Summary

HWE histidine kinase

Two-component systems, consisting of a histidine kinase and a cognate response regulator protein, represent the best-known apparatus for transducing external cues into a physiological response in bacteria. The HWE domain is found in a subset of two-component system kinases, belonging to the same superfamily as PF00512 [1]. The family was defined by [1] the presence of a highly conserved H residue in the kinase domain and a WxE motif in a C-terminal ATPase domain that is related to PF02518. These proteins are found in a variety of alpha- and gamma-proteobacteria, with significant enrichment in the rhizobia.

Literature references

Karniol B, Vierstra RD; , J Bacteriol 2004;186:445-453.: The HWE Histidine Kinases, a New Family of Bacterial Two-Component Sensor Kinases with Potentially Diverse Roles in Environmental Signaling. PUBMED:14702314

InterPro entry IPR011102

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions PUBMED:16176121. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk PUBMED:18076326. These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more PUBMED:12372152. Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) PUBMED:10966457. The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response PUBMED:11934609, PUBMED:11489844.

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, PUBMED:11406410. Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation PUBMED:10426948, and CheA, which plays a central role in the chemotaxis system PUBMED:9989504. 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 (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water PUBMED:11145881. The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.

HKs can be roughly divided into two classes: orthodox and hybrid kinases PUBMED:8029829, PUBMED:1482126. Most orthodox HKs, typified by the Escherichia coli EnvZ protein, function as periplasmic membrane receptors and have a signal peptide and transmembrane segment(s) that separate the protein into a periplasmic N-terminal sensing domain and a highly conserved cytoplasmic C-terminal kinase core. Members of this family, however, have an integral membrane sensor domain. Not all orthodox kinases are membrane bound, e.g., the nitrogen regulatory kinase NtrB (GlnL) is a soluble cytoplasmic HK PUBMED:10966457. Hybrid kinases contain multiple phosphodonor and phosphoacceptor sites and use multi-step phospho-relay schemes instead of promoting a single phosphoryl transfer. In addition to the sensor domain and kinase core, they contain a CheY-like receiver domain and a His-containing phosphotransfer (HPt) domain.

The HWE domain is found in a subset of two-component system kinases, belonging to the same superfamily as PUBMED:14702314. In PUBMED:14702314, the HWE family was defined by the presence of conserved a H residue and a WXE motifs and was limited to members of the proteobacteria. However, many homologues of this domain are lack the WXE motif. Furthermore, homologues are found in a wide range of Gram-positive and Gram-negative bacteria as well as in several archaea.

Clan

This family is a member of clan His_Kinase_A (CL0025), which contains the following 6 members:

DUF2328 HATPase_c HisKA HisKA_2 HisKA_3 HWE_HK

External database links

PANDIT:	PF07536
SYSTERS:	HWE_HK

Domain organisation

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

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

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Alignment:	Seed (44) Full (513) NCBI (1001) Metagenomics (212)
Viewer:

Formatting options

Alignment:	Seed (44) Full (513)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (44) Full (513) NCBI (1001) Metagenomics (212)
Full length sequences	Full-sequences (513)

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 HMMER2.

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...

Trees

This page displays the phylogenetic tree for this family. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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

Seed source:

[1]

Previous IDs:

none

Type:

Domain

Author:

Studholme DJ

Number in seed:

44

Number in full:

513

Average length of the domain:

82.20 aa

Average identity of full alignment:

32 %

Average coverage of the sequence by the domain:

14.06 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	21.1	21.1
Trusted cut-off	21.2	21.2
Noise cut-off	20.9	21.0

Model length:

83

Family (HMM) version:

7

Download:

download the raw HMM for this family

Species distribution

Tree controls

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

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Family: HWE_HK (PF07536)

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