Second Src homology 3 domain of the RhoGEF kinase, Kalirin
Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.
Jiyao W et al.(2023). "The conserved domain database in 2023.",