| 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 (pqac-00000001, pqac-00000011, pqac-00000017) | (pqac-00000001, pqac-00000011, pqac-00000017) |
| 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 (pqac-00000003, pqac-00000007, pqac-00000013) | (pqac-00000003, pqac-00000007, pqac-00000013) |
| 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 (pqac-00000000, pqac-00000002, pqac-00000009, pqac-00000011, pqac-00000012) | (pqac-00000000, pqac-00000002, pqac-00000009, pqac-00000011, pqac-00000012) |
| 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 (pqac-00000011) | (pqac-00000011) |
| 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 (pqac-00000005, pqac-00000014, pqac-00000016) | (pqac-00000005, pqac-00000014, pqac-00000016) |
| 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 (pqac-00000015) | (pqac-00000015) |
| 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 (pqac-00000013) | (pqac-00000013) |
| 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 (pqac-00000006, pqac-00000008) | (pqac-00000006, pqac-00000008) |
| 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 (pqac-00000008, pqac-00000013) | (pqac-00000008, pqac-00000013) |
| 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 (pqac-00000004, pqac-00000009, pqac-00000012, pqac-00000017) | (pqac-00000004, pqac-00000009, pqac-00000012, pqac-00000017) |
| 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 (pqac-00000008) | (pqac-00000008) |
| 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 (pqac-00000008, pqac-00000011, pqac-00000017) | (pqac-00000008, pqac-00000011, pqac-00000017) |


*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.*