Existing Annotations Review

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...	KEEP AS NON CORE	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: Records the functionally important DRG2-RWDD1/DFRP2 interaction, but the term is uninformative; the regulatory relationship is described in the gene narrative. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16189514 UniProtKB:Q9H446 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.	KEEP AS NON CORE	Summary: Y2H interactome interaction with RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative. Reason: Records the DRG2-RWDD1 interaction but uninformative term; not core. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25416956 UniProtKB:Q9H446
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	KEEP AS NON CORE	Summary: Interactome interaction with RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative. Reason: Records the DRG2-RWDD1 interaction but uninformative term; not core. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28514442 UniProtKB:Q9H446
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	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: Records real interactions (RWDD1, JMJD7) but uninformative term; captured by the regulatory/PTM narrative. Other partners are likely incidental Y2H hits. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:P0C870
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	KEEP AS NON CORE	Summary: Neurodegeneration interactome capturing DRG2 interactions with SPRED1 (Q7Z699) and JPH3 (Q8WXH2). Bare protein binding is uninformative and these are isolated HT hits. Reason: Isolated high-throughput interactions with partners unrelated to DRG2's GTPase/translation function; uninformative term, not core. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32814053 UniProtKB:Q7Z699
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: BioPlex affinity-purification capturing DRG2-RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative. Reason: Records the DRG2-RWDD1 interaction but uninformative term; not core. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q9H446
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	KEEP AS NON CORE	Summary: Multimodal cell-maps interactome capturing DRG2-RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative. Reason: Records the DRG2-RWDD1 interaction but uninformative term; not core. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:Q9H446
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. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0005829 cytosol cellular_component ECO:0000314 IDA
GO:0005829 cytosol	TAS Reactome:R-HSA-9629578	ACCEPT	Summary: Reactome curated cytosolic localization, consistent with the IDA cytosol annotation. Reason: Correct cytosolic localization. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-9629578
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...	KEEP AS NON CORE	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: Records the functionally relevant DRG2-JMJD7 (hydroxylase) interaction, but the term is uninformative; the PTM relationship is captured in the gene narrative. 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: file:human/DRG2/DRG2-goa.tsv GO:0005634 nucleus cellular_component ECO:0000314 IDA PMID:29915238
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: file:human/DRG2/DRG2-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000314 IDA PMID:29915238
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. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0016020 membrane cellular_component ECO:0007005 HDA PMID:19946888
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: file:human/DRG2/DRG2-goa.tsv GO:0005525 GTP binding molecular_function ECO:0000304 TAS PMID:7929244
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. Supporting Evidence: file:human/DRG2/DRG2-goa.tsv GO:0007165 signal transduction biological_process ECO:0000304 TAS PMID:7929244

Core Functions

Translational GTPase of the DRG/OBG family that catalyzes hydrolysis of GTP to GDP (Mg2+-dependent); functions in association with its DFRP2/RWDD1 cofactor and is implicated in regulation of translation.

Molecular Function:

GTPase activity

Cellular Locations:

cytoplasm nucleus

Supporting Evidence:

file:human/DRG2/DRG2-uniprot.txt
Catalyzes the conversion of GTP to GDP through hydrolysis of
file:human/DRG2/DRG2-uniprot.txt
Belongs to the TRAFAC class OBG-HflX-like GTPase

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms.

GO_REF:0000033

Annotation inferences using phylogenetic trees.

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping.

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data.

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods.

PMID:16189514

Towards a proteome-scale map of the human protein-protein interaction network.

PMID:19946888

Defining the membrane proteome of NK cells.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:29915238

The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases.

DRG2 is a TRAFAC GTPase that hydrolyzes GTP, binds RNA, and is a substrate of JMJD7-catalyzed (3S)-lysyl hydroxylation; interacts directly with JMJD7.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

PMID:7929244

A novel GTP-binding protein which is selectively repressed in SV40 transformed fibroblasts.

Original identification of DRG2 as a GTP-binding protein selectively repressed in SV40-transformed fibroblasts.

Reactome:R-HSA-9629578

Reactome cytosolic localization annotation for DRG2.

file:human/DRG2/DRG2-deep-research-falcon.md

Falcon deep research report for DRG2

DRG2, with its paralog DRG1, is reported as a translation factor that associates with stalled/paused ribosomes via its DFRP2 partner; human-specific GTPase biochemistry is largely inferred from DRG1 and ortholog studies.

file:human/DRG2/DRG2-uniprot.txt

UniProt entry P55039 (DRG2_HUMAN), Developmentally-regulated GTP-binding protein 2.

DRG2 is a TRAFAC-class OBG/DRG-family GTPase that hydrolyzes GTP to GDP (Mg2+ cofactor); when hydroxylated at Lys-21 by JMJD7 it may bind RNA and act in translation; stabilized by DFRP2/RWDD1; localizes to cytoplasm and nucleus.

Suggested Experiments

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.

Deep Research

Falcon

(DRG2-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 25 citations 2 artifacts 2026-06-20T06:59:18.594140

Edison artifact artifact-00 (text/markdown)

Edison artifact artifact-01 (text/markdown)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive Research Report: DRG2 (Developmentally-Regulated GTP-Binding Protein 2)

Gene: DRG2
UniProt Accession: P55039
Organism: Homo sapiens (Human)
Protein Classification: TRAFAC class OBG-HflX-like GTPase

Gene Identity Verification

The literature search confirmed that the target gene DRG2 (UniProt P55039) corresponds to the developmentally-regulated GTP-binding protein 2, also designated as Translation Factor GTPase DRG2 (EC 3.6.5.-) (westrip2021developmentallyregulatedgtpases pages 1-3, westrip2021developmentallyregulatedgtpases pages 3-5). This protein is a member of the TRAFAC (translation factor) class of GTPases within the OBG-HflX superfamily and is highly conserved across eukaryotes (westrip2021developmentallyregulatedgtpases pages 1-3, westrip2021developmentallyregulatedgtpases pages 3-5, chakraborty2022thestructure–functionanalysis pages 1-2). Human DRG2 shares 57% sequence identity with its paralog DRG1, and both proteins possess conserved domain architecture including a helix-turn-helix (HTH) domain, a canonical GTPase domain (G-domain) with five characteristic G1-G5 motifs, an S5D2L (ribosomal protein S5 domain 2-like) insertion domain, and a C-terminal TGS (ThrRS, GTPase, SpoT) domain (westrip2021developmentallyregulatedgtpases pages 1-3, westrip2021developmentallyregulatedgtpases pages 3-5).

Primary Molecular Function and Enzymatic Activity

GTPase Activity and Catalytic Mechanism

DRG2 functions primarily as a GTPase that catalyzes the hydrolysis of guanosine triphosphate (GTP) to guanosine diphosphate (GDP) and inorganic phosphate (westrip2021developmentallyregulatedgtpases pages 1-3, chakraborty2022thestructure–functionanalysis pages 1-2). This enzymatic activity is central to its role as a molecular switch, cycling between a GTP-bound "active" state and a GDP-bound "inactive" state. While direct biochemical characterization of human DRG2's GTPase properties is limited, the high sequence conservation with DRG1 strongly suggests that DRG2 possesses potassium-dependent intrinsic GTPase activity, as demonstrated for DRG1 (beljan2022structureandfunction pages 1-2, westrip2021developmentallyregulatedgtpases pages 5-6). Importantly, DRG proteins do not require classical GTPase-activating proteins (GAPs) or guanine nucleotide exchange factors (GEFs) for their catalytic cycle, distinguishing them from many other GTPases (westrip2021developmentallyregulatedgtpases pages 5-6).

Translation Factor Function: Ribosome-Associated Activity

Breakthrough research published in 2024 has established DRG2 and its paralog DRG1 as a new class of general translation factors that promote protein synthesis in stalled or paused ribosomes (jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4, jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7). These studies demonstrate that DRG proteins, including their bacterial orthologs (Obg GTPases), rescue cellular growth and translation defects caused by ribosomal stalling. Specifically, DRG proteins:

Target stalled ribosomes: DRG2, in complex with its binding partner DFRP2, associates with ribosomes that have paused or stalled during translation elongation (jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4, westrip2024rewiringproteinbinding pages 3-6, hawk2024conservedfunctionof pages 4-7).
Stimulate peptidyl transfer: In vitro biochemical assays demonstrate that Obg-GTP (the bacterial DRG ortholog) stimulates peptidyl transfer, the key catalytic function of the ribosome (jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4). This mechanism likely explains how DRG proteins enable stalled ribosomes to resume productive translation rather than triggering ribosome-associated quality control pathways.
Require GTPase activity for function: Mutations in conserved G1 motif residues that abolish GTP hydrolysis activity completely eliminate DRG's ability to rescue translation defects, confirming that catalytic competence is essential for ribosome-associated function (jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7).

