GPN-loop GTPase 1 (GPN1)

GPN-loop GTPase 1 (GPN1) is an evolutionarily conserved GTPase characterized by a signature Gly-Pro-Asn (GPN) motif, widely present in eukaryotes and archaea but not in bacteria[1][2]. GPN1 is essential for the assembly and nuclear import of the 12-subunit RNA polymerase II (Pol II) complex. It functions as a molecular chaperone, facilitating the correct assembly of RNA polymerase II by transiently binding hydrophobic peptide regions in newly synthesized polymerase subunits and promoting their proper interface formation upon GTP hydrolysis[1]. Structural studies demonstrate that GPN1 undergoes major conformational changes between its GDP- and GTP-bound states, using a "lock-switch-rock" mechanism to regulate substrate binding and release[2]. Depletion or mutation of GPN1 disrupts polymerase II biogenesis and can result in cytoplasmic accumulation of its key subunits, highlighting its essential role in basic gene expression machinery. Though dysfunctions in GPN1 have been linked to neuromuscular pathologies in humans, and its activity is vital for cell survival in yeast, it is not currently known to be the direct target of therapeutic drugs[1][2]. Note: There are currently no known drugs, mechanisms of action, biomarkers, or specific safety concerns directly associated with targeting GPN1 in the therapeutic context.

Other names

MBDINRPAP4XAB1HUSSY-23MBDinNTPBPATPBD1AMBD2-interacting proteinRNAPII-associated protein 4XPA-binding protein 1RNA polymerase II associated protein 4ATP(GTP)-binding protein