FTP |
Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
586 structures 1648 species 0 interactions 1201914 sequences 14182 architectures
Family: zf-C2H2 (PF00096)
Loading page components…
Domain organisation
HMM logo
Curation & model
AlphaFold Structures
trRosetta Structure
Summary: Zinc finger, C2H2 type
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
Wikipedia: Zinc finger
This is the Wikipedia entry entitled "Zinc finger". 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:
Five pillars
Policies and quidelines
Wikipedia help contents
Wikipedia Tips
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 pfam-help@sanger.ac.uk 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.
Zinc finger Edit Wikipedia article
Small structural protein motif found mostly in transcriptional proteins
Cartoon representation of the Cys2His2 zinc finger motif, consisting of an α helix and an antiparallel β sheet. The zinc ion (green) is coordinated by two histidine residues and two cysteine residues.
Cartoon representation of the protein Zif268 (blue) containing three zinc fingers in complex with DNA (orange). The coordinating amino acid residues and zinc ions (green) are highlighted.
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. Originally coined to describe the finger-like appearance of a hypothesized structure from Xenopus laevis transcription factor IIIA, the zinc finger name has now come to encompass a wide variety of differing protein structures.[1] Xenopus laevis TFIIIA was originally demonstrated to contain zinc and require the metal for function in 1983, the first such reported zinc requirement for a gene regulatory protein.[2][3] It often appears as a metal-binding domain in multi-domain proteins.[3]
Proteins that contain zinc fingers (zinc finger proteins) are classified into several different structural families. Unlike many other clearly defined supersecondary structures such as Greek keys or β hairpins, there are a number of types of zinc fingers, each with a unique three-dimensional architecture. A particular zinc finger protein's class is determined by this three-dimensional structure, but it can also be recognized based on the primary structure of the protein or the identity of the ligands coordinating the zinc ion. In spite of the large variety of these proteins, however, the vast majority typically function as interaction modules that bind DNA, RNA, proteins, or other small, useful molecules, and variations in structure serve primarily to alter the binding specificity of a particular protein.
Since their original discovery and the elucidation of their structure, these interaction modules have proven ubiquitous in the biological world and may be found in 3% of the genes of the human genome.[4] In addition, zinc fingers have become extremely useful in various therapeutic and research capacities. Engineering zinc fingers to have an affinity for a specific sequence is an area of active research, and zinc finger nucleases and zinc finger transcription factors are two of the most important applications of this to be realized to date.
3.1 Cys2His2
3.2 Gag-knuckle
3.3 Treble-clef
3.4 Zinc ribbon
3.5 Zn2/Cys6
4.1 Zinc finger nucleases
4.2 Methods of engineering zinc finger arrays
Zinc fingers were first identified in a study of transcription in the African clawed frog, Xenopus laevis in the laboratory of Aaron Klug. A study of the transcription of a particular RNA sequence revealed that the binding strength of a small transcription factor (transcription factor IIIA; TFIIIA) was due to the presence of zinc-coordinating finger-like structures.[5] Amino acid sequencing of TFIIIA revealed nine tandem sequences of 30 amino acids, including two invariant pairs of cysteine and histidine residues. Extended x-ray absorption fine structure confirmed the identity of the zinc ligands: two cysteines and two histidines.[4] The DNA-binding loop formed by the coordination of these ligands by zinc were thought to resemble fingers, hence the name.[1] More recent work in the characterization of proteins in various organisms has revealed the importance of zinc ions in polypeptide stabilization.[6][7]
The crystal structures of zinc finger-DNA complexes solved in 1991 and 1993 revealed the canonical pattern of interactions of zinc fingers with DNA.[8][9] The binding of zinc finger is found to be distinct from many other DNA-binding proteins that bind DNA through the 2-fold symmetry of the double helix, instead zinc fingers are linked linearly in tandem to bind nucleic acid sequences of varying lengths.[4] Zinc fingers often bind to a sequence of DNA known as the GC box.[10] The modular nature of the zinc finger motif allows for a large number of combinations of DNA and RNA sequences to be bound with high degree of affinity and specificity, and is therefore ideally suited for engineering protein that can be targeted to and bind specific DNA sequences. In 1994, it was shown that an artificially-constructed three-finger protein can block the expression of an oncogene in a mouse cell line. Zinc fingers fused to various other effector domains, some with therapeutic significance, have since been constructed.[4]
Zinc finger (Znf) domains are relatively small protein motifs that contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not, instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein, and/or lipid substrates.[11][12][13][14][15] Their binding properties depend on the amino acid sequence of the finger domains and on the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. Znf motifs occur in several unrelated protein superfamilies, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g., some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organization, epithelial development, cell adhesion, protein folding, chromatin remodeling, and zinc sensing, to name but a few.[16] Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
Initially, the term zinc finger was used solely to describe DNA-binding motif found in Xenopus laevis; however, it is now used to refer to any number of structures related by their coordination of a zinc ion. In general, zinc fingers coordinate zinc ions with a combination of cysteine and histidine residues. Originally, the number and order of these residues was used to classify different types of zinc fingers ( e.g., Cys2His2, Cys4, and Cys6). More recently, a more systematic method has been used to classify zinc finger proteins instead. This method classifies zinc finger proteins into "fold groups" based on the overall shape of the protein backbone in the folded domain. The most common "fold groups" of zinc fingers are the Cys2His2-like (the "classic zinc finger"), treble clef, and zinc ribbon.[17]
The following table[17] shows the different structures and their key features:
Fold Group
Representative structure
Ligand placement
Cys2His2 Two ligands from a knuckle and two more from the c terminus of a helix.