Substrate Specificity

The catalytic substrate of DRG2 is GTP, which is hydrolyzed to GDP. However, unlike simple GTPases, DRG2's functional "substrate" in the broader biological sense is the stalled ribosome itself. DRG2 acts on ribosomes that have encountered obstacles during translation elongation, including those paused at rare codons, collided with upstream ribosomes, or stalled due to mRNA secondary structures (jin2024conservedfunctionof pages 1-6, jin2024conservedfunctionof pages 6-9, westrip2024rewiringproteinbinding pages 3-6, hawk2024conservedfunctionof pages 4-7).

Biological Processes and Signaling Pathways

Translation Regulation Pathway

DRG2's primary biological role is in the regulation of cytoplasmic protein translation, specifically in resolving ribosomal pauses and collisions (jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4, jin2024conservedfunctionof pages 6-9, westrip2024rewiringproteinbinding pages 3-6, hawk2024conservedfunctionof pages 4-7). During active translation, ribosomes frequently encounter sequences or conditions that slow elongation. Rather than defaulting to quality control mechanisms that would degrade the nascent peptide and mRNA, DRG2 provides a rescue pathway that allows productive translation to continue. This function positions DRG2 at a critical decision point between productive protein synthesis and activation of ribosome-associated quality control (RQC) pathways (jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 4-7).

The DRG2/DFRP2 complex is proposed to be recruited to collided ribosomes through an interaction with Gcn1, a pathway distinct from DRG1/DFRP1 recruitment (westrip2024rewiringproteinbinding pages 3-6). The RWD domain of DFRP2 may be critical for this Gcn1 interaction, suggesting that the two DRG paralogs have evolved specialized functions in translation quality control despite their sequence similarity (westrip2024rewiringproteinbinding pages 3-6).

Endosomal Trafficking Pathway

In addition to its translation function, DRG2 plays an important role in endosomal membrane trafficking. DRG2 localizes to Rab5-containing early endosomes and regulates the deactivation of Rab5, a critical step required for endosomal maturation and cargo recycling (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2). Loss of DRG2 causes defective Rab5 deactivation, leading to impaired recycling of internalized membrane receptors back to the cell surface (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5).

This trafficking function has been shown to regulate the surface localization of multiple receptors, including:
- PD-L1 (Programmed Death-Ligand 1): DRG2 depletion impairs the recycling of endosomal PD-L1, reducing surface PD-L1 levels despite increased total cellular PD-L1 (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2).
- Transferrin receptor: Previous work cited in recent studies demonstrated that DRG2 loss delays transferrin receptor recycling (choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2).
- EGFR (Epidermal Growth Factor Receptor): DRG2 affects EGFR trafficking and degradation kinetics (choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2).

Immune Checkpoint Regulation

A clinically significant finding from 2024 research demonstrates that DRG2 is required for the efficacy of anti-PD-1 cancer immunotherapy (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5). By controlling PD-L1 recycling to the cell surface, DRG2 determines whether tumor cells can effectively engage PD-1 on T cells to suppress immune responses. Melanoma cells depleted of DRG2 showed reduced surface PD-L1, impaired PD-1 binding, and failed to respond to anti-PD-1 therapy in mouse models. Importantly, cohort analysis of melanoma patients revealed that those with low DRG2 protein levels were resistant to anti-PD-1 therapy, identifying DRG2 as a potential biomarker for immunotherapy response (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2).

Post-Translational Modification Pathway

DRG2 undergoes (3S)-lysyl hydroxylation at a conserved lysine residue (Lys21 in human DRG2, Lys22 in DRG1) catalyzed by the 2-oxoglutarate and Fe(II)-dependent oxygenase JMJD7 (markolovic2018thejumonjicoxygenase pages 1-3, markolovic2018thejumonjicoxygenase pages 5-6, markolovic2018thejumonjicoxygenase pages 8-10). This represents a rare post-translational modification that enhances DRG2's ability to bind RNA. Mass spectrometric analyses identified DRG2 as an activity-dependent JMJD7 interactor, and amino acid analysis confirmed (3S)-stereochemistry of the hydroxylated lysine (markolovic2018thejumonjicoxygenase pages 1-3, markolovic2018thejumonjicoxygenase pages 5-6). JMJD7 knockdown reduced DRG2's RNA-binding affinity, while mutation of the hydroxylation site (K21) also impaired RNA interaction, localizing the RNA-binding function to the HTH domain (markolovic2018thejumonjicoxygenase pages 8-10). Notably, this modification does not significantly alter DRG2 protein stability, DFRP2 binding, or intrinsic GTPase activity, but specifically modulates nucleic acid interactions (markolovic2018thejumonjicoxygenase pages 8-10).

Subcellular Localization

DRG2 exhibits dynamic subcellular localization reflecting its multiple cellular functions:

Cytoplasm: DRG2 predominantly localizes to the cytoplasm, where it co-localizes with its obligate binding partner DFRP2 (westrip2024rewiringproteinbinding pages 1-3, westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6).
Ribosome-associated: DRG2 associates with stalled or collided cytoplasmic ribosomes. Structural studies of the yeast ortholog (Rbg2) indicate that DRG proteins contact the 60S ribosomal subunit through their HTH and GTPase domains, while the S5D2L domain interacts with the A-site tRNA (westrip2021developmentallyregulatedgtpases pages 3-5).
Endosomal compartments: DRG2 localizes to Rab5-positive early endosomes, where it carries out its endosomal trafficking function (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2).
Nuclear and cytoplasmic: Confocal microscopy studies examining JMJD7-DRG2 interactions observed significant co-localization in both nuclear and cytoplasmic compartments, though the functional significance of nuclear localization remains unclear (markolovic2018thejumonjicoxygenase pages 1-3, markolovic2018thejumonjicoxygenase pages 5-6).

The compartmentalization of DRG2 function—translation regulation at the ribosome, membrane trafficking at endosomes—suggests that cellular localization is dynamically regulated to coordinate these distinct activities.

