Summary: Bacterial regulatory protein, arsR family
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Helix-turn-helix Edit Wikipedia article
In proteins, the helix-turn-helix (HTH) is a major structural motif capable of binding DNA. Each monomer incorporates two Î± helices, joined by a short strand of amino acids, that bind to the major groove of DNA. The HTH motif occurs in many proteins that regulate gene expression. It should not be confused with the helix-loop-helix motif.
The discovery of the helix-turn-helix motif was based on similarities between several genes encoding transcription regulatory proteins from bacteriophage lambda and Escherichia coli: Cro, CAP, and Î» repressor, which were found to share a common 20-25 amino acid sequence that facilitates DNA recognition.
The helix-turn-helix motif is a DNA-binding motif. The recognition and binding to DNA by helix-turn-helix proteins is done by the two Î± helices, one occupying the N-terminal end of the motif, the other at the C-terminus. In most cases, such as in the Cro repressor, the second helix contributes most to DNA recognition, and hence it is often called the "recognition helix". It binds to the major groove of DNA through a series of hydrogen bonds and various Van der Waals interactions with exposed bases. The other Î± helix stabilizes the interaction between protein and DNA, but does not play a particularly strong role in its recognition. The recognition helix and its preceding helix always have the same relative orientation.
Classification of helix-turn-helix motifs
The di-helical helix-turn-helix motif is the simplest helix-turn-helix motif. A fragment of Engrailed homeodomain encompassing only the two helices and the turn was found to be an ultrafast independently folding protein domain.
The tetra-helical helix-turn-helix motif has an additional C-terminal helix compared to the tri-helical motifs. These include the LuxR-type DNA-binding HTH domain found in bacterial transcription factors and the helix-turn-helix motif found in the TetR repressors. Multihelical versions with additional helices also occur.
The winged helix-turn-helix (wHTH) motif is formed by a 3-helical bundle and a 3- or 4-strand beta-sheet (wing). The topology of helices and strands in the wHTH motifs may vary. In the transcription factor ETS wHTH folds into a helix-turn-helix motif on a four-stranded anti-parallel beta-sheet scaffold arranged in the order Î±1-Î²1-Î²2-Î±2-Î±3-Î²3-Î²4 where the third helix is the DNA recognition helix.
Other modified helix-turn-helix motifs
Other derivatives of the helix-turn-helix motif include the DNA-binding domain found in MarR, a regulator of multiple antibiotic resistance, which forms a winged helix-turn-helix with an additional C-terminal alpha helix.
- Brennan RG, Matthews BW (February 1989). "The helix-turn-helix DNA binding motif". The Journal of Biological Chemistry. 264 (4): 1903â€“6. PMID 2644244.
- Matthews BW, Ohlendorf DH, Anderson WF, Takeda Y (March 1982). "Structure of the DNA-binding region of lac repressor inferred from its homology with cro repressor". Proceedings of the National Academy of Sciences of the United States of America. 79 (5): 1428â€“32. doi:10.1073/pnas.79.5.1428. PMC 345986. PMID 6951187.
- Anderson WF, Ohlendorf DH, Takeda Y, Matthews BW (April 1981). "Structure of the cro repressor from bacteriophage lambda and its interaction with DNA". Nature. 290 (5809): 754â€“8. doi:10.1038/290754a0. PMID 6452580.
- McKay DB, Steitz TA (April 1981). "Structure of catabolite gene activator protein at 2.9 A resolution suggests binding to left-handed B-DNA". Nature. 290 (5809): 744â€“9. doi:10.1038/290744a0. PMID 6261152.
- Pabo CO, Lewis M (July 1982). "The operator-binding domain of lambda repressor: structure and DNA recognition". Nature. 298 (5873): 443â€“7. doi:10.1038/298443a0. PMID 7088190.
- Wintjens R, Rooman M (September 1996). "Structural classification of HTH DNA-binding domains and protein-DNA interaction modes". Journal of Molecular Biology. 262 (2): 294â€“313. doi:10.1006/jmbi.1996.0514. PMID 8831795.
- Suzuki M, Brenner SE (September 1995). "Classification of multi-helical DNA-binding domains and application to predict the DBD structures of sigma factor, LysR, OmpR/PhoB, CENP-B, Rapl, and Xy1S/Ada/AraC". FEBS Letters. 372 (2â€“3): 215â€“21. doi:10.1016/0014-5793(95)00988-L. PMID 7556672.
- Aravind L, Anantharaman V, Balaji S, Babu MM, Iyer LM (April 2005). "The many faces of the helix-turn-helix domain: transcription regulation and beyond". FEMS Microbiology Reviews. 29 (2): 231â€“62. doi:10.1016/j.femsre.2004.12.008. PMID 15808743.