Gag knuckle Two ligands from a knuckle and two more from a short helix or loop.
Treble clef Two ligands from a knuckle and two more from the N terminus of a helix.
Zinc ribbon Two ligands each from two knuckles.
Zn2/Cys6 Two ligands from the N terminus of a helix and two more from a loop.
TAZ2 domain like Two ligands from the termini of two helices.
Cys2His2
Zinc finger, C2H2 type
zf-C2H2
Pfam clan
Available protein structures:
structures / ECOD
RCSB PDB; PDBe; PDBj
PDBsum
structure summary
The Cys2His2-like fold group (C2H2) is by far the best-characterized class of zinc fingers, and is common in mammalian transcription factors. Such domains adopt a simple ββα fold and have the amino acid sequence motif:[18]
X2-Cys-X2,4-Cys-X12-His-X3,4,5-His
This class of zinc fingers can have a variety of functions such as binding RNA and mediating protein-protein interactions, but is best known for its role in sequence-specific DNA-binding proteins such as Zif268 (Egr1). In such proteins, individual zinc finger domains typically occur as tandem repeats with two, three, or more fingers comprising the DNA-binding domain of the protein. These tandem arrays can bind in the major groove of DNA and are typically spaced at 3-bp intervals. The α-helix of each domain (often called the "recognition helix") can make sequence-specific contacts to DNA bases; residues from a single recognition helix can contact four or more bases to yield an overlapping pattern of contacts with adjacent zinc fingers.
Gag-knuckle
Zinc knuckle
zf-CCHC
This fold group is defined by two short β-strands connected by a turn (zinc knuckle) followed by a short helix or loop and resembles the classical Cys2His2 motif with a large portion of the helix and β-hairpin truncated.
The retroviral nucleocapsid (NC) protein from HIV and other related retroviruses are examples of proteins possessing these motifs. The gag-knuckle zinc finger in the HIV NC protein is the target of a class of drugs known as zinc finger inhibitors.
Treble-clef
The treble-clef motif consists of a β-hairpin at the N-terminus and an α-helix at the C-terminus that each contribute two ligands for zinc binding, although a loop and a second β-hairpin of varying length and conformation can be present between the N-terminal β-hairpin and the C-terminal α-helix. These fingers are present in a diverse group of proteins that frequently do not share sequence or functional similarity with each other. The best-characterized proteins containing treble-clef zinc fingers are the nuclear hormone receptors.
Zinc ribbon
TFIIB zinc-binding
TF_Zn_Ribbon
Zn_Beta_Ribbon
The zinc ribbon fold is characterised by two beta-hairpins forming two structurally similar zinc-binding sub-sites.
Zn2/Cys6
Fungal Zn(2)-Cys(6) binuclear cluster domain
Zn_clus
GAL4
The canonical members of this class contain a binuclear zinc cluster in which two zinc ions are bound by six cysteine residues. These zinc fingers can be found in several transcription factors including the yeast Gal4 protein.