Protein-Protein Interactions and Structural Features

Key Binding Partners

Interacting Partner/Domain	Interaction Details/Function	Structural/Binding Information	Key Citations
DFRP2 / RWDD1	Cognate obligate binding partner of human DRG2; stabilizes DRG2 protein, prevents degradation, and helps define DRG2-specific functions distinct from DRG1	DFRP2 binds DRG2 specifically in endogenous and ectopic assays; the conserved DFRP domain wraps around DRG proteins and contacts the GTPase and TGS regions; DFRP2 also contains an N-terminal RWD domain, unlike DFRP1, suggesting distinct recruitment/regulatory functions (westrip2024rewiringproteinbinding pages 1-3, westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6)	(westrip2024rewiringproteinbinding pages 1-3, westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6)
JMJD7	2-oxoglutarate/Fe(II)-dependent oxygenase that binds DRG2 and catalyzes (3S)-lysyl hydroxylation, linking DRG2 to post-translational regulation	JMJD7 hydroxylates DRG2 at conserved Lys21 in the N-terminal HTH region; JMJD7 and DRG2 co-localize in nuclear and cytoplasmic compartments; hydroxylation did not consistently alter DRG stability or GTPase activity but promoted RNA binding (markolovic2018thejumonjicoxygenase pages 1-3, markolovic2018thejumonjicoxygenase pages 5-6, markolovic2018thejumonjicoxygenase pages 8-10)	(markolovic2018thejumonjicoxygenase pages 1-3, markolovic2018thejumonjicoxygenase pages 5-6, markolovic2018thejumonjicoxygenase pages 8-10)
Ribosome / stalled or collided ribosomes	Core functional association underlying DRG2’s likely primary role in translation regulation; proposed to help resolve pauses/collisions and promote productive elongation	DRG/DFRP complexes are implicated in recruitment to slowly elongating, stalled, or collided ribosomes; recent work proposes DRG proteins as general translation factors that enhance protein synthesis in stalled ribosomes and stimulate peptidyl transfer; DRG2 is inferred to share the conserved ribosome-directed mechanism with other DRGs (jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4, jin2024conservedfunctionof pages 6-9, westrip2024rewiringproteinbinding pages 3-6, hawk2024conservedfunctionof pages 4-7)	(jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4, jin2024conservedfunctionof pages 6-9, westrip2024rewiringproteinbinding pages 3-6, hawk2024conservedfunctionof pages 4-7)
Gcn1	Proposed factor linking DRG2/DFRP2 to a specific collided-ribosome pathway	DFRP2 may recruit DRG2 to collided ribosomes through a mechanism involving Gcn1; the DFRP2 RWD domain has been proposed as important for this interaction, suggesting pathway specialization relative to DRG1/DFRP1 (westrip2024rewiringproteinbinding pages 3-6)	(westrip2024rewiringproteinbinding pages 3-6)
Rab5	Endosomal trafficking partner; DRG2 regulates Rab5-positive early endosome function and cargo recycling	DRG2 was reported to interact with Rab5 on early endosomes; loss of DRG2 causes defective Rab5 deactivation and impaired endosomal recycling, altering trafficking of receptors such as PD-L1, transferrin receptor, and EGFR (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2)	(choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2)
DNAJC2	Chaperone-network interactor potentially linking DRG2 to co-translational folding or translational quality control	DNAJC2 co-immunoprecipitated with DRG1 and DRG2 in HEK293T cells; authors interpret this as a potential functional link between DRGs and Hsp70/J-domain co-chaperone pathways in translation-associated quality control (piette2021comprehensiveinteractomeprofiling pages 5-8)	(piette2021comprehensiveinteractomeprofiling pages 5-8)
RNA	Likely functional ligand relevant to translation/ribonucleoprotein biology	DRG2 bound RNA affinity columns; mutation of hydroxylated Lys21 reduced RNA affinity, and JMJD7 knockdown also reduced RNA binding, localizing part of the RNA-binding function to the HTH region (markolovic2018thejumonjicoxygenase pages 8-10)	(markolovic2018thejumonjicoxygenase pages 8-10)
DNA	Likely weak or non-specific nucleic-acid interaction inferred from DRG family architecture and paralog studies	DRG family proteins have been reported to bind RNA and DNA non-specifically; DRG architecture includes HTH and S5D2L folds often associated with nucleic-acid interactions, although direct mechanistic evidence for human DRG2-DNA function remains limited (beljan2022structureandfunction pages 1-2, westrip2021developmentallyregulatedgtpases pages 3-5)	(beljan2022structureandfunction pages 1-2, westrip2021developmentallyregulatedgtpases pages 3-5)
HTH domain (N-terminus)	N-terminal regulatory/nucleic-acid interaction domain important for DRG function	Contains the conserved lysine hydroxylated in DRG2 (Lys21); the apex of this HTH motif contributes to RNA binding and is functionally important in DRG family proteins; likely projects outward for molecular interactions (westrip2021developmentallyregulatedgtpases pages 3-5, markolovic2018thejumonjicoxygenase pages 8-10)	(westrip2021developmentallyregulatedgtpases pages 3-5, markolovic2018thejumonjicoxygenase pages 8-10)
G-domain / GTPase domain	Catalytic core responsible for GTP binding and hydrolysis, central to DRG2 molecular activity	Contains canonical G1-G5 motifs shared with OBG/HflX-like TRAFAC GTPases; supports intrinsic GTP hydrolysis and participates in DFRP binding; DRG catalytic activity is required for conserved translation-related function (westrip2021developmentallyregulatedgtpases pages 1-3, jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7, westrip2021developmentallyregulatedgtpases pages 5-6)	(westrip2021developmentallyregulatedgtpases pages 1-3, jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7, westrip2021developmentallyregulatedgtpases pages 5-6)
S5D2L insertion domain	Inserted domain implicated in ribosome/tRNA-facing interactions	In yeast ortholog structures, this domain protrudes from the GTPase core and contacts the A-site tRNA; by homology, DRG2 is expected to possess the same fold and likely contributes to ribosome-associated translation control (westrip2021developmentallyregulatedgtpases pages 3-5)	(westrip2021developmentallyregulatedgtpases pages 3-5)
TGS domain (C-terminus)	C-terminal interaction platform involved in partner binding and possibly nucleic-acid-related functions	The TGS domain contributes to DFRP binding in DRG family structures; in related proteins it has also been proposed to participate in nucleic-acid interactions, though this remains less certain for DRG2 specifically (westrip2021developmentallyregulatedgtpases pages 3-5, westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6)	(westrip2021developmentallyregulatedgtpases pages 3-5, westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6)

Table: This table summarizes the best-supported binding partners and structural domains of human DRG2, emphasizing how its interaction network supports roles in translation, endosomal trafficking, and post-translational regulation. It is useful for separating direct evidence from homology-based inference where DRG2-specific structural data remain limited.

DFRP2/RWDD1: DRG2 forms a specific obligate heterodimer with DFRP2 (DRG family regulatory protein 2, also known as RWDD1) (westrip2024rewiringproteinbinding pages 1-3, westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6). This interaction is essential for DRG2 stability; loss of DFRP2 leads to rapid degradation of DRG2, likely via the ubiquitin-proteasome system (westrip2024rewiringproteinbinding pages 1-3, westrip2021developmentallyregulatedgtpases pages 5-6). Unlike the DRG1/DFRP1 complex, where DFRP1 stimulates DRG1 GTPase activity, DFRP2 binding does not enhance DRG1 GTPase activity in biochemical assays, suggesting functional specialization (westrip2024rewiringproteinbinding pages 1-3, westrip2024rewiringproteinbinding pages 3-6). The DFRP2 protein contains an N-terminal RWD domain (absent in DFRP1) and a conserved DFRP domain that wraps around DRG2, contacting both the GTPase and TGS regions (westrip2024rewiringproteinbinding pages 1-3, westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6).

JMJD7: The JmjC-domain containing protein JMJD7 catalyzes the (3S)-lysyl hydroxylation of DRG2 at Lys21 (markolovic2018thejumonjicoxygenase pages 1-3, markolovic2018thejumonjicoxygenase pages 5-6, markolovic2018thejumonjicoxygenase pages 8-10). Proteomics studies using activity-dependent immunoprecipitation identified DRG1 and DRG2 as the primary JMJD7 substrates. This hydroxylation enhances DRG2's ability to bind RNA, potentially modulating its ribosome-associated or other ribonucleoprotein functions (markolovic2018thejumonjicoxygenase pages 8-10).

Ribosome: DRG2 interacts with stalled or collided ribosomes, the central functional interaction underlying its role as a translation factor (jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4, jin2024conservedfunctionof pages 6-9, westrip2024rewiringproteinbinding pages 3-6, hawk2024conservedfunctionof pages 4-7). Recent cryo-EM and biochemical studies with yeast orthologs demonstrate that DRG proteins contact the 60S ribosomal subunit and the A-site tRNA (westrip2021developmentallyregulatedgtpases pages 3-5).

Rab5: DRG2 associates with Rab5 on early endosomes, where it regulates Rab5 deactivation and endosomal cargo sorting (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2).

Gcn1: The DRG2/DFRP2 complex may interact with Gcn1 to achieve recruitment to collided ribosomes, a pathway potentially distinct from DRG1 recruitment mechanisms (westrip2024rewiringproteinbinding pages 3-6).

DNAJC2: DRG2 was identified as a binding partner of DNAJC2, an Hsp70 co-chaperone in the J-domain protein family, potentially linking DRG2 to co-translational protein folding or translational quality control pathways (piette2021comprehensiveinteractomeprofiling pages 5-8).

RNA/DNA: DRG2 binds RNA and DNA non-specifically, with RNA binding localized to the HTH domain and enhanced by JMJD7-mediated lysyl hydroxylation (beljan2022structureandfunction pages 1-2, westrip2021developmentallyregulatedgtpases pages 3-5, markolovic2018thejumonjicoxygenase pages 8-10).

