Summary: Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
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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 | |||||||||||
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| Identifiers | |||||||||||
| Symbol | HATPase_c | ||||||||||
| Pfam | PF02518 | ||||||||||
| InterPro | IPR003594 | ||||||||||
| SMART | HATPase_c | ||||||||||
| SCOP2 | 1ei1 / SCOPe / SUPFAM | ||||||||||
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The GHKL domain (Gyrase, Hsp90, Histidine Kinase, MutL) is an evolutionary conserved protein domain.
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,[1] heat shock protein HSP90,[2][3][4] phytochrome-like ATPases and DNA mismatch repair proteins. More information about this protein can be found at Protein of the Month: DNA Topoisomerase.[5]
Subfamilies
Members
- BCKDK
- HSP90AA1, HSP90AB1, HSP90B1
- MLH1, MLH3, MORC1, MORC2, MORC3, MORC4
- PDK1, PDK2, PDK3, PDK4
- PMS1, PMS2, PMS2L1, PMS2L11, PMS2L3, PMS4L
- TOP2A, TOP2B
- TRAP1, TRRAP
References
- ^ Bellon S, Parsons JD, Wei Y, Hayakawa K, Swenson LL, Charifson PS, Lippke JA, Aldape R, Gross CH (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. PMC 400558. PMID 15105144.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Immormino RM, Dollins DE, Shaffer PL, Soldano KL, Walker MA, Gewirth DT (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Roe SM, Ali MM, Meyer P, Vaughan CK, Panaretou B, Piper PW, Prodromou C, Pearl LH (2004). "The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37)". Cell. 116 (1): 87–98. PMID 14718169.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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 (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ McDowall J (2006). "DNA Topoisomerase". Protein of the month. InterPro.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help)
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This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This is the Wikipedia entry entitled "Hsp90". More...
Hsp90 Edit Wikipedia article
The molecular chaperone Hsp90 (Wegele et al. 2004) is one of the most abundant proteins in unstressed cells. It is an ubiquitous molecular chaperone found in eubacteria and all branches of eukarya, but it is apparently absent in archaea. Whereas cytoplasmic Hsp90 is essential for viability under all conditions in eukaryotes, the bacterial homologue HtpG is dispensable under non heat stress conditions. In mammalian cells, there are two genes encoding cytosolic Hsp90 homologues, with the human Hsp90a showing 85% sequence identity to Hsp90b. There is also high homology to Hsp90 from lower eukaryotes and prokaryotes: yeast Hsp90 is 60% identical to human Hsp90a and HtpG is still 34% identical to human Hsp90a.
Structural properties of Hsp90
Hsp90 is an elongated dimer with a low dissociation constant. The quaternary structure is important for the ATPase activity and associated conformational changes. Hsp90 consists of three major domains: a highly conserved amino-terminal ATPase domain, a middle domain, and a carboxy-terminal dimerization domain.
The Hsp90 ATPase activity
ATP hydrolysis seems to be of crucial importance for Hsp90 function in vivo, because mutants that do not hydrolyze ATP do not support the functions of Hsp90 essential for viability. The crystal structure of the amino-terminal domain of Hsp90 in complex with ADP showed that, in contrast to most other ATP hydrolyzing proteins, ATP is bound in an unusually kinked conformation.
Inhibitors
Known inhibitors of the ATPase hydrolysis function of Hsp90 are the fungal antibiotics Geldanamycin and Radicicol
Functional properties
In the mammalian system, the molecular chaperones Hsp70 and Hsp90 are involved in the folding and maturation of key regulatory proteins, like steroid hormone receptors, transcription factors like the tumor suppressor protein p53, and kinases, some of which are involved in cancer progression. Hsp70 and Hsp90 form a multichaperone complex, in which both are connected by a third protein called Hop. The connection of and the interplay between the two chaperone machineries is of crucial importance for cell viability.
References
- Wegele H, Muller L, Buchner J. (2004). Hsp70 and Hsp90 - a relay team for protein folding. Rev Physiol Biochem Pharmacol 151:1-44
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-, DNA gyrase B-, and HSP90-like ATPase Provide feedback
This family represents the structurally related ATPase domains of histidine kinase, DNA gyrase B and HSP90.
Literature references
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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
| SCOOP: | HATPase_c_2 HATPase_c_3 HATPase_c_5 HPTransfase |
| Similarity to PfamA using HHSearch: | HATPase_c_2 HATPase_c_3 HATPase_c_5 |
External database links
| SCOP: | 1ei1 |
| SMART: | HATPase_c |
This tab holds annotation information from the InterPro database.
InterPro entry IPR003594
This domain is found in several ATP-binding proteins, including: histidine kinase [ PUBMED:15157101 ], 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.
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_HKAlignments
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...
View options
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.
| Seed (658) |
Full (300774) |
Representative proteomes | UniProt (1393617) |
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| RP15 (38009) |
RP35 (144799) |
RP55 (308725) |
RP75 (539024) |
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| Jalview | |||||||
| HTML | |||||||
| PP/heatmap | 1 | ||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
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Download options
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.
| Seed (658) |
Full (300774) |
Representative proteomes | UniProt (1393617) |
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|---|---|---|---|---|---|---|---|
| RP15 (38009) |
RP35 (144799) |
RP55 (308725) |
RP75 (539024) |
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| Raw Stockholm | |||||||
| Gzipped | |||||||
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...
Trees
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
| Seed source: | SMART |
| Previous IDs: | none |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
SMART, Griffiths-Jones SR 
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| Number in seed: | 658 |
| Number in full: | 300774 |
| Average length of the domain: | 117.1 aa |
| Average identity of full alignment: | 25 % |
| Average coverage of the sequence by the domain: | 17.95 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 112 | ||||||||||||
| Family (HMM) version: | 29 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Colour assignments
Archea
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Eukaryota
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Bacteria
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Other sequences
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Viruses
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Unclassified
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Viroids
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Unclassified sequence
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Selections
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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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Structures
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 domain has been found. There are 1131 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.
