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]
The human RDH13 gene is on the 19th chromosome, with its specific localization being 19q13.42. The gene contains 12 exons in total.[5]
Structureedit
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]
Functionedit
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 significanceedit
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]
^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. PMC2112113. 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. PMC2573044. 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.
^ abHaeseleer 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. PMC1435693. 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.
Further readingedit
Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Mar 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chemico-Biological Interactions. 178 (1–3): 94–8. Bibcode:2009CBI...178...94P. doi:10.1016/j.cbi.2008.10.040. PMC2896744. PMID 19027726.
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. PMC2573044. PMID 18039331.
Alkhaja AK, Jans DC, Nikolov M, Vukotic M, Lytovchenko O, Ludewig F, Schliebs W, Riedel D, Urlaub H, Jakobs S, Deckers M (Jan 2012). "MINOS1 is a conserved component of mitofilin complexes and required for mitochondrial function and cristae organization". Molecular Biology of the Cell. 23 (2): 247–57. doi:10.1091/mbc.E11-09-0774. PMC3258170. PMID 22114354.
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. PMC1435693. PMID 12226107.
rdh13, retinol, dehydrogenase, trans, protein, that, humans, encoded, gene, this, gene, encodes, mitochondrial, short, chain, dehydrogenase, reductase, which, catalyzes, reduction, oxidation, retinoids, encoded, enzyme, function, retinoic, acid, production, al. 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 RDH13IdentifiersAliasesRDH13 SDR7C3 retinol dehydrogenase 13 all trans 9 cis retinol dehydrogenase 13External IDsMGI 1918732 HomoloGene 121782 GeneCards RDH13Gene location Human Chr Chromosome 19 human 1 Band19q13 42Start55 039 108 bp 1 End55 071 291 bp 1 Gene location Mouse Chr Chromosome 7 mouse 2 Band7 7 A1Start4 424 770 bp 2 End4 445 649 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inskin of abdomenplacentaminor salivary glandsleft ventriclevaginabody of stomachright lobe of thyroid glandleft lobe of thyroid glandduodenumbody of pancreasTop expressed insacculeotic placodemedullary collecting ductgastric mucosasuperior frontal gyrusmucous cell of stomachepithelium of stomachplantaris musclepyloric antrumextensor digitorum longus muscleMore reference expression dataBioGPSn aGene ontologyMolecular functionNADP retinol dehydrogenase activity oxidoreductase activityCellular componentmitochondrial inner membrane mitochondrion membraneBiological processresponse to high light intensity retina layer formation eye photoreceptor cell development retinol metabolic process retinal metabolic processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez112724108841EnsemblENSG00000278284ENSG00000274418ENSG00000276341ENSG00000275474ENSG00000274504ENSG00000273944ENSG00000276684ENSG00000278149ENSG00000276826ENSG00000160439ENSMUSG00000008435UniProtQ8NBN7Q8CEE7RefSeq mRNA NM 001145971NM 138412NM 001290409NM 001290411NM 175372RefSeq protein NP 001139443NP 612421NP 001277338NP 001277340NP 780581Location UCSC Chr 19 55 04 55 07 MbChr 7 4 42 4 45 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Gene 2 Structure 3 Function 4 Clinical significance 5 References 6 Further readingGene editThe human RDH13 gene is on the 19th chromosome with its specific localization being 19q13 42 The gene contains 12 exons in total 5 Structure editThe 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 editRDH13 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 editRDH13 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 edit 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 Further reading editPersson B Kallberg Y Bray JE Bruford E Dellaporta SL Favia AD Duarte RG Jornvall H Kavanagh KL Kedishvili N Kisiela M Maser E Mindnich R Orchard S Penning TM Thornton JM Adamski J Oppermann U Mar 2009 The SDR short chain dehydrogenase reductase and related enzymes nomenclature initiative Chemico Biological Interactions 178 1 3 94 8 Bibcode 2009CBI 178 94P doi 10 1016 j cbi 2008 10 040 PMC 2896744 PMID 19027726 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 Alkhaja AK Jans DC Nikolov M Vukotic M Lytovchenko O Ludewig F Schliebs W Riedel D Urlaub H Jakobs S Deckers M Jan 2012 MINOS1 is a conserved component of mitofilin complexes and required for mitochondrial function and cristae organization Molecular Biology of the Cell 23 2 247 57 doi 10 1091 mbc E11 09 0774 PMC 3258170 PMID 22114354 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 This article incorporates text from the United States National Library of Medicine which is in the public domain nbsp This article on a gene on human chromosome 19 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title RDH13 amp oldid 1222978174, wikipedia, wiki, book, books, library,