Structural Domains

Function Category	Specific Function	Molecular Mechanism	Evidence/Key Findings	Citations
GTPase activity	DRG2 is a TRAFAC/OBG-family guanine nucleotide hydrolase	Binds GTP through a canonical G domain with conserved G1-G5 motifs and hydrolyzes GTP to GDP; like other DRGs, functions through the GTPase cycle and does not appear to require classical GAPs or GEFs	Reviews of DRG proteins place human DRG2 in the OBG/HflX-like TRAFAC GTPase family and describe conserved G-domain architecture and intrinsic GTP hydrolysis as core biochemical activity (westrip2021developmentallyregulatedgtpases pages 1-3, westrip2021developmentallyregulatedgtpases pages 3-5, chakraborty2022thestructure–functionanalysis pages 1-2)	(westrip2021developmentallyregulatedgtpases pages 1-3, westrip2021developmentallyregulatedgtpases pages 3-5, chakraborty2022thestructure–functionanalysis pages 1-2)
GTPase activity	Substrate specificity: guanine nucleotides, especially GTP	The catalytic substrate is GTP; hydrolysis generates GDP + Pi, consistent with the canonical molecular-switch mechanism of TRAFAC GTPases	DRG1/2 are described as GTP-binding proteins with conserved G motifs; reviews explicitly define DRGs as GTPases cycling between GTP-bound and GDP-bound states (westrip2021developmentallyregulatedgtpases pages 1-3, chakraborty2022thestructure–functionanalysis pages 1-2)	(westrip2021developmentallyregulatedgtpases pages 1-3, chakraborty2022thestructure–functionanalysis pages 1-2)
GTPase activity	Potassium-responsive intrinsic activity is inferred for DRG2 from close paralogy with DRG1	DRG1 has potassium-dependent intrinsic GTPase activity, and the high sequence similarity between DRG1 and DRG2 suggests analogous regulation, though direct biochemical confirmation for DRG2 remains limited	Review literature states DRG1 GTPase activity is strongly stimulated by potassium and notes DRG2 likely behaves similarly because of high sequence conservation, but stops short of direct proof for DRG2 (beljan2022structureandfunction pages 1-2, westrip2021developmentallyregulatedgtpases pages 5-6)	(beljan2022structureandfunction pages 1-2, westrip2021developmentallyregulatedgtpases pages 5-6)
GTPase activity regulation	Regulation by DFRP2/RWDD1	DRG2 forms a specific obligate heterodimer with DFRP2; DFRP2 stabilizes DRG2 protein and is thought to be required for normal function, though unlike DFRP1-DRG1, stimulation of GTPase activity has not been demonstrated for DFRP2	Endogenous and overexpression studies show strict DRG2-DFRP2 pairing; DFRP binding prevents DRG degradation. A 2024 preprint specifically reports that DFRP1 stimulates DRG1 GTPase activity whereas DFRP2 binding does not stimulate DRG1, underscoring functional divergence among paralogous complexes (westrip2024rewiringproteinbinding pages 1-3, westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6)	(westrip2024rewiringproteinbinding pages 1-3, westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6)
Translation function	General translation factor promoting protein synthesis under ribosome pausing/stalling	DRG proteins act on stalled/paused ribosomes to enhance productive translation rather than defaulting to quality-control disposal	2024 studies propose DRG proteins as a new class of general translation factors that promote protein biosynthesis in halted ribosomes across evolution; rescue of growth/translation defects in DRG-deficient yeast and human cells supports a conserved role (jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4, jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7)	(jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4, jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7)
Translation function	Ribosome binding during elongation stress/collision	DRG2/DFRP2 is proposed to associate with collided or slowly elongating ribosomes, potentially via DFRP2-dependent recruitment mechanisms distinct from DRG1/DFRP1	Recent structural/functional synthesis states DRG2/DFRP2 may bind collided ribosomes together with Gcn1, with the DFRP2 RWD domain implicated in this pathway; DRG/DFRP complexes are repeatedly linked to elongation control on slow or stalled ribosomes (westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6)	(westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6)
Translation function	Promotion of peptidyl transfer and stall resolution	GTP-bound DRG/Obg-like proteins enhance ribosome catalytic activity, likely by stimulating peptidyl transfer, thereby helping paused ribosomes resume productive elongation	2024 DRG/Obg work reports that Obg-GTP stimulates peptidyl transfer, the key catalytic function of the ribosome, and that DRG proteins alleviate anisomycin- or poly(A)-induced translational stalling in yeast and human cells (jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4, jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7)	(jin2024conservedfunctionof pages 1-6, hawk2024conservedfunctionof pages 1-4, jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7)
Translation function	Requirement for GTPase activity in translation-associated cellular function	Catalytic competence of the G domain is necessary for ribosome-associated function	Mutations in the conserved G1 motif that impair GTP hydrolysis abolish functional rescue and reduce ribosome association in yeast ortholog studies, supporting a conserved requirement for GTPase activity in DRG-mediated translation control (jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7)	(jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7)
Post-translational modification	JMJD7-mediated (3S)-lysyl hydroxylation of DRG2	JMJD7, a 2-oxoglutarate/Fe(II)-dependent oxygenase, hydroxylates a conserved lysine in the N-terminal HTH region of DRG2 (K21)	Proteomics, cellular co-IP, MS, and peptide assays identified DRG1/2 as JMJD7 substrates and mapped hydroxylation to the conserved N-terminal lysine; JMJD7 and DRG2 co-localize in nuclear and cytoplasmic compartments (markolovic2018thejumonjicoxygenase pages 1-3, markolovic2018thejumonjicoxygenase pages 5-6)	(markolovic2018thejumonjicoxygenase pages 1-3, markolovic2018thejumonjicoxygenase pages 5-6)
Post-translational modification	Functional effect of DRG2 hydroxylation: enhanced RNA interaction rather than altered stability or GTPase activity	The hydroxylated lysine lies in the HTH domain and promotes RNA binding; available data did not show major effects on DRG stability, DFRP binding, or GTPase activity	JMJD7 depletion reduced DRG2 RNA-binding affinity, while hydroxylation-site mutation also impaired RNA interaction; the same study found no consistent change in DRG expression, thermal stability, DFRP association, or GTPase activity (markolovic2018thejumonjicoxygenase pages 8-10)	(markolovic2018thejumonjicoxygenase pages 8-10)
Endosomal trafficking	Regulation of Rab5-positive early endosome function	DRG2 localizes to Rab5-containing early endosomes and promotes Rab5 deactivation, a step needed for endosomal maturation and recycling	Prior work summarized in the 2024 melanoma study states that DRG2 interacts with Rab5 on early endosomes; DRG2 loss causes defects in Rab5 deactivation and endosomal recycling (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2)	(choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2)
Endosomal trafficking	Control of receptor recycling, including PD-L1 and transferrin receptor	By supporting endosomal recycling, DRG2 helps return internalized cargo from endosomes to the plasma membrane; depletion traps cargo intracellularly	The 2024 cancer study reports that DRG2 deficiency impairs recycling of endosomal PD-L1 and lowers its surface abundance despite increased total PD-L1; prior work cited there also linked DRG2 loss to delayed transferrin receptor recycling and altered EGFR trafficking (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2)	(choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5, mani2025regulatorymechanismsand pages 1-2)
Endosomal trafficking / immunobiology	Support of tumor-cell surface PD-L1 localization and anti-PD-1 response	DRG2 promotes recycling of internalized PD-L1 back to the plasma membrane, enabling productive PD-L1:PD-1 interaction	In melanoma models, DRG2 depletion reduced surface PD-L1, impaired PD-1 binding, prevented anti-PD-1-induced expansion of effector-like T cells, and was associated with resistance to anti-PD-1 therapy in patient cohort analysis (choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5)	(choi2024drg2isrequired pages 1-2, choi2024drg2isrequired pages 3-5)

Table: This table summarizes the main experimentally supported molecular functions of human DRG2, emphasizing its GTPase activity, translation-related role on stalled ribosomes, JMJD7-mediated hydroxylation, and endosomal trafficking functions. It is useful for quickly separating firmly supported findings from mechanistic inferences, especially where DRG2 evidence is extrapolated from the closely related DRG1 paralog.

DRG2's multi-domain architecture enables its diverse functions:

HTH domain (N-terminus): Contains the conserved Lys21 hydroxylation site and contributes to RNA binding (westrip2021developmentallyregulatedgtpases pages 3-5, markolovic2018thejumonjicoxygenase pages 8-10).
G-domain (GTPase domain): Contains the canonical G1-G5 motifs that bind and hydrolyze GTP; essential for catalytic activity and ribosome-associated function (westrip2021developmentallyregulatedgtpases pages 1-3, jin2024conservedfunctionof pages 6-9, hawk2024conservedfunctionof pages 4-7, westrip2021developmentallyregulatedgtpases pages 5-6).
S5D2L insertion domain: Projects from the GTPase core and contacts the ribosomal A-site tRNA in structural studies of yeast orthologs (westrip2021developmentallyregulatedgtpases pages 3-5).
TGS domain (C-terminus): Participates in DFRP2 binding and potentially contributes to nucleic acid interactions (westrip2021developmentallyregulatedgtpases pages 3-5, westrip2024rewiringproteinbinding pages 3-6, westrip2021developmentallyregulatedgtpases pages 5-6).

Summary

DRG2 (UniProt P55039) is a ~40 kDa TRAFAC class GTPase that functions primarily as a translation factor, promoting protein synthesis in stalled or paused ribosomes by stimulating peptidyl transfer and preventing premature activation of ribosome-associated quality control pathways. DRG2 catalyzes intrinsic GTP hydrolysis (likely potassium-dependent, by analogy to DRG1) and cycles between GTP-bound and GDP-bound states without requiring classical GAPs or GEFs. The protein functions as an obligate heterodimer with DFRP2/RWDD1, which stabilizes DRG2 and directs it to specific ribosomal contexts, particularly collided ribosomes in association with Gcn1.

