Active breakpoint cluster region-related protein is a protein that in humans is encoded by the ABR gene.
Gene The ABR activator of RhoGEF and GTPase, also symbolized as ABR, gene has a reported 13 alternatively spliced transcript variants. This gene is found to have ubiquitous expression within 23 human tissues, including the heart and brain. The protein encoded by ABR shares homology with the Breakpoint Cluster Region (BCR) gene located on chromosome 22 and has shown to share similar protein functions.
Function
The protein encoded by this gene contains a GTPase-activating protein domain, a domain found in members of the Rho family of GTP-binding protein. They are selective for Rac. Despite their "GTPase-activating" domain they actually reduce the activity of Rac. They keep mature innate immune system cells from becoming overactive.
The ABR is an inhibitor of ras-related C3 botulinum toxin substrate 1 (RAC1), a protein found to influence cell growth, motility of the cell, and maintain adhesion to neighboring epithelial cells. Recent papers suggest ABR has tumor suppressor properties in leukemia because of its role as a RAC1 inhibitor and is being researched as a potential therapy treatment in leukemia patients. Other studies suggest ABR plays an important role in vestibular morphogenesis.
Knockout phenotype Double-knockout of ABR and BCR in vitro causes macrophage overactivation. Double-knockout of ABR and BCR in mice lead to dysfunctional astroglia and abnormal postnatal development of the cerebellum.
Single ABR and single BCR knockout mice are each more sensitive to intraperitoneal LPS than normal mice and recover more slowly. Double knockout mice failed to make any recovery and all died within 2 days.
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