MxA/MX1/IFI78K [MD226R]

Interferon-induced GTP-binding protein Mx1 (UniProt P20591; also known as IFI-78K, Interferon-induced protein p78, Interferon-inducible protein p78, Interferon-regulated resistance GTP-binding protein MxA, Myxoma resistance protein 1, Myxovirus resistance 1) is encoded by the MX1 (also known as MX, IFI78) gene (Gene ID 4599) in human. The interferon-inducible myxovirus resistance (Mx) proteins belong to the family of large GTPases and are highly homologous with dynamins within their GTP-binding domain. Mx proteins differ from small GTPases and heterotrimeric G proteins in features such as their large size (70–100 kDa), a relatively low affinity for GTP, and a high intrinsic rate of GTP hydrolysis. Mx proteins contain a highly conserved tripartite GTP-binding motif within the N-terminal G domain, while their less conserved C-terminal half serves different functions such as homooligomerization and association with binding partners. Two distinct regions of human MxA, a central interactive region (amino acids 372–540) and a C-terminal leucine zipper motif (amino acids 564–662), are responsible for intra- and intermolecular interactions. MxA/Mx1 is cytosolic, while two MxB/Mx forms exist, a 78 kDa nuclear form and a 76 kDa cytosolic form lacking the N-terminal nuclear localization signal (NLS). Mx proteins are induced by type I IFNs and possess important antiviral properties. Human MxA and rodent MxB (Mx2), in particular, confer resistance against influenza virus and hantaviruses, including Seoul virus, Puumala virus, Hantaan virus, and Andes virus, in vitro. Human MxB is also reported to inhibit HIV-1 infection by reducing the level of integrated viral DNA.