{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:26:01Z","timestamp":1772252761808,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["Norte-01-0145-FEDER-000036"],"award-info":[{"award-number":["Norte-01-0145-FEDER-000036"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Fishes"],"abstract":"<jats:p>Nucleobase-Ascorbate Transporter (NAT) family includes ascorbic acid, nucleobases, and uric acid transporters: With broad evolutionary distribution. In vertebrates, four members have been previously recognized, the ascorbate transporters Slc23a1 and Slc3a2, the nucleobase transporter Slc23a4 and an orphan transporter Slc23a3. Using phylogenetic and synteny analysis, we identify a fifth member of the vertebrate slc23 complement (slc23a5), present in neopterygians (gars and teleosts) and amphibians, and clarify the evolutionary relationships between the novel gene and known slc23 genes. Further comparative analysis puts forward uric acid as the preferred substrate for Slc23a5. Gene expression quantification, using available transcriptomic data, suggests kidney and testis as major expression sites in Xenopus tropicalis (western clawed frog) and Danio rerio (zebrafish). Additional expression in brain was detected in D. rerio, while in the Neoteleostei Oryzias latipes (medaka) slc23a5 expression is restricted to the brain. The biological relevance of the retention of an extra transporter in fish and amphibians is discussed.<\/jats:p>","DOI":"10.3390\/fishes4010001","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T03:36:30Z","timestamp":1546486590000},"page":"1","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of a Novel Nucleobase-Ascorbate Transporter Family Member in Fish and Amphibians"],"prefix":"10.3390","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5803-185X","authenticated-orcid":false,"given":"Diogo","family":"Oliveira","sequence":"first","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, U. Porto\u2014University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6857-7581","authenticated-orcid":false,"given":"Andr\u00e9","family":"M. Machado","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, U. Porto\u2014University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5943-0481","authenticated-orcid":false,"given":"Tiago","family":"Cardoso","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, U. Porto\u2014University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-4730","authenticated-orcid":false,"given":"M\u00f3nica","family":"Lopes-Marques","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, U. Porto\u2014University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"given":"L. Filipe","family":"C. Castro","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, U. Porto\u2014University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Department of Biology, Faculty of Sciences, U. Porto\u2014University of Porto, Rua do Campo Alegre 1021\/1055, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2412-8730","authenticated-orcid":false,"given":"Raquel","family":"Ruivo","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, U. Porto\u2014University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.mam.2012.12.002","article-title":"The sodium-dependent ascorbic acid transporter family SLC23","volume":"34","author":"Burzle","year":"2013","journal-title":"Mol. Aspects Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1742-4658.2006.05607.x","article-title":"Vitamin C","volume":"274","author":"Linster","year":"2007","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2174\/138920211796429736","article-title":"The genetics of vitamin C loss in vertebrates","volume":"12","author":"Drouin","year":"2011","journal-title":"Curr. Genomics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0020-711X(73)90053-0","article-title":"Synthesis of l-ascorbic acid from d-glucurono-1,4-lactone conjugates by different species of animals","volume":"4","author":"Choudhury","year":"1973","journal-title":"Int. J. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1242\/jeb.198.2.273","article-title":"Nitrogen excretion: Three end products, many physiological roles","volume":"198","author":"Wright","year":"1995","journal-title":"J. Exp. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1053\/j.ackd.2012.07.009","article-title":"Renal transport of uric acid: Evolving concepts and uncertainties","volume":"19","author":"Bobulescu","year":"2012","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_7","unstructured":"Alvarez-Lario, B., and Macarr\u00f3n-Vicente, J. (2001). Evolution of Uric Acid Metabolism in Humans. eLS, John Wiley & Sons, Ltd."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1093\/oxfordjournals.molbev.a004123","article-title":"Loss of urate oxidase activity in hominoids and its evolutionary implications","volume":"19","author":"Oda","year":"2002","journal-title":"Mol. Biol. Evol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.abb.2010.05.014","article-title":"Cellular pathways for transport and efflux of ascorbate and dehydroascorbate","volume":"500","author":"Corti","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00726-007-0555-7","article-title":"SVCT1 and SVCT2: Key proteins for vitamin C uptake","volume":"34","author":"Savini","year":"2008","journal-title":"Amino Acids"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6522","DOI":"10.1074\/jbc.M109.032961","article-title":"Identification and functional characterization of the first nucleobase transporter in mammals: Implication in the species difference in the intestinal absorption mechanism of nucleobases and their analogs between higher primates and other mammals","volume":"285","author":"Yamamoto","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.jmb.2005.04.076","article-title":"The nucleobase-ascorbate transporter (NAT) signature motif in UapA defines the function of the purine translocation pathway","volume":"350","author":"Koukaki","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15684","DOI":"10.1074\/jbc.M112.355818","article-title":"Substrate selectivity of YgfU, a uric acid transporter from Escherichia coli","volume":"287","author":"Papakostas","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: Improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/sysbio\/syq010","article-title":"New algorithms and methods to estimate maximum-likelihood phylogenies: Assessing the performance of PhyML 3.0","volume":"59","author":"Guindon","year":"2010","journal-title":"Syst. