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179  structures 8830  species 0  interactions 109086  sequences 849  architectures

Family: KH_1 (PF00013)

Summary: KH domain

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This is the Wikipedia entry entitled "KH domain". More...

KH domain Edit Wikipedia article

KH domain
PDB 2anr EBI.png
Structure of a KH domain from the human protein vigilin.
Pfam clanCL0007
KH domain

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 an 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" (PDF). 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. Autoantibodies to Nova, a KH domain protein, cause paraneoplastic opsoclonus ataxia.

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. Musco G, Stier G, Joseph C, Castiglione Morelli MA, Nilges M, Gibson TJ, Pastore A; , Cell 1996;85:237-245.: Three-dimensional structure and stability of the KH domain: molecular insights into the fragile X syndrome. PUBMED:8612276 EPMC:8612276

Internal database links

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 14 members:

DUF2096 DUF370 KH_1 KH_10 KH_2 KH_4 KH_5 KH_6 KH_7 KH_8 KH_9 MOEP19 MRP-S24 SLS


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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Published_alignment
Previous IDs: KH-domain; KH;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Eddy SR , Finn RD
Number in seed: 783
Number in full: 109086
Average length of the domain: 65.10 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 22.52 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.5 21.5
Trusted cut-off 21.5 21.5
Noise cut-off 21.4 21.4
Model length: 66
Family (HMM) version: 32
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Species distribution

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Colour assignments

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_1 domain has been found. There are 179 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0B4J1B0 View 3D Structure Click here
A0A0B4KGY6 View 3D Structure Click here
A0A0G2JVW3 View 3D Structure Click here
A0A0G2JXZ5 View 3D Structure Click here
A0A0G2K0Y2 View 3D Structure Click here
A0A0G2K916 View 3D Structure Click here
A0A0G2KAA1 View 3D Structure Click here
A0A0N7KCM4 View 3D Structure Click here
A0A0N7KR20 View 3D Structure Click here
A0A0P0V3L2 View 3D Structure Click here
A0A0P0V4C6 View 3D Structure Click here
A0A0P0VE90 View 3D Structure Click here
A0A0P0VRQ0 View 3D Structure Click here
A0A0P0XB22 View 3D Structure Click here
A0A0P0XCV9 View 3D Structure Click here
A0A0P0XUW3 View 3D Structure Click here
A0A0P0XW96 View 3D Structure Click here
A0A0P0YCA1 View 3D Structure Click here
A0A0R0EVK5 View 3D Structure Click here
A0A0R0EX89 View 3D Structure Click here
A0A0R0FKW9 View 3D Structure Click here
A0A0R0G6M7 View 3D Structure Click here
A0A0R0ID14 View 3D Structure Click here
A0A0R0IQI3 View 3D Structure Click here
A0A0R0JC83 View 3D Structure Click here
A0A0R0K7Z7 View 3D Structure Click here
A0A0R4IBT0 View 3D Structure Click here
A0A0R4IJS6 View 3D Structure Click here
A0A0R4ILY0 View 3D Structure Click here
A0A0R4ISK8 View 3D Structure Click here
A0A0R4IVY2 View 3D Structure Click here
A0A0R4J498 View 3D Structure Click here
A0A1D6DW04 View 3D Structure Click here
A0A1D6E652 View 3D Structure Click here
A0A1D6E8E9 View 3D Structure Click here
A0A1D6ECT3 View 3D Structure Click here
A0A1D6FP21 View 3D Structure Click here
A0A1D6FSF0 View 3D Structure Click here
A0A1D6FU64 View 3D Structure Click here
A0A1D6G6T5 View 3D Structure Click here