Summary: Osmosensitive K+ channel His kinase sensor domain
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Two-component regulatory system Edit Wikipedia article
|His Kinase A (phospho-acceptor) domain|
solved structure of the homodimeric domain of EnvZ from Escherichia coli by multi-dimensional NMR.
|SCOPe||1b3q / SUPFAM|
|Signal transducing histidine kinase, homodimeric domain|
structure of CheA domain p4 in complex with TNP-ATP
|SCOPe||1b3q / SUPFAM|
|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. Two-component systems 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. Although two-component signaling systems are found in all domains of life, they are most common by far in bacteria, particularly in Gram-negative and cyanobacteria; both histidine kinases and response regulators are among the largest gene families in bacteria. They are much less common in archaea and eukaryotes; although they do appear in yeasts, filamentous fungi, and slime molds, and are common in plants, two-component systems have been described as "conspicuously absent" from animals.
Two-component systems accomplish signal transduction through the phosphorylation of a response regulator (RR) by a histidine kinase (HK). Histidine kinases are typically homodimeric transmembrane proteins containing a histidine phosphotransfer domain and an ATP binding domain, though there are reported examples of histidine kinases in the atypical HWE and HisKA2 families that are not homodimers. Response regulators may consist only of a receiver domain, but usually are multi-domain proteins with a receiver domain and at least one effector or output domain, often involved in DNA binding. Upon detecting a particular change in the extracellular environment, the HK performs an autophosphorylation reaction, transferring a phosphoryl group from adenosine triphosphate (ATP) to a specific histidine residue. The cognate response regulator (RR) then catalyzes the transfer of the phosphoryl group to an aspartate residue on the response regulator's receiver domain. This typically triggers a conformational change that activates the RR's effector domain, which in turn produces the cellular response to the signal, usually by stimulating (or repressing) expression of target genes.
Many HKs are bifunctional and possess phosphatase activity against their cognate response regulators, so that their signaling output reflects a balance between their kinase and phosphatase activities. Many response regulators also auto-dephosphorylate, and the relatively labile phosphoaspartate can also be hydrolyzed non-enzymatically. The overall level of phosphorylation of the response regulator ultimately controls its activity.
Some histidine kinases are hybrids that contain an internal receiver domain. In these cases, a hybrid HK autophosphorylates and then transfers the phosphoryl group to its own 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. This system is called a phosphorelay. Almost 25% of bacterial HKs are of the hybrid type, as are the large majority of eukaryotic HKs.
Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions. 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. The average number of two-component systems in a bacterial genome has been estimated as around 30, or about 1-2% of a prokaryote's genome. A few bacteria have none at all - typically endosymbionts and pathogens - and others contain over 200. All such systems must be closely regulated to prevent cross-talk, which is rare in vivo.
In Escherichia coli, the osmoregulatory EnvZ/OmpR two-component 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.
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 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.
The number of two-component systems present in a bacterial genome is highly correlated with genome size as well as ecological niche; bacteria that occupy niches with frequent environmental fluctuations possess more histidine kinases and response regulators. New two-component systems may arise by gene duplication or by lateral gene transfer, and the relative rates of each process vary dramatically across bacterial species. In most cases, response regulator genes are located in the same operon as their cognate histidine kinase; lateral gene transfers are more likely to preserve operon structure than gene duplications.
Two-component systems are rare in eukaryotes. They appear in yeasts, filamentous fungi, and slime molds, and are relatively common in plants, but have been described as "conspicuously absent" from animals. Two-component systems in eukaryotes likely originate from lateral gene transfer, often from endosymbiotic organelles, and are typically of the hybrid kinase phosphorelay type. For example, in the yeast Candida albicans, genes found in the nuclear genome likely originated from endosymbiosis and remain targeted to the mitochondria. Two-component systems are well-integrated into developmental signaling pathways in plants, but the genes probably originated from lateral gene transfer from chloroplasts. An example is the chloroplast sensor kinase (CSK) gene in Arabidopsis thaliana, derived from chloroplasts but now integrated into the nuclear genome. CSK function provides a redox-based regulatory system that couples photosynthesis to chloroplast gene expression; this observation has been described as a key prediction of the CoRR hypothesis, which aims to explain the retention of genes encoded by endosymbiotic organelles.
