RDH13

RDH13
Identifiers
Aliases	RDH13, SDR7C3, retinol dehydrogenase 13 (all-trans/9-cis), retinol dehydrogenase 13
External IDs	MGI: 1918732; HomoloGene: 121782; GeneCards: RDH13; OMA:RDH13 - orthologs
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 leg; ; skin of abdomen; ; mucosa of transverse colon; ; apex of heart; ; placenta; ; minor salivary glands; ; left ventricle; ; vagina; ; body of stomach; ; right lobe of thyroid gland;
	Top expressed in
	otic vesicle; ; saccule; ; otic placode; ; medullary collecting duct; ; gastric mucosa; ; cardiac muscle tissue of left ventricle; ; superior frontal gyrus; ; mucous cell of stomach; ; epithelium of stomach; ; primary visual cortex;
	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
	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

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]

References

^ ^a ^b ^c 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
^ ^a ^b ^c 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.
^ ^a ^b "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.
^ ^a ^b 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.