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127  structures 8198  species 0  interactions 188697  sequences 11051  architectures

Family: HisKA (PF00512)

Summary: His Kinase A (phospho-acceptor) domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Two-component regulatory system". More...

Two-component regulatory system Edit Wikipedia article

Two-component systems serve as a basic stimulus-response coupling mechanism to allow organisms to sense and respond to changes in many different environmental conditions.[1] They consist of a membrane-bound histidine kinase that senses a specific environmental stimulus and a corresponding response regulator that mediates the cellular response, mostly through differential expression of target genes.[2]


  1. ^ Stock AM, Robinson VL, Goudreau PN (2000). "Two-component signal transduction". Annu. Rev. Biochem. 69: 183–215. doi:10.1146/annurev.biochem.69.1.183. PMID 10966457.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Mascher T, Helmann JD, Unden G (2006). "Stimulus perception in bacterial signal-transducing histidine kinases". Microbiol. Mol. Biol. Rev. 70 (4): 910–38. doi:10.1128/MMBR.00020-06. PMID 17158704.{{cite journal}}: CS1 maint: multiple names: authors list (link)

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

His Kinase A (phospho-acceptor) domain Provide feedback

Dimerisation and phospho-acceptor domain of histidine kinases.

Literature references

  1. Bilwes AM, Alex LA, Crane BR, Simon MI; , Cell 1999;96:131-141.: Structure of CheA, a signal-transducing histidine kinase. PUBMED:9989504 EPMC:9989504

  2. Li Y, Bahti P, Shaw N, Song G, Chen S, Zhang X, Zhang M, Cheng C, Yin J, Zhu JY, Zhang H, Che D, Xu H, Abbas A, Wang BC, Liu ZJ;, Proteins 2008;71:2109-13.: Crystal structure of a novel non-Pfam protein AF1514 from Archeoglobus fulgidus DSM 4304 solved by S-SAD using a Cr X-ray source. PUBMED:18361456 EPMC:18361456

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003661

This entry represents the dimerisation and phosphoacceptor domain found in some histidine kinases. Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms [ PUBMED:8868347 ]. Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation [ PUBMED:10426948 ]. Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and the phosphotransfer from aspartyl phosphate back to ADP or to water [ PUBMED:11145881 ]. The homodimeric domain includes the site of histidine autophosphorylation and phosphate transfer reactions. The structure of the homodimeric domain comprises a closed, four-helical bundle with a left-handed twist, formed by two identical alpha-hairpin subunits [ PUBMED:11406410 ].

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 His_Kinase_A (CL0025), which has the following description:

This is the dimerisation and phospho-acceptor domain of a sub-family of histidine kinases. It shares sequence similarity with Pfam:PF00512 and Pfam:PF07536. It is usually found adjacent to a C-terminal ATPase domain (Pfam:PF02518). This domain is found in a wide range of Bacteria and also several Archaea. It comprises one of the fundamental units of the two-component signal transduction system [2-7].

The clan contains the following 11 members:

H-kinase_dim HATPase_c HATPase_c_2 HATPase_c_3 HATPase_c_4 HATPase_c_5 HisKA HisKA_2 HisKA_3 HPTransfase HWE_HK


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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Representative proteomes UniProt

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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

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

HMM logo

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.

Note: You can also download the data file for the tree.

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: SMART
Previous IDs: signal;
Type: Domain
Sequence Ontology: SO:0000417
Author: SMART
Number in seed: 265
Number in full: 188697
Average length of the domain: 68 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 10.05 %

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 26.9 26.9
Trusted cut-off 26.9 26.9
Noise cut-off 26.8 26.8
Model length: 67
Family (HMM) version: 28
Download: download the raw HMM for this family

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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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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The tree shows the occurrence of this domain across different species. More...


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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 HisKA domain has been found. There are 127 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
A0A077Z953 View 3D Structure Click here
A0A077ZBE8 View 3D Structure Click here
A0A077ZEG6 View 3D Structure Click here
A0A077ZF75 View 3D Structure Click here
A0A077ZGU7 View 3D Structure Click here
A0A077ZHC6 View 3D Structure Click here
A0A077ZII7 View 3D Structure Click here
A0A077ZIK0 View 3D Structure Click here
A0A077ZM46 View 3D Structure Click here
A0A0D2DR06 View 3D Structure Click here
A0A0D2F223 View 3D Structure Click here
A0A0D2F2W2 View 3D Structure Click here
A0A0D2FB00 View 3D Structure Click here
A0A0D2FDB6 View 3D Structure Click here
A0A0D2FI18 View 3D Structure Click here
A0A0D2G2S2 View 3D Structure Click here
A0A0D2GFN6 View 3D Structure Click here
A0A0D2H179 View 3D Structure Click here
A0A0D2H214 View 3D Structure Click here
A0A0D2H4S0 View 3D Structure Click here
A0A0D2HH14 View 3D Structure Click here
A0A0D2HLJ0 View 3D Structure Click here
A0A0H3GHQ0 View 3D Structure Click here
A0A0H3GHZ7 View 3D Structure Click here
A0A0H3GK10 View 3D Structure Click here
A0A0H3GKS7 View 3D Structure Click here
A0A0H3GNY2 View 3D Structure Click here
A0A0H3GPB5 View 3D Structure Click here
A0A0H3GPJ3 View 3D Structure Click here
A0A0H3GPN8 View 3D Structure Click here
A0A0H3GQH3 View 3D Structure Click here
A0A0H3GQJ4 View 3D Structure Click here
A0A0H3GRS8 View 3D Structure Click here
A0A0H3GSM3 View 3D Structure Click here
A0A0H3GST5 View 3D Structure Click here
A0A0H3GSY4 View 3D Structure Click here
A0A0H3GTK9 View 3D Structure Click here
A0A0H3GUH1 View 3D Structure Click here
A0A0H3GYJ2 View 3D Structure Click here
A0A0H3GZ10 View 3D Structure Click here