InterPro domain: IPR004044

The K homology (KH) domain was first identified in the human heterogeneousnuclear ribonucleoprotein (hnRNP) K. It is a domain of around 70 amino acidsthat is present in a wide variety of quite diverse nucleic acid-bindingproteins [ 1 ]. It has been shown to bind RNA [ 2 , 3 ]. Like many other RNA-binding motifs, KH motifs are found in one or multiple copies (14 copies in chicken vigilin) and, at least for hnRNP K (three copies) and FMR-1 (two copies), each motif is necessary for in vitro RNA binding activity, suggesting that they may function cooperatively or, in the case of single KH motif proteins (for example, Mer1p), independently [ 4 ].

According to structural analyses [ 4 , 4 , 4 ], the KH domain can be separated in two groups. The first group or type-1 contain a beta-alpha-alpha-beta-beta-alpha structure, whereas in the type-2 the two last beta-sheets are located in the N-terminal part of the domain (alpha-beta-beta-alpha-alpha-beta). Sequence similarity between these two folds are limited to a short region (VIGXXGXXI) in the RNA binding motif. This motif is located between helice 1 and 2 in type-1 and between helice 2 and 3 in type-2. Proteins known to contain a type-2 KH domain include eukaryotic and prokaryotic S3 family of ribosomal proteins, and the prokaryotic GTP-binding protein era.

1. Conserved structures and diversity of functions of RNA-binding proteins. Science 265, 615-21
2. The solution structure of the first KH domain of FMR1, the protein responsible for the fragile X syndrome. Nat. Struct. Biol. 4, 712-6
3. High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor. J. Mol. Biol. 289, 949-62
4. KH domain: one motif, two folds. Nucleic Acids Res. 29, 638-43