DLC1
Domain
The SAM domain mediates interaction with EF1A1, and functions as an autoinhibitory regulator of RhoGAP Activity.
The polybasic cluster is required for activation and mediates binding to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) containing membranes.
Function
Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality. Required for growth factor-induced epithelial cell migration; in resting cells, interacts with TNS3 while PTEN interacts with the p85 regulatory subunit of the PI3K kinase complex but growth factor stimulation induces phosphorylation of TNS3 and PTEN, causing them to change their binding preference so that PTEN interacts with DLC1 and TNS3 interacts with p85 (PubMed:26166433). The PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA while the TNS3-p85 complex translocates to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433).
Tissue Specificity
Highest level of expression in the spleen, with rather lower levels in prostate, testis, ovary, small intestine and colon, but none in the thymus.
Cellular localization
- Cytoplasm
- Cell junction
- Focal adhesion
- Membrane
- Peripheral membrane protein
- Colocalizes with EF1A1 at actin-rich regions in the cell periphery.
Alternative names
ARHGAP7, KIAA1723, STARD12, DLC1, Rho GTPase-activating protein 7, Deleted in liver cancer 1 protein, HP protein, Rho-type GTPase-activating protein 7, START domain-containing protein 12, StAR-related lipid transfer protein 12, DLC-1, StARD12