Protein uS12 is located at the very heart of the small ribosomal subunit, in the direct vicinity of the ribosomal decoding center.
uS12 is the only ribosomal protein that directly binds ribosome-targeting antibiotics, such as dityromycin and GE82832 (while other ribosome-targeting drugs typically bind rRNA rather than ribosomal proteins) .
In bacteria, uS12 carries an unusual post-translationally modified residue, β-methylthio-aspartate (msD88), which is essential in E. coli. Crystal structures of bacterial ribosome revealed that msD88 interacts with a post-transcriptionally modified nucleotide of the 16S rRNA, m7G527, suggesting that msD88 and m7G527 cooperate during ribosome biogenesis to stabilize energetically unfavorable structure of the decoding center .
The N-terminus of uS12 have exceptionally divergent structure across species: although this protein segment has comparable size in different species (and although this segment stabilizes a conserved intrahelical junction at the border of the three major domains of 16S rRNA), the structure of this segment is dissimilar in bacterial and eukaryotic ribosomes. In eukaryotes, this N-terminal extension of uS12 carries a function of nuclear/nucleolar localization signal, providing a clue to why this protein has different N-termini in bacteria and eukaryotes.