Sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1)
The protein contains 1023 amino acids for an estimated molecular weight of 112896 Da.
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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Biological Process
Cardiac muscle cell action potential involved in contraction
Cardiac muscle contraction
Cell communication by electrical coupling involved in cardiac conduction
Cellular potassium ion homeostasis
Cellular response to mechanical stimulus
Cellular response to steroid hormone stimulus
Cellular sodium ion homeostasis
Ion transmembrane transport
Membrane hyperpolarization
Membrane repolarization
Membrane repolarization during cardiac muscle cell action potential
Negative regulation of glucocorticoid biosynthetic process
Negative regulation of heart contraction
Positive regulation of heart contraction
Positive regulation of striated muscle contraction
Potassium ion import
Potassium ion import across plasma membrane
Proton transmembrane transport
Regulation of blood pressure
Regulation of cardiac conduction
Regulation of cardiac muscle cell contraction
Regulation of sodium ion transport
Regulation of the force of heart contraction
Relaxation of cardiac muscle
Response to drug
Response to glycoside
Sodium ion export across plasma membrane
Transmembrane transport
Cellular Component
Apical plasma membrane
Basolateral plasma membrane
Caveola
Endoplasmic reticulum
Endosome
Extracellular exosome
Extracellular vesicle
Golgi apparatus
Integral component of membrane
Intercalated disc
Lateral plasma membrane
Melanosome
Membrane
Membrane raft
Myelin sheath
Obsolete cell
Organelle membrane
Photoreceptor inner segment membrane
Plasma membrane
Postsynaptic density
Protein complex
Protein-containing complex
Sarcolemma
Sodium:potassium-exchanging ATPase complex
Sperm flagellum
T-tubule
Vesicle
Molecular Function
ADP binding
Ankyrin binding
ATP binding
Chaperone binding
P-type sodium:potassium-exchanging transporter activity
Phosphatase activity
Phosphatidylinositol 3-kinase binding
Potassium ion binding
Potassium transmembrane transporter activity, phosphorylative mechanism
Protein domain specific binding
Protein heterodimerization activity
Protein kinase binding
Sodium ion binding
Steroid hormone binding
The reference OMIM entry for this protein is 182310
Atpase, na+/k+ transporting, alpha-1 polypeptide; atp1a1
Sodium-potassium-atpase, alpha-1 polypeptide
Na,k-atpase, alpha-a catalytic polypeptide
DESCRIPTION
The ATP1A1 gene encodes the alpha-1 isoform of the Na(+),K(+)-ATPase (EC 3.6.1.9), an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. As these gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle, the enzyme plays an essential role in cellular physiology. It is composed of at least 2 subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta) (ATP1B1; 182330). ATP1A1 and ATP1A2 (182340) are isoforms of the catalytic subunit. Kidney contains predominantly ATP1A1, whereas both subunits are found in brain, adipose tissue, and skeletal muscle (summary by Shull and Lingrel, 1987).CLONING
Shull and Lingrel (1987) identified separate genes encoding the alpha (ATP1A1) and alpha(+) (ATP1A2; 182340) isoforms. In addition, they isolated 2 other genes, termed alpha-C (ATP1A3; 182350) and alpha-D (ATP1A4; 607321), one of which is physically linked to the ATP1A2 gene; these genes showed nucleotide and deduced amino acid homology to the catalytic subunit cDNA sequences but did not correspond to any previously identified isoforms. Chehab et al. (1987) cloned from human placenta a 2.2-kb clone comprising a major portion of the coding sequence of the alpha subunit. They found that its sequence was identical to that encoding the alpha subunit of the human kidney and HeLa cells. Southern blot analysis revealed a RFLP.MAPPING
Kent et al. (1987) used a panel of mouse-hamster somatic cell hybrids and restriction fragment length polymorphisms between 2 mouse species (Mus musculus and Mus spretus) to determine the chromosomal localization of genes encoding the alpha and beta subunits of Na,K-ATPase. Three isoforms of the alpha subunit mapped to 3 different chromosomes: alpha-1 to mouse chromosome 3; alpha-2 to mouse chromosome 7; and alpha-3 to mouse chromosome 1. The beta-subunit gene mapped to the same region of chromosome 1 but was not tightly linked to the alpha-3 gene. Sverdlov et al. (1987) demonstrated intra-individual RFLPs in DNA isolated from different tissues of mouse, rabbit, and humans. They suggested that these tissue-specific RFLPs could be the result of rearrangements in the gene loci for the alpha and beta subunits of ATPase. By hybridization to flow-sorted chromosomes and by in situ hybridization, Chehab et al. (1987) showed that the gene for the alpha subunit is on chromosome 1p13-p11. Yang-Feng et al. (1988) assigned the ATP1A1 gene to 1p21-cen by Southern analysis of DNA from panels of rodent/human somatic cell hybrid lines. The gene for this type of alpha chain appears to be expressed in most tissues.MOLECULAR GENETICS
Based on observations that the ATP1A1 and NKCC2 (SLC12A1; 600839) genes interactively increase susceptibility to hypertension in the Dahl salt-sensitive hypertensive rat model, Glorioso et al. (2001) genotyped a relatively genetically homogeneous cohort in northern Sardinia to find whether parallel molecular genetic mechanisms exist in human essential hypertension. Their data indicated that ATP1A1 and NKCC2 are candidate interacting hypertension susceptibility loci in human essential hypertension. - Somatic Mutation Beuschlein et al. (2013) performed exome sequencing of aldosterone-producing adenomas and identified somatic hot ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: comparative model for a membrane protein was added.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 182310 was added.