Selenoproteins contain the amino acid selenocysteine which is encoded by a UGA 
Sec codon. Recoding UGA Sec requires a complex mechanism, comprising the 
cis-acting SECIS RNA hairpin in the 3'UTR of selenoprotein mRNAs, and 
trans-acting factors. Among these, the SECIS Binding Protein 2 (SBP2) is central 
to the mechanism. SBP2 has been so far functionally characterized only in rats 
and humans. In this work, we report the characterization of the Drosophila 
melanogaster SBP2 (dSBP2). Despite its shorter length, it retained the same 
selenoprotein synthesis-promoting capabilities as the mammalian counterpart. 
However, a major difference resides in the SECIS recognition pattern: while 
human SBP2 (hSBP2) binds the distinct form 1 and 2 SECIS RNAs with similar 
affinities, dSBP2 exhibits high affinity toward form 2 only. In addition, we 
report the identification of a K (lysine)-rich domain in all SBP2s, essential 
for SECIS and 60S ribosomal subunit binding, differing from the 
well-characterized L7Ae RNA-binding domain. Swapping only five amino acids 
between dSBP2 and hSBP2 in the K-rich domain conferred reversed SECIS-binding 
properties to the proteins, thus unveiling an important sequence for form 1 
binding.