Git2

GIT2 (G protein-coupled receptor kinase interacting protein 2) is a protein encoded by the GIT2 gene in humans. It is a member of the GIT family of proteins, which are involved in cell signaling and cytoskeletal organization.

Structure

GIT2 is a multidomain protein that contains several functional domains:

• ArfGAP domain: This domain provides GTPase-activating protein (GAP) activity for ADP-ribosylation factor (Arf) proteins, which are small GTPases involved in vesicular trafficking.
• ANK repeats: These are ankyrin repeat motifs that are involved in protein-protein interactions.
• SHD (Spa homology domain): This domain is involved in binding to other proteins, such as paxillin and PIX proteins.
• CC (coiled-coil) domain: This domain facilitates dimerization and interaction with other proteins.

Function

GIT2 plays a crucial role in various cellular processes, including:

• Cell migration: GIT2 is involved in the regulation of cell movement by interacting with paxillin and PIX proteins, which are components of focal adhesions.
• Signal transduction: It acts as a scaffold protein that organizes signaling complexes, particularly those involving G protein-coupled receptors (GPCRs).
• Cytoskeletal dynamics: GIT2 regulates the actin cytoskeleton, influencing cell shape and motility.
• Endocytosis: It is involved in the internalization of GPCRs and other membrane proteins.

Clinical Significance

GIT2 has been implicated in several diseases and conditions:

• Cancer: Altered expression of GIT2 has been observed in various cancers, where it may influence tumor cell migration and invasion.
• Neurological disorders: GIT2 is expressed in the central nervous system and may play a role in neurodegenerative diseases.
• Metabolic disorders: It has been linked to insulin signaling and may be involved in type 2 diabetes.

Interactions

GIT2 interacts with a variety of proteins, including:

• Paxillin: A focal adhesion protein that links GIT2 to the actin cytoskeleton.
• PIX proteins: These are guanine nucleotide exchange factors (GEFs) for Rac and Cdc42, small GTPases involved in actin remodeling.
• GPCR kinases: GIT2 interacts with these kinases, influencing GPCR signaling pathways.

Research Directions

Ongoing research is focused on understanding the precise mechanisms by which GIT2 regulates cellular processes and its potential as a therapeutic target in diseases such as cancer and diabetes.

See Also

• GIT1
• ArfGAP
• Focal adhesion

External Links

• [UniProt entry for GIT2](https://www.uniprot.org/uniprot/Q14161)
• [GeneCards entry for GIT2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=GIT2)

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