Beyond its primary translation function, DRG2 plays important roles in endosomal membrane trafficking by regulating Rab5 deactivation on early endosomes, thereby controlling the recycling of internalized receptors including PD-L1, transferrin receptor, and EGFR. This trafficking function has clinical significance: DRG2 is required for surface localization of PD-L1 and the efficacy of anti-PD-1 cancer immunotherapy, identifying it as a potential biomarker for immunotherapy response.

DRG2 undergoes post-translational (3S)-lysyl hydroxylation at Lys21 by the 2-oxoglutarate-dependent oxygenase JMJD7, which enhances its RNA-binding capacity. The protein localizes predominantly to the cytoplasm but associates with ribosomes during translation and with Rab5-positive endosomes during membrane trafficking.

Structurally, DRG2 comprises an N-terminal HTH domain, a central GTPase domain with conserved G-motifs, an S5D2L insertion domain, and a C-terminal TGS domain. This architecture enables interactions with diverse partners including DFRP2, ribosomes, Rab5, JMJD7, DNAJC2, and nucleic acids, supporting DRG2's roles in coordinating translation, membrane trafficking, and potentially linking these processes to cellular stress responses and immune regulation.

Key Recent Publications:
- Jin & Hawk (2024): Discovery of DRG proteins as conserved general translation factors (doi:10.21203/rs.3.rs-5125626/v1)
- Hawk & Jin (2024): Conserved function in promoting protein synthesis in stalled ribosomes (doi:10.1101/2024.04.20.590341)
- Westrip et al. (2024): Binding specificity in DRG/DFRP complexes (doi:10.1101/2023.05.31.543024)
- Choi et al. (2024): DRG2 regulation of PD-L1 and anti-PD-1 therapy (doi:10.1038/s41420-024-02027-x)
- Westrip et al. (2021): Comprehensive review of DRG structure, function and disease roles (doi:10.1007/s00018-021-03961-0)
- Markolovic et al. (2018): JMJD7-catalyzed lysyl hydroxylation of DRG proteins (doi:10.1038/s41589-018-0071-y)

References

(westrip2021developmentallyregulatedgtpases pages 1-3): Christian A. E. Westrip, Qinqin Zhuang, Charlotte Hall, Charlotte D. Eaton, and Mathew L. Coleman. Developmentally regulated gtpases: structure, function and roles in disease. Cellular and Molecular Life Sciences: CMLS, 78:7219-7235, Oct 2021. URL: https://doi.org/10.1007/s00018-021-03961-0, doi:10.1007/s00018-021-03961-0. This article has 29 citations.
(westrip2021developmentallyregulatedgtpases pages 3-5): Christian A. E. Westrip, Qinqin Zhuang, Charlotte Hall, Charlotte D. Eaton, and Mathew L. Coleman. Developmentally regulated gtpases: structure, function and roles in disease. Cellular and Molecular Life Sciences: CMLS, 78:7219-7235, Oct 2021. URL: https://doi.org/10.1007/s00018-021-03961-0, doi:10.1007/s00018-021-03961-0. This article has 29 citations.
(chakraborty2022thestructure–functionanalysis pages 1-2): Asmita Chakraborty, Sheta Halder, Purvi Kishore, Disha Saha, Sujata Saha, Kunal Sikder, and Arnab Basu. The structure–function analysis of obg‐like gtpase proteins along the evolutionary tree from bacteria to humans. Genes to Cells, 27:469-481, May 2022. URL: https://doi.org/10.1111/gtc.12942, doi:10.1111/gtc.12942. This article has 17 citations and is from a peer-reviewed journal.
(beljan2022structureandfunction pages 1-2): Silvestar Beljan, Kristina Dominko, Antea Talajić, Andrea Hloušek-Kasun, Nikolina Škrobot Vidaček, Maja Herak Bosnar, Kristian Vlahoviček, and Helena Ćetković. Structure and function of cancer-related developmentally regulated gtp-binding protein 1 (drg1) is conserved between sponges and humans. Scientific Reports, Jul 2022. URL: https://doi.org/10.1038/s41598-022-15242-2, doi:10.1038/s41598-022-15242-2. This article has 11 citations and is from a peer-reviewed journal.
(westrip2021developmentallyregulatedgtpases pages 5-6): Christian A. E. Westrip, Qinqin Zhuang, Charlotte Hall, Charlotte D. Eaton, and Mathew L. Coleman. Developmentally regulated gtpases: structure, function and roles in disease. Cellular and Molecular Life Sciences: CMLS, 78:7219-7235, Oct 2021. URL: https://doi.org/10.1007/s00018-021-03961-0, doi:10.1007/s00018-021-03961-0. This article has 29 citations.
(jin2024conservedfunctionof pages 1-6): Hong Jin and Christopher Hawk. Conserved function of drg gtpases to promote protein synthesis in the ribosome. Unknown journal, Dec 2024. URL: https://doi.org/10.21203/rs.3.rs-5125626/v1, doi:10.21203/rs.3.rs-5125626/v1.
(hawk2024conservedfunctionof pages 1-4): Christopher W. Hawk and Hong Jin. Conserved function of drg gtpases in promoting protein synthesis in stalled ribosomes. bioRxiv, Apr 2024. URL: https://doi.org/10.1101/2024.04.20.590341, doi:10.1101/2024.04.20.590341. This article has 1 citations.
(jin2024conservedfunctionof pages 6-9): Hong Jin and Christopher Hawk. Conserved function of drg gtpases to promote protein synthesis in the ribosome. Unknown journal, Dec 2024. URL: https://doi.org/10.21203/rs.3.rs-5125626/v1, doi:10.21203/rs.3.rs-5125626/v1.
(hawk2024conservedfunctionof pages 4-7): Christopher W. Hawk and Hong Jin. Conserved function of drg gtpases in promoting protein synthesis in stalled ribosomes. bioRxiv, Apr 2024. URL: https://doi.org/10.1101/2024.04.20.590341, doi:10.1101/2024.04.20.590341. This article has 1 citations.
(westrip2024rewiringproteinbinding pages 3-6): Christian A. E. Westrip, Stephen J Smerdon, and Mathew L. Coleman. Rewiring protein binding specificity in paralogous drg/dfrp complexes. bioRxiv, Jun 2024. URL: https://doi.org/10.1101/2023.05.31.543024, doi:10.1101/2023.05.31.543024. This article has 3 citations.
(choi2024drg2isrequired pages 1-2): Seong Hee Choi, Muralidharan Mani, Jeonghwan Kim, Wha Ja Cho, Thomas F. J. Martin, Jee Hyun Kim, Hun Su Chu, Won Jin Jeong, Young-Wook Won, Byung Ju Lee, Byungyong Ahn, Junil Kim, Do Yong Jeon, and Jeong Woo Park. Drg2 is required for surface localization of pd-l1 and the efficacy of anti-pd-1 therapy. Cell Death Discovery, May 2024. URL: https://doi.org/10.1038/s41420-024-02027-x, doi:10.1038/s41420-024-02027-x. This article has 8 citations and is from a peer-reviewed journal.
(choi2024drg2isrequired pages 3-5): Seong Hee Choi, Muralidharan Mani, Jeonghwan Kim, Wha Ja Cho, Thomas F. J. Martin, Jee Hyun Kim, Hun Su Chu, Won Jin Jeong, Young-Wook Won, Byung Ju Lee, Byungyong Ahn, Junil Kim, Do Yong Jeon, and Jeong Woo Park. Drg2 is required for surface localization of pd-l1 and the efficacy of anti-pd-1 therapy. Cell Death Discovery, May 2024. URL: https://doi.org/10.1038/s41420-024-02027-x, doi:10.1038/s41420-024-02027-x. This article has 8 citations and is from a peer-reviewed journal.
(mani2025regulatorymechanismsand pages 1-2): Muralidharan Mani, Jeong Woo Park, and Thomas F. J. Martin. Regulatory mechanisms and therapeutic targeting of pd-l1 trafficking and stability in cancer immunotherapy. Cancers, 17:1747, May 2025. URL: https://doi.org/10.3390/cancers17111747, doi:10.3390/cancers17111747. This article has 10 citations.
(markolovic2018thejumonjicoxygenase pages 1-3): Suzana Markolovic, Qinqin Zhuang, Sarah E. Wilkins, Charlotte D. Eaton, Martine I. Abboud, Maximiliano J. Katz, Helen E. McNeil, Robert K. Leśniak, Charlotte Hall, Weston B. Struwe, Rebecca Konietzny, Simon Davis, Ming Yang, Wei Ge, Justin L. P. Benesch, Benedikt M. Kessler, Peter J. Ratcliffe, Matthew E. Cockman, Roman Fischer, Pablo Wappner, Rasheduzzaman Chowdhury, Mathew L. Coleman, and Christopher J. Schofield. The jumonji-c oxygenase jmjd7 catalyzes (3s)-lysyl hydroxylation of trafac gtpases. Jun 2018. URL: https://doi.org/10.1038/s41589-018-0071-y, doi:10.1038/s41589-018-0071-y. This article has 49 citations and is from a highest quality peer-reviewed journal.
(markolovic2018thejumonjicoxygenase pages 5-6): Suzana Markolovic, Qinqin Zhuang, Sarah E. Wilkins, Charlotte D. Eaton, Martine I. Abboud, Maximiliano J. Katz, Helen E. McNeil, Robert K. Leśniak, Charlotte Hall, Weston B. Struwe, Rebecca Konietzny, Simon Davis, Ming Yang, Wei Ge, Justin L. P. Benesch, Benedikt M. Kessler, Peter J. Ratcliffe, Matthew E. Cockman, Roman Fischer, Pablo Wappner, Rasheduzzaman Chowdhury, Mathew L. Coleman, and Christopher J. Schofield. The jumonji-c oxygenase jmjd7 catalyzes (3s)-lysyl hydroxylation of trafac gtpases. Jun 2018. URL: https://doi.org/10.1038/s41589-018-0071-y, doi:10.1038/s41589-018-0071-y. This article has 49 citations and is from a highest quality peer-reviewed journal.
(markolovic2018thejumonjicoxygenase pages 8-10): Suzana Markolovic, Qinqin Zhuang, Sarah E. Wilkins, Charlotte D. Eaton, Martine I. Abboud, Maximiliano J. Katz, Helen E. McNeil, Robert K. Leśniak, Charlotte Hall, Weston B. Struwe, Rebecca Konietzny, Simon Davis, Ming Yang, Wei Ge, Justin L. P. Benesch, Benedikt M. Kessler, Peter J. Ratcliffe, Matthew E. Cockman, Roman Fischer, Pablo Wappner, Rasheduzzaman Chowdhury, Mathew L. Coleman, and Christopher J. Schofield. The jumonji-c oxygenase jmjd7 catalyzes (3s)-lysyl hydroxylation of trafac gtpases. Jun 2018. URL: https://doi.org/10.1038/s41589-018-0071-y, doi:10.1038/s41589-018-0071-y. This article has 49 citations and is from a highest quality peer-reviewed journal.
(westrip2024rewiringproteinbinding pages 1-3): Christian A. E. Westrip, Stephen J Smerdon, and Mathew L. Coleman. Rewiring protein binding specificity in paralogous drg/dfrp complexes. bioRxiv, Jun 2024. URL: https://doi.org/10.1101/2023.05.31.543024, doi:10.1101/2023.05.31.543024. This article has 3 citations.
(piette2021comprehensiveinteractomeprofiling pages 5-8): Benjamin L. Piette, Nader Alerasool, Zhen-Yuan Lin, Jessica Lacoste, Mandy Hiu Yi Lam, Wesley Wei Qian, Stephanie Tran, Brett Larsen, Eric Campos, Jian Peng, Anne-Claude Gingras, and Mikko Taipale. Comprehensive interactome profiling of the human hsp70 network highlights functional differentiation of j domains. Molecular Cell, 81:2549-2565.e8, Jun 2021. URL: https://doi.org/10.1016/j.molcel.2021.04.012, doi:10.1016/j.molcel.2021.04.012. This article has 100 citations and is from a highest quality peer-reviewed journal.