zf-C2HC
solution structure of a cchhc domain of neural zinc finger factor-1
zf-C2HC5
Various protein engineering techniques can be used to alter the DNA-binding specificity of zinc fingers[18] and tandem repeats of such engineered zinc fingers can be used to target desired genomic DNA sequences.[19] Fusing a second protein domain such as a transcriptional activator or repressor to an array of engineered zinc fingers that bind near the promoter of a given gene can be used to alter the transcription of that gene.[19] Fusions between engineered zinc finger arrays and protein domains that cleave or otherwise modify DNA can also be used to target those activities to desired genomic loci.[19] The most common applications for engineered zinc finger arrays include zinc finger transcription factors and zinc finger nucleases, but other applications have also been described. Typical engineered zinc finger arrays have between 3 and 6 individual zinc finger motifs and bind target sites ranging from 9 basepairs to 18 basepairs in length. Arrays with 6 zinc finger motifs are particularly attractive because they bind a target site that is long enough to have a good chance of being unique in a mammalian genome.[20]
Zinc finger nucleases
Engineered zinc finger arrays are often fused to a DNA cleavage domain (usually the cleavage domain of FokI) to generate zinc finger nucleases. Such zinc finger-FokI fusions have become useful reagents for manipulating genomes of many higher organisms including Drosophila melanogaster, Caenorhabditis elegans, tobacco, corn,[21] zebrafish,[22] various types of mammalian cells,[23] and rats.[24] Targeting a double-strand break to a desired genomic locus can be used to introduce frame-shift mutations into the coding sequence of a gene due to the error-prone nature of the non-homologous DNA repair pathway. If a homologous DNA "donor sequence" is also used then the genomic locus can be converted to a defined sequence via the homology directed repair pathway. An ongoing clinical trial is evaluating Zinc finger nucleases that disrupt the CCR5 gene in CD4+ human T-cells as a potential treatment for HIV/AIDS.[25]
Methods of engineering zinc finger arrays
The majority of engineered zinc finger arrays are based on the zinc finger domain of the murine transcription factor Zif268, although some groups have used zinc finger arrays based on the human transcription factor SP1. Zif268 has three individual zinc finger motifs that collectively bind a 9 bp sequence with high affinity.[26] The structure of this protein bound to DNA was solved in 1991[8] and stimulated a great deal of research into engineered zinc finger arrays. In 1994 and 1995, a number of groups used phage display to alter the specificity of a single zinc finger of Zif268.[27][28][29][30] There are two main methods currently used to generate engineered zinc finger arrays, modular assembly, and a bacterial selection system, and there is some debate about which method is best suited for most applications.[31][32]
The most straightforward method to generate new zinc finger arrays is to combine smaller zinc finger "modules" of known specificity. The structure of the zinc finger protein Zif268 bound to DNA described by Pavletich and Pabo in their 1991 publication has been key to much of this work and describes the concept of obtaining fingers for each of the 64 possible base pair triplets and then mixing and matching these fingers to design proteins with any desired sequence specificity.[8] The most common modular assembly process involves combining separate zinc fingers that can each recognize a 3-basepair DNA sequence to generate 3-finger, 4-, 5-, or 6-finger arrays that recognize target sites ranging from 9 basepairs to 18 basepairs in length. Another method uses 2-finger modules to generate zinc finger arrays with up to six individual zinc fingers.[21] The Barbas Laboratory of The Scripps Research Institute used phage display to develop and characterize zinc finger domains that recognize most DNA triplet sequences[33][34][35] while another group isolated and characterized individual fingers from the human genome.[36] A potential drawback with modular assembly in general is that specificities of individual zinc finger can overlap and can depend on the context of the surrounding zinc fingers and DNA. A recent study demonstrated that a high proportion of 3-finger zinc finger arrays generated by modular assembly fail to bind their intended target with sufficient affinity in a bacterial two-hybrid assay and fail to function as zinc finger nucleases, but the success rate was somewhat higher when sites of the form GNNGNNGNN were targeted.[37]
A subsequent study used modular assembly to generate zinc finger nucleases with both 3-finger arrays and 4-finger arrays and observed a much higher success rate with 4-finger arrays.[38] A variant of modular assembly that takes the context of neighboring fingers into account has also been reported and this method tends to yield proteins with improved performance relative to standard modular assembly.[39]
Numerous selection methods have been used to generate zinc finger arrays capable of targeting desired sequences. Initial selection efforts utilized phage display to select proteins that bound a given DNA target from a large pool of partially randomized zinc finger arrays. This technique is difficult to use on more than a single zinc finger at a time, so a multi-step process that generated a completely optimized 3-finger array by adding and optimizing a single zinc finger at a time was developed.[40] More recent efforts have utilized yeast one-hybrid systems, bacterial one-hybrid and two-hybrid systems, and mammalian cells. A promising new method to select novel 3-finger zinc finger arrays utilizes a bacterial two-hybrid system and has been dubbed "OPEN" by its creators.[41] This system combines pre-selected pools of individual zinc fingers that were each selected to bind a given triplet and then utilizes a second round of selection to obtain 3-finger arrays capable of binding a desired 9-bp sequence. This system was developed by the Zinc Finger Consortium as an alternative to commercial sources of engineered zinc finger arrays. It is somewhat difficult to directly compare the binding properties of proteins generated with this method to proteins generated by modular assembly as the specificity profiles of proteins generated by the OPEN method have never been reported.
