PROSITE documentation PDOC50084
KH domain profiles


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 [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 [1].

According to structural [2,3,4] analysis the KH domain can be separated in two groups. The first group or type-1 contain a β-α-α-β-β-α structure, whereas in the type-2 the two last β-sheet are located in the N terminal part of the domain (α-β-β-α-α-β). 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
  • 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.

Last update:

December 2001 / First entry.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

KH_TYPE_1, PS50084; Type-1 KH domain profile  (MATRIX)

KH_TYPE_2, PS50823; Type-2 KH domain profile  (MATRIX)


1AuthorsBurd C.G. Dreyfuss G.
TitleConserved structures and diversity of functions of RNA-binding proteins.
SourceScience 265:615-621(1994).
PubMed ID8036511

2AuthorsMusco G. Kharrat A. Stier G. Fraternali F. Gibson T.J. Nilges M. Pastore A.
TitleThe solution structure of the first KH domain of FMR1, the protein responsible for the fragile X syndrome.
SourceNat. Struct. Biol. 4:712-716(1997).
PubMed ID9302998

3AuthorsBaber J.L. Libutti D. Levens D. Tjandra N.
TitleHigh precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor.
SourceJ. Mol. Biol. 289:949-962(1999).
PubMed ID10369774

4AuthorsGrishin N.V.
TitleKH domain: one motif, two folds.
SourceNucleic Acids Res. 29:638-643(2001).
PubMed ID11160884

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)