SLIT-ROBO Rho GTPase-activating protein 2B (SRGAP2B)

SLIT-ROBO Rho GTPase-activating protein 2B (SRGAP2B) is a human-specific, truncated paralog of SRGAP2A, resulting from a partial segmental duplication event in the SRGAP2 gene family. SRGAP2B encodes a protein largely comprised of the extended F-BAR domain of SRGAP2A but lacks the C-terminal RhoGAP and SH3 domains that mediate direct GTPase regulation and signaling. This results in SRGAP2B being a truncated, likely non-functional variant biochemically, but it retains the ability to affect neuronal cell biology through inhibition of SRGAP2A, altering actin cytoskeleton remodeling and cell migration. SRGAP2B is itself often described as a pseudogene or non-functional copy (labeled as a pseudogene in major databases and protein catalogues). It may participate in the regulation of cortical neuron migration and differentiation indirectly by forming insoluble aggregates with SRGAP2A, and possibly modulates protein turnover by promoting proteasomal degradation, thereby influencing synaptic density during brain development. SRGAP2B does not possess typical activity of enzyme/druggable targets such as GTPase activation/inhibition or receptor function, and there are no known small molecules or drugs targeting this protein. Its primary significance is evolutionary, as part of the gene duplication events that contributed to human cognitive evolution, and in the genetic and molecular study of human brain development. SRGAP2B is not considered a therapeutic target due to its function as a truncated paralog/pseudogene and lack of enzymatic, receptor, or transporter activity.

Other names

SRGAP2BSRGAP2P2SLIT-ROBO Rho GTPase activating protein 2 pseudogene 2SRGAP2L