It is unclear why canonical two-component systems are rare in eukaryotes, with many similar functions having been taken over by signaling systems based on serine, threonine, or tyrosine kinases; it has been speculated that the chemical instability of phosphoaspartate is responsible, and that increased stability is needed to transduce signals in the more complex eukaryotic cell. Notably, cross-talk between signaling mechanisms is very common in eukaryotic signaling systems but rare in bacterial two-component systems.
Because of their sequence similarity and operon structure, many two-component systems - particularly histidine kinases - are relatively easy to identify through bioinformatics analysis. (By contrast, eukaryotic kinases are typically easily identified, but they are not easily paired with their substrates.) A database of prokaryotic two-component systems called P2CS has been compiled to document and classify known examples, and in some cases to make predictions about the cognates of "orphan" histidine kinase or response regulator proteins that are genetically unlinked to a partner.
- http://www.p2cs.org: The Prokaryotic 2-Component Systems Database
- Stock AM, Robinson VL, Goudreau PN (2000). "Two-component signal transduction". Annual Review of Biochemistry. 69 (1): 183â€“215. doi:10.1146/annurev.biochem.69.1.183. PMID 10966457.
- Mascher T, Helmann JD, Unden G (Dec 2006). "Stimulus perception in bacterial signal-transducing histidine kinases". Microbiology and Molecular Biology Reviews. 70 (4): 910â€“38. doi:10.1128/MMBR.00020-06. PMC 1698512. PMID 17158704.
- Capra EJ, Laub MT (2012). "Evolution of two-component signal transduction systems". Annual Review of Microbiology. 66: 325â€“47. doi:10.1146/annurev-micro-092611-150039. PMC 4097194. PMID 22746333.
- Herrou, J; Crosson, S; Fiebig, A (Feb 2017). "Structure and function of HWE/HisKA2-family sensor histidine kinases". Curr. Opin. Microbiol. 36: 47â€“54. doi:10.1016/j.mib.2017.01.008. PMC 5534388. PMID 28193573.
- Sanders DA, Gillece-Castro BL, Stock AM, Burlingame AL, Koshland DE (Dec 1989). "Identification of the site of phosphorylation of the chemotaxis response regulator protein, CheY". The Journal of Biological Chemistry. 264 (36): 21770â€“8. PMID 2689446.
- Sanders DA, Gillece-Castro BL, Burlingame AL, Koshland DE (Aug 1992). "Phosphorylation site of NtrC, a protein phosphatase whose covalent intermediate activates transcription". Journal of Bacteriology. 174 (15): 5117â€“22. doi:10.1128/jb.174.15.5117-5122.1992. PMC 206329. PMID 1321122.
- West AH, Stock AM (Jun 2001). "Histidine kinases and response regulator proteins in two-component signaling systems". Trends in Biochemical Sciences. 26 (6): 369â€“76. doi:10.1016/s0968-0004(01)01852-7. PMID 11406410.
- Stock JB, Ninfa AJ, Stock AM (Dec 1989). "Protein phosphorylation and regulation of adaptive responses in bacteria". Microbiological Reviews. 53 (4): 450â€“90. PMC 372749. PMID 2556636.
- Varughese KI (Apr 2002). "Molecular recognition of bacterial phosphorelay proteins". Current Opinion in Microbiology. 5 (2): 142â€“8. doi:10.1016/S1369-5274(02)00305-3. PMID 11934609.
- Hoch JA, Varughese KI (Sep 2001). "Keeping signals straight in phosphorelay signal transduction". Journal of Bacteriology. 183 (17): 4941â€“9. doi:10.1128/jb.183.17.4941-4949.2001. PMC 95367. PMID 11489844.
- Skerker JM, Prasol MS, Perchuk BS, Biondi EG, Laub MT (Oct 2005). "Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis". PLoS Biology. 3 (10): e334. doi:10.1371/journal.pbio.0030334. PMC 1233412. PMID 16176121.
