Summary: Histidine kinase N terminal
This is the Wikipedia entry entitled "Two-component regulatory system". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at firstname.lastname@example.org and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Two-component regulatory system Edit Wikipedia article
|His Kinase A (phospho-acceptor) domain|
solution structure of the homodimeric domain of envz from escherichia coli by multi-dimensional nmr.
|Signal transducing histidine kinase, homodimeric domain|
structure of chea domain p4 in complex with tnp-atp
|Histidine kinase N terminal|
|Osmosensitive K+ channel His kinase sensor domain|
In the field of molecular biology, a two-component regulatory system serves as a basic stimulus-response coupling mechanism to allow organisms to sense and respond to changes in many different environmental conditions. They typically 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. Two component signaling systems are widely occurring in prokaryotes whereas only a few two-component systems have been identified in eukaryotic organisms.
Mechanism of action
Signal transduction occurs through the transfer of phosphoryl groups from adenosine triphosphate (ATP) to a specific histidine residue in the histidine kinases (HK). This is an autophosphorylation reaction. The response regulators (RRs) were shown to be phosphorylated on an aspartate residue and to be protein phosphatases for the histidine kinases. The response regulators are therefore enzymes with a covalent intermediate that alters response-regulator output function. Phosphorylation causes the response regulator's conformation to change, usually activating an attached output domain, which then leads to the stimulation (or repression) of expression of target genes. The level of phosphorylation of the response regulator controls its activity. 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.
Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk. These pathways have been adapted to respond to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, temperature, chemoattractants, pH and more. In Escherichia coli, the EnvZ/OmpR osmoregulation system controls the differential expression of the outer membrane porin proteins OmpF and OmpC. The KdpD sensor kinase proteins regulate the kdpFABC operon responsible for potassium transport in bacteria including E. coli and Clostridium acetobutylicum. The N-terminal domain of this protein forms part of the cytoplasmic region of the protein, which may be the sensor domain responsible for sensing turgor pressure.
A variant of the two-component system is the phospho-relay system. Here a hybrid HK autophosphorylates 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.
Signal transducing histidine kinases are the key elements in two-component signal transduction systems. Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation, and CheA, which plays a central role in the chemotaxis system. 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. 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. Most orthodox HKs, typified by the E. 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. 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.
- P2CS database
- Stock AM, Robinson VL, Goudreau PN (2000). "Two-component signal transduction". Annu. Rev. Biochem. 69 (1): 183–215. doi:10.1146/annurev.biochem.69.1.183. PMID 10966457.
- 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. PMC 1698512. PMID 17158704.
- Stock JB, Ninfa AJ, Stock AM (1989). "Protein phosphorylation and regulation of adaptive responses in bacteria". Microbiol. Rev. 53 (4): 450–90. PMC 372749. PMID 2556636.
- 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.
- Skerker JM, Prasol MS, Perchuk BS, Biondi EG, Laub MT (October 2005). "Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis". PLoS Biol. 3 (10): e334. doi:10.1371/journal.pbio.0030334. PMC 1233412. PMID 16176121.
- Laub MT, Goulian M (2007). "Specificity in two-component signal transduction pathways". Annu. Rev. Genet. 41: 121–45. doi:10.1146/annurev.genet.41.042007.170548. PMID 18076326.
- Wolanin PM, Thomason PA, Stock JB (September 2002). "Histidine protein kinases: key signal transducers outside the animal kingdom". Genome Biol. 3 (10): REVIEWS3013. doi:10.1186/gb-2002-3-10-reviews3013. PMC 244915. PMID 12372152.
- Attwood PV, Piggott MJ, Zu XL, Besant PG (2007). "Focus on phosphohistidine". Amino Acids 32 (1): 145–56. doi:10.1007/s00726-006-0443-6. PMID 17103118.
