Chimerin 1

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Chimerin 1 is a protein that in humans is encoded by the CHN1 gene. It is a member of the chimerin family of non-receptor RhoGAPs (Rho GTPase-activating proteins). Chimerin 1 plays a crucial role in the regulation of the Rho family of GTPases, which are involved in various cellular processes including cytoskeleton organization, cell migration, and cell cycle progression.

Structure

Chimerin 1 contains several important domains that contribute to its function:

• The SH2 domain (Src Homology 2 domain) which allows it to interact with phosphorylated tyrosine residues on other proteins.
• The C1 domain (Cysteine-rich domain) which binds to diacylglycerol (DAG) and phorbol esters, mediating its translocation to the membrane.
• The RhoGAP domain which is responsible for its GTPase-activating function.

Function

Chimerin 1 acts as a GTPase-activating protein (GAP) for Rac1, a member of the Rho family of GTPases. By stimulating the intrinsic GTPase activity of Rac1, Chimerin 1 converts Rac1 from its active GTP-bound form to its inactive GDP-bound form. This regulation is essential for controlling the dynamics of the actin cytoskeleton, which in turn affects cell shape, motility, and growth.

Clinical Significance

Mutations in the CHN1 gene have been associated with Duane retraction syndrome, a congenital eye movement disorder. This condition is characterized by the inability to move the eye outward (abduction) and sometimes inward (adduction), often accompanied by retraction of the eyeball into the socket.

Interactions

Chimerin 1 interacts with several proteins and signaling molecules, including:

• Rac1
• Phosphatidylserine
• Diacylglycerol

These interactions are crucial for its role in modulating the activity of Rac1 and other downstream signaling pathways.

Research

Ongoing research is focused on understanding the broader implications of Chimerin 1 in various cellular processes and its potential role in other diseases. Studies are also exploring the therapeutic potential of targeting Chimerin 1 in diseases characterized by abnormal cell migration and invasion, such as cancer.

See Also

• RhoGAP
• Rac1
• Duane retraction syndrome
• Cytoskeleton