DENR (Density-regulated protein, DRP) — research notes

UniProt O43583. 198 aa. Contains a C-terminal SUI1 domain (eIF1-like). Member of the DENR family; homologous to the C-terminal region of Ligatin/eIF2D, while MCTS1 is homologous to the N-terminal region.

Core function

DENR forms a heterodimer with MCTS1; the MCTS1–DENR complex is a non-canonical translation (re)initiation and 40S recycling factor. It is the functional equivalent of eIF2D split into two polypeptides.

• PMID:20713520
• PMID:20713520
• UniProt FUNCTION: "Translation regulator forming a complex with MCTS1 to promote translation reinitiation ... Firstly, the dissociation of deacylated tRNAs from post-termination 40S ribosomal complexes during ribosome recycling. Secondly, the recruitment in an EIF2-independent manner of aminoacylated initiator tRNA to P site of 40S ribosomes for a new round of translation."
• DENR–MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation [PMID:29889857 title]. DENR contributes the SUI1 (PUA-interacting) module; MCTS1 PUA domain binds DENR.
• MCTS1-dependent reinitiation translates specific mRNAs incl. JAK2; essential for IFN-γ immunity [PMID:37875108 title].

Interactions (IPI)

• MCTS1 (Q9ULC4): the physiological obligate partner — many entries (16169070, 21516116, 32296183, 33961781, 40205054, 16982740). Best captured as MCTS1 binding / heterodimerization, not bare protein binding.
• MAPT (P10636, tau), MARCHF5 (Q9NX47), NELFB/UBC: high-throughput, peripheral.

Localization

Cytoplasm (IDA, PMID:16982740). Also reported in stress granules / nucleolus (CD-CODE) but cytoplasmic ribosome-associated is the functional site.

Decisions

• Reinitiation, preinitiation complex formation, ribosome disassembly (recycling), eIF2-independent tRNA delivery = core.
• MF: translation initiation factor activity (GO:0003743) is supported (eIF2D-like). Core MF.
• protein binding IPI with MCTS1 → MODIFY to protein heterodimerization/MCTS1 binding context; non-MCTS1 ones KEEP_AS_NON_CORE or over-annotated.
• IRES-dependent viral translational initiation (GO:0075522) — supported by 20713520 (HCV-like IRES P-site delivery). KEEP_AS_NON_CORE.