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5  structures 340  species 0  interactions 959  sequences 145  architectures

Family: KH_3 (PF13014)

Summary: KH domain

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KH domain Edit Wikipedia article

KH domain
PDB 2anr EBI.png
Structure of a KH domain from the human protein vigilin.
Symbol KH_1
Pfam PF00013
Pfam clan CL0007
InterPro IPR018111
SCOP 1vig
KH domain
Symbol KH_2
Pfam PF07650
InterPro IPR004044

The K Homology (KH) domain is a protein domain that was first identified in the human heterogeneous nuclear ribonucleoprotein (hnRNP) K. An evolutionarily conserved sequence of around 70 amino acids, the KH domain is present in a wide variety of nucleic acid-binding proteins. The KH domain binds RNA, and can function in RNA recognition.[1] It is found in multiple copies in several proteins, where they can function cooperatively or independently. For example, in the AU-rich element RNA-binding protein KSRP, which has 4 KH domains, KH domains 3 and 4 behave as independent binding modules to interact with different regions of the AU-rich RNA targets.[1] The solution structure of the first KH domain of FMR1 and of the C-terminal KH domain of hnRNP K determined by nuclear magnetic resonance (NMR) revealed a beta-alpha-alpha-beta-beta-alpha structure.[2][3] Autoantibodies to NOVA1, a KH domain protein, cause paraneoplastic opsoclonus ataxia. The KH domain is found at the N-terminus of the ribosomal protein S3. This domain is unusual in that it has a different fold compared to the normal KH domain.[4]

Nucleic acid binding

KH domains bind to either RNA or single stranded DNA. The nucleic acid is bound in en extended conformation across one side of the domain. The binding occurs in a cleft formed between alpha helix 1, alpha helix 2 the GXXG loop (contains a highly conserved sequence motif) and the variable loop.[5] The binding cleft is hydrophobic in nature with a variety of additional protein specific interactions to stabilise the complex. Valverde and colleagues note that, "Nucleic acid base-to-protein aromatic side chain stacking interactions which are prevalent in other types of single stranded nucleic acid binding motifs, are notably absent in KH domain nucleic acid recognition".[5]

Structural groups

The two types of KH domain.

Structurally there are two different types of KH domains identified by Grishin which are called type I and type II.[4] The type I domains are mainly found in eukaryotic proteins, while the type II domains are predominantly found in prokaryotes. While both types share a minimal consensus sequence motif they have different structural folds. The type I KH domains have a three stranded beta-sheet where all three strands are anti-parallel. In the type II domain two of the three beta strands are in a parallel orientation. While type I domains are usually found in multiple copies within proteins, the type II are typically found in a single copy per protein.[5]

Human proteins containing this domain



  1. ^ a b García-Mayoral MF, Hollingworth D, Masino L; et al. (April 2007). "The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation". Structure 15 (4): 485–98. doi:10.1016/j.str.2007.03.006. PMID 17437720. 
  2. ^ Musco G, Kharrat A, Stier G; et al. (September 1997). "The solution structure of the first KH domain of FMR1, the protein responsible for the fragile X syndrome". Nat. Struct. Biol. 4 (9): 712–6. doi:10.1038/nsb0997-712. PMID 9302998. 
  3. ^ Baber JL, Libutti D, Levens D, Tjandra N (June 1999). "High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor". J. Mol. Biol. 289 (4): 949–62. doi:10.1006/jmbi.1999.2818. PMID 10369774. 
  4. ^ a b Grishin NV (February 2001). "KH domain: one motif, two folds". Nucleic Acids Res. 29 (3): 638–43. doi:10.1093/nar/29.3.638. PMC 30387. PMID 11160884. 
  5. ^ a b c Valverde R, Edwards L, Regan L (June 2008). "Structure and function of KH domains". FEBS J. 275 (11): 2712–26. doi:10.1111/j.1742-4658.2008.06411.x. PMID 18422648. 

This article incorporates text from the public domain Pfam and InterPro IPR004088

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KH domain Provide feedback

KH motifs bind RNA in vitro [1]. This RNA-binding domain is required for the efficient anchoring of ASH1-mRNA to the distal tip of the daughter cell. ASH1 is a specific repressor of transcription that localizes asymmetrically to the daughter cell nucleus. RNA localisation is a widespread mechanism for achieving localised protein synthesis [2].

Literature references

  1. Burd CG, Dreyfuss G; , Science 1994;265:615-621.: Conserved structures and diversity of functions of RNA-binding proteins. PUBMED:8036511 EPMC:8036511

  2. Irie K, Tadauchi T, Takizawa PA, Vale RD, Matsumoto K, Herskowitz I;, EMBO J. 2002;21:1158-1167.: The Khd1 protein, which has three KH RNA-binding motifs, is required for proper localization of ASH1 mRNA in yeast. PUBMED:11867544 EPMC:11867544

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004088

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 [PUBMED:8036511]. It has been shown to bind RNA [PUBMED:9302998, PUBMED:10369774]. 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 [PUBMED:8036511].

According to structural [PUBMED:9302998, PUBMED:10369774, PUBMED:11160884] 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. Proteins known to contain a type-1 KH domain include bacterial polyribonucleotide nucleotidyltransferases (EC); vertebrate fragile X mental retardation protein 1 (FMR1); eukaryotic heterogeneous nuclear ribonucleoprotein K (hnRNP K), one of at least 20 major proteins that are part of hnRNP particles in mammalian cells; mammalian poly(rC) binding proteins; Artemia salina glycine-rich protein GRP33; yeast PAB1-binding protein 2 (PBP2); vertebrate vigilin; and human high-density lipoprotein binding protein (HDL-binding protein).

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan KH (CL0007), which has the following description:

The KH domain is thought to be the second most prevalent RNA binding motif in proteins. The motif is characterised by a conserved GXXXGXXG in the middle of the domain. Structures of KH reveal that the KH domain is arranged as either a beta-alpha-alpha-beta-beta (mini-KH domain) or beta-alpha-alpha-beta-beta-alpha (maxi-KH domain). The secondary elements are separated by at least four loop segments. The second loop is located between beta-1 and al The KH domain can be found either as single or multiple copies. The KH domain usually binds RNA as a multimer.

The clan contains the following 7 members:

KH_1 KH_2 KH_3 KH_4 KH_5 KH_6 MOEP19


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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Curation and family details

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Seed source: Wood V
Previous IDs: none
Type: Domain
Author: Coggill P
Number in seed: 711
Number in full: 959
Average length of the domain: 42.40 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 9.15 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.6 21.6
Trusted cut-off 21.6 21.6
Noise cut-off 21.5 21.5
Model length: 43
Family (HMM) version: 2
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the KH_3 domain has been found. There are 5 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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