A plexin is a protein which acts as a receptor for semaphorin family signaling proteins. It is classically known for its expression on the surface of axon growth cones and involvement in signal transduction to steer axon growth away from the source of semaphorin. Plexin also has implications in development of other body systems by activating GTPase enzymes to induce a number of intracellular biochemical changes leading to a variety of downstream effects. Structure Extracellular All plexins have an extracellular SEMA domain at their N-terminus. This is a structural motif common among all semaphorins and plexins and is responsible for this binding of semaphorin dimers, which are the native conformation for these ligands in vivo. This is followed by alternating plexin, semaphorin, and integrin (PSI) domains and immunoglobulin-like, plexin, and transcription factors (IPT) domains. Each of these is named for the proteins in which their structure is conserved. Collectively, the extracellular region resembles a curved stalk projecting in a clockwise direction. Before bindings its semaphorin dimer ligand, associations between the extracellular domains of pre-formed plexin dimers keeps their intracellular domains segregated and inactive. This allows for co-localization of plexin dimers to be primed for binding of semaphorin dimers and activation of intracellular machinery. Intracellular Highly conserved intracellular domains consisting of a bipartite segment which functions as a GTPase-Activating Protein (GAP). Plexin is the only known receptor molecule to have a GAP domain. In the inactive state, these two sections are separated by a Rho-GTPase binding domain (RBD). When the RBD bind to a Rnd-family Rho-GTPases along with plexin dimerization and semaphoring binding, the intracellular segment undergoes conformational changes which allow the separate GAP domains to interact and become active in turning Rap family Rho-GTPases. These GTPases can have a number of downstream effects, but in particular to Plexin expressed on axonal growth cones, the concentration the secondary messenger cyclic guanosine monophosphate (cGMP) increases within the cell. Classes Nine genes have been identified which divide plexins into four subclasses based on structure and homology. These genes include: Class A: PLXNA1, PLXNA2, PLXNA3, PLXNA4A Class B: PLXNB1, PLXNB2, PLXNB3 Class C: Class D: PLXND1 Class A plexins interact with neuropilin co-receptor proteins to strengthen semaphorin binding interactions without altering the mode of binding. The structure of the Class B plexins has an additional extracellular site for cleavage by convertases, enzymes which modify plexin precursor polypeptides into their final peptide sequence, as well