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3  structures 5154  species 0  interactions 5779  sequences 12  architectures

Family: HrcA (PF01628)

Summary: HrcA protein C terminal domain

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HrcA protein C terminal domain Provide feedback

HrcA is found to negatively regulate the transcription of heat shock genes [1,2]. HrcA contains an amino terminal helix-turn-helix domain, however this corresponds to the carboxy terminal domain.

Literature references

  1. Schulz A, Schumann W; , J Bacteriol 1996;178:1088-1093.: hrcA, the first gene of the Bacillus subtilis dnaK operon encodes a negative regulator of class I heat shock genes. PUBMED:8576042 EPMC:8576042

  2. Roberts RC, Toochinda C, Avedissian M, Baldini RL, Gomes SL, Shapiro L; , J Bacteriol 1996;178:1829-1841.: Identification of a Caulobacter crescentus operon encoding hrcA, involved in negatively regulating heat-inducible transcription, and the chaperone gene grpE. PUBMED:8606155 EPMC:8606155

This tab holds annotation information from the InterPro database.

InterPro entry IPR021153

This entry represents the C terminus of HrcA, consisting of the GAF-like domain with the inserted dimerising domain.

Prokaryotic cells have a defence mechanism against a sudden heat-shock stress. Commonly, they induce a set of proteins that protect cellular proteins from being denatured by heat. Among such proteins are the GroE and DnaK chaperones whose transcription is regulated by a heat-shock repressor protein HrcA. HrcA is a winged helix-turn-helix repressor that negatively regulates the transcription of dnaK and groE operons by binding the upstream CIRCE (controlling inverted repeat of chaperone expression) element. In Bacillus subtilis this element is a perfect 9 base pair inverted repeat separated by a 9 base pair spacer.

The crystal structure of a heat-inducible transcriptional repressor, HrcA, from Thermotoga maritima has been reported at 2.2A resolution. HrcA is composed of three domains: an N-terminal winged helix-turn-helix domain (WHTH), a GAF-like domain, and an inserted dimerizing domain (IDD). The IDD shows a unique structural fold with an anti-parallel beta-sheet composed of three beta-strands sided by four alpha-helices. HrcA crystallises as a dimer, which is formed through hydrophobic contact between the IDDs and a limited contact that involves conserved residues between the GAF-like domains [ PUBMED:15979091 ]. The structural studies suggest that the inactive form of HrcA is the dimer and this is converted to its DNA-binding form by interaction with GroEL, which binds to a conserved C-terminal sequence region [ PUBMED:19277496 , PUBMED:15979091 ]. Comparison of the HrcA-CIRCE complexes from B. subtilis and Bacillus thermoglucosidasius (Geobacillus thermoglucosidasius), which grow at vastly different ranges of temperature shows that the thermostability profiles were consistent with the difference in the growth temperatures suggesting that HrcA can function as a thermosensor to detect temperature changes in cells [ PUBMED:12486078 ]. Any increase in temperature causes the dissociation of the HrcA from the CIRCE complex with the concomitant activation of transcription of the groE and dnaK operons.

Gene Ontology

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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 GAF (CL0161), which has the following description:

A clan of related transcriptional regulator domains.

The clan contains the following 18 members:

Autoind_bind bHLH-MYC_N CCB2_CCB4 CodY DraK_HK_N DUF3369 DUF484 DUF5628 GAF GAF_2 GAF_3 HbpS-like HNOBA HrcA IclR PdtaS_GAF PHY SpoVT_C


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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: Pfam-B_1133 (release 4.1)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 581
Number in full: 5779
Average length of the domain: 219.80 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 63.87 %

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 22.2 22.2
Trusted cut-off 22.4 24.9
Noise cut-off 22.1 21.5
Model length: 219
Family (HMM) version: 24
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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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 HrcA domain has been found. There are 3 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
P9WMK3 View 3D Structure Click here
Q2FXZ0 View 3D Structure Click here