DRG2 (Developmentally-regulated GTP-binding protein 2) is a translational GTPase of the TRAFAC class, OBG-HflX-like superfamily (DRG/OBG GTPase family). It catalyzes hydrolysis of GTP to GDP, using Mg2+ as cofactor, and belongs to the conserved DRG family of ribosome-associated GTPases. DRG2 is stabilized by and functions together with its DFRP (DRG family regulatory protein) cofactor DFRP2/RWDD1, whose binding protects DRG2 from polyubiquitination and proteolytic degradation. DRG2 is a substrate of the JmjC oxygenase JMJD7, which catalyzes (3S)-lysyl hydroxylation at Lys-21; this modification is associated with RNA binding and a role in translation. DRG2 is found in both the cytoplasm and the nucleus and is most highly expressed in skeletal muscle, heart and kidney. Through its GTPase activity and ribosome/translation association it is implicated in regulation of protein synthesis, and at the cellular level it has been linked to cell proliferation and growth control.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002181 cytoplasmic translation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: DRG2 is a ribosome-associated translational GTPase, so a broad "cytoplasmic translation" process annotation is plausible by phylogenetic inference. Recent work frames DRG2 (with its paralog DRG1) as a translation factor that associates with stalled/paused ribosomes through its DFRP2 partner, but the detailed mechanism (e.g. stimulation of peptidyl transfer) is largely extrapolated from DRG1, bacterial Obg, and yeast Rbg2 orthologs rather than directly demonstrated for human DRG2. The specific regulatory role of human DRG2 in translation therefore remains imprecisely defined, so this broad term is retained as non-core. Reason: DRG/OBG-family GTPases associate with translating ribosomes, but the broad cytoplasmic translation term does not capture a specific mechanism; the informative core is the GTPase activity. The falcon deep-research synthesis supports a ribosome/translation association for DRG2 but the stalled-ribosome rescue mechanism is inferred from paralogs and ortholog structures, so the term is kept non-core in line with handling of broad translation terms for ribosome-associated factors. Supporting Evidence: file:human/DRG2/DRG2-uniprot.txt may bind to RNA and play a role in translation file:human/DRG2/DRG2-deep-research-falcon.md DRG2, in complex with its binding partner DFRP2, associates with ribosomes that have paused or stalled during translation elongation |
| GO:0003924 GTPase activity | IEA GO_REF:0000120 | ACCEPT | Summary: DRG2 hydrolyzes GTP to GDP; GTPase activity is the core molecular function. Electronic transfer here agrees with direct experimental (IDA) evidence. Reason: GTPase activity is experimentally demonstrated and is the defining catalytic function of DRG2. Supporting Evidence: file:human/DRG2/DRG2-uniprot.txt Catalyzes the conversion of GTP to GDP through hydrolysis of |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: DRG2 binds GTP as the substrate for its GTPase activity. GTP binding is a structural prerequisite for, and subordinate to, the catalytic GTPase function. Reason: GTP binding is real but the informative core molecular function is GTPase activity; retained as a supporting non-core annotation. Supporting Evidence: file:human/DRG2/DRG2-uniprot.txt hydrolysis of the gamma-phosphate bond in GTP |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: DRG2 has a documented nuclear pool, consistent with the experimental (IDA) nuclear localization. Reason: Nuclear localization is experimentally supported; DRG2 is both nuclear and cytoplasmic. Supporting Evidence: file:human/DRG2/DRG2-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: DRG2 is cytoplasmic, consistent with its ribosome/translation association and with the experimental (IDA) cytoplasm annotation. Reason: Cytoplasmic localization is experimentally supported and consistent with its function. Supporting Evidence: file:human/DRG2/DRG2-uniprot.txt Cytoplasm |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Interaction with RWDD1/DFRP2 (Q9H446), the DRG-family regulatory cofactor that stabilizes DRG2. The bare protein binding term is uninformative, though this is DRG2's key functional partner; the falcon deep-research synthesis reiterates that DFRP2 binding is essential for DRG2 protein stability and its loss leads to rapid DRG2 degradation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. Supporting Evidence: file:human/DRG2/DRG2-deep-research-falcon.md This interaction is essential for DRG2 stability; loss of DFRP2 leads to rapid degradation of DRG2 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Y2H interactome interaction with RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Interactome interaction with RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary interactome capturing multiple DRG2 interactions including RWDD1/DFRP2 (Q9H446), JMJD7 (P0C870), EIF4A3 (P38919), NAB2 (Q15742) and TSSK3 (Q96PN8). Bare protein binding is uninformative; RWDD1 and JMJD7 are the biologically meaningful partners. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Neurodegeneration interactome capturing DRG2 interactions with SPRED1 (Q7Z699) and JPH3 (Q8WXH2). Bare protein binding is uninformative and these are isolated HT hits. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: BioPlex affinity-purification capturing DRG2-RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Multimodal cell-maps interactome capturing DRG2-RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence cytosolic localization, consistent with DRG2's cytoplasmic site of action. Reason: Direct evidence for cytosolic localization, consistent with function. Independent immunofluorescence shows a cytoplasmic DRG2 pool, and DRG2 is a soluble translation-associated GTPase without membrane or organellar targeting. Supporting Evidence: PMID:29915238 we observed significant co-localization of JMJD7 with DRG1 and DRG2 in both nuclear and cytoplasmic compartments file:human/DRG2/DRG2-uniprot.txt When hydroxylated at C-3 of 'Lys-21' by JMJD7, may bind to RNA and play a role in translation |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9629578 | ACCEPT | Summary: Reactome curated cytosolic localization, consistent with the IDA cytosol annotation. Reason: Correct cytosolic localization. Consistent with the IDA cytosol row; immunofluorescence shows a cytoplasmic DRG2 pool for this soluble GTPase. Supporting Evidence: PMID:29915238 we observed significant co-localization of JMJD7 with DRG1 and DRG2 in both nuclear and cytoplasmic compartments |
