Disease relevance of Rdh16

• The combination of tumor-specific replication and enhanced infectivity generates a more potent CRAD vector for gene therapy of melanoma [1].

High impact information on Rdh16

• These data provide insight into the features necessary to orient type III (reverse signal-anchor) proteins and demonstrate that Rdh1, Crad1, and other short-chain dehydrogenases/reductases, which share similar N-terminal signaling sequences such as human Rdh5 and mouse Rdh4, orient with their catalytic domains facing the cytoplasm [2].
• RALDH4 recognizes as substrate 9-cis-retinal generated in transfected cells by the short-chain dehydrogenases CRAD1, CRAD3, or RDH1, to reconstitute a path of 9-cis-retinoic acid biosynthesis in situ [3].
• This cis-retinol/androgen dehydrogenase type 2 (CRAD2) shares close amino acid similarity with mouse retinol dehydrogenase isozyme types 1 and 2 and CRAD1 (86, 84, and 87%, respectively) [4].
• Unlike recombinant retinol dehydrogenase isozymes, recombinant CRAD was inhibited by 4-methylpyrazole, was not stimulated by ethanol, and did not require phosphatidylcholine for optimal activity [5].
• CRAD mRNA expression was widespread (relative abundance): kidney (100) > liver (92) > small intestine (9) = heart (9) > retinal pigment epithelium and sclera (4.5) > brain (2) > retina and vitreous (1.6) > spleen (0.7) > testis (0.6) > lung (0.4) [5].

Biological context of Rdh16

• Recombinant CRAD uses NAD+ as its preferred cofactor and exhibits cooperative kinetics for cis-retinoids, but Michaelis-Menten kinetics for 3alpha-hydroxysterols [5].
• Rdh6 spans more than 38 kb and consists of four exons ranging from 164 to 2200 bp, and three introns ranging from 550 bp to greater than 18 kb [6].

Anatomical context of Rdh16

• An N-terminal signaling sequence of 22 residues, consisting of a hydrophobic helix ending in a net positive charge, anchors Rdh1 and Crad1 in the endoplasmic reticulum facing the cytoplasm [2].

Associations of Rdh16 with chemical compounds

• This cis-retinol/androgen dehydrogenase (CRAD) shares closest amino acid similarity with mouse retinol dehydrogenase isozymes types 1 and 2 (86 and 91%, respectively) [5].
• CRAD may catalyze the first step in an enzymatic pathway from 9-cis-retinol to generate the retinoid X receptor ligand 9-cis-retinoic acid and/or may regenerate dihydrotestosterone from its catabolite 5alpha-androstan-3alpha,17beta-diol [5].
• CRAD3 has apparent efficiency (V/K(m)) for 9-cis-retinol about equivalent to that for CRAD1 and 3 orders of magnitude greater than that for RDH4 [7].
• CRAD3 shares amino acid similarity with other retinoid/steroid short-chain dehydrogenases/reductases: CRAD1, CRAD2, and RDH4 [7].
• Relative to CRAD1, CRAD3 has greater 9-cis-retinol/all-trans-retinol discrimination and lower efficiency as an androgen dehydrogenase [7].

References