- Buckler DR, Anand GS, Stock AM (2000). "Response-regulator phosphorylation and activation: a two-way street?". Trends Microbiol. 8 (4): 153–6. doi:10.1016/S0966-842X(00)01707-8. PMID 10754569.
- Treuner-Lange A, Kuhn A, Durre P (July 1997). "The kdp system of Clostridium acetobutylicum: cloning, sequencing, and transcriptional regulation in response to potassium concentration". J. Bacteriol. 179 (14): 4501–12. PMC 179285. PMID 9226259.
- Walderhaug MO, Polarek JW, Voelkner P, Daniel JM, Hesse JE, Altendorf K, Epstein W (April 1992). "KdpD and KdpE, proteins that control expression of the kdpABC operon, are members of the two-component sensor-effector class of regulators". J. Bacteriol. 174 (7): 2152–9. PMC 205833. PMID 1532388.
- Varughese KI (April 2002). "Molecular recognition of bacterial phosphorelay proteins". Curr. Opin. Microbiol. 5 (2): 142–8. doi:10.1016/S1369-5274(02)00305-3. PMID 11934609.
- Hoch JA, Varughese KI (September 2001). "Keeping signals straight in phosphorelay signal transduction". J. Bacteriol. 183 (17): 4941–9. doi:10.1128/jb.183.17.4941-4949.2001. PMC 95367. PMID 11489844.
- Perego M, Hoch JA (March 1996). "Protein aspartate phosphatases control the output of two-component signal transduction systems". Trends Genet. 12 (3): 97–101. doi:10.1016/0168-9525(96)81420-X. PMID 8868347.
- West AH, Stock AM (June 2001). "Histidine kinases and response regulator proteins in two-component signaling systems". Trends Biochem. Sci. 26 (6): 369–76. doi:10.1016/S0968-0004(01)01852-7. PMID 11406410.
- Tomomori C, Tanaka T, Dutta R, Park H, Saha SK, Zhu Y, Ishima R, Liu D, Tong KI, Kurokawa H, Qian H, Inouye M, Ikura M (August 1999). "Solution structure of the homodimeric core domain of Escherichia coli histidine kinase EnvZ". Nat. Struct. Biol. 6 (8): 729–34. doi:10.1038/11495. PMID 10426948.
- Bilwes AM, Alex LA, Crane BR, Simon MI (January 1999). "Structure of CheA, a signal-transducing histidine kinase". Cell 96 (1): 131–41. doi:10.1016/S0092-8674(00)80966-6. PMID 9989504.
- Vierstra RD, Davis SJ (December 2000). "Bacteriophytochromes: new tools for understanding phytochrome signal transduction". Semin. Cell Dev. Biol. 11 (6): 511–21. doi:10.1006/scdb.2000.0206. PMID 11145881.
- Alex LA, Simon MI (April 1994). "Protein histidine kinases and signal transduction in prokaryotes and eukaryotes". Trends Genet. 10 (4): 133–8. doi:10.1016/0168-9525(94)90215-1. PMID 8029829.
- Parkinson JS, Kofoid EC (1992). "Communication modules in bacterial signaling proteins". Annu. Rev. Genet. 26: 71–112. doi:10.1146/annurev.ge.26.120192.000443. PMID 1482126.
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 N terminal Provide feedback
This domain is found at the N terminal of sensor histidine kinase proteins.
External database links
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Loading domain graphics...
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
If you find these logos useful in your own work, please consider citing the following article:
Note: You can also download the data file for the tree.
Curation and family details
|Number in seed:||7|
|Number in full:||130|
|Average length of the domain:||137.40 aa|
|Average identity of full alignment:||58 %|
|Average coverage of the sequence by the domain:||43.26 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||5|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
How the sunburst is generated
Colouring and labels
Anomalies in the taxonomy tree
Missing taxonomic levels
Unmapped species names
Too many species/sequences
The tree shows the occurrence of this domain across different species. More...
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
There is 1 interaction for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 HisK_N 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 seqence.
Loading structure mapping...