| GO:0003723 RNA binding | IDA PMID:29915238 The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxyla... | KEEP AS NON CORE | Summary: DRG2 binds RNA, an activity linked to JMJD7-mediated (3S)-lysyl hydroxylation at Lys-21 and to its translation role. A real but conditional/secondary activity. Reason: RNA binding is experimentally demonstrated but is a hydroxylation-dependent, secondary activity relative to the core GTPase function. Supporting Evidence: file:human/DRG2/DRG2-uniprot.txt When hydroxylated at C-3 of 'Lys-21' by JMJD7, may bind to RNA and play a role in translation |
| GO:0003924 GTPase activity | IDA PMID:29915238 The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxyla... | ACCEPT | Summary: Direct experimental demonstration that DRG2 hydrolyzes GTP. This is the core molecular function. Reason: IDA evidence for GTP hydrolysis establishes GTPase activity as DRG2's core catalytic function. Supporting Evidence: file:human/DRG2/DRG2-uniprot.txt Catalyzes the conversion of GTP to GDP through hydrolysis of |
| GO:0005515 protein binding | IPI PMID:29915238 The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxyla... | REMOVE | Summary: Direct interaction with JMJD7 (P0C870), the JmjC oxygenase that hydroxylates DRG2 at Lys-21. Bare protein binding is uninformative, but this is a biologically meaningful enzyme-substrate interaction. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. Supporting Evidence: file:human/DRG2/DRG2-uniprot.txt Interacts with JMJD7; this interaction is direct |
| GO:0005634 nucleus | IDA PMID:29915238 The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxyla... | ACCEPT | Summary: Direct evidence for nuclear localization of DRG2. Reason: Experimentally supported nuclear pool. Supporting Evidence: PMID:29915238 we observed significant co-localization of JMJD7 with DRG1 and DRG2 in both nuclear and cytoplasmic compartments |
| GO:0005737 cytoplasm | IDA PMID:29915238 The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxyla... | ACCEPT | Summary: Direct evidence for cytoplasmic localization of DRG2. Reason: Experimentally supported cytoplasmic localization, consistent with function. Supporting Evidence: PMID:29915238 we observed significant co-localization of JMJD7 with DRG1 and DRG2 in both nuclear and cytoplasmic compartments |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: DRG2 appeared in a high-throughput NK-cell membrane-proteome dataset. Generic, non-specific localization for a cytosolic/nuclear GTPase. Reason: Generic "membrane" from a high-throughput proteomics survey; uninformative and inconsistent with DRG2's documented cytoplasmic/nuclear localization. The survey itself notes that most identified proteins were not integral membrane proteins. Supporting Evidence: PMID:19946888 The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes. |
| GO:0005525 GTP binding | TAS PMID:7929244 A novel GTP-binding protein which is selectively repressed i... | KEEP AS NON CORE | Summary: Original (1994) identification of DRG2 as a GTP-binding protein. GTP binding is real but subordinate to the GTPase catalytic function. Reason: GTP binding is supported but the informative core MF is GTPase activity; retained as a supporting non-core annotation. Supporting Evidence: PMID:7929244 It contains the five sequence motifs G1-G5 that are conserved in all GTP-binding proteins. |
| GO:0007165 signal transduction | TAS PMID:7929244 A novel GTP-binding protein which is selectively repressed i... | MARK AS OVER ANNOTATED | Summary: A vague legacy "signal transduction" inference from the 1994 paper that identified DRG2 as a GTP-binding protein repressed in SV40-transformed fibroblasts. No specific signaling pathway is established; DRG2 is a translational GTPase, not a classical signaling GTPase. Reason: Over-broad, unsupported by a defined pathway; DRG2's function is as a translational GTPase rather than a signal-transducing GTPase. The source paper only speculates about a growth-control role. Supporting Evidence: PMID:7929244 it may play a role in the expression of the transformed phenotype or in growth control |
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Download this section (compressed HTML)Q: Does human DRG2 physically associate with translating ribosomes (as known for DRG-family GTPases) and at what step does its GTPase cycle act on translation?
Q: How does DFRP2/RWDD1 binding regulate DRG2's GTPase activity, stability, and ribosome association?
Q: What is the functional role of JMJD7-mediated Lys-21 hydroxylation in switching DRG2 between GTPase and RNA-binding/translation activities?
Experiment: Ribosome co-sedimentation / polysome profiling with tagged DRG2 (with and without RWDD1) to test ribosome association and translational state dependence.
Experiment: In vitro GTP-hydrolysis assays of DRG2 alone and in complex with DFRP2/RWDD1 to define cofactor effects on GTPase kinetics.
Experiment: Compare RNA binding and translation phenotypes of wild-type DRG2 versus a Lys-21 hydroxylation-deficient mutant and in JMJD7-knockout cells.
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