- Religa TL, Johnson CM, Vu DM, Brewer SH, Dyer RB, Fersht AR (May 2007). "The helix-turn-helix motif as an ultrafast independently folding domain: the pathway of folding of Engrailed homeodomain". Proceedings of the National Academy of Sciences of the United States of America. 104 (22): 9272â€“7. doi:10.1073/pnas.0703434104. PMC 1890484. PMID 17517666.
- Ogata K, Hojo H, Aimoto S, Nakai T, Nakamura H, Sarai A, Ishii S, Nishimura Y (July 1992). "Solution structure of a DNA-binding unit of Myb: a helix-turn-helix-related motif with conserved tryptophans forming a hydrophobic core". Proceedings of the National Academy of Sciences of the United States of America. 89 (14): 6428â€“32. doi:10.1073/pnas.89.14.6428. PMC 49514. PMID 1631139.
- Hinrichs W, Kisker C, DÃ¼vel M, MÃ¼ller A, Tovar K, Hillen W, Saenger W (April 1994). "Structure of the Tet repressor-tetracycline complex and regulation of antibiotic resistance". Science. 264 (5157): 418â€“20. doi:10.1126/science.8153629. PMID 8153629.
- Iwahara J, Clubb RT (November 1999). "Solution structure of the DNA binding domain from Dead ringer, a sequence-specific AT-rich interaction domain (ARID)". The EMBO Journal. 18 (21): 6084â€“94. doi:10.1093/emboj/18.21.6084. PMC 1171673. PMID 10545119.
- Donaldson LW, Petersen JM, Graves BJ, McIntosh LP (January 1996). "Solution structure of the ETS domain from murine Ets-1: a winged helix-turn-helix DNA binding motif". The EMBO Journal. 15 (1): 125â€“34. doi:10.2210/pdb1etc/pdb. PMC 449924. PMID 8598195.
- Sharrocks AD, Brown AL, Ling Y, Yates PR (December 1997). "The ETS-domain transcription factor family". The International Journal of Biochemistry & Cell Biology. 29 (12): 1371â€“87. doi:10.1016/S1357-2725(97)00086-1. PMID 9570133.
- Alekshun MN, Levy SB, Mealy TR, Seaton BA, Head JF (August 2001). "The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 A resolution". Nature Structural Biology. 8 (8): 710â€“4. doi:10.1038/90429. PMID 11473263.
- Struhl K (April 1989). "Helix-turn-helix, zinc-finger, and leucine-zipper motifs for eukaryotic transcriptional regulatory proteins". Trends in Biochemical Sciences. 14 (4): 137â€“40. doi:10.1016/0968-0004(89)90145-X. PMID 2499084.
- Gajiwala KS, Burley SK (February 2000). "Winged helix proteins". Current Opinion in Structural Biology. 10 (1): 110â€“6. doi:10.1016/S0959-440X(99)00057-3. PMID 10679470.
- Santos CL, Tavares F, Thioulouse J, Normand P (March 2009). "A phylogenomic analysis of bacterial helix-turn-helix transcription factors". FEMS Microbiology Reviews. 33 (2): 411â€“29. doi:10.1111/j.1574-6976.2008.00154.x. PMID 19076237.
- Hoskisson PA, Rigali S (2009). "Chapter 1: Variation in form and function the helix-turn-helix regulators of the GntR superfamily". Advances in Applied Microbiology. 69: 1â€“22. doi:10.1016/S0065-2164(09)69001-8. PMID 19729089.
- Brennan RG (September 1993). "The winged-helix DNA-binding motif: another helix-turn-helix takeoff". Cell. 74 (5): 773â€“6. doi:10.1016/0092-8674(93)90456-Z. PMID 8374950.
- Huffman JL, Brennan RG (February 2002). "Prokaryotic transcription regulators: more than just the helix-turn-helix motif". Current Opinion in Structural Biology. 12 (1): 98â€“106. doi:10.1016/s0959-440x(02)00295-6. PMID 11839496.
- Helix-turn-helix motif, lambda-like repressor, from EMBL
- Full PDB entry for PDB ID 1LMB
- Cro/C1-type HTH domain, more HTHs in PROSITE
|Pfam infoboxes for Helix-turn-helix domains|
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.
Bacterial regulatory protein, arsR family Provide feedback
Members of this family contains a DNA binding 'helix-turn-helix' motif. This family includes other proteins which are not included in the Prosite definition.
