Cytohesin-1 (CYTH1)

Cytohesin-1 (CYTH1) is a cytoplasmic guanine nucleotide exchange factor primarily for the ADP-ribosylation factor (ARF) family of small GTPases, playing a central role in regulating membrane trafficking and integrin-mediated cell adhesion, especially in immune cells such as lymphocytes and natural killer cells. Structurally, CYTH1 includes an N-terminal coiled-coil domain (involved in dimerization and interaction with scaffolding proteins), a central Sec7 domain (conferring GEF activity), and a C-terminal pleckstrin homology (PH) domain (mediating association with membrane phospholipids). CYTH1 is essential for “inside-out” signaling that activates integrins—critical for immune cell motility, adhesion, and phagocytosis. It also participates in protein sorting, vesicle-mediated transport, and cytoskeletal rearrangements orchestrated by ARF GTPases. Genetic studies indicate that loss-of-function mutations can affect cytokinesis or karyokinesis, with some mouse models showing immune and cell biology phenotypes. Currently, CYTH1 itself is not yet a direct therapeutic drug target, but it is integral to pathways relevant for immune cell activation and migration, and interacts with several protein partners that modulate its role in immune signaling. Note: No approved drugs are known to target CYTH1 directly, and it is not classified as a receptor, enzyme, channel, or transporter in major pharmacological databases. Its role is primarily as a signal mediator via activation of ARF GTPases.

Other names

PSCD1SEC7B2-1D17S811Ecytohesin 1CYTOHESIN-1SEC7 homolog B2-1pleckstrin homology, Sec7 and coiled-coil domains 1

Guanine-nucleotide exchange on ARF1, ARF5, and ARF6 (activation of ARF factors through GDP-GTP exchange); Modulation of integrin activation and adhesion signaling