ABCC - ATP binding cassette subfamily C | Elisa - Clia - Antibody - Protein

Background

The ABCC family, a subfamily of the larger ATP-binding cassette (ABC) transporters, comprises a group of proteins that utilize ATP hydrolysis to transport various substrates across cellular membranes. The ABCC subfamily, also known as the multidrug resistance-associated proteins (MRPs), plays vital roles in drug resistance, ion transport, and the efflux of metabolic products.The ABCC subfamily of ATP-binding cassette transporters is essential for the transport of a wide variety of substrates, including drugs, metabolites, and ions. These transporters play crucial roles in multidrug resistance, ion transport, and metabolic processes. Dysregulation or mutations in ABCC proteins can lead to significant clinical conditions, such as cystic fibrosis, multidrug resistance in cancer, and metabolic disorders, underscoring their importance in human health and disease.

Protein Structure

ABCC transporters share common structural features typical of ABC proteins:

• Transmembrane Domains (TMDs): These domains form the pathway through which substrates are transported across the membrane. ABCC proteins usually have 12 or more transmembrane helices.
• Nucleotide Binding Domains (NBDs): These domains bind and hydrolyze ATP to drive the transport process. Each ABCC protein typically has two NBDs.

Some ABCC members have additional regulatory (R) domains that modulate their activity and function.

Classification and Subtypes

The ABCC family includes several important members, with notable examples being:

• ABCC1 (MRP1): Involved in the efflux of organic anions and drugs, contributing to multidrug resistance.
• ABCC2 (MRP2): Plays a role in the transport of conjugated bilirubin and other organic anions into bile.
• ABCC3 (MRP3): Transports bile acids, glucuronides, and other organic anions.
• ABCC4 (MRP4): Involved in the transport of cyclic nucleotides and antiviral drugs.
• ABCC5 (MRP5): Transports cyclic nucleotides and various drugs.
• ABCC6 (MRP6): Associated with the transport of organic anions and related to certain metabolic disorders.
• ABCC7 (CFTR): Functions as a chloride channel and is critical for ion transport in epithelial cells.
• ABCC8 (SUR1) and ABCC9 (SUR2): Regulatory subunits of ATP-sensitive potassium channels involved in insulin secretion and cardiovascular function.

Function and Biological Significance

ABCC transporters have diverse and significant biological roles:

1. Multidrug Resistance: ABCC1 (MRP1) and other MRPs export drugs and toxic compounds out of cells, contributing to chemotherapy resistance in cancer.
2. Ion Transport: ABCC7 (CFTR) regulates chloride and bicarbonate transport in epithelial tissues, critical for maintaining fluid and electrolyte balance.
3. Organic Anion Transport: Various MRPs (e.g., ABCC2, ABCC3) transport conjugated bilirubin, bile acids, and other metabolites, facilitating their excretion.
4. Regulation of Cyclic Nucleotide Levels: ABCC4 and ABCC5 are involved in the efflux of cAMP and cGMP, influencing signal transduction pathways.
5. Insulin Secretion and Cardiovascular Function: ABCC8 and ABCC9 (SUR1 and SUR2) are key components of ATP-sensitive potassium channels, affecting insulin release from pancreatic β-cells and cardiac muscle function.

Interactions

ABCC transporters interact with a variety of molecules and regulatory proteins:

1. Substrate Interaction: They bind and transport a wide range of substrates, including drugs, metabolites, ions, and conjugates.
2. Regulatory Proteins: CFTR (ABCC7) interacts with various regulatory proteins, such as kinases and phosphatases, which modulate its activity.
3. Cofactors: Some ABCC proteins require specific cofactors or accessory proteins for optimal function and regulation.

Clinical Issues

Mutations and dysregulation of ABCC transporters are associated with numerous clinical conditions:

1. Cystic Fibrosis: Mutations in CFTR (ABCC7) cause cystic fibrosis, a severe genetic disorder affecting the respiratory, digestive, and reproductive systems.
2. Dubin-Johnson Syndrome: Mutations in ABCC2 (MRP2) lead to impaired bilirubin transport, causing this liver disorder.
3. Multidrug Resistance in Cancer: Overexpression of ABCC1 (MRP1) and other MRPs contributes to resistance to chemotherapy in various cancers.
4. Pseudoxanthoma Elasticum (PXE): Mutations in ABCC6 (MRP6) result in this connective tissue disorder, characterized by calcification of elastic fibers.
5. Hyperinsulinism: Mutations in ABCC8 (SUR1) can cause congenital hyperinsulinism, leading to persistent hypoglycemia.