Ecto-ADP-ribosyltransferase 4 (ART4) (ART4)

Ecto-ADP-ribosyltransferase 4 (ART4), also known as the Dombrock blood group carrier protein or CD297, is a glycosylphosphatidylinositol (GPI)-anchored protein primarily expressed on the surface of erythrocytes and various immune cell types (UniProt P49588). Although it belongs to the mono-ADP-ribosyltransferase family, human ART4 is often characterized as a pseudo-enzyme due to variations in its catalytic site, suggesting it may function as a signaling scaffold or ligand rather than a traditional enzyme (NCBI Gene ID 420). The protein is clinically significant as the carrier for the Dombrock blood group system, where specific polymorphisms are responsible for the Doa, Dob, and other antigens that can cause serious transfusion reactions or hemolytic disease of the newborn (PubMed: 10426993). In recent years, ART4 has gained attention in oncology as a potential therapeutic target because of its presence in the tumor microenvironment and its putative role in modulating immune cell activity and evasion (PubMed: 29777158). Therapeutic approaches are currently in the discovery and preclinical stages, focusing on antibody-mediated blocking of the protein to disrupt immune suppression. However, drug development is complicated by its constitutive expression on red blood cells, which raises substantial safety concerns regarding potential hemolytic toxicity.

Other names

CD297ARTC4Dombrock blood group carrier proteinMono-ADP-ribosyltransferase 4DODombrock blood group carrier molecule

Antagonism or antibody-mediated blocking of the protein surface interaction to modulate immune evasion in tumors or to prevent alloimmune reactions in hematologic contexts.