Serine protease auto-transporters (SPATEs) belong to a group of virulent proteins that are secreted via the type V auto-transporter pathway by pathogenic enterobacteria. Structural analysis shows that proteins in this family have amino acid identities ranging from 35% to 55%, comprising a cleavable N-terminal signal sequence, an internal passenger domain, and a C-terminal translocator domain. N-terminal signal peptides help proteins to transfer SPATEs through inner membrane structure, the structural arrangement of the passenger domain determines the protein’s virulence among other functions, and the C-terminal domain allows secretion of the passenger protein. The linker of all known SPATEs is a conserved 14 amino acid sequence EVNNLNKRMGDLRD, which plays an important role in the protein’s secretion and maturation. Researchers are now focusing on the development of new anti-microbial agents targeting this conserved 14 amino acid sequence. In this review, the special virulent proteins will be discussed by analyzing their structure, transportation, secretion, and virulent functions.