ADAM22 - ADAM metallopeptidase domain 22 | Elisa - Clia - Antibody - Protein

Background

ADAM22 is a member of the ADAM (A Disintegrin And Metalloprotease domain) family, a group of membrane-anchored proteins structurally akin to snake venom disintegrins. These proteins play roles in of biological processes, orchestrating cell-cell and cell-matrix interactions such as fertilization, muscle development, and neurogenesis. Particularly abundant in the brain, ADAM22 likely serves as an integrin ligand within this organ. Its genetic makeup is subject to alternative splicing, yielding various transcript variants. Notably, ADAM22 exhibits interactions with DLG4, a member of the membrane-associated guanylate kinase (MAGUK) family, further expanding its functional repertoire within neural contexts.

Protein Structure

ADAM22 has a complex 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 is cleaved off to activate the enzyme.
• Metalloprotease Domain: Though it contains this domain, ADAM22 is considered catalytically inactive due to the absence of key residues necessary for protease activity.
• Disintegrin Domain: Facilitates interactions with integrins and other cell surface receptors, contributing to cell adhesion.
• Cysteine-Rich Domain: Contributes to protein 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

ADAM22 belongs to the ADAM family but is unique in that it lacks proteolytic activity. It is categorized as a non-proteolytic ADAM protein due to mutations in the metalloprotease domain that render it inactive.

Function and Biological Significance

ADAM22 is involved in several critical biological functions:

1. Neuronal Development: Plays a crucial role in the development and function of the nervous system.
2. Synaptic Function: Important for synapse formation and maintenance, contributing to neuronal communication.
3. Cell Adhesion: The disintegrin domain facilitates interactions with integrins, promoting cell-cell and cell-matrix adhesion.
4. Signal Transduction: Participates in signaling pathways that regulate neural plasticity and synaptic transmission.

Interactions

ADAM22 interacts with various proteins and cellular components:

1. LGI1: Interacts with the leucine-rich glioma inactivated 1 (LGI1) protein, which is critical for synaptic function and is implicated in epilepsy.
2. Integrins: The disintegrin domain mediates interactions with integrins, affecting cell adhesion and signaling.
3. Neurexins and Neuroligins: May interact with these synaptic cell adhesion molecules, influencing synapse formation and function.
4. Cytoskeletal Proteins: The cytoplasmic tail interacts with cytoskeletal elements, contributing to cell structure and signaling.

Clinical Significance

ADAM22's function and regulation have important implications in various neurological conditions:

1. Epilepsy: Mutations in ADAM22 or its interacting partners, like LGI1, are associated with epilepsy and other seizure disorders.
2. Neurodevelopmental Disorders: Abnormalities in ADAM22 function can lead to neurodevelopmental issues, impacting learning and memory.
3. Neurodegenerative Diseases: Dysregulation of ADAM22 may be involved in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease.
4. Cancer: Though primarily expressed in the nervous system, aberrant expression of ADAM22 has been implicated in certain cancers.

Summary

ADAM22, a member of the ADAM family, is crucial for neural development and synaptic function. Although it contains a metalloprotease domain, it is catalytically inactive, functioning primarily through its disintegrin domain to mediate cell adhesion and signaling. ADAM22 interacts with proteins such as LGI1, integrins, neurexins, and neuroligins. Clinically, ADAM22 is significant in the context of epilepsy, neurodevelopmental disorders, neurodegenerative diseases, and cancer. Understanding its structure, function, interactions, and clinical implications provides valuable insights into its role in the nervous system and potential as a therapeutic target.