The present invention provides proteins comprising immunoglobulin-type binding regions for cell-type specific targeting and Shiga toxin A Subunit effector regions for Shiga toxin effector functions (e.g. cellular internalization, directing subcellular routing, and/or cytotoxicity), wherein the binding regions and Shiga toxin effector regions are combined such that the Shiga toxin effector regions are proximal to the amino-terminals of the proteins. The presently disclosed proteins can comprise additional exogenous materials, such as, e.g., antigens, cytotoxic agents, and detection-promoting agents, and are capable of targeted delivery of these additional exogenous materials into the interiors of target cells. The proteins of the present invention have uses in methods such as, e.g., methods involving targeted killing of target cells, delivering exogenous materials into target cells, labeling subcellular compartments of target cells, and diagnosing and/or treating a variety of conditions including cancers, tumors, other growth abnormalities, immune disorders, and microbial infections.