BCR : BCR activator of RhoGEF and GTPase

Description

The BCR (BCR activator of RhoGEF and GTPase) is a protein-coding gene located on chromosome 22.

The BCR gene provides instructions for making a protein whose function is not completely understood. Studies show that the BCR protein may act as a GTPase activating protein (GAP). GAPs turn off (inactivate) proteins called GTPases, which play an important role in chemical signaling within cells. Often referred to as molecular switches, GTPases can be turned on and off. They are turned on (active) when they are attached (bound) to a molecule called GTP and are turned off when they are bound to another molecule called GDP. The BCR protein inactivates a GTPase known as Rac1 by stimulating a reaction that turns the attached GTP into GDP. Through this activity, the BCR protein helps regulate the movement (migration) and function of cells. The BCR protein can also act as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. BCR's kinase activity is likely involved in regulating signaling within cells, although its exact role is unclear.

BCR protein possesses a distinctive structure with two opposing regulatory functions concerning small GTP-binding proteins. The C-terminal region features a GTPase-activating protein (GAP) domain, which activates GTP hydrolysis by RAC1, RAC2, and CDC42. This acceleration of GTP hydrolysis in RAC1 and CDC42 leads to a decrease in the active, GTP-bound form of these proteins. Conversely, the central Dbl homology (DH) domain acts as a guanine nucleotide exchange factor (GEF) that regulates the GTPases CDC42, RHOA, and RAC1. It promotes the transition of these GTPases from their GDP-bound inactive state to their GTP-bound active form. The amino terminus exhibits an intrinsic kinase activity, suggesting involvement in regulating cellular signaling. BCR acts as a key negative regulator of neuronal RAC1 activity. It also modulates macrophage functions, including CSF1-directed motility and phagocytosis, through the regulation of RAC1 activity. Notably, BCR plays a prominent role as a RHOA GEF in keratinocytes, contributing to focal adhesion formation and keratinocyte differentiation.

BCR is also known as ALL, BCR1, CML, D22S11, D22S662, PHL.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing