Potassium-transporting ATPase alpha chain 2 (ATP12A)
The protein contains 1039 amino acids for an estimated molecular weight of 115511 Da.
The catalytic subunit of a H(+)/K(+) ATPase and/or Na(+)/K(+) ATPase pump which transports K(+) ions in exchange for Na(+) and/or H(+) ions across the apical membrane of epithelial cells. Uses ATP as an energy source to pump K(+) ions into the cell while transporting Na(+) and/or H(+) ions to the extracellular compartment (PubMed:9774385, PubMed:7485470, PubMed:8853415, PubMed:11341842). Involved in the maintenance of electrolyte homeostasis through K(+) ion absorption in kidney and colon (By similarity). In the airway epithelium, may play a primary role in mucus acidification regulating its viscosity and clearance (PubMed:29391451). (updated: June 2, 2021)
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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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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| Variant | Description |
|---|---|
| dbSNP:rs2289909 |
Biological Process
ATP hydrolysis coupled proton transport
Cellular potassium ion homeostasis
Cellular sodium ion homeostasis
Ion transmembrane transport
Potassium ion homeostasis
Potassium ion import
Potassium ion import across plasma membrane
Proton transmembrane transport
Regulation of pH
Sodium ion export across plasma membrane
Transmembrane transport
The reference OMIM entry for this protein is 182360
Atpase, h+/k+ transporting, nongastric, alpha polypeptide; atp12a
Hydrogen/potassium-exchanging atpase 12a
Atpase, na+/k+ transporting, alpha polypeptide-like 1; atp1al1
Sodium/potassium-atpase, alpha polypeptide-like
CLONING
By screening human kidney and skin cDNA libraries, Grishin et al. (1994) cloned ATP12A, which they called ATP1AL1. The deduced 1,039-amino acid protein has a calculated molecular mass of 114.5 kD. ATP1AL1 has all the features of catalytic subunits of P-type ion-transporting ATPases, including a catalytic phosphorylation site (asp391), components of the ATP-binding site (asp732 and asp736), and 10 potential transmembrane domains spaced throughout the molecule. Highest ATP1AL1 expression was detected in skin. Using immunofluorescence analysis of transfected MDCK canine kidney cells, Reinhardt et al. (2002) showed that human ATP1AL1 localized to the apical plasma membrane when coexpressed with gastric H,K-ATPase beta subunit (ATP4B; 137217).GENE FUNCTION
Grishin and Caplan (1998) showed that the ATP1AL1-ATP4B heterodimer functioned predominantly as an Na,K-ATPase rather than an H,K-ATPase when expressed in transfected HEK293 cells. The Na+ extrusion activity was sensitive to 1 millimolar ouabain, an inhibitor of Na,K-ATPases, but not to 1 micromolar ouabain. Reinhardt et al. (2002) showed that coexpression of ATP1AL1 and ATP4B was necessary for trafficking of the ion pump to the plasma membrane of MDCK cells. In this system, the ATP1AL1-ATP4B dimer functioned as a proton pump. Phorbol ester-mediated activation of protein kinase C (see PRKCA; 176960) led to clathrin (see CLTC; 118955)-dependent internalization and intracellular accumulation of the dimer, leading to reduced proton extrusion capacity. Internalization and inactivation of the ion pump was prevented by a PKC blocker.GENE STRUCTURE
Sverdlov et al. (1996) showed that the ATP1AL1 gene contains 23 exons and spans 32 kb. A CpG island was identified in the 5-prime flanking region and 2 potential polyadenylation signals were found in the 3-prime untranslated region that may function in a tissue-specific manner.MAPPING
An alpha subunit gene for sodium-potassium ATPase of unknown function was isolated by molecular cloning and mapped to 13q21-q31 by Southern analysis of DNA from panels of rodent/human somatic cell hybrids (Yang-Feng et al., 1988). In the CEPH consortium linkage map of chromosome 13 reported by Bowcock et al. (1993), the ATP1AL1 locus was much more proximally situated, being the most centromeric of the expressed genes tested and proximal to ATRC1 at 13q12.3. ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for ATP12A
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 182360 was added.