ADAM19 - ADAM metallopeptidase domain 19 | Elisa - Clia - Antibody - Protein

Background

ADAM19, or ADAM metallopeptidase domain 19, is a member of the ADAM (a disintegrin and metalloproteinase) family of proteins. These proteins are characterized by their multidomain structure, which includes a metalloproteinase domain responsible for enzymatic activity, a disintegrin domain involved in cell adhesion, and other functional domains such as cysteine-rich and EGF-like domain. ADAM19 is involved in various cellular processes, including cell adhesion, migration, and proteolysis. It has been implicated in the regulation of cell-cell and cell-matrix interactions, as well as in the proteolytic processing of membrane-bound proteins. The exact substrates and biological functions of ADAM19 are still being elucidated, but it is thought to play roles in development, tissue remodeling, and possibly in diseases. ADAM19 has been studied in the context of development, particularly in the central nervous system (CNS). It is expressed in regions of the brain and spinal cord during embryonic development, suggesting potential roles in neural development and circuit formation. Studies in animal models have shown that ADAM19 knockout mice exhibit abnormalities in neural tube closure, indicating its importance in early embryonic development.While the specific roles of ADAM19 in disease pathogenesis are not fully understood, alterations in its expression and activity have been reported in various pathological conditions. Dysregulation of ADAM19 has been observed in cancer, where it may contribute to tumor progression and metastasis by affecting cell adhesion and migration. Additionally, ADAM19 expression has been associated with certain cardiovascular diseases and inflammatory disorders, although further research is needed to fully elucidate its contributions to these conditions.

Protein Structure

ADAM19 features a multi-domain structure typical of the ADAM family:

• Signal Peptide: Directs the nascent protein to the secretory pathway.
• Prodomain: Maintains the enzyme in an inactive form until it reaches its proper cellular location and is cleaved off to activate the enzyme.
• Metalloprotease Domain: Contains the catalytic site with a zinc-binding motif essential for its proteolytic function.
• Disintegrin Domain: Facilitates interactions with integrins and other cell surface receptors, contributing to cell adhesion and signaling.
• Cysteine-Rich Domain: Contributes to the protein’s stability and interactions.
• EGF-Like Domain: Involved in protein-protein interactions.
• Transmembrane Domain: Anchors the protein in the cell membrane.
• Cytoplasmic Tail: Involved in intracellular signaling and interactions with cytoskeletal elements.

Classification and Subtypes

ADAM19 belongs to the ADAM family, which includes proteins with both metalloprotease and disintegrin domains. It is classified under metalloproteases due to its catalytic activity in proteolysis.

Function and Biological Significance

ADAM19 performs several critical functions:

1. Proteolysis: The metalloprotease domain is responsible for cleaving the ectodomains of various transmembrane proteins, a process known as "shedding."
2. Cell Adhesion: The disintegrin domain interacts with integrins, mediating cell-cell and cell-matrix adhesion.
3. Embryonic Development: Essential for proper development of the heart, neural tube, and other tissues during embryogenesis.
4. Neural Development: Involved in the development of the nervous system, including the differentiation and migration of neural cells.
5. Cardiovascular System: Plays a role in the development and maintenance of the cardiovascular system by regulating the shedding of key receptors and ligands.

Interactions

ADAM19 interacts with various proteins and cellular components:

1. Integrins: The disintegrin domain mediates interactions with integrins, affecting cell adhesion and signaling.
2. Growth Factors and Receptors: ADAM19 can shed precursors of growth factors and receptors, modulating their activity and downstream signaling pathways.
3. Extracellular Matrix Proteins: Involved in the remodeling of the extracellular matrix, which is crucial for tissue development and repair.
4. Cytoskeletal Elements: The cytoplasmic tail interacts with components of the cytoskeleton, influencing cell shape and motility.

Clinical Significance

The function and regulation of ADAM19 have significant implications in various diseases and conditions:

1. Cardiovascular Diseases: Dysregulation of ADAM19 activity can lead to cardiovascular defects, given its role in heart development and function.
2. Neurodevelopmental Disorders: Altered ADAM19 activity has been linked to neural developmental issues, impacting brain development and function.
3. Cancer: ADAM19 may play roles in cancer progression and metastasis through its involvement in cell adhesion, migration, and proteolysis.
4. Inflammatory Diseases: ADAM19’s role in shedding inflammatory mediators suggests it may be involved in the regulation of inflammatory responses.
5. Congenital Disorders: Mutations or dysregulation of ADAM19 can result in congenital defects, particularly affecting the cardiovascular and nervous systems.

Summary

ADAM19, a member of the ADAM family, is crucial for processes such as proteolysis, cell adhesion, embryonic development, neural development, and cardiovascular system maintenance. It has a multi-domain structure, including a metalloprotease domain for proteolytic activity and a disintegrin domain for cell adhesion. ADAM19 interacts with integrins, growth factors, receptors, extracellular matrix proteins, and cytoskeletal elements. Clinically, ADAM19 is significant in the context of cardiovascular diseases, neurodevelopmental disorders, cancer, inflammatory diseases, and congenital disorders. Understanding its structure, function, interactions, and clinical implications provides valuable insights into its role in cellular processes and potential as a therapeutic target.