Cook WJ, Kar SR, Taylor KB, Hall LM; , J Mol Biol 1998;275:337-346.: Crystal structure of the cyanobacterial metallothionein repressor SmtB: a model for metalloregulatory proteins. PUBMED:9466913 EPMC:9466913
Internal database links
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001845
The arsR-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain present in transcription regulators of the arsR/smtB family, involved in stress-response to heavy metal ions. This family of prokaryotic metal-sensing transcription repressors is named after Escherichia coli arsR, an arsenic-responsive repressor of the ars operon for arsenate reductase and metal ion extrusion, and after Synechococcus PCC 7942 smtB, a Zn(II)-responsive repressor of the smtA gene for a Zn sequestering metallothionein [ PUBMED:12829264 ]. ArsR/smtB-like repressors of metal resistance operons specifically bind to the operator/promoter and seem to dissociate from the DNA in the presence of metal ions, permitting transcription of proteins involved in metal-ions efflux and/or detoxification.
The crystal structure of the cyanobacterial smtB shows a fold of five alpha-helices (H) and a pair of antiparallel beta-strands (B) in the topology H1-H2-H3-H4-B1-B2-H5. Helices 3 and 4 comprise the helix-turn-helix motif and the beta-sheet is called the wing as in other wHTH, such as the dtxR-type or the merR-type. Helix 4 is termed the recognition helix, like in other HTHs where it binds the DNA major groove. Most arsR/smtB-like metalloregulators form homodimers [ PUBMED:14568530 ]. The dimer interface is formed by helix 5 and an N-terminal part [ PUBMED:9466913 ]. Two distinct metal-binding sites have been identified. The first site comprises cysteine thiolates located in the HTH in helix 3 and for some cases in the N terminus, called the alpha3(N) site [ PUBMED:12829264 , PUBMED:14568530 , PUBMED:8506147 ]. The second metal-binding site is located in helix 5 (and C terminus) and is called the alpha5(C) site. The alpha3N site binds large thiophilic, toxic metals including Cd, Pb, and Bi, as in S. aureus cadC. ArsR lacks the N-terminal arm and its alpha3 site coordinates smaller thiophilic ions like As and Sb. The alpha5 site contains carboxylate and imidazole ligands and interacts preferentially with biologically required metal ions including Zn, Co, and Ni. ArsR-type metalloregulators contain one of these sites, both, or other potential metal-binding sites [ PUBMED:12829264 , PUBMED:14960585 ]. Binding of metal ions to these sites leads to allosteric changes that can derepress the operator/promoter DNA. The metal-inducible operons contain one or two imperfect 12-2-12 inverted repeats, which can be recognised by multimeric arsR-type metalloregulators.
Some proteins known to contain an arsR-type HTH domain:
- Escherichia coli arsR, an arsenic-responsive transcription repressor of the arsenic resistance operon (ars) which encodes an arsenate reductase and metal exporters.
- Synechococcus PCC 7942 smtB, a Zn(II)-responsive transcription repressor of the smtA gene that codes for a metallothionein. SmtB senses Co(II) and Cd(II) too, but Zn(II) is the preferred effector.
- Staphylococcus aureus cadC, a transcription regulator of the cadmium resistance (cad) operon which encodes a Cd/Pb-specific efflux ATPase [ PUBMED:7543476 ].
- Mycobacterium tuberculosis cmtR, a Pb(II)/Cd(II)-sensing repressor [ PUBMED:15966722 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||DNA-binding transcription factor activity (GO:0003700)|
|Biological process||regulation of transcription, DNA-templated (GO:0006355)|
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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a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
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This family contains a diverse range of mostly DNA-binding domains that contain a helix-turn-helix motif.
