Target Information

Target General Information

Target ID

T86731 (Former ID: TTDR00214)

Target Name

Sodium pump alpha-2 (ATP1A2)

Synonyms

Sodium/potassium-transporting ATPase subunit alpha-2; Sodium/potassium-transporting ATPase alpha2; Sodium pump 2; Na+/K+ ATPase 2; Na(+)/K(+) ATPase alpha-2 subunit; KIAA0778; Alpha(+)Sodium/potassium-transporting ATPase alpha-2 chain

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Gene Name

ATP1A2

Target Type

Literature-reported target

[1]

Function

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, providing the energy for active transport of various nutrients.

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BioChemical Class

Cation transporting ATPase

UniProt ID

AT1A2_HUMAN

EC Number

EC 7.2.2.13

Sequence

MGRGAGREYSPAATTAENGGGKKKQKEKELDELKKEVAMDDHKLSLDELGRKYQVDLSKG
LTNQRAQDVLARDGPNALTPPPTTPEWVKFCRQLFGGFSILLWIGAILCFLAYGIQAAME
DEPSNDNLYLGVVLAAVVIVTGCFSYYQEAKSSKIMDSFKNMVPQQALVIREGEKMQINA
EEVVVGDLVEVKGGDRVPADLRIISSHGCKVDNSSLTGESEPQTRSPEFTHENPLETRNI
CFFSTNCVEGTARGIVIATGDRTVMGRIATLASGLEVGRTPIAMEIEHFIQLITGVAVFL
GVSFFVLSLILGYSWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKNLE
AVETLGSTSTICSDKTGTLTQNRMTVAHMWFDNQIHEADTTEDQSGATFDKRSPTWTALS
RIAGLCNRAVFKAGQENISVSKRDTAGDASESALLKCIELSCGSVRKMRDRNPKVAEIPF
NSTNKYQLSIHEREDSPQSHVLVMKGAPERILDRCSTILVQGKEIPLDKEMQDAFQNAYM
ELGGLGERVLGFCQLNLPSGKFPRGFKFDTDELNFPTEKLCFVGLMSMIDPPRAAVPDAV
GKCRSAGIKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPMSQVNPREAKAC
VVHGSDLKDMTSEQLDEILKNHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVNDSP
ALKKADIGIAMGISGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSN
IPEITPFLLFIIANIPLPLGTVTILCIDLGTDMVPAISLAYEAAESDIMKRQPRNSQTDK
LVNERLISMAYGQIGMIQALGGFFTYFVILAENGFLPSRLLGIRLDWDDRTMNDLEDSYG
QEWTYEQRKVVEFTCHTAFFASIVVVQWADLIICKTRRNSVFQQGMKNKILIFGLLEETA
LAAFLSYCPGMGVALRMYPLKVTWWFCAFPYSLLIFIYDEVRKLILRRYPGGWVEKETYY

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3D Structure

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AlphaFold

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
cGMP-PKG signaling pathway	hsa04022	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
cAMP signaling pathway	hsa04024	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Cardiac muscle contraction	hsa04260	Affiliated Target
Class: Organismal Systems => Circulatory system	Pathway Hierarchy
Adrenergic signaling in cardiomyocytes	hsa04261	Affiliated Target
Class: Organismal Systems => Circulatory system	Pathway Hierarchy
Insulin secretion	hsa04911	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Thyroid hormone synthesis	hsa04918	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Thyroid hormone signaling pathway	hsa04919	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Aldosterone synthesis and secretion	hsa04925	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Aldosterone-regulated sodium reabsorption	hsa04960	Affiliated Target
Class: Organismal Systems => Excretory system	Pathway Hierarchy
Endocrine and other factor-regulated calcium reabsorption	hsa04961	Affiliated Target
Class: Organismal Systems => Excretory system	Pathway Hierarchy
Proximal tubule bicarbonate reclamation	hsa04964	Affiliated Target
Class: Organismal Systems => Excretory system	Pathway Hierarchy
Salivary secretion	hsa04970	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Gastric acid secretion	hsa04971	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Pancreatic secretion	hsa04972	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Carbohydrate digestion and absorption	hsa04973	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Protein digestion and absorption	hsa04974	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Bile secretion	hsa04976	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Mineral absorption	hsa04978	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	3	Degree centrality	3.22E-04	Betweenness centrality	2.20E-08
Closeness centrality	1.27E-01	Radiality	1.09E+01	Clustering coefficient	3.33E-01
Neighborhood connectivity	4.67E+00	Topological coefficient	7.22E-01	Eccentricity	15
Download	Click to Download the Full PPI Network of This Target

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

References

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REF 1

Sodium pump isoform expression in heart failure: implication for treatment. Basic Res Cardiol. 2002;97 Suppl 1:I25-30.

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