PROSITE documentation PDOC51061

R3H domain profile

The R3H domain is a conserved sequence motif found in proteins from a diverse range of organisms including eubacteria, green plants, fungi and various groups of metazoans, but not in archaea and Escherichia coli. The R3H domain contains an invariant arginine and a highly conserved histidine, that are separated by three residues. It also displays a conserved pattern of hydrophobic residues, prolines and glycines. It can be found alone, in association with AAA domain (see <PDOC00572>) or with various DNA/RNA binding domains like DSRM, KH, G-patch (see <PDOC50174>), PHD (see <PDOC50016>), DEAD box (see <PDOC00039>), or RRM (see <PDOC00030>). The functions of these domains indicate that the R3H domain might be involved in polynucleotide-binding, including DNA, RNA and single-stranded DNA [1].

The 3D structure of the R3H domain has been solved (see <PDB:1MSZ>). The fold presents a small motif, consisting of a three-stranded antiparallel β-sheet, against which two α-helices pack from one side. This fold is related to the structures of the YhhP protein and the C-terminal domain of the translational initiation factor IF3. Three conserved basic residues cluster on the same face of the R3H domain and could play a role in nucleic acid recognition. An extended hydrophobic area at a different site of the molecular surface could act as a protein-binding site [2].

Proteins currently known to contain an R3H domain are:

• Mammalian SMB2-related proteins, which are involved in DNA-binding, and are specific to a 5'-phosphorylated single-stranded guanine-rich sequence related to the immunoglobulin mu chain switch region.
• Bacterial JAG proteins.
• Mammalian R3H domain protein 1.

The profile developed covers the entire R3H structure.