Artifacts

Citations

westrip2021developmentallyregulatedgtpases pages 5-6
westrip2024rewiringproteinbinding pages 3-6
markolovic2018thejumonjicoxygenase pages 8-10
westrip2021developmentallyregulatedgtpases pages 3-5
piette2021comprehensiveinteractomeprofiling pages 5-8
westrip2021developmentallyregulatedgtpases pages 1-3
beljan2022structureandfunction pages 1-2
jin2024conservedfunctionof pages 1-6
hawk2024conservedfunctionof pages 1-4
jin2024conservedfunctionof pages 6-9
hawk2024conservedfunctionof pages 4-7
mani2025regulatorymechanismsand pages 1-2
markolovic2018thejumonjicoxygenase pages 1-3
markolovic2018thejumonjicoxygenase pages 5-6
westrip2024rewiringproteinbinding pages 1-3
https://doi.org/10.1007/s00018-021-03961-0,
https://doi.org/10.1111/gtc.12942,
https://doi.org/10.1038/s41598-022-15242-2,
https://doi.org/10.21203/rs.3.rs-5125626/v1,
https://doi.org/10.1101/2024.04.20.590341,
https://doi.org/10.1101/2023.05.31.543024,
https://doi.org/10.1038/s41420-024-02027-x,
https://doi.org/10.3390/cancers17111747,
https://doi.org/10.1038/s41589-018-0071-y,
https://doi.org/10.1016/j.molcel.2021.04.012,

📚 Additional Documentation

Notes

(DRG2-notes.md)

DRG2 research notes

UniProt P55039 (DRG2_HUMAN), Developmentally-regulated GTP-binding protein 2.

Family / core function

DRG2 is a translational GTPase of the TRAFAC class, OBG-HflX-like superfamily, OBG GTPase family (the DRG/Developmentally Regulated GTP-binding protein family) [UniProt SIMILARITY: "Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family."].
- UniProt FUNCTION: "Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP. When hydroxylated at C-3 of 'Lys-21' by JMJD7, may bind to RNA and play a role in translation."
- Catalytic activity: GTP + H2O = GDP + phosphate + H+ (RHEA:19669), Mg2+ cofactor PMID:29915238.
- DRG GTPases associate with translating ribosomes and partner with DFRP (DRG family regulatory protein) cofactors: DRG2 partners with DFRP2 / RWDD1. The RWDD1 interaction "confers protection to polyubiquitination and proteolytic degradation" (UniProt SUBUNIT, By similarity).
- DRG2 (and DRG1) are substrates of the JmjC oxygenase JMJD7, which catalyzes (3S)-lysyl hydroxylation; the modification may regulate RNA binding / translation role PMID:29915238.

Annotations review

GO:0003924 GTPase activity (IEA + IDA PMID:29915238) — CORE MF. ACCEPT.
GO:0005525 GTP binding (IEA, TAS) — supporting/structural; KEEP_AS_NON_CORE (the informative MF is GTPase activity; per batch guidance avoid bare GTP binding as the sole core).
GO:0002181 cytoplasmic translation (IBA) — DRG2 is a ribosome-associated translational GTPase; the broad "cytoplasmic translation" term is the inferred process. KEEP_AS_NON_CORE (broad translation term; the specific regulatory role is not well-defined for human DRG2). Mirrors batch guidance on keeping broad translation terms non-core for ribosome-associated factors.
GO:0003723 RNA binding (IDA PMID:29915238) — hydroxylation-dependent RNA binding. KEEP_AS_NON_CORE (real but conditional/secondary to GTPase activity).
nucleus + cytoplasm (IDA PMID:29915238) — ACCEPT both (DRG2 is both nuclear and cytoplasmic).
cytosol (IDA HPA; TAS Reactome) — ACCEPT.
membrane (HDA PMID:19946888, NK-cell membrane proteome) — generic HT proteomics; MARK_AS_OVER_ANNOTATED.
GO:0007165 signal transduction (TAS PMID:7929244) — this 1994 paper just identifies a novel GTP-binding protein repressed in SV40-transformed fibroblasts; "signal transduction" is a vague legacy inference. MARK_AS_OVER_ANNOTATED (no specific signaling pathway established; DRG2 is a translational GTPase, not a signaling GTPase).
protein binding IPI: RWDD1 (Q9H446, DFRP2 — the key regulatory partner, recurrent across many screens), JMJD7 (P0C870, the hydroxylase), EIF4A3 (P38919), NAB2 (Q15742), TSSK3 (Q96PN8), SPRED1 (Q7Z699), JPH3 (Q8WXH2). Uninformative term -> KEEP_AS_NON_CORE; RWDD1/JMJD7 are meaningful but captured by the GTPase/regulation narrative.

Curation conclusions

CORE MF: GTPase activity (GO:0003924) — translational GTPase.
Locations: cytoplasm/cytosol + nucleus.
GTP binding, RNA binding, cytoplasmic translation = non-core. signal transduction + membrane = over-annotated.