- Wolanin PM, Thomason PA, Stock JB (Sep 2002). "Histidine protein kinases: key signal transducers outside the animal kingdom". Genome Biology. 3 (10): REVIEWS3013. doi:10.1186/gb-2002-3-10-reviews3013. PMC 244915. PMID 12372152.
- Attwood PV, Piggott MJ, Zu XL, Besant PG (Jan 2007). "Focus on phosphohistidine". Amino Acids. 32 (1): 145â€“56. doi:10.1007/s00726-006-0443-6. PMID 17103118.
- Schaller, GE; Shiu, SH; Armitage, JP (10 May 2011). "Two-component systems and their co-option for eukaryotic signal transduction". Current Biology. 21 (9): R320â€“30. doi:10.1016/j.cub.2011.02.045. PMID 21549954.
- Salvado, B; Vilaprinyo, E; Sorribas, A; Alves, R (2015). "A survey of HK, HPt, and RR domains and their organization in two-component systems and phosphorelay proteins of organisms with fully sequenced genomes". PeerJ. 3: e1183. doi:10.7717/peerj.1183. PMC 4558063. PMID 26339559.
- Wuichet, K; Cantwell, BJ; Zhulin, IB (April 2010). "Evolution and phyletic distribution of two-component signal transduction systems". Current Opinion in Microbiology. 13 (2): 219â€“25. doi:10.1016/j.mib.2009.12.011. PMC 3391504. PMID 20133179.
- Shi, X; Wegener-FeldbrÃ¼gge, S; Huntley, S; Hamann, N; Hedderich, R; SÃ¸gaard-Andersen, L (January 2008). "Bioinformatics and experimental analysis of proteins of two-component systems in Myxococcus xanthus". Journal of Bacteriology. 190 (2): 613â€“24. doi:10.1128/jb.01502-07. PMC 2223698. PMID 17993514.
- Laub MT, Goulian M (2007). "Specificity in two-component signal transduction pathways". Annual Review of Genetics. 41: 121â€“45. doi:10.1146/annurev.genet.41.042007.170548. PMID 18076326.
- Buckler DR, Anand GS, Stock AM (Apr 2000). "Response-regulator phosphorylation and activation: a two-way street?". Trends in Microbiology. 8 (4): 153â€“6. doi:10.1016/S0966-842X(00)01707-8. PMID 10754569.
- Treuner-Lange A, Kuhn A, DÃ¼rre P (Jul 1997). "The kdp system of Clostridium acetobutylicum: cloning, sequencing, and transcriptional regulation in response to potassium concentration". Journal of Bacteriology. 179 (14): 4501â€“12. doi:10.1128/jb.179.14.4501-4512.1997. PMC 179285. PMID 9226259.
- Walderhaug MO, Polarek JW, Voelkner P, Daniel JM, Hesse JE, Altendorf K, Epstein W (Apr 1992). "KdpD and KdpE, proteins that control expression of the kdpABC operon, are members of the two-component sensor-effector class of regulators". Journal of Bacteriology. 174 (7): 2152â€“9. doi:10.1128/jb.174.7.2152-2159.1992. PMC 205833. PMID 1532388.
- Perego M, Hoch JA (Mar 1996). "Protein aspartate phosphatases control the output of two-component signal transduction systems". Trends in Genetics. 12 (3): 97â€“101. doi:10.1016/0168-9525(96)81420-X. PMID 8868347.
- West AH, Stock AM (Jun 2001). "Histidine kinases and response regulator proteins in two-component signaling systems". Trends in Biochemical Sciences. 26 (6): 369â€“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 (Aug 1999). "Solution structure of the homodimeric core domain of Escherichia coli histidine kinase EnvZ". Nature Structural Biology. 6 (8): 729â€“34. doi:10.1038/11495. PMID 10426948.
- Bilwes AM, Alex LA, Crane BR, Simon MI (Jan 1999). "Structure of CheA, a signal-transducing histidine kinase". Cell. 96 (1): 131â€“41. doi:10.1016/S0092-8674(00)80966-6. PMID 9989504.
