PROSITE documentation PDOC52071GPN-loop GTPase core domain profile
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GTPases are a large family of GTP-binding and -hydrolyzing enzymes that are widely distributed across all three domains of life. They contain a highly conserved GTPase domain (G domain) housing five fingerprint motifs responsible for coordination of GTP and catalysis: G1 (also P-loop or Walker A motif) interacts with the 5' phosphate moieties of GTP, the G2 and G3 motifs are required for coordination of a magnesium ion essential for catalysis, the latter of which specifically accommodates the5' γ-phosphate of GTP, and G4 and G5 establish specific binding of the nucleotides' guanine base. As GTPases cycle between their GTP and GDP-bound states via their intrinsic GTP hydrolytic activity, they often function as molecular switches differentially regulating a plethora of downstream effector proteins involved in crucial cellular processes.
GPN-loop GTPases are assembly chaperones for RNA polymerase II (Pol II) and other protein complexes. This family of conserved GTPases has been named GPN-loop GTPases due to the presence of a conserved Gly-Pro-Asn motif inserted into the GTPase core-fold. They occur only in Archaea and Eukaryotes, but not in bacteria. Whereas a single GPN protein is found in Archaea, Eukaryotes typically feature three GPN-loop GTPase paralogs, each having a non-redundant essential function in cell: GPN1 (also called Npa3, XAB1, or MBDin), GPN2 and GPN3. These paralogs play essential roles in nuclear localization and biogenesis of Pol II. GPN-loop GTPases from archaea share a closer relation to GPN1 than to GPN2 and GPN3 [1,2,3,4].
GPN-loop GTPases form homo- and heterodimers. They consist of a central GTPase core and a C-terminal tail. The C-terminal tail is poorly conserved among Eukaryotes and is absent in Archaea. The GPN-loop GTPase core harbors motifs G1 to G5 that are required for GTP binding and hydrolysis and consists of a central, 5/6-stranded, parallel β-sheet surrounded by helices (see <PDB:5HCI>). The GPN loop of one monomer protrudes into the active site of the other monomer, where it binds the hydrolyzed GTP γ-phosphate [1,3,4].
The profile we developed covers the GPN-loop GTPase core domain.
Last update:June 2025 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Gras S. Chaumont V. Fernandez B. Carpentier P. Charrier-Savournin F. Schmitt S. Pineau C. Flament D. Hecker A. Forterre P. Armengaud J. Housset D. |
| Title | Structural insights into a new homodimeric self-activated GTPase family. | |
| Source | EMBO. Rep. 8:569-575(2007). | |
| PubMed ID | 17468740 | |
| DOI | 10.1038/sj.embor.7400958 |
| 2 | Authors | Alonso B. Beraud C. Meguellati S. Chen S.W. Pellequer J.L. Armengaud J. Godon C. |
| Title | Eukaryotic GPN-loop GTPases paralogs use a dimeric assembly reminiscent of archeal GPN. | |
| Source | Cell. Cycle. 12:463-472(2013). | |
| PubMed ID | 23324351 | |
| DOI | 10.4161/cc.23367 |
| 3 | Authors | Niesser J. Wagner F.R. Kostrewa D. Muhlbacher W. Cramer P. |
| Title | Structure of GPN-Loop GTPase Npa3 and Implications for RNA Polymerase II Assembly. | |
| Source | Mol. Cell. Biol. 36:820-831(2015). | |
| PubMed ID | 26711263 | |
| DOI | 10.1128/MCB.01009-15 |
| 4 | Authors | Korf L. Ye X. Vogt M.S. Steinchen W. Watad M. van der Does C. Tourte M. Sivabalasarma S. Albers S.-V. Essen L.-O. |
| Title | Archaeal GPN-loop GTPases involve a lock-switch-rock mechanism for GTP hydrolysis. | |
| Source | mBio 14:E0085923-E0085923(2023). | |
| PubMed ID | 37962382 | |
| DOI | 10.1128/mbio.00859-23 |
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