The K homology (KH) domain was first identified in the human heterogeneous
nuclear ribonucleoprotein (hnRNP) K. It is a domain of around 70 amino acids
that is present in a wide variety of quite diverse nucleic acid-binding
proteins
[3]. It has been shown to bind RNA
[4][1]. 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
[3].
According to structural
[4][1][2] analysis 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-sheet 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.
Some proteins known to contain a type-1 KH domain are listed below:
- Bacterial polyribonucleotide nucleotidyltransferases (EC 2.7.7.8).
- Vertebrate fragile X mental retardation protein 1 (FMR1). Associated to
polysomes and might be involved in the transport of mRNA from the nucleus
to the cytoplasm.
- Eukaryotic heterogeneous nuclear ribonucleoprotein K (hnRNP K), one of at
least 20 major proteins that are part of hnRNP particles in mammalian
cells. It is presumed to be involved in transport and/or processing of
heterogeneous nuclear and mature RNA.
- Mammalian poly(rC) binding proteins.
- Artemia salina glycine-rich protein GRP33.
- Yeast PAB1-binding protein 2 (PBP2).
- Vertebrate vigilin. An oestrogen-inducible protein in polysome extracts
which binds specifically to a segment of the 3'untranslated region (UTR) of
estrogen-stabilized vitellogenin mRNA.
- Human high-density lipoprotein binding protein (HDL-binding protein).
- Human onconeural ventral antigen-1 (NOVA-1). May regulate RNA splicing or
metabolism in a specific subset of developing neurons.
Proteins known to contain a type-2 KH domain are listed below:
- Eukaryotic and prokaryotic S3 family of ribosomal proteins.
- Prokaryotic GTP-binding protein era.
To identify KH domains we developed two profiles, one specific for type-1 and
the other type-2. Both profiles cover the whole domain.