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8  structures 10441  species 0  interactions 17637  sequences 256  architectures

Family: HATPase_c_2 (PF13581)

Summary: Histidine kinase-like ATPase domain

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

GHKL domain Edit Wikipedia article

Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
PDB 1ah6 EBI.jpg
Structure of the N-terminal domain of the yeast Hsp90 chaperone.[1]
Symbol HATPase_c
Pfam PF02518
InterPro IPR003594
SCOP 1ei1
CDD cd00075

The GHKL domain (Gyrase, Hsp90, Histidine Kinase, MutL) is an evolutionary conserved protein domain.[2]

This family represents the structurally related ATPase domains of histidine kinase, DNA gyrase B and HSP90. This domain is found in several ATP-binding proteins for example: histidine kinase, DNA gyrase B, topoisomerases,[3] heat shock protein HSP90,[4][5][6] phytochrome-like ATPases and DNA mismatch repair proteins. More information about this protein can be found at Protein of the Month: DNA Topoisomerase.[7]


  • Histidine kinase related protein, C-terminal IPR004358



  1. ^ Prodromou C, Roe SM, Piper PW, Pearl LH (June 1997). "A molecular clamp in the crystal structure of the N-terminal domain of the yeast Hsp90 chaperone". Nat. Struct. Biol. 4 (6): 477–82. doi:10.1038/nsb0697-477. PMID 9187656. 
  2. ^ Dutta R, Inouye M (January 2000). "GHKL, an emergent ATPase/kinase superfamily". Trends Biochem. Sci. 25 (1): 24–8. doi:10.1016/S0968-0004(99)01503-0. PMID 10637609. 
  3. ^ Bellon S, Parsons JD, Wei Y, Hayakawa K, Swenson LL, Charifson PS, Lippke JA, Aldape R, Gross CH (May 2004). "Crystal Structures of Escherichia coli Topoisomerase IV ParE Subunit (24 and 43 Kilodaltons): a Single Residue Dictates Differences in Novobiocin Potency against Topoisomerase IV and DNA Gyrase". Antimicrob. Agents Chemother. 48 (5): 1856–64. doi:10.1128/AAC.48.5.1856-1864.2004. PMC 400558. PMID 15105144. 
  4. ^ Immormino RM, Dollins DE, Shaffer PL, Soldano KL, Walker MA, Gewirth DT (October 2004). "Ligand-induced conformational shift in the N-terminal domain of GRP94, an Hsp90 chaperone". J. Biol. Chem. 279 (44): 46162–71. doi:10.1074/jbc.M405253200. PMID 15292259. 
  5. ^ Roe SM, Ali MM, Meyer P, Vaughan CK, Panaretou B, Piper PW, Prodromou C, Pearl LH (January 2004). "The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37)". Cell 116 (1): 87–98. doi:10.1016/S0092-8674(03)01027-4. PMID 14718169. 
  6. ^ Wright L, Barril X, Dymock B, Sheridan L, Surgenor A, Beswick M, Drysdale M, Collier A, Massey A, Davies N, Fink A, Fromont C, Aherne W, Boxall K, Sharp S, Workman P, Hubbard RE (June 2004). "Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms". Chem. Biol. 11 (6): 775–85. doi:10.1016/j.chembiol.2004.03.033. PMID 15217611. 
  7. ^ McDowall J (2006). "DNA Topoisomerase". Protein of the month. InterPro. 

This article incorporates text from the public domain Pfam and InterPro IPR003594

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.

Histidine kinase-like ATPase domain Provide feedback

No Pfam abstract.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003594

This domain is found in several ATP-binding proteins for example: histidine kinase, DNA gyrase B, topoisomerases [PUBMED:15105144], heat shock protein HSP90 [PUBMED:15292259, PUBMED:14718169, PUBMED:15217611], phytochrome-like ATPases and DNA mismatch repair proteins. The fold of this domain consists of two layers, alpha/beta, which contains an 8-stranded mixed beta-sheet.

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 9 members:

H-kinase_dim HATPase_c HATPase_c_2 HATPase_c_3 HATPase_c_5 HisKA HisKA_2 HisKA_3 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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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 NCBI
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Representative proteomes NCBI

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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.

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

External links

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.

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: Jackhmmer:D3Q5R6
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 78
Number in full: 17637
Average length of the domain: 123.90 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 40.53 %

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 27.4 27.4
Trusted cut-off 27.4 27.4
Noise cut-off 27.3 27.3
Model length: 125
Family (HMM) version: 2
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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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 HATPase_c_2 domain has been found. There are 8 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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