Editing Sodium–potassium pump (section)

== Parallel evolution of cardiotonic steroid resistance in vertebrates ==
Several studies have detailed the evolution of cardiotonic steroid resistance of the alpha-subunit gene family of Na/K-ATPase (ATP1A) in vertebrates via amino acid substitutions most often located in the first extracellular loop domain.<ref name=":0">{{Cite journal |last1=Moore |first1=David J. |last2=Halliday |first2=Damien C. T. |last3=Rowell |first3=David M. |last4=Robinson |first4=Anthony J. |last5=Keogh |first5=J. Scott |date=2009-08-23 |title=Positive Darwinian selection results in resistance to cardioactive toxins in true toads (Anura: Bufonidae) |journal=Biology Letters |volume=5 |issue=4 |pages=513–516 |doi=10.1098/rsbl.2009.0281 |issn=1744-9561 |pmc=2781935 |pmid=19465576}}</ref><ref name=":1">Hernández Poveda M (2022) Convergent evolution of neo-functionalized duplications of ATP1A1 in dendrobatid and grass frogs. MS Thesis Dissertation. Universidad de los Andes</ref><ref name=":2">{{Cite journal |last1=Mohammadi |first1=Shabnam |last2=Yang |first2=Lu |last3=Harpak |first3=Arbel |last4=Herrera-Álvarez |first4=Santiago |last5=Rodríguez-Ordoñez |first5=María del Pilar |last6=Peng |first6=Julie |last7=Zhang |first7=Karen |last8=Storz |first8=Jay F. |last9=Dobler |first9=Susanne |last10=Crawford |first10=Andrew J. |last11=Andolfatto |first11=Peter |date=2021-06-21 |title=Concerted evolution reveals co-adapted amino acid substitutions in frogs that prey on toxic toads |journal=Current Biology  |volume=31 |issue=12 |pages=2530–2538.e10 |doi=10.1016/j.cub.2021.03.089 |issn=0960-9822 |pmc=8281379 |pmid=33887183}}</ref><ref>{{Cite journal |last1=Mohammadi |first1=Shabnam |last2=Brodie |first2=Edmund D. |last3=Neuman-Lee |first3=Lorin A. |last4=Savitzky |first4=Alan H. |date=2016-05-01 |title=Mutations to the cardiotonic steroid binding site of Na+/K+-ATPase are associated with high level of resistance to gamabufotalin in a natricine snake |url=https://www.sciencedirect.com/science/article/pii/S0041010116300368 |journal=Toxicon |volume=114 |pages=13–15 |doi=10.1016/j.toxicon.2016.02.019 |pmid=26905927 |issn=0041-0101}}</ref><ref name=":3">{{Cite journal |last1=Mohammadi |first1=Shabnam |last2=Herrera-Álvarez |first2=Santiago |last3=Yang |first3=Lu |last4=Rodríguez-Ordoñez |first4=María del Pilar |last5=Zhang |first5=Karen |last6=Storz |first6=Jay F. |last7=Dobler |first7=Susanne |last8=Crawford |first8=Andrew J. |last9=Andolfatto |first9=Peter |date=2022-08-16 |title=Constraints on the evolution of toxin-resistant Na,K-ATPases have limited dependence on sequence divergence |journal=PLOS Genetics |volume=18 |issue=8 |pages=e1010323 |doi=10.1371/journal.pgen.1010323 |issn=1553-7390 |pmc=9462791 |pmid=35972957 |doi-access=free }}</ref><ref>{{Cite journal |last1=Mohammadi |first1=Shabnam |last2=Özdemir |first2=Halil İbrahim |last3=Ozbek |first3=Pemra |last4=Sumbul |first4=Fidan |last5=Stiller |first5=Josefin |last6=Deng |first6=Yuan |last7=Crawford |first7=Andrew J |last8=Rowland |first8=Hannah M |last9=Storz |first9=Jay F |last10=Andolfatto |first10=Peter |last11=Dobler |first11=Susanne |date=2022-12-06 |title=Epistatic Effects Between Amino Acid Insertions and Substitutions Mediate Toxin resistance of Vertebrate Na+,K+-ATPases |journal=Molecular Biology and Evolution |volume=39 |issue=12 |pages=msac258 |doi=10.1093/molbev/msac258 |issn=0737-4038 |pmc=9778839 |pmid=36472530}}</ref><ref>{{Cite journal |last1=Ujvari |first1=Beata |last2=Mun |first2=Hee-chang |last3=Conigrave |first3=Arthur D. |last4=Bray |first4=Alessandra |last5=Osterkamp |first5=Jens |last6=Halling |first6=Petter |last7=Madsen |first7=Thomas |date=January 2013 |title=Isolation Breeds Naivety: Island Living Robs Australian Varanid Lizards of Toad-Toxin Immunity Via Four-Base-Pair Mutation |journal=Evolution |language=en |volume=67 |issue=1 |pages=289–294 |doi=10.1111/j.1558-5646.2012.01751.x|doi-access=free |pmid=23289579 }}</ref> Amino acid substitutions conferring cardiotonic steroid resistance have evolved independently many times in all major groups of tetrapods.<ref name=":3" /> ATP1A1 has been duplicated in some groups of frogs and neofunctionlised duplicates carry the same cardiotonic steroid resistance substitutions (Q111R and N122D) found in mice, rats and other muroids.<ref>{{Cite journal |last1=Price |first1=Elmer M. |last2=Lingrel |first2=Jerry B. |date=1988-11-01 |title=Structure-function relationships in the sodium-potassium ATPase .alpha. subunit: site-directed mutagenesis of glutamine-111 to arginine and asparagine-122 to aspartic acid generates a ouabain-resistant enzyme |url=https://pubs.acs.org/doi/abs/10.1021/bi00422a016 |journal=Biochemistry |language=en |volume=27 |issue=22 |pages=8400–8408 |doi=10.1021/bi00422a016 |pmid=2853965 |issn=0006-2960}}</ref><ref name=":0" /><ref name=":1" /><ref name=":2" />