Rho GTPase-activating protein 45 (ARHGAP45)

Rho GTPase-activating protein 45 (ARHGAP45), also known as minor histocompatibility antigen HA-1 (HMHA1), is an enzyme predominantly expressed in hematopoietic cells that serves dual biological roles—as a negative regulator of Rho family small GTPases (especially RHOA, and to a lesser extent RHOC and RAC1), controlling the actin cytoskeleton, cell deformability, chemotaxis, and lymphocyte trafficking; and as the precursor for the immunodominant HA-1 antigen presented by HLA-A molecules. The HA-1 peptide, derived from ARHGAP45, is a minor histocompatibility antigen recognizable by donor T cells after allogeneic stem cell transplantation, mediating both graft-versus-leukemia and graft-versus-host effects. ARHGAP45 contains a BAR domain (membrane binding and autoinhibitory) and a RhoGAP domain. Deficiency in ARHGAP45 impairs T and B cell entry into lymph nodes and hematopoietic progenitor cell engraftment. Aberrant ARHGAP45 expression is linked to increased aggressiveness in certain cancers, such as melanoma[1][2][4][5][6].

Other names

Minor histocompatibility antigen HA-1HMHA1KIAA0223mHag HA-1HLA-HA1histocompatibility (minor) HA-1minor histocompatibility protein HA-1

For immune responses, ARHGAP45-derived antigenic peptide (HA-1) is presented by MHC class I (HLA-A*0201 or others) and recognized by cytotoxic T lymphocytes, leading to immune-mediated cell lysis and influencing graft-versus-host or graft-versus-leukemia reactions[4].