{PDOC52071}
{PS52071; GPN_LOOP_GTPASE}
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* GPN-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' gamma-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   beta-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 gamma-phosphate [1,3,4].

The profile we developed covers the GPN-loop GTPase core domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2025 / First entry.

[ 1] 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.
     "Structural insights into a new homodimeric self-activated GTPase
     family."
     EMBO. Rep. 8:569-575(2007).
     PubMed=17468740; DOI=10.1038/sj.embor.7400958
[ 2] Alonso B., Beraud C., Meguellati S., Chen S.W., Pellequer J.L.,
     Armengaud J., Godon C.
     "Eukaryotic GPN-loop GTPases paralogs use a dimeric assembly
     reminiscent of  archeal GPN."
     Cell. Cycle. 12:463-472(2013).
     PubMed=23324351; DOI=10.4161/cc.23367
[ 3] Niesser J., Wagner F.R., Kostrewa D., Muhlbacher W., Cramer P.
     "Structure of GPN-Loop GTPase Npa3 and Implications for RNA Polymerase
     II  Assembly."
     Mol. Cell. Biol. 36:820-831(2015).
     PubMed=26711263; DOI=10.1128/MCB.01009-15
[ 4] 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.
     "Archaeal GPN-loop GTPases involve a lock-switch-rock mechanism for
     GTP  hydrolysis."
     mBio 14:E0085923-E0085923(2023).
     PubMed=37962382; DOI=10.1128/mbio.00859-23

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