Alternative titles; symbols
HGNC Approved Gene Symbol: ATP1B2
Cytogenetic location: 17p13.1 Genomic coordinates (GRCh38): 17:7,646,627-7,657,770 (from NCBI)
The Na+/K+ ATPase is a plasma membrane pump with numerous physiologic functions. It maintains ionic homeostasis that is critical for cell survival, differentiation, and apoptosis. The Na+/K+ ATPase holoenzyme consists of a catalytic alpha subunit (see 182310), a beta subunit, and a modulatory gamma subunit (FXYD2; 601814). Beta subunits, such as ATP1B2, are responsible for formation and structural integrity of the Na+/K+ ATPase holoenzyme (summary by Li et al., 2011).
ATP1B2 is predominantly expressed in brain and preferentially binds to ATP1A2 (182340), which is mainly found in astrocytes after completion of development. The main task of the ATP1A2-ATP1B2 Na+/K+ ATPase in astrocytes is to restore extracellular K+ homeostasis following neuronal depolarization (Mauri et al., 2017).
Martin-Vasallo et al. (1989) isolated cDNA clones from rat brain and human liver encoding a putative isoform of the Na,K-ATPase beta subunit, termed beta-2. The rat cDNA encodes a deduced protein of 290 amino acids with a molecular mass of 33.4 kD. The protein sequence shows 98% sequence identity to the human counterpart.
Gloor et al. (1990) found that the sequence of mouse Amog (adhesion molecular on glia) is 97% identical to the rat Na,K-ATPase beta-2 subunit identified by Martin-Vasallo et al. (1989). Mouse Amog is an integral membrane glycoprotein with a molecular mass of 45-50 kD that is expressed by glial cells and mediates granule neuron migration along Bergmann glial cells in the developing cerebellum. The cDNA sequence of the mouse gene was shown by Pagliusi et al. (1989) to have structural similarity to the beta-1 subunit of Na,K-ATPase (ATP1B1; 182330). Like ATP1B1, AMOG is molecularly associated with the alpha subunit and influences its catalytic activity.
Malo et al. (1990) mapped the beta-2 subunit of sodium-potassium-ATPase in the mouse to chromosome 11 in a segment that is conserved on the pericentromeric region of human chromosome 17. Thus, Malo et al. (1990) speculated that the human ATP1B2 gene is on the proximal short arm or pericentric area of chromosome 17. By somatic cell hybrid analysis, Hsieh et al. (1990) demonstrated that the gene is indeed located on human chromosome 17 and confirmed the assignment to mouse chromosome 11.
By study of recombinant inbred strains, Hsieh et al. (1990) placed the Amog locus close to the genes for zinc finger protein-3 (194480) and the asialoglycoprotein receptor (108360, 108361) in a region of mouse chromosome 11 that is homologous to human 17p.
Gross (2014) mapped the ATP1B2 gene to chromosome 17p13.1 based on an alignment of the ATP1B2 sequence (GenBank AF007876) with the genomic sequence (GRCh37).
Spongy degeneration with cerebellar ataxia is a recessively inherited and genetically heterogeneous neurodegenerative disorder in Malinois dogs, 1 of the 4 varieties of the Belgian Shepherd breed. Using linkage analysis and homozygosity mapping, Mauri et al. (2017) identified an approximately 10.6-Mb critical interval on chromosome 5 in a Malinois family with 4 puppies affected by cerebellar dysfunction and variable neuropathologic findings, including autolysis of the central nervous system and vacuolation of the neuropil. Whole-genome sequencing data from 1 affected puppy revealed a 227-bp SINE insertion within exon 2 of the Atp1b2 gene, including a 15-bp duplication flanking the insertion site. Sanger sequencing confirmed that the insertion was present in all 4 affected puppies from the same family, as well as in an isolated case. The parents of the 4 affected puppies were heterozygous for the insertion. The variant was found in heterozygous state in dogs from 3 of the 4 varieties of Belgian Shepherds, but it was not found outside the Belgian Shepherd breed. The insertion caused aberrant RNA splicing in skin of 1 affected puppy, but all mutant transcripts maintained their reading frame. Immunohistochemical analysis revealed reduced or absent expression of Atp1b2 protein in central nervous system of affected puppies.
Gloor, S., Antonicek, H., Sweadner, K. J., Pagliusi, S., Frank, R., Moos, M., Schachner, M. The adhesion molecule on glia (AMOG) is a homologue of the beta subunit of the Na,K-ATPase. J. Cell Biol. 110: 165-174, 1990. [PubMed: 1688561] [Full Text: https://doi.org/10.1083/jcb.110.1.165]
Gross, M. B. Personal Communication. Baltimore, Md. 4/11/2014.
Hsieh, C.-L., Cheng-Deutsch, A., Gloor, S., Schachner, M., Francke, U. Assignment of Amog (adhesion molecule on glia) gene to mouse chromosome 11 near Zfp-3 and Asgr-1,2 and to human chromosome 17. Somat. Cell Molec. Genet. 16: 401-405, 1990. [PubMed: 1699290] [Full Text: https://doi.org/10.1007/BF01232468]
Li, Y., Yang, J., Li, S., Zhang, J., Zheng, J., Hou, W., Zhao, H., Guo, Y., Liu, X., Dou, K., Situ, Z., Yao, L. N-myc downstream-regulated gene 2, a novel estrogen-targeted gene, is involved in the regulation of Na+/K(+)-ATPase. J. Biol. Chem. 286: 32289-32299, 2011. [PubMed: 21771789] [Full Text: https://doi.org/10.1074/jbc.M111.247825]
Malo, D., Schurr, E., Levenson, R., Gros, P. Assignment of Na,K-ATPase beta-(2)-subunit gene (Atpb-2) to mouse chromosome 11. Genomics 6: 697-699, 1990. [PubMed: 1971252] [Full Text: https://doi.org/10.1016/0888-7543(90)90507-q]
Martin-Vasallo, P., Dackowski, P., Emanuel, J. R., Levenson, R. Identification of a putative isoform of the Na,K-ATPase beta subunit: primary structure and tissue-specific expression. J. Biol. Chem. 264: 4613-4618, 1989. [PubMed: 2538450]
Mauri, N., Kleiter, M., Dietsch, E., Leschnik, M., Hogler, S., Wiedmer, M., Dietrich, J., Henke, D., Steffen, F., Schuller, S., Gurtner, C., Stokar-Regenscheit, N., O'Toole, D., Bilzer, T., Herden, C., Oevermann, A., Jagannathan, V., Leeb, T. A SINE insertion in ATP1B2 in Belgian Shepherd dogs affected by spongy degeneration with cerebellar ataxia (SDCA2). G3 (Bethesda) 7: 2729-2737, 2017. [PubMed: 28620085] [Full Text: https://doi.org/10.1534/g3.117.043018]
Pagliusi, S., Antonicek, H., Gloor, S., Frank, R., Moos, M., Schachner, M. Identification of a cDNA clone specific for the neural adhesion molecule AMOG. J. Neurosci. Res. 22: 113-119, 1989. Note: Erratum: J. Neurosci. Res. 24: 567 only, 1989. [PubMed: 2468782] [Full Text: https://doi.org/10.1002/jnr.490220202]