The human RDH13 gene is on the 19th chromosome, with its specific localization being 19q13.42. The gene contains 12 exons in total.
Structure
The analysis of the submitochondrial localization of RDH13 indicates its association with the inner mitochondrial membrane. The primary structure of RDH13 contains two hydrophobic segments, 2–21 and 242–261, which are sufficiently long to serve as transmembrane segments; however, as shown in the present study, alkaline extraction completely removes the protein from the membrane, indicating that RDH13 is a peripheral membrane protein. The peripheral association of RDH13 with the membrane further distinguishes this protein from the microsomal retinaldehyde reductases, which are integral membrane proteins that appear to be anchored in the membrane via their N-terminal hydrophobic segments.
Function
RDH13 is most closely related to the NADP+-dependent microsomal enzymes RDH11, RDH12 and RDH14. Purified RDH13 acts on retinoids in an oxidative reductive manner, and strongly prefers the cofactor NADPH over NADH. Moreover, RDH13 is much has much more efficient reductase activity than dehydrogenase activity. RDH13 as a retinaldehyde reductase is significantly less active than that of a related protein RDH11, primarily because of the much higher Km value for retinaldehyde. However, the kcat value of RDH13 for retinaldehyde reduction. arable with that of RDH11, and the Km values of the two enzymes for NADPH are also very similar. Thus, consistent with its sequence similarity to RDH11, RDH12 and RDH14, RDH13 acts as an NADP+-dependent retinaldehyde reductase. RDH13 is localized in the mitochondria, which is different from the other members of this family, as they localize to the endoplasmic reticulum. The exact sequence targeting RDH13 to the mitochondria remains to be established.
Clinical significance
RDH13 is part of a subfamily of four retinol dehydrogenases, RDH11, RDH12, RDH13, and RDH14, that display dual-substrate specificity, uniquely metabolizing all-trans- and cis-retinols with C pro-R specificity. The metabolites involved in these reactions are known as retinoids, which are chromophores involved in vision, transcriptional regulation, and cellular differentiation. RDH11-14 could be involved in the first step of all-trans- and 9-cis-retinoic acid production in many tissues. RDH11-14 fill the gap in our understanding of 11-cis-retinal and all-trans-retinal transformations in photoreceptor and retinal pigment epithelial cells. The dual-substrate specificity of this subfamily explains the minor phenotype associated with mutations in 11-cis-retinol dehydrogenase causing fundus albipunctatus in humans.