- Vierstra RD, Davis SJ (Dec 2000). "Bacteriophytochromes: new tools for understanding phytochrome signal transduction". Seminars in Cell & Developmental Biology. 11 (6): 511â€“21. doi:10.1006/scdb.2000.0206. PMID 11145881.
- Alex LA, Simon MI (Apr 1994). "Protein histidine kinases and signal transduction in prokaryotes and eukaryotes". Trends in Genetics. 10 (4): 133â€“8. doi:10.1016/0168-9525(94)90215-1. PMID 8029829.
- Parkinson JS, Kofoid EC (1992). "Communication modules in bacterial signaling proteins". Annual Review of Genetics. 26: 71â€“112. doi:10.1146/annurev.ge.26.120192.000443. PMID 1482126.
- Galperin MY (Jun 2006). "Structural classification of bacterial response regulators: diversity of output domains and domain combinations". Journal of Bacteriology. 188 (12): 4169â€“82. doi:10.1128/JB.01887-05. PMC 1482966. PMID 16740923.
- Alm E, Huang K, Arkin A (Nov 2006). "The evolution of two-component systems in bacteria reveals different strategies for niche adaptation". PLoS Computational Biology. 2 (11): e143. doi:10.1371/journal.pcbi.0020143. PMC 1630713. PMID 17083272.
- Mavrianos J, Berkow EL, Desai C, Pandey A, Batish M, Rabadi MJ, Barker KS, Pain D, Rogers PD, Eugenin EA, Chauhan N (Jun 2013). "Mitochondrial two-component signaling systems in Candida albicans". Eukaryotic Cell. 12 (6): 913â€“22. doi:10.1128/EC.00048-13. PMC 3675996. PMID 23584995.
- Puthiyaveetil S, Kavanagh TA, Cain P, Sullivan JA, Newell CA, Gray JC, Robinson C, van der Giezen M, Rogers MB, Allen JF (Jul 2008). "The ancestral symbiont sensor kinase CSK links photosynthesis with gene expression in chloroplasts". Proceedings of the National Academy of Sciences of the United States of America. 105 (29): 10061â€“6. doi:10.1073/pnas.0803928105. PMC 2474565. PMID 18632566.
- Allen JF (Aug 2015). "Why chloroplasts and mitochondria retain their own genomes and genetic systems: Colocation for redox regulation of gene expression". Proceedings of the National Academy of Sciences of the United States of America. 112 (33): 10231â€“8. doi:10.1073/pnas.1500012112. PMC 4547249. PMID 26286985.
- Rowland MA, Deeds EJ (Apr 2014). "Crosstalk and the evolution of specificity in two-component signaling". Proceedings of the National Academy of Sciences of the United States of America. 111 (15): 5550â€“5. doi:10.1073/pnas.1317178111. PMC 3992699. PMID 24706803.
- Barakat M, Ortet P, Whitworth DE (Jan 2011). "P2CS: a database of prokaryotic two-component systems". Nucleic Acids Research. 39 (Database issue): D771â€“6. doi:10.1093/nar/gkq1023. PMC 3013651. PMID 21051349.
- Ortet P, Whitworth DE, Santaella C, Achouak W, Barakat M (Jan 2015). "P2CS: updates of the prokaryotic two-component systems database". Nucleic Acids Research. 43 (Database issue): D536â€“41. doi:10.1093/nar/gku968. PMC 4384028. PMID 25324303.
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.
Osmosensitive K+ channel His kinase sensor domain Provide feedback
This is a family of KdpD sensor kinase proteins that regulate the kdpFABC operon responsible for potassium transport . The aligned region corresponds to the N-terminal cytoplasmic part of the protein which functions as the sensor domain responsible for sensing turgor pressure . It recognises C-di-AMP and K+ (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).
