Sterile alpha motif

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PDB 1uqv EBI

Sterile alpha motif (SAM) is a type of protein domain that is involved in a wide range of biological processes, including gene expression, development, and cell signaling. SAM domains are found in a variety of eukaryotic proteins and are known for their ability to mediate protein-protein interactions. These interactions are crucial for the assembly of protein complexes that are involved in cellular signaling and the regulation of gene expression.

Structure

The SAM domain is typically around 70 amino acids in length and forms a small helix-turn-helix structure. This compact structure is characterized by the presence of five alpha helices, which are arranged in a small bundle. The SAM domain can bind to other SAM domains, forming homo- or hetero-oligomeric complexes, which is a key feature of its function in mediating protein-protein interactions.

Function

SAM domains are involved in a variety of cellular processes. One of their key roles is in the regulation of gene expression by interacting with components of the transcription machinery. They are also involved in the signal transduction pathways, where they mediate interactions between kinases, phosphatases, and other signaling molecules. In addition, SAM domains play a role in the development and organization of the cytoskeleton, influencing cell shape and motility.

In the context of development, SAM domain-containing proteins are crucial for the proper functioning of signal transduction pathways that govern developmental processes. For example, they are involved in the Eph receptor signaling pathway, which is important for cell migration and axon guidance in the developing nervous system.

Examples

Some well-known proteins that contain SAM domains include:

- Ephrin receptors (Ephs), which are involved in cell communication that guides cell positioning within a variety of tissues. - Polyhomeotic proteins, which are part of the Polycomb-group proteins involved in the regulation of gene expression during development. - SAMD9 and SAMD9L, which are involved in the immune response and have been implicated in certain genetic disorders.

Clinical Significance

Mutations in SAM domain-containing proteins have been linked to a variety of diseases. For example, mutations in the SAMD9 and SAMD9L genes are associated with a spectrum of inherited conditions that affect the bone marrow, skin, and endocrine system. Understanding the function of SAM domains and the proteins that contain them can therefore have significant implications for the diagnosis and treatment of these diseases.

Research

Research into SAM domains continues to uncover their roles in various cellular processes and diseases. Studies are focused on understanding the molecular details of SAM domain interactions and how these interactions influence cellular functions and disease states. This research has the potential to identify new targets for therapeutic intervention in diseases caused by dysregulation of SAM domain-containing proteins.

Sterile alpha motif Resources
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