ATP1B3 - ATPase Na+/K+ transporting subunit beta 3 |Elisa - Clia - Antibody - Protein

Background

The ATPase Na+/K+ transporting subunit beta 3 (ATP1B3) is a critical protein involved in maintaining cellular ionic balance through the sodium-potassium (Na+/K+) pump, an essential enzyme for cellular homeostasis. ATP1B3 is one of the beta subunits of this Na+/K+-ATPase complex, which actively transports sodium (Na+) out of cells and potassium (K+) into cells against their concentration gradients using energy from ATP hydrolysis. The proper functioning of this pump is vital for generating the membrane potential, controlling cell volume, and enabling various cellular processes such as nerve impulse transmission, muscle contraction, and maintaining cell polarity. ATP1B3 is expressed in many tissues, particularly in those involved in high rates of ion transport, such as neural, cardiac, and renal tissues.

Protein Structure

The ATP1B3 protein structure is crucial to its function within the Na+/K+-ATPase complex. ATP1B3, as a beta subunit, primarily has a supportive role in the structural integrity, stability, and regulation of the enzyme. Here’s a closer look at the structural components:

Transmembrane Domain:

• The ATP1B3 protein has a single transmembrane helix that anchors it within the lipid bilayer. This transmembrane region allows the beta subunit to interact closely with the alpha subunit, ensuring a stable and efficient Na+/K+ pump structure.

Extracellular Domain:

• ATP1B3 contains a significant extracellular domain, characterized by multiple glycosylation sites. Glycosylation is essential for protein stability, trafficking, and the regulation of cell adhesion functions. The glycosylated extracellular domain of ATP1B3 also interacts with cell adhesion molecules, contributing to intercellular communication and attachment, particularly in neural and cardiac tissues.

Cytoplasmic Tail:

• ATP1B3 has a short cytoplasmic tail that is involved in interactions with other intracellular proteins, allowing for signaling regulation. This region may be implicated in cellular processes responsive to ion gradients or cellular stress signals.

Alpha-Beta Interaction:

• The ATP1B3 subunit associates closely with the catalytic alpha subunit of the Na+/K+-ATPase complex. This interaction is vital for the correct assembly, stability, and function of the pump. The beta subunit plays a role in determining the kinetic properties and ion affinity of the pump by influencing the alpha subunit.

Classification and Subtypes

The Na+/K+-ATPase is a heterodimeric enzyme complex composed of alpha, beta, and gamma subunits. The beta subunits (including ATP1B3) are classified based on their genetic and structural characteristics and tissue distribution. In the Na+/K+-ATPase complex:

• Alpha Subunit: The catalytic subunit responsible for ATP hydrolysis and ion translocation.
• Beta Subunit: There are multiple isoforms of the beta subunit: ATP1B1, ATP1B2, ATP1B3, and ATP1B4. Each of these isoforms is tissue-specific, with ATP1B3 found in a variety of tissues but highly expressed in cardiac and neural tissues.
• Gamma Subunit (also known as FXYD proteins): Regulatory subunits that fine-tune the enzyme’s response to various physiological conditions, such as changes in intracellular sodium levels.

Function and Biological Significance

The biological significance of ATP1B3 lies in its role as part of the Na+/K+-ATPase complex. ATP1B3 contributes to multiple essential functions:

Ion Homeostasis:

• ATP1B3, through its association with the alpha subunit, helps maintain cellular ion gradients by regulating the transport of Na+ and K+ ions across the plasma membrane. This regulation is critical for cell survival, as it establishes the electrochemical gradient required for cellular activities like nutrient uptake, waste removal, and volume control.

Membrane Potential and Excitability:

• By establishing and maintaining the Na+/K+ gradients, ATP1B3 is indirectly involved in generating membrane potential. This is particularly crucial in excitable cells, such as neurons and muscle cells, where action potentials and signal transmission rely on these ionic gradients.

Cell Adhesion and Signaling:

• The extracellular domain of ATP1B3 interacts with cell adhesion molecules, such as neural cell adhesion molecules (NCAMs). This interaction contributes to cell-cell adhesion and plays a role in tissue organization and the maintenance of epithelial and neuronal structures. Additionally, ATP1B3’s extracellular interactions may facilitate signaling pathways involved in cellular responses to changes in the extracellular environment.

Protein Stabilization and Folding:

• ATP1B3 also has a role in the biosynthesis and stability of the Na+/K+-ATPase complex. The beta subunit assists in the proper folding and assembly of the alpha subunit, ensuring that it reaches the plasma membrane in a functionally active form. Without ATP1B3, the alpha subunit is prone to misfolding and degradation.

Apoptotic Regulation:

• ATP1B3, as part of the Na+/K+ pump, is also implicated in apoptotic signaling. The disruption of Na+/K+ homeostasis can trigger apoptosis, linking ATP1B3 indirectly to programmed cell death pathways. In contexts of cellular stress or ion imbalance, ATP1B3 may thus have a regulatory role in cell survival and apoptosis.

Clinical Issues

Cardiac Disorders:

• ATP1B3, expressed in cardiac tissues, is implicated in cardiac disorders, including arrhythmias and congestive heart failure. Dysregulation or mutations in ATP1B3 can affect the Na+/K+ pump’s ability to maintain ionic balance, leading to impaired cardiac contractility, arrhythmogenesis, and potentially contributing to heart failure.

Neurological Conditions:

• ATP1B3 is significantly expressed in the central nervous system, and disturbances in its function have been linked to neurological disorders. Impaired Na+/K+ pump function can alter neuronal excitability, contributing to neurodegenerative diseases like Alzheimer’s disease and conditions associated with altered synaptic transmission, such as epilepsy. Additionally, ATP1B3 dysfunction may be implicated in mental health conditions that involve ion transport and neurotransmission abnormalities.

Hypertension:

• Changes in the activity or expression of ATP1B3 have been associated with hypertension. The Na+/K+ pump is essential for vascular smooth muscle cell function, and its dysregulation can lead to increased vascular resistance and blood pressure.

Autoimmune Disorders:

• ATP1B3 expression on immune cells has been associated with autoimmune diseases. For example, altered expression of Na+/K+ ATPase has been observed in patients with multiple sclerosis and rheumatoid arthritis, suggesting that ion imbalance might contribute to immune dysregulation and inflammation.

Cancer:

• Dysregulation of ATP1B3 has also been implicated in cancer biology. Na+/K+ ATPase is known to play a role in regulating cell volume and adhesion, and disruptions can lead to altered cell proliferation and metastasis. Altered expression of ATP1B3 has been observed in certain cancer types, potentially impacting cell-cell adhesion and cancer cell invasiveness.

Summary

ATP1B3, the beta 3 subunit of the Na+/K+-ATPase complex, plays a fundamental role in maintaining ion homeostasis and supporting cellular functions related to membrane potential and cell adhesion. Its structure, comprising a transmembrane domain, extracellular glycosylated domain, and cytoplasmic tail, is essential for its function within the Na+/K+ pump and its interactions with other cellular components. ATP1B3’s presence in diverse tissues, including neural and cardiac tissues, underscores its broad physiological significance, particularly in excitable cells.

Clinically, ATP1B3 is implicated in various health conditions, including cardiac arrhythmias, neurological disorders, hypertension, and autoimmune diseases, with potential roles in cancer. Its role in maintaining cellular ion gradients makes it a vital component in excitable tissues, and disruptions in its function can have significant pathological consequences. The study of ATP1B3 continues to provide insights into the complex regulatory networks underlying ion transport, cellular excitability, and intercellular communication, emphasizing its potential as a therapeutic target for conditions involving ion imbalance and cellular signaling.