
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U2 - 10.1006/geno.2000.6476
DO - 10.1006/geno.2000.6476
M3 - Article
C2 - 11401432
AN - SCOPUS:0035280250
SN - 0888-7543
VL - 72
SP - 193
EP - 202
JO - Genomics
JF - Genomics
IS - 2
ER -