ABR, RhoGEF and GTPase activating protein
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
Active breakpoint cluster region-related protein is a protein that in humans is encoded by the ABR gene.[5]
Gene
The ABR activator of RhoGEF and GTPase, also symbolized as ABR, gene has a reported 13 alternatively spliced transcript variants.[6] This gene is found to have ubiquitous expression within 23 human tissues, including the heart and brain.[7] 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.[8]
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.[9] Despite their "GTPase-activating" domain they actually reduce the activity of Rac.[8] They keep mature innate immune system cells from becoming overactive.[9]
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.[10] 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.[11] Other studies suggest ABR plays an important role in vestibular morphogenesis.[12]
Knockout phenotype
Double-knockout of ABR and BCR in vitro causes macrophage overactivation.[8] Double-knockout of ABR and BCR in mice lead to dysfunctional astroglia and abnormal postnatal development of the cerebellum.[13]
Single ABR and single BCR knockout mice are each more sensitive to intraperitoneal LPS than normal mice and recover more slowly.[9] Double knockout mice failed to make any recovery and all died within 2 days.[9]