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D710","DOI":"10.1093\/nar\/gkv1157","article-title":"Ensembl 2016","volume":"44","author":"Yates","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"D733","DOI":"10.1093\/nar\/gkv1189","article-title":"Reference sequence (RefSeq) database at NCBI: Current status, taxonomic expansion, and functional annotation","volume":"44","author":"Wright","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics, 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10157-011-0532-z","article-title":"Recent advances in renal urate transport: Characterization of candidate transporters indicated by genome-wide association studies","volume":"16","author":"Anzai","year":"2012","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/nrd1578","article-title":"Making protein interactions druggable: Targeting PDZ domains","volume":"3","author":"Dev","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.clinre.2010.11.009","article-title":"Roles of the scaffolding proteins NHERF in liver biology","volume":"35","author":"Mergey","year":"2011","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1073\/pnas.98.3.1300","article-title":"Regulation of cystic fibrosis transmembrane conductance regulator single-channel gating by bivalent PDZ-domain-mediated interaction","volume":"98","author":"Raghuram","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0092-8674(00)00096-9","article-title":"Accessory Protein Facilitated CFTR-CFTR Interaction, a Molecular Mechanism to Potentiate the Chloride Channel Activity","volume":"103","author":"Wang","year":"2000","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/S1055-937X(98)80044-3","article-title":"Comparative renal function in reptiles, birds, and mammals","volume":"7","author":"Braun","year":"1998","journal-title":"Semin. Avian Exotic. Pet. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S1096-4959(03)00027-7","article-title":"Do mammals, birds, reptiles and fish have similar nitrogen conserving systems?","volume":"134","author":"Singer","year":"2003","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1023\/A:1007886121663","article-title":"The presence of uric acid, an antioxidantive substance, in fish seminal plasma","volume":"21","author":"Ciereszko","year":"1999","journal-title":"Fish Physiol. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1007\/s10695-014-9963-2","article-title":"The antioxidant system of sterlet seminal fluid in testes and Wolffian ducts","volume":"40","author":"Dzyuba","year":"2014","journal-title":"Fish Physiol. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.aquaculture.2010.07.011","article-title":"A comparative study on antioxidant systems in semen of species of the Percidae, Salmonidae, Cyprinidae, and Lotidae for improving semen storage techniques","volume":"307","author":"Lahnsteiner","year":"2010","journal-title":"Aquaculture"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.anireprosci.2010.01.010","article-title":"Antioxidant systems of brown trout (Salmo trutta f. fario) semen","volume":"119","author":"Lahnsteiner","year":"2010","journal-title":"Anim. Reprod. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.anireprosci.2017.05.008","article-title":"The effect of antioxidants on sperm motility activation in the Booroolong frog","volume":"183","author":"Keogh","year":"2017","journal-title":"Anim. Reprod. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1098\/rstb.2001.0958","article-title":"Life-history correlates of the evolution of live bearing in fishes","volume":"357","author":"Goodwin","year":"2002","journal-title":"Philos. Trans. R. Soc. Lond. B. Biol. Sci"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bl\u00fcn, V. (1986). Comparative Anatomy of the Urogenital System. Vertebrate Reproduction, a Textbook, Springer.","DOI":"10.1007\/978-3-642-71074-2_3"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.repbio.2014.01.003","article-title":"In vitro sperm maturation in sterlet, Acipenser ruthenus","volume":"14","author":"Dzyuba","year":"2014","journal-title":"Reprod. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1095\/biolreprod52.5.982","article-title":"Sperm quality and ascorbic acid concentration in rainbow trout semen are affected by dietary vitamin C: An across-season study","volume":"52","author":"Ciereszko","year":"1995","journal-title":"Biol. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1023\/A:1009253330451","article-title":"Effect of ascorbic acid supplement in vitro onrainbow trout sperm viability","volume":"8","author":"Ciereszko","year":"2000","journal-title":"Aquacult. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1111\/j.1095-8649.2000.tb00271.x","article-title":"Biosynthesis of ascorbic acid by extant actinopterygians","volume":"57","author":"Moreau","year":"2000","journal-title":"J. Fish Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1111\/jfb.12712","article-title":"Pike Esox lucius as an emerging model organism for studies in ecology and evolutionary biology: A review","volume":"87","author":"Forsman","year":"2015","journal-title":"J. Fish Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bone, Q., and Moore, R.H. (2008). Biology of Fishes, Taylor & Francis Group.","DOI":"10.1201\/9781134186310"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1095-8649.1976.tb03906.x","article-title":"The reproductive biology of Scleropages formosus (M\u00fcller & Schlegel) (Osteoglossomorpha, Osteoglossidae) in Malaya, and the morphology of its pituitary gland","volume":"8","author":"Scott","year":"1976","journal-title":"J. Fish Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/icb\/44.5.333","article-title":"Evolution and phylogeny of gonad morphology in bony fishes","volume":"44","author":"Parenti","year":"2004","journal-title":"Integr. Comp. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2174\/157015909787602823","article-title":"Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options","volume":"7","author":"Uttara","year":"2009","journal-title":"Curr. Neuropharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Abele, D., Vazquez-Medina, J.P., and Zenteno-Savin, T. (2011). Oxidative Stress in Sharks and Rays. Oxidative Stress in Aquatic Ecosystems, Wiley-Blackwell.","DOI":"10.1002\/9781444345988"}],"container-title":["Fishes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2410-3888\/4\/1\/1\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:23:02Z","timestamp":1760185382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2410-3888\/4\/1\/1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,1]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["fishes4010001"],"URL":"https:\/\/doi.org\/10.3390\/fishes4010001","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/287870","asserted-by":"object"}]},"ISSN":["2410-3888"],"issn-type":[{"value":"2410-3888","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,1]]}}}