CTU2

Model summary

A cytoplasmic assembly factor that organizes the cytosolic machinery responsible for installing sulfur at the wobble uridine of select tRNAs. By forming a multivalent platform that binds partner proteins and positions substrate tRNA, it enables the late steps of 2-thiolation required for efficient and accurate decoding during translation. Operating in the cytosol as part of a larger soluble complex, it coordinates sulfur transfer chemistry that finalizes the thiolation of tRNA(Lys), tRNA(Glu), and tRNA(Gln).

Predicted Gene Ontology terms

1. 01

   I begin with the InterPro architecture.

   The core scaffold is IPR014729 (Rossmann-like alpha/beta/alpha sandwich fold, residues 26–406), a classical nucleotide/RNA-associated fold that frequently underpins ligand-binding and assembly of multi-subunit machines rather than direct catalysis. Encompassing and extending beyond this core is IPR019407 (Cytoplasmic tRNA 2-thiolation protein 2 family, residues 21–501), which specifies membership in the cytoplasmic 2-thiolation machinery that modifies tRNA. The ordered layout—an extensive Rossmann-like fold embedded within a thiolation-family envelope—argues that this polypeptide forms a structural platform that binds partners and tRNA to enable sulfur transfer chemistry executed within a larger assembly.

2. 02

   This architecture drives the molecular function toward multivalent assembly rather than standalone catalysis.

   The Rossmann-like fold provides a stable cradle for macromolecular contacts, and the thiolation-family signature dictates that the protein operates in a cytoplasmic complex that installs sulfur into the wobble position of specific tRNAs. Such a role inherently requires broad protein–protein interfaces to recruit enzymatic and adaptor subunits; this supports GO:0005515 protein binding as the operative molecular function.

3. 03

   From function to process, the thiolation-family identity causally ties the protein to GO:0034227 tRNA thio-modification.

   The explicit specialization for wobble-base chemistry places it in GO:0002098 tRNA wobble uridine modification. In human cytoplasm, this pathway culminates in the 2-thiolation of U34 in tRNA(Lys), tRNA(Glu), and tRNA(Gln), which tunes decoding fidelity and efficiency during translation. The platform-like architecture explains how the protein stabilizes and coordinates the thiolation sequence: recruiting the sulfur-donating module and positioning substrate tRNA for the final thiolation step.

4. 04

   Cellular context follows directly.

   The absence of transmembrane features and the thiolation-family designation point to a soluble cytoplasmic assembly. This aligns with localization to the cytoplasm and, more specifically, the GO:0005829 cytosol, where cytosolic tRNA pools and translation machinery reside. The reliance on multi-subunit assembly further situates it within GO:0032991 protein-containing complex, consistent with a cytosolic thiolation ensemble.

5. 05

   Mechanistically, I infer that the Rossmann-like core organizes a cytosolic thiolation hub that binds partner proteins and tRNA to channel persulfide sulfur into the wobble uridine.

   The protein likely captures or stabilizes the sulfur-transfer module and orients tRNA for efficient 2-thiolation. In this role, it plausibly engages cytosolic tRNA thiolation partners and transiently contacts elongation and aminoacylation factors to synchronize modification with translational demand. Candidate partners include the cytoplasmic tRNA thiolation machinery (e.g., assembly and sulfur-donation subunits), as well as translation-associated factors that handle wobble-tRNA pools in the cytosol.