Pn Notes

(DRG2-pn-notes.md)

DRG2 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: P55039
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-07c
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/DRG2/DRG2-ai-review.yaml
AIGR review HTML: present - genes/human/DRG2/DRG2-ai-review.html
Gene notes: present - genes/human/DRG2/DRG2-notes.md
GOA TSV: present - genes/human/DRG2/DRG2-goa.tsv
UniProt record: present - genes/human/DRG2/DRG2-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/DRG2.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/DRG2.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

Description: 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.
Existing/core annotation action counts: ACCEPT: 8; KEEP_AS_NON_CORE: 12; MARK_AS_OVER_ANNOTATED: 2

PN Consistency Summary

Consistency: Review and notes are consistent with each other (DRG2 = TRAFAC/OBG-family translational GTPase; core MF GO:0003924 GTPase activity; JMJD7-hydroxylation/RNA-binding context; DFRP2/RWDD1 cofactor). They are NOT consistent with the PN placement: nothing in the review, notes, or GOA establishes DRG2 as a ribosome-associated quality-control / surveillance factor. The review even keeps the broad GO:0002181 cytoplasmic translation as non-core because "the specific regulatory role of human DRG2 in translation is not precisely defined."
PN story / NEW pressure: Dossier projects GO:0006515 protein QC as new_to_goa. No evidence (GOA has GO:0002181 + GO:0003924 only; no QC/RQC/rescue terms) supports DRG2 as an RQC factor. Asserting GO:0006515 would be an unsupported functional claim, not merely a broad umbrella — over-reaches. No defensible NEW term; if anything the gene is at most a generic ribosome-associated GTPase.
Evidence alignment: Dossier provides no reference titles. Review anchors are PMID:29915238 (JMJD7/GTPase, VERIFIED) and PMID:7929244 (original cloning, VERIFIED) — both about GTPase identity, neither about RQC. Divergence: dossier RQC framing has no supporting citation.
Verdict: GTPase biology is solid, but the PN RQC placement and GO:0006515 projection are unsupported for DRG2. Recommended edits: [MAP] do not project GO:0006515 (protein QC) to DRG2 — no RQC/surveillance evidence; GTPase activity (GO:0003924) is the supported core.

Full Consistency Review

UniProt: P55039 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
PN placement: Translation|Cytosolic translation|Ribosome-associated QC|other RQC processes ; PN-node mapping: type other RQC processes no_mapping; group Ribosome-associated QC → GO:0006515 protein QC (mapped, ok_for_propagation); class/branch context_only.
Consistency: Review and notes are consistent with each other (DRG2 = TRAFAC/OBG-family translational GTPase; core MF GO:0003924 GTPase activity; JMJD7-hydroxylation/RNA-binding context; DFRP2/RWDD1 cofactor). They are NOT consistent with the PN placement: nothing in the review, notes, or GOA establishes DRG2 as a ribosome-associated quality-control / surveillance factor. The review even keeps the broad GO:0002181 cytoplasmic translation as non-core because "the specific regulatory role of human DRG2 in translation is not precisely defined."
PN story / NEW pressure: Dossier projects GO:0006515 protein QC as new_to_goa. No evidence (GOA has GO:0002181 + GO:0003924 only; no QC/RQC/rescue terms) supports DRG2 as an RQC factor. Asserting GO:0006515 would be an unsupported functional claim, not merely a broad umbrella — over-reaches. No defensible NEW term; if anything the gene is at most a generic ribosome-associated GTPase.
Mapping strategy: This gene weakens the Ribosome-associated QC group → GO:0006515 mapping: DRG2's membership in "other RQC processes" looks like taxonomic placement of a ribosome-associated GTPase rather than a demonstrated QC role. Recommend NOT projecting GO:0006515 onto DRG2 (no QC evidence).
Evidence alignment: Dossier provides no reference titles. Review anchors are PMID:29915238 (JMJD7/GTPase, VERIFIED) and PMID:7929244 (original cloning, VERIFIED) — both about GTPase identity, neither about RQC. Divergence: dossier RQC framing has no supporting citation.
Verdict: GTPase biology is solid, but the PN RQC placement and GO:0006515 projection are unsupported for DRG2. Recommended edits: [MAP] do not project GO:0006515 (protein QC) to DRG2 — no RQC/surveillance evidence; GTPase activity (GO:0003924) is the supported core.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-07c
review_yaml: genes/human/DRG2/DRG2-ai-review.yaml
PN workbook rows: 1

PN row 1: Translation | Cytosolic translation | Ribosome-associated QC | other RQC processes

UniProt: P55039
In branches: TR
PN-node mapping records (path + ancestors):
- [type] Translation|Cytosolic translation|Ribosome-associated QC|other RQC processes
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [group] Translation|Cytosolic translation|Ribosome-associated QC
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0006515 protein quality control for misfolded or incompletely synthesized proteins]
  rationale: The PN ribosome-associated quality-control group covers surveillance and disposal of stalled or defective nascent-chain translation products. GO lacks a dedicated ribosome-associated QC term in the local cache, so the broader protein-quality-control process is the best supported target.
- [class] Translation|Cytosolic translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
  rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
- [branch] Translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
  rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

Projected GO annotations (1)

GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome-associated QC

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: P55039
gene_symbol: DRG2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
- term:
    id: GO:0002181
    label: cytoplasmic translation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: KEEP_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.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-uniprot.txt
      supporting_text: may bind to RNA and play a role in translation
    - reference_id: file:human/DRG2/DRG2-deep-research-falcon.md
      supporting_text: DRG2, in complex with its binding partner DFRP2, associates with ribosomes that have paused or stalled during translation elongation
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: DRG2 hydrolyzes GTP to GDP; GTPase activity is the core molecular function. Electronic transfer here agrees with direct experimental (IDA) evidence.
    action: ACCEPT
    reason: GTPase activity is experimentally demonstrated and is the defining catalytic function of DRG2.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-uniprot.txt
      supporting_text: Catalyzes the conversion of GTP to GDP through hydrolysis of
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: GTP binding is real but the informative core molecular function is GTPase activity; retained as a supporting non-core annotation.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-uniprot.txt
      supporting_text: hydrolysis of the gamma-phosphate bond in GTP
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: DRG2 has a documented nuclear pool, consistent with the experimental (IDA) nuclear localization.
    action: ACCEPT
    reason: Nuclear localization is experimentally supported; DRG2 is both nuclear and cytoplasmic.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Nucleus'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: DRG2 is cytoplasmic, consistent with its ribosome/translation association and with the experimental (IDA) cytoplasm annotation.
    action: ACCEPT
    reason: Cytoplasmic localization is experimentally supported and consistent with its function.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-uniprot.txt
      supporting_text: Cytoplasm
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally important DRG2-RWDD1/DFRP2 interaction, but the term is uninformative; the regulatory relationship is described in the gene narrative.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16189514 UniProtKB:Q9H446
    - reference_id: file:human/DRG2/DRG2-deep-research-falcon.md
      supporting_text: This interaction is essential for DRG2 stability; loss of DFRP2 leads to rapid degradation of DRG2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Y2H interactome interaction with RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the DRG2-RWDD1 interaction but uninformative term; not core.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25416956 UniProtKB:Q9H446
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Interactome interaction with RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the DRG2-RWDD1 interaction but uninformative term; not core.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28514442 UniProtKB:Q9H446
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Records real interactions (RWDD1, JMJD7) but uninformative term; captured by the regulatory/PTM narrative. Other partners are likely incidental Y2H hits.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:P0C870
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Neurodegeneration interactome capturing DRG2 interactions with SPRED1 (Q7Z699) and JPH3 (Q8WXH2). Bare protein binding is uninformative and these are isolated HT hits.
    action: KEEP_AS_NON_CORE
    reason: Isolated high-throughput interactions with partners unrelated to DRG2's GTPase/translation function; uninformative term, not core.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32814053 UniProtKB:Q7Z699
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-purification capturing DRG2-RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the DRG2-RWDD1 interaction but uninformative term; not core.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q9H446
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-maps interactome capturing DRG2-RWDD1/DFRP2 (Q9H446). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the DRG2-RWDD1 interaction but uninformative term; not core.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:Q9H446
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence cytosolic localization, consistent with DRG2's cytoplasmic site of action.
    action: ACCEPT
    reason: Direct evidence for cytosolic localization, consistent with function.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000314 IDA
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9629578
  qualifier: located_in
  review:
    summary: Reactome curated cytosolic localization, consistent with the IDA cytosol annotation.
    action: ACCEPT
    reason: Correct cytosolic localization.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-9629578
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IDA
  original_reference_id: PMID:29915238
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: RNA binding is experimentally demonstrated but is a hydroxylation-dependent, secondary activity relative to the core GTPase function.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-uniprot.txt
      supporting_text: When hydroxylated at C-3 of 'Lys-21' by JMJD7, may bind to RNA and play a role in translation
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IDA
  original_reference_id: PMID:29915238
  qualifier: enables
  review:
    summary: Direct experimental demonstration that DRG2 hydrolyzes GTP. This is the core molecular function.
    action: ACCEPT
    reason: IDA evidence for GTP hydrolysis establishes GTPase activity as DRG2's core catalytic function.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-uniprot.txt
      supporting_text: Catalyzes the conversion of GTP to GDP through hydrolysis of
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29915238
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally relevant DRG2-JMJD7 (hydroxylase) interaction, but the term is uninformative; the PTM relationship is captured in the gene narrative.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-uniprot.txt
      supporting_text: Interacts with JMJD7; this interaction is direct
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:29915238
  qualifier: located_in
  review:
    summary: Direct evidence for nuclear localization of DRG2.
    action: ACCEPT
    reason: Experimentally supported nuclear pool.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005634 nucleus cellular_component ECO:0000314 IDA PMID:29915238
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:29915238
  qualifier: located_in
  review:
    summary: Direct evidence for cytoplasmic localization of DRG2.
    action: ACCEPT
    reason: Experimentally supported cytoplasmic localization, consistent with function.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component ECO:0000314 IDA PMID:29915238
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: DRG2 appeared in a high-throughput NK-cell membrane-proteome dataset. Generic, non-specific localization for a cytosolic/nuclear GTPase.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic "membrane" from a high-throughput proteomics survey; uninformative and inconsistent with DRG2's documented cytoplasmic/nuclear localization.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0016020 membrane cellular_component ECO:0007005 HDA PMID:19946888
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: TAS
  original_reference_id: PMID:7929244
  qualifier: enables
  review:
    summary: Original (1994) identification of DRG2 as a GTP-binding protein. GTP binding is real but subordinate to the GTPase catalytic function.
    action: KEEP_AS_NON_CORE
    reason: GTP binding is supported but the informative core MF is GTPase activity; retained as a supporting non-core annotation.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0005525 GTP binding molecular_function ECO:0000304 TAS PMID:7929244
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: TAS
  original_reference_id: PMID:7929244
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-broad, unsupported by a defined pathway; DRG2's function is as a translational GTPase rather than a signal-transducing GTPase.
    supported_by:
    - reference_id: file:human/DRG2/DRG2-goa.tsv
      supporting_text: GO:0007165 signal transduction biological_process ECO:0000304 TAS PMID:7929244
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms.
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees.
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping.
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data.
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods.
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:29915238
  title: The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publication (publications/PMID_29915238.md) PubMed title
      matches the YAML title exactly; body explicitly names developmentally regulated
      GTP-binding proteins 1 and 2 (DRG1/2) as TRAFAC-family GTPases and JMJD7
      substrates, supporting DRG2's core GTPase molecular function and the JMJD7
      hydroxylation/RNA-binding context."
  findings:
  - statement: DRG2 is a TRAFAC GTPase that hydrolyzes GTP, binds RNA, and is a substrate of JMJD7-catalyzed (3S)-lysyl hydroxylation; interacts directly with JMJD7.
    reference_section_type: RESULTS
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:7929244
  title: A novel GTP-binding protein which is selectively repressed in SV40 transformed fibroblasts.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Original DRG2 cloning paper. Verified against a checkable anchor:
      UniProt P55039 (DRG2_HUMAN, 364 AA) cites PubMed=7929244 as its nucleotide
      sequence reference, and the cached abstract (364-aa, ~41 kDa GTP-binding protein
      with conserved G1-G5 motifs defining a new GTPase subfamily) matches DRG2.
      Establishes DRG2 as a GTP-binding protein, the basis for its core GTPase MF."
  findings:
  - statement: Original identification of DRG2 as a GTP-binding protein selectively repressed in SV40-transformed fibroblasts.
    reference_section_type: RESULTS
- id: Reactome:R-HSA-9629578
  title: Reactome cytosolic localization annotation for DRG2.
  findings: []
- id: file:human/DRG2/DRG2-deep-research-falcon.md
  title: Falcon deep research report for DRG2
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: "LLM-synthesized (Edison/Falcon) deep-research report; treated as
      UNVERIFIED pending primary-source checking. DRG2-SPECIFIC, well-anchored claims:
      DRG2 forms an obligate heterodimer with DFRP2/RWDD1 that stabilizes it against
      degradation; DRG2 is a JMJD7 substrate hydroxylated at Lys21 in the N-terminal
      HTH domain, which promotes RNA binding without altering stability/GTPase
      activity (Markolovic 2018, PMID:29915238); DRG2 localizes to cytoplasm, nucleus
      and Rab5-positive early endosomes; the DRG2-specific endosomal/Rab5 and PD-L1
      recycling role derives from a genuine DRG2 paper (Choi 2024,
      doi:10.1038/s41420-024-02027-x). GENERALIZED / EXTRAPOLATED-FROM-PARALOG claims
      to treat cautiously: the 'general translation factor that rescues stalled/paused
      ribosomes and stimulates peptidyl transfer' mechanism rests on DRG1, bacterial
      Obg, and yeast Rbg2 orthologs plus 2024 preprints (jin2024/hawk2024,
      westrip2024), and the report itself states direct biochemical characterization
      of human DRG2 GTPase activity (e.g. K+-dependence) is limited and inferred from
      DRG1. The Gcn1-mediated collided-ribosome recruitment and DNAJC2/co-chaperone
      links are speculative. No annotation was added or removed on the basis of this
      report alone; it is used only to corroborate the existing ribosome/translation
      framing."
  findings:
  - statement: DRG2, with its paralog DRG1, is reported as a translation factor that
      associates with stalled/paused ribosomes via its DFRP2 partner; human-specific
      GTPase biochemistry is largely inferred from DRG1 and ortholog studies.
    reference_section_type: RESULTS
- id: file:human/DRG2/DRG2-uniprot.txt
  title: UniProt entry P55039 (DRG2_HUMAN), Developmentally-regulated GTP-binding protein 2.
  findings:
  - statement: DRG2 is a TRAFAC-class OBG/DRG-family GTPase that hydrolyzes GTP to GDP (Mg2+ cofactor); when hydroxylated at Lys-21 by JMJD7 it may bind RNA and act in translation; stabilized by DFRP2/RWDD1; localizes to cytoplasm and nucleus.
    reference_section_type: OTHER
core_functions:
- description: Translational GTPase of the DRG/OBG family that catalyzes hydrolysis of GTP to GDP (Mg2+-dependent); functions in association with its DFRP2/RWDD1 cofactor and is implicated in regulation of translation.
  molecular_function:
    id: GO:0003924
    label: GTPase activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: file:human/DRG2/DRG2-uniprot.txt
    supporting_text: Catalyzes the conversion of GTP to GDP through hydrolysis of
  - reference_id: file:human/DRG2/DRG2-uniprot.txt
    supporting_text: Belongs to the TRAFAC class OBG-HflX-like GTPase
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: How does DFRP2/RWDD1 binding regulate DRG2's GTPase activity, stability, and ribosome association?
- question: What is the functional role of JMJD7-mediated Lys-21 hydroxylation in switching DRG2 between GTPase and RNA-binding/translation activities?
suggested_experiments:
- description: Ribosome co-sedimentation / polysome profiling with tagged DRG2 (with and without RWDD1) to test ribosome association and translational state dependence.
- description: In vitro GTP-hydrolysis assays of DRG2 alone and in complex with DFRP2/RWDD1 to define cofactor effects on GTPase kinetics.
- description: Compare RNA binding and translation phenotypes of wild-type DRG2 versus a Lys-21 hydroxylation-deficient mutant and in JMJD7-knockout cells.

DRG2

Gene Description

Existing Annotations Review

Core Functions

Translational GTPase of the DRG/OBG family that catalyzes hydrolysis of GTP to GDP (Mg2+-dependent); functions in association with its DFRP2/RWDD1 cofactor and is implicated in regulation of translation.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Comprehensive Research Report: DRG2 (Developmentally-Regulated GTP-Binding Protein 2)

Gene Identity Verification

Primary Molecular Function and Enzymatic Activity

Biological Processes and Signaling Pathways

Subcellular Localization

Protein-Protein Interactions and Structural Features

Summary

Artifacts

Citations

📚 Additional Documentation

Notes

DRG2 research notes

Family / core function

Annotations review

Curation conclusions

Pn Notes

DRG2 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Translation | Cytosolic translation | Ribosome-associated QC | other RQC processes

Projected GO annotations (1)

Note

📄 View Raw YAML