ABCA13 - ATP Binding Cassette Transporter A13 |Elisa - Clia - Antibody - Protein

Background

ABCA13 (ATP-binding cassette subfamily A member 13) is a member of the ATP-binding cassette (ABC) transporter superfamily, a large group of proteins that facilitate the transport of various substrates across cellular membranes. ABCA13, encoded by the ABCA13 gene on chromosome 7p12, is the largest known ABC transporter, with a coding sequence of over 5000 amino acids. Although the precise substrates transported by ABCA13 remain to be fully elucidated, its expression in neural and psychiatric contexts has drawn attention to its potential role in the central nervous system. Emerging studies suggest its involvement in lipid transport, vesicle trafficking, and membrane organization.

ABCA13 is predominantly expressed in the brain, particularly in regions associated with neural activity, such as the hippocampus, cortex, and striatum. It has also been detected in other tissues, including the lungs and liver, albeit at lower levels. Dysregulation of ABCA13 has been implicated in neuropsychiatric conditions, such as schizophrenia, bipolar disorder, and depression.

Protein Structure

Primary Structure:

• ABCA13 is a very large protein, composed of approximately 5,058 amino acids, making it the largest member of the ABCA subfamily.
• The protein is encoded by the ABCA13 gene located on chromosome 7p12.
• The sequence contains characteristic ABC transporter motifs, including conserved ATP-binding domains and multiple transmembrane helices.

Domain Organization:

• ATP-Binding Domains:
• ABCA13 contains two nucleotide-binding domains (NBDs), each harboring Walker A, Walker B motifs, and the ABC signature sequence.
• These domains bind and hydrolyze ATP, providing energy for substrate transport.
• Transmembrane Domains:
• ABCA13 has 12 predicted transmembrane helices organized into two large transmembrane regions.
• These helices are hypothesized to form a substrate-binding channel, allowing the translocation of hydrophobic molecules, potentially lipids or lipid derivatives, across the membrane.
• Regulatory Domains:
• ABCA13 features large cytoplasmic loops and extracellular regions that may contribute to regulatory interactions and substrate specificity.

Post-Translational Modifications:

• Glycosylation: The extracellular regions of ABCA13 are likely glycosylated, which may stabilize the protein or modulate its activity.
• Phosphorylation: Regulatory phosphorylation sites may influence the protein’s function or localization.

Structural Insights:

• ABCA13 shares structural homology with other ABCA family members, such as ABCA1 and ABCA12, which are known to transport lipids. Despite its size, ABCA13’s functional conformation likely undergoes ATP-dependent cyclic changes, alternating between inward- and outward-facing states.

Localization:

• ABCA13 is an integral membrane protein, localized primarily to the plasma membrane or intracellular vesicular compartments in neurons and other cell types.

Classification and Subtypes

Classification:

• ABCA13 belongs to the ABCA subfamily of the ABC transporter superfamily, characterized by its role in lipid transport and cellular homeostasis.
• Unlike other ABCA family members with well-defined substrates (e.g., cholesterol for ABCA1, ceramides for ABCA12), the precise substrates of ABCA13 remain under investigation.

Subtypes:

• There are no distinct subtypes of ABCA13. However, variations in the gene, including single nucleotide polymorphisms (SNPs) and alternative splicing, may result in functional differences.

Function and Biological Significance

Putative Lipid Transport:

• ABCA13 is postulated to mediate the transport of lipids or lipid-like molecules across cellular membranes, based on homology with other ABCA transporters.

Role in Neural Processes:

• High expression of ABCA13 in the brain suggests it may be involved in synaptic vesicle trafficking, neurotransmitter regulation, or membrane remodeling in neurons.
• It may also play a role in maintaining the integrity of lipid rafts, which are critical for signaling pathways in neurons.

Cellular Homeostasis:

• ABCA13 may contribute to the regulation of intracellular vesicles and organelles involved in lipid storage and metabolism.

Developmental Roles:

• ABCA13 expression patterns suggest its involvement in brain development, particularly in regions associated with higher cognitive functions.

Clinical Issues

Neuropsychiatric Disorders:

• Schizophrenia:
• Reduced expression or mutations in ABCA13 have been associated with schizophrenia. Defective lipid transport or synaptic function may contribute to disease pathogenesis.
• Bipolar Disorder and Major Depression:
• Variants in the ABCA13 gene have been linked to susceptibility to these disorders, implicating lipid dysregulation in their molecular mechanisms.
• Mechanisms:
• Impaired ABCA13 function may disrupt neuronal membrane composition, synaptic signaling, or neurotransmitter homeostasis.

Cancer:

• Aberrant expression of ABCA13 has been noted in certain cancers, suggesting a possible role in tumor progression or chemoresistance, although this area requires further research.

Rare Genetic Variants:

• Rare, deleterious mutations in ABCA13 have been identified in genomic studies, with potential links to neurodevelopmental or metabolic disorders.

Potential Biomarker:

• Given its association with neuropsychiatric and possibly oncologic conditions, ABCA13 may serve as a biomarker for diagnostic or prognostic purposes.

Summary

ABCA13, the largest member of the ABC transporter family, plays an essential but not fully understood role in lipid transport and cellular homeostasis. Structurally, it features conserved ATP-binding and transmembrane domains characteristic of ABC transporters, suggesting a function in translocating hydrophobic molecules, potentially lipids, across cellular membranes. Its high expression in the brain and association with psychiatric disorders underscore its significance in neural health, particularly in maintaining synaptic integrity and vesicle trafficking.

Clinically, mutations or dysregulation of ABCA13 have been implicated in schizophrenia, bipolar disorder, and other psychiatric conditions, while emerging evidence suggests potential links to cancer biology. As research continues to elucidate its functions and substrates, ABCA13 may emerge as a critical player in understanding the molecular basis of neuropsychiatric disorders and lipid metabolism, as well as a potential therapeutic target.