RDH13

retinol dehydrogenase 13 (all-trans/9-cis)
Identifiers
Aliases RDH13, SDR7C3
External IDs MGI: 1918732 HomoloGene: 121782 GeneCards: 112724
Orthologs
Species Human Mouse
Entrez

112724

108841

Ensembl

n/a

ENSMUSG00000008435

UniProt

Q8NBN7
K7EMY5

Q8CEE7

RefSeq (mRNA)

NM_001290409
NM_001290411
NM_175372
XM_006539464
XM_011250412

RefSeq (protein)

NP_001277338.1
NP_001277340.1
NP_780581.1

Location (UCSC) Chr 19: 55.04 – 55.07 Mb Chr 7: 4.42 – 4.45 Mb
PubMed search
Wikidata
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Retinol dehydrogenase 13 (all-trans/9-cis) is a protein that in humans is encoded by the RDH13 gene. This gene encodes a mitochondrial short-chain dehydrogenase/reductase, which catalyzes the reduction and oxidation of retinoids. The encoded enzyme may function in retinoic acid production and may also protect the mitochondria against oxidative stress. Alternatively spliced transcript variants have been described.[1]

Gene

The human RDH13 gene is on the 19th chromosome, with its specific localization being 19q13.42. The gene contains 12 exons in total.[1]

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.[2] 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.[3]

Function

RDH13 is most closely related to the NADP+-dependent microsomal enzymes RDH11, RDH12 and RDH14.[4][5] 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.[6]

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(15) 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 (RDH5) causing fundus albipunctatus in humans.[5]

References

  1. 1 2 "Entrez Gene: Retinol dehydrogenase 13 (all-trans/9-cis)".
  2. ↑ Fujiki Y, Hubbard AL, Fowler S, Lazarow PB (Apr 1982). "Isolation of intracellular membranes by means of sodium carbonate treatment: application to endoplasmic reticulum". The Journal of Cell Biology 93 (1): 97–102. doi:10.1083/jcb.93.1.97. PMID 7068762.
  3. ↑ Belyaeva OV, Korkina OV, Stetsenko AV, Kedishvili NY (Jan 2008). "Human retinol dehydrogenase 13 (RDH13) is a mitochondrial short-chain dehydrogenase/reductase with a retinaldehyde reductase activity". The FEBS Journal 275 (1): 138–47. doi:10.1111/j.1742-4658.2007.06184.x. PMC 2573044. PMID 18039331.
  4. ↑ Kedishvili NY, Chumakova OV, Chetyrkin SV, Belyaeva OV, Lapshina EA, Lin DW, Matsumura M, Nelson PS (Aug 2002). "Evidence that the human gene for prostate short-chain dehydrogenase/reductase (PSDR1) encodes a novel retinal reductase (RalR1)". The Journal of Biological Chemistry 277 (32): 28909–15. doi:10.1074/jbc.M202588200. PMID 12036956.
  5. 1 2 Haeseleer F, Jang GF, Imanishi Y, Driessen CA, Matsumura M, Nelson PS, Palczewski K (Nov 2002). "Dual-substrate specificity short chain retinol dehydrogenases from the vertebrate retina". The Journal of Biological Chemistry 277 (47): 45537–46. doi:10.1074/jbc.M208882200. PMC 1435693. PMID 12226107.
  6. ↑ Belyaeva OV, Stetsenko AV, Nelson P, Kedishvili NY (Dec 2003). "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". Biochemistry 42 (50): 14838–45. doi:10.1021/bi035288u. PMID 14674758.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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