DRG1
Domain
The ThrRS, GTPase, SpoT (TGS) domain is not necessary for GTP binding nor for the GTPase activity. It appears to play a regulatory role favoring GTP hydrolysis mediated by DFRP1/ZC3H15.
Function
Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP (PubMed:23711155, PubMed:29915238, PubMed:37179472). Appears to have an intrinsic GTPase activity that is stimulated by ZC3H15/DFRP1 binding likely by increasing the affinity for the potassium ions (PubMed:23711155). When hydroxylated at C-3 of 'Lys-22' by JMJD7, may bind to RNA and play a role in translation (PubMed:19819225, PubMed:29915238). Binds to microtubules and promotes microtubule polymerization and stability that are required for mitotic spindle assembly during prophase to anaphase transition. GTPase activity is not necessary for these microtubule-related functions (PubMed:28855639).
Involvement in disease
Tan-Almurshedi syndrome
TANALS
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, intellectual deficit, poor or absent speech, failure to thrive, short stature, microcephaly, and craniofacial anomalies.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Sumoylated by UBE2I in response to MEKK1-mediated stimuli.
Phosphorylated at Thr-100 by STK16.
Hydroxylated (with S stereochemistry) at C-3 of Lys-22 by JMJD7; this modification hinders trypsin-catalyzed proteolysis in vitro.
Polyubiquitinated; this modification induces proteolytic degradation and is impaired by interaction with ZC3H15.
Sequence Similarities
Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family.
Tissue Specificity
High levels in skeletal muscle, heart, and kidney. Intermediate levels in liver, placenta and brain. Low levels in colon, thymus, spleen, small intestine, lung and leukocytes.
Cellular localization
- Nucleus
- Cytoplasm
- The DRG1-ZC3H15/DFRP1 complex associates with polysomes.
Alternative names
NEDD3, DRG1, Developmentally-regulated GTP-binding protein 1, DRG-1, Neural precursor cell expressed developmentally down-regulated protein 3, Translation factor GTPase DRG1, NEDD-3, TRAFAC GTPase DRG1