SHANK - SH3 and multiple ankyrin repeat domains 1 | Elisa - Clia - Antibody - Protein

Background

SHANK1 (SH3 and multiple ankyrin repeat domains 1) is a member of the SHANK family of proteins, which play a pivotal role in the organization of the postsynaptic density (PSD) in excitatory synapses. SHANK proteins are essential scaffolding proteins that help in the assembly of various receptors, ion channels, and signaling proteins at the synapse. SHANK1 is predominantly expressed in the brain and is crucial for synaptic structure and function. Disruptions in SHANK1 and other SHANK family members have been linked to various neuropsychiatric disorders, including autism spectrum disorders (ASD), schizophrenia, and intellectual disability.

Protein Structure

The SHANK1 protein consists of several distinct domains that facilitate its role as a scaffolding protein:

• SH3 Domain: Located at the N-terminal, this domain is involved in protein-protein interactions, particularly with proteins containing proline-rich motifs.
• Multiple Ankyrin Repeats: These repeats are responsible for binding to other proteins and are critical for the structural stability of the PSD.
• PDZ Domain: This domain interacts with the C-terminal sequences of other proteins, such as neuroligins and NMDA receptors.
• Proline-rich Region: Located between the PDZ and SAM domains, this region binds to proteins with SH3 domains.
• SAM Domain: The sterile alpha motif (SAM) domain is involved in homo- and hetero-dimerization, aiding in the formation of multimeric protein complexes.

Classification and Subtypes

SHANK1 is one of three SHANK family members, which also includes SHANK2 and SHANK3. These proteins share similar domain structures but differ in their expression patterns and specific functions in the brain. SHANK1 is primarily found in the central nervous system and is highly expressed in the cerebral cortex, hippocampus, and cerebellum.

Function and Biological Significance

SHANK1 serves as a critical scaffolding protein in the PSD of excitatory synapses. Its primary functions include:

• Synaptic Organization: SHANK1 helps organize and stabilize the PSD by interacting with various synaptic proteins, receptors, and signaling molecules.
• Signal Transduction: It plays a role in modulating synaptic signaling pathways by anchoring and clustering receptors and enzymes involved in neurotransmission.
• Synaptic Plasticity: SHANK1 is involved in synaptic plasticity, which is crucial for learning and memory. It participates in the regulation of synaptic strength and the formation of new synapses.

Clinical Issues

Mutations and deletions in the SHANK1 gene have been associated with neuropsychiatric disorders, particularly autism spectrum disorders. Studies have shown that disruptions in SHANK1 function can lead to abnormalities in synaptic structure and function, contributing to the cognitive and behavioral deficits observed in these conditions. Moreover, alterations in SHANK1 expression have been linked to schizophrenia and intellectual disability, further highlighting its importance in normal brain function and development.

Summary

SHANK1 is a vital scaffolding protein in the postsynaptic density of excitatory synapses, playing a crucial role in synaptic organization, signal transduction, and synaptic plasticity. Its structure includes multiple domains that facilitate interactions with a variety of synaptic proteins, enabling it to maintain synaptic stability and function. Disruptions in SHANK1 are associated with several neuropsychiatric disorders, underscoring its significance in brain health and disease. Understanding the molecular mechanisms involving SHANK1 can provide insights into the pathophysiology of these disorders and potential therapeutic targets.