RDH13

RDH13
Identifiers
Aliases	RDH13 , SDR7C3, retinol dehydrogenase 13 (all-trans/9-cis), retinol dehydrogenase 13
External IDs	MGI: 1918732 HomoloGene: 121782 GeneCards: RDH13
Gene location (Human)
Chr.	Chromosome 19 (human)
End	55,071,291 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	4,445,649 bp
RNA expression pattern
	Top expressed in
	skin of abdomen; ; placenta; ; minor salivary gland; ; left ventricle; ; vagina; ; body of stomach; ; right lobe of thyroid gland; ; left lobe of thyroid gland; ; duodenum; ; body of pancreas;
	Top expressed in
	saccule; ; otic placode; ; medullary collecting duct; ; gastric mucosa; ; superior frontal gyrus; ; mucous cell of stomach; ; Epithelium of stomach; ; plantaris muscle; ; pyloric antrum; ; extensor digitorum longus muscle;
	More reference expression data
	n/a
Gene ontology
Molecular function	NADP-retinol dehydrogenase activity ; oxidoreductase activity ;
Cellular component	mitochondrial inner membrane ; mitochondrion ; membrane ;
Biological process	response to high light intensity ; retina layer formation ; eye photoreceptor cell development ; retinol metabolic process ; retinal metabolic process ;
	Sources:Amigo / QuickGO
Orthologs
	112724
	108841
ENSG00000278284 ; ENSG00000274418 ; ENSG00000276341 ; ENSG00000275474 ; ENSG00000274504 ;
	ENSG00000273944 ; ENSG00000276684 ; ENSG00000278149 ; ENSG00000276826 ; ENSG00000160439 Contents Gene ; Structure ; Function ; Clinical significance ; References ; Further reading ;
	ENSMUSG00000008435
	Q8NBN7
	Q8CEE7
	NM_001145971 ; NM_138412
	NM_001290409 ; NM_001290411 ; NM_175372
	NP_001139443 ; NP_612421
	NP_001277338 ; NP_001277340 ; NP_780581
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated September 30, 2022

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.^[5]

Gene

The human RDH13 gene is on the 19th chromosome, with its specific localization being 19q13.42. The gene contains 12 exons in total.^[5]

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.^[6] 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.^[7]

Function

RDH13 is most closely related to the NADP+-dependent microsomal enzymes RDH11, RDH12 and RDH14.^[8]^[9] 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.^[10]

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.^[9]

Related Research Articles

Retinal is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision).

Retinoic acid (used simplified here for all-trans-retinoic acid) is a metabolite of vitamin A₁ (all-trans-retinol) that mediates the functions of vitamin A₁ required for growth and development. All-trans-retinoic acid is required in chordate animals, which includes all higher animals from fish to humans. During early embryonic development, all-trans-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages.

17β-Hydroxysteroid dehydrogenases, also 17-ketosteroid reductases (17-KSR), are a group of alcohol oxidoreductases which catalyze the reduction of 17-ketosteroids and the dehydrogenation of 17β-hydroxysteroids in steroidogenesis and steroid metabolism. This includes interconversion of DHEA and androstenediol, androstenedione and testosterone, and estrone and estradiol.

In enzymology, a retinol dehydrogenase (RDH) (EC 1.1.1.105) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Retinal dehydrogenase</span>

In enzymology, a retinal dehydrogenase, also known as retinaldehyde dehydrogenase (RALDH), catalyzes the chemical reaction converting retinal to retinoic acid. This enzyme belongs to the family of oxidoreductases, specifically the class acting on aldehyde or oxo- donor groups with NAD⁺ or NADP⁺ as acceptor groups, the systematic name being retinal:NAD⁺ oxidoreductase. This enzyme participates in retinol metabolism. The general scheme for the reaction catalyzed by this enzyme is:

Retinal pigment epithelium-specific 65 kDa protein, also known as retinoid isomerohydrolase, is an enzyme of the vertebrate visual cycle that is encoded in humans by the RPE65 gene. RPE65 is expressed in the retinal pigment epithelium and is responsible for the conversion of all-trans-retinyl esters to 11-cis-retinol during phototransduction. 11-cis-retinol is then used in visual pigment regeneration in photoreceptor cells. RPE65 belongs to the carotenoid oxygenase family of enzymes.

11-cis retinol dehydrogenase is an enzyme that in humans is encoded by the RDH5 gene.

Retinol dehydrogenase 11 is an enzyme that in humans is encoded by the RDH11 gene.

Retinol dehydrogenase 12 is an enzyme that in humans is encoded by the RDH12 gene.

Retinol dehydrogenase 14 is an enzyme that in humans is encoded by the RDH14 gene.

D-beta-hydroxybutyrate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the BDH1 gene.

Short-chain dehydrogenase/reductase 3 is an enzyme that in humans is encoded by the DHRS3 gene.

Dehydrogenase/reductase SDR family member 9 is an enzyme that in humans is encoded by the DHRS9 gene.

Hydroxysteroid 17-beta dehydrogenase 6 is an enzyme that in humans is encoded by the HSD17B6 gene.

Retinol dehydrogenase 8 is an enzyme that in humans is encoded by the RDH8 gene.

Dehydrogenase/reductase SDR family member 4 is an enzyme that in humans is encoded by the DHRS4 gene.

Lecithin retinol acyltransferase is an enzyme that in humans is encoded by the LRAT gene.

Retinol dehydrogenase 16 (all-trans) is a protein that in humans is encoded by the RDH16 gene. The gene is also known as RODH-4 and SDR9C8.

NADP-retinol dehydrogenase (EC 1.1.1.300, all-trans retinal reductase, all-trans-retinol dehydrogenase, NADP(H)-dependent retinol dehydrogenase/reductase, RDH11, RDH12, RDH13, RDH14, retinol dehydrogenase 12, retinol dehydrogenase 14, retinol dehydrogenase (NADP⁺), RalR1, PSDR1) is an enzyme with systematic name retinol:NADP⁺ oxidoreductase. This enzyme catalyses the following chemical reaction

11-cis-retinol dehydrogenase (EC 1.1.1.315, RDH5 (gene)) is an enzyme with systematic name 11-cis-retinol:NAD⁺ oxidoreductase. This enzyme catalyses the following chemical reaction

References

1 2 3 ENSG00000274418, ENSG00000276341, ENSG00000275474, ENSG00000274504, ENSG00000273944, ENSG00000276684, ENSG00000278149, ENSG00000276826, ENSG00000160439 GRCh38: Ensembl release 89: ENSG00000278284, ENSG00000274418, ENSG00000276341, ENSG00000275474, ENSG00000274504, ENSG00000273944, ENSG00000276684, ENSG00000278149, ENSG00000276826, ENSG00000160439 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000008435 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 "Entrez Gene: Retinol dehydrogenase 13 (all-trans/9-cis)".
↑ 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. PMC 2112113 . PMID 7068762.
↑ 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.
↑ 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.
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.
↑ 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.