Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Chem Biol Interact
2017 Oct 01;276:88-94. doi: 10.1016/j.cbi.2016.10.019.
Show Gene links
Show Anatomy links
Characterization of human short chain dehydrogenase/reductase SDR16C family members related to retinol dehydrogenase 10.
Adams MK
,
Lee SA
,
Belyaeva OV
,
Wu L
,
Kedishvili NY
.
???displayArticle.abstract???
All-trans-retinoic acid (RA) is a bioactive derivative of vitamin A that serves as an activating ligand for nuclear transcription factors, retinoic acid receptors. RA biosynthesis is initiated by the enzymes that oxidize retinol to retinaldehyde. It is well established that retinol dehydrogenase 10 (RDH10, SDR16C4), which belongs to the 16C family of the short chain dehydrogenase/reductase (SDR) superfamily of proteins, is the major enzyme responsible for the oxidation of retinol to retinaldehyde for RA biosynthesis during embryogenesis. However, several lines of evidence point towards the existence of additional retinol dehydrogenases that contribute to RA biosynthesis in vivo. In close proximity to RDH10 gene on human chromosome 8 are located two genes that are phylogenetically related to RDH10. The predicted protein products of these genes, retinol dehydrogenase epidermal 2 (RDHE2, SDR16C5) and retinol dehydrogenase epidermal 2-similar (RDHE2S, SDR16C6), share 59% and 56% sequence similarity with RDH10, respectively. Previously, we showed that the single ortholog of the human RDHE2 and RDHE2S in frogs, Xenopus laevis rdhe2, oxidizes retinol to retinaldehyde and is essential for frog embryonic development. In this study, we explored the potential of each of the two human proteins to contribute to RA biosynthesis. The results of this study demonstrate that human RDHE2 exhibits a relatively low but reproducible activity when expressed in either HepG2 or HEK293 cells. Expression of the native RDHE2 is downregulated in the presence of elevated levels of RA. On the other hand, the protein encoded by the human RDHE2S gene is unstable when expressed in HEK293 cells. RDHE2S protein produced in Sf9 cells is stable but has no detectable catalytic activity towards retinol. We conclude that the human RDHE2S does not contribute to RA biosynthesis, whereas the low-activity RA-sensitive human RDHE2 may have a role in adjusting the cellular levels of RA in accord with specific physiological conditions.
Adams,
The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis.
2014, Pubmed
Adams,
The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis.
2014,
Pubmed
Ashique,
Morphological defects in a novel Rdh10 mutant that has reduced retinoic acid biosynthesis and signaling.
2012,
Pubmed
Bai,
Identification of genes related to beak deformity of chickens using digital gene expression profiling.
2014,
Pubmed
Balmer,
Gene expression regulation by retinoic acid.
2002,
Pubmed
Banerjee,
Retrovirus-mediated gene transfer to analyze HPV gene regulation and protein functions in organotypic "raft" cultures.
2005,
Pubmed
Belyaeva,
Properties of short-chain dehydrogenase/reductase RalR1: characterization of purified enzyme, its orientation in the microsomal membrane, and distribution in human tissues and cell lines.
2003,
Pubmed
Belyaeva,
Kinetic analysis of human enzyme RDH10 defines the characteristics of a physiologically relevant retinol dehydrogenase.
2008,
Pubmed
Belyaeva,
Short chain dehydrogenase/reductase rdhe2 is a novel retinol dehydrogenase essential for frog embryonic development.
2012,
Pubmed
,
Xenbase
Belyaeva,
Evolutionary origins of retinoid active short-chain dehydrogenases/reductases of SDR16C family.
2015,
Pubmed
Belyaeva,
Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): catalytic efficiency toward retinoids and C9 aldehydes and effects of cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein (CRALBP) on the oxidation and reduction of retinoids.
2005,
Pubmed
Boerman,
Characterization of a microsomal retinol dehydrogenase: a short-chain alcohol dehydrogenase with integral and peripheral membrane forms that interacts with holo-CRBP (type I).
1995,
Pubmed
Cunningham,
Rdh10 mutants deficient in limb field retinoic acid signaling exhibit normal limb patterning but display interdigital webbing.
2011,
Pubmed
Everts,
Endogenous retinoids in the hair follicle and sebaceous gland.
2012,
Pubmed
Ghyselinck,
Cellular retinol-binding protein I is essential for vitamin A homeostasis.
1999,
Pubmed
Gudbjartsson,
Many sequence variants affecting diversity of adult human height.
2008,
Pubmed
Hall,
The role of retinoic acid in tolerance and immunity.
2011,
Pubmed
Jiao,
Feed intake, average daily gain, feed efficiency, and real-time ultrasound traits in Duroc pigs: II. Genomewide association.
2014,
Pubmed
Kang,
Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation.
1995,
Pubmed
Karim,
Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature.
2011,
Pubmed
Kedishvili,
Enzymology of retinoic acid biosynthesis and degradation.
2013,
Pubmed
Lee,
Retinol dehydrogenase 10 but not retinol/sterol dehydrogenase(s) regulates the expression of retinoic acid-responsive genes in human transgenic skin raft culture.
2011,
Pubmed
Lee,
Biochemical characterization of human epidermal retinol dehydrogenase 2.
2009,
Pubmed
Lettre,
Identification of ten loci associated with height highlights new biological pathways in human growth.
2008,
Pubmed
Littlejohn,
Genetic variation in PLAG1 associates with early life body weight and peripubertal weight and growth in Bos taurus.
2012,
Pubmed
Matsuzaka,
hRDH-E2 gene polymorphisms, variable transcriptional start sites, and psoriasis.
2004,
Pubmed
Matsuzaka,
Identification of the hRDH-E2 gene, a novel member of the SDR family, and its increased expression in psoriatic lesion.
2002,
Pubmed
Nishimura,
Genome-wide association study identified three major QTL for carcass weight including the PLAG1-CHCHD7 QTN for stature in Japanese Black cattle.
2012,
Pubmed
Persson,
The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative.
2009,
Pubmed
Pryce,
Polymorphic regions affecting human height also control stature in cattle.
2011,
Pubmed
Rhinn,
Retinoic acid signalling during development.
2012,
Pubmed
Rhinn,
Involvement of retinol dehydrogenase 10 in embryonic patterning and rescue of its loss of function by maternal retinaldehyde treatment.
2011,
Pubmed
Ruiz,
Biological role of aldo-keto reductases in retinoic Acid biosynthesis and signaling.
2012,
Pubmed
Sandell,
RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ development.
2007,
Pubmed
Sandell,
RDH10 oxidation of Vitamin A is a critical control step in synthesis of retinoic acid during mouse embryogenesis.
2012,
Pubmed
Stern,
Psoriasis.
1997,
Pubmed
Tong,
Retinol dehydrogenase 10 is indispensible for spermatogenesis in juvenile males.
2013,
Pubmed
Weedon,
Genome-wide association analysis identifies 20 loci that influence adult height.
2008,
Pubmed
Wu,
Cloning and characterization of a novel all-trans retinol short-chain dehydrogenase/reductase from the RPE.
2002,
Pubmed
Xiong,
Identification of quantitative trait transcripts for growth traits in the large scales of liver and muscle samples.
2015,
Pubmed