Treuner-Lange A, Kuhn A, Durre P; , J Bacteriol 1997;179:4501-4512.: The kdp system of Clostridium acetobutylicum: cloning, sequencing, and transcriptional regulation in response to potassium concentration. PUBMED:9226259 EPMC:9226259
Walderhaug MO, Polarek JW, Voelkner P, Daniel JM, Hesse JE, Altendorf K, Epstein W; , J Bacteriol 1992;174:2152-2159.: KdpD and KdpE, proteins that control expression of the kdpABC operon, are members of the two-component sensor-effector class of regulators. PUBMED:1532388 EPMC:1532388
Internal database links
|SCOOP:||AAA AAA_16 AAA_21 AAA_22 AAA_25 AAA_30 ABC_tran ATPase DnaB_C SMC_N SRP54|
This tab holds annotation information from the InterPro database.
InterPro entry IPR003852
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.
This entry represents the N-terminal domain found in KdpD sensor kinase proteins, which regulate the kdpFABC operon responsible for potassium transport [ PUBMED:9226259 ]. The N-terminal domain forms part of the cytoplasmic region of the protein, which may be the sensor domain responsible for sensing turgor pressure [ PUBMED:1532388 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||membrane (GO:0016020)|
|Molecular function||phosphorelay sensor kinase activity (GO:0000155)|
|protein histidine kinase activity (GO:0004673)|
|Biological process||phosphorelay signal transduction system (GO:0000160)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes .
The clan contains the following 245 members:6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_5 AAA_6 AAA_7 AAA_8 AAA_9 AAA_PrkA ABC_ATPase ABC_tran ABC_tran_Xtn Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arf ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 ATPase ATPase_2 Bac_DnaA BCA_ABC_TP_C Beta-Casp bpMoxR BrxC_BrxD BrxL_ATPase Cas_Csn2 Cas_St_Csn2 CbiA CBP_BcsQ CDC73_C CENP-M CFTR_R CLP1_P CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CSM2 CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 divDNAB DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DO-GTPase1 DO-GTPase2 DUF1611 DUF2075 DUF2326 DUF2478 DUF257 DUF2813 DUF3584 DUF463 DUF4914 DUF5906 DUF6079 DUF815 DUF835 DUF87 DUF927 Dynamin_N Dynein_heavy Elong_Iki1 ELP6 ERCC3_RAD25_C Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GBP_C GpA_ATPase GpA_nuclease GTP_EFTU Gtr1_RagA Guanylate_kin GvpD_P-loop HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD HerA_C Herpes_Helicase Herpes_ori_bp Herpes_TK HydF_dimer HydF_tetramer Hydin_ADK IIGP IPPT IPT iSTAND IstB_IS21 KAP_NTPase KdpD Kinase-PPPase Kinesin KTI12 LAP1_C LpxK MCM MeaB MEDS Mg_chelatase Microtub_bd MipZ MMR_HSR1 MMR_HSR1_C MobB MukB Mur_ligase_M MutS_V Myosin_head NACHT NAT_N NB-ARC NOG1 NTPase_1 NTPase_P4 ORC3_N P-loop_TraG ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Ploopntkinase1 Ploopntkinase2 Ploopntkinase3 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK PSY3 Rad17 Rad51 Ras RecA ResIII RHD3_GTPase RhoGAP_pG1_pG2 RHSP RNA12 RNA_helicase Roc RsgA_GTPase RuvB_N SbcC_Walker_B SecA_DEAD Senescence Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2-rel_dom SpoIVA_ATPase Spore_III_AA SRP54 SRPRB SulA Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulfotransfer_4 Sulfotransfer_5 Sulphotransf SWI2_SNF2 T2SSE T4SS-DNA_transf TerL_ATPase Terminase_3 Terminase_6N Thymidylate_kin TIP49 TK TmcA_N TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind TsaE UvrB UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE YqeC Zeta_toxin Zot
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...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
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 UniProtKB sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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...
If you find these logos useful in your own work, please consider citing the following article:
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.
|Author:||Bashton M , Bateman A|
|Number in seed:||222|
|Number in full:||3495|
|Average length of the domain:||206.60 aa|
|Average identity of full alignment:||54 %|
|Average coverage of the sequence by the domain:||28.19 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||20|
|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
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
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.
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
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
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 KdpD domain has been found. There are 2 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.
Loading structure mapping...
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|
|P21865||View 3D Structure||Click here|
|P9WGL3||View 3D Structure||Click here|
|Q2FWH7||View 3D Structure||Click here|