The clan contains the following 381 members:AbiEi_3_N AbiEi_4 ANAPC2 AphA_like AraR_C Arg_repressor ARID ArsR B-block_TFIIIC B5 Bac_DnaA_C Baculo_PEP_N BetR BHD_3 BLACT_WH Bot1p BrkDBD BrxA BsuBI_PstI_RE_N C_LFY_FLO CaiF_GrlA CarD_CdnL_TRCF CDC27 Cdc6_C Cdh1_DBD_1 CDT1 CDT1_C CENP-B_N Costars CPSase_L_D3 Cro Crp CSN4_RPN5_eIF3a CSN8_PSD8_EIF3K CtsR Cullin_Nedd8 CUT CUTL CvfB_WH DBD_HTH DDRGK DEP Dimerisation Dimerisation2 DNA_binding_1 DNA_meth_N DpnI_C DprA_WH DsrC DsrD DUF1016_N DUF1133 DUF1153 DUF1323 DUF134 DUF1376 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2513 DUF2551 DUF2582 DUF3116 DUF3161 DUF3253 DUF3489 DUF3853 DUF3860 DUF3895 DUF3908 DUF433 DUF434 DUF4364 DUF4373 DUF4423 DUF4447 DUF4777 DUF480 DUF4817 DUF5635 DUF573 DUF5805 DUF6088 DUF6262 DUF6362 DUF6432 DUF6462 DUF6471 DUF722 DUF739 DUF742 DUF937 DUF977 E2F_TDP EAP30 eIF-5_eIF-2B ELL ESCRT-II Ets EutK_C Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC FokI_D1 FokI_dom_2 Forkhead FtsK_gamma FUR GcrA GerE GntR GP3_package HARE-HTH HemN_C HNF-1_N Homeobox_KN Homeodomain Homez HPD HrcA_DNA-bdg HSF_DNA-bind HTH_1 HTH_10 HTH_11 HTH_12 HTH_13 HTH_15 HTH_16 HTH_17 HTH_18 HTH_19 HTH_20 HTH_21 HTH_22 HTH_23 HTH_24 HTH_25 HTH_26 HTH_27 HTH_28 HTH_29 HTH_3 HTH_30 HTH_31 HTH_32 HTH_33 HTH_34 HTH_35 HTH_36 HTH_37 HTH_38 HTH_39 HTH_40 HTH_41 HTH_42 HTH_43 HTH_45 HTH_46 HTH_47 HTH_48 HTH_49 HTH_5 HTH_50 HTH_51 HTH_52 HTH_53 HTH_54 HTH_55 HTH_56 HTH_57 HTH_58 HTH_59 HTH_6 HTH_60 HTH_61 HTH_7 HTH_8 HTH_9 HTH_ABP1_N HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_micro HTH_OrfB_IS605 HTH_PafC HTH_ParB HTH_psq HTH_SUN2 HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_2 HTH_Tnp_4 HTH_Tnp_IS1 HTH_Tnp_IS630 HTH_Tnp_ISL3 HTH_Tnp_Mu_1 HTH_Tnp_Mu_2 HTH_Tnp_Tc3_1 HTH_Tnp_Tc3_2 HTH_Tnp_Tc5 HTH_WhiA HxlR IBD IF2_N IRF KicB KilA-N Kin17_mid KORA KorB La LacI LexA_DNA_bind Linker_histone LZ_Tnp_IS481 MADF_DNA_bdg MAGE MARF1_LOTUS MarR MarR_2 MC6 MC7 MC8 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 MogR_DNAbind Mor MotA_activ MqsA_antitoxin MRP-L20 Mrr_N MukE Myb_DNA-bind_2 Myb_DNA-bind_3 Myb_DNA-bind_4 Myb_DNA-bind_5 Myb_DNA-bind_6 Myb_DNA-bind_7 Myb_DNA-binding Neugrin NFRKB_winged NOD2_WH NUMOD1 ORC_WH_C OST-HTH P22_Cro PaaX PadR PapB PAX PCI Penicillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_NinH Phage_Nu1 Phage_rep_O Phage_rep_org_N Phage_terminase PheRS_DBD1 PheRS_DBD2 PheRS_DBD3 PhetRS_B1 Pou Pox_D5 PqqD PRC2_HTH_1 PUFD PuR_N Put_DNA-bind_N pXO2-72 Raf1_HTH Rap1-DNA-bind Rep_3 RepA_C RepA_N RepB RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S18 Ribosomal_S19e Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RNA_pol_Rpc82 RNase_H2-Ydr279 ROQ_II ROXA-like_wH RP-C RPA RPA_C RPN6_C_helix RQC Rrf2 RTP RuvB_C S10_plectin SAC3_GANP SANT_DAMP1_like SatD SelB-wing_1 SelB-wing_2 SelB-wing_3 SgrR_N Sigma54_CBD Sigma54_DBD Sigma70_ECF Sigma70_ner Sigma70_r2 Sigma70_r3 Sigma70_r4 Sigma70_r4_2 SinI SKA1 Ski_Sno SLIDE Slx4 SMC_Nse1 SMC_ScpB SoPB_HTH SpoIIID SRP19 SRP_SPB STN1_2 Stn1_C Stork_head Sulfolobus_pRN Suv3_N Swi6_N SWIRM Tau95 TBPIP TEA Terminase_5 TetR_N TFA2_Winged_2 TFIIE_alpha TFIIE_beta TFIIF_alpha TFIIF_beta Tn7_Tnp_TnsA_C Tn916-Xis TraI_2_C Trans_reg_C TrfA TrmB tRNA_bind_2 tRNA_bind_3 Trp_repressor UPF0122 UPF0175 Vir_act_alpha_C XPA_C Xre-like-HTH YdaS_antitoxin YidB YjcQ YokU z-alpha
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:
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You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
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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.
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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.
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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.
|Seed source:||Pfam-B_139 (release 3.0)|
|Number in seed:||37|
|Number in full:||24700|
|Average length of the domain:||46.90 aa|
|Average identity of full alignment:||33 %|
|Average coverage of the sequence by the domain:||32.17 %|
|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:||23|
|Download:||download the raw HMM for this family|
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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 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 HTH_5 domain has been found. There are 90 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.