This entry represents the CysCysHisCys (C2HC) type zinc finger domain found in eukaryotes. Proteins containing these domains include:
MYST family histone acetyltransferases[42][43]
Myelin transcription factor Myt1[44]
Suppressor of tumourigenicity protein 18 (ST18)[45]
Biology portal
Technology portal
B-box zinc finger
DNA-binding protein
Krüppel associated box
RING finger domain
Sequence motif
Steroid hormone receptor
Structural motif
TAL effector
Transcription Activator-Like Effector Nuclease
Zinc finger inhibitor
Zinc finger nuclease
Zinc Finger Transcription Factor
^ a b Klug A, Rhodes D (1987). "Zinc fingers: a novel protein fold for nucleic acid recognition". Cold Spring Harbor Symposia on Quantitative Biology. 52: 473–82. doi:10.1101/sqb.1987.052.01.054. PMID 3135979.
^ Hanas JS, Hazuda DJ, Bogenhagen DF, Wu FY, Wu CW (December 1983). "Xenopus transcription factor A requires zinc for binding to the 5 S RNA gene". The Journal of Biological Chemistry. 258 (23): 14120–5. PMID 6196359.
^ a b Berg JM (April 1990). "Zinc fingers and other metal-binding domains. Elements for interactions between macromolecules". The Journal of Biological Chemistry. 265 (12): 6513–6. PMID 2108957.
^ a b c d Klug A (2010). "The discovery of zinc fingers and their applications in gene regulation and genome manipulation". Annual Review of Biochemistry. 79: 213–31. doi:10.1146/annurev-biochem-010909-095056. PMID 20192761. – via Annual Reviews (subscription required)
^ Miller J, McLachlan AD, Klug A (June 1985). "Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes". The EMBO Journal. 4 (6): 1609–14. doi:10.1002/j.1460-2075.1985.tb03825.x. PMC 554390. PMID 4040853.
^ Miller Y, Ma B, Nussinov R (May 2010). "Zinc ions promote Alzheimer Abeta aggregation via population shift of polymorphic states". Proceedings of the National Academy of Sciences of the United States of America. 107 (21): 9490–5. Bibcode:2010PNAS..107.9490M. doi:10.1073/pnas.0913114107. PMC 2906839. PMID 20448202.
^ Low LY, Hernández H, Robinson CV, O'Brien R, Grossmann JG, Ladbury JE, Luisi B (May 2002). "Metal-dependent folding and stability of nuclear hormone receptor DNA-binding domains". Journal of Molecular Biology. 319 (1): 87–106. doi:10.1016/S0022-2836(02)00236-X. PMID 12051939.
^ a b c Pavletich NP, Pabo CO (May 1991). "Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A". Science. 252 (5007): 809–17. Bibcode:1991Sci...252..809P. doi:10.1126/science.2028256. PMID 2028256.
^ Fairall L, Schwabe JW, Chapman L, Finch JT, Rhodes D (December 1993). "The crystal structure of a two zinc-finger peptide reveals an extension to the rules for zinc-finger/DNA recognition". Nature. 366 (6454): 483–7. Bibcode:1993Natur.366..483F. doi:10.1038/366483a0. PMID 8247159.
^ Lundin, M.; Nehlin, J. O.; Ronne, H. (1994-03-01). "Importance of a flanking AT-rich region in target site recognition by the GC box-binding zinc finger protein MIG1". Molecular and Cellular Biology. 14 (3): 1979–1985. doi:10.1128/MCB.14.3.1979. ISSN 0270-7306. PMC 358557. PMID 8114729.
^ Klug A (October 1999). "Zinc finger peptides for the regulation of gene expression". Journal of Molecular Biology. 293 (2): 215–8. doi:10.1006/jmbi.1999.3007. PMID 10529348.
^ Hall TM (June 2005). "Multiple modes of RNA recognition by zinc finger proteins". Current Opinion in Structural Biology. 15 (3): 367–73. doi:10.1016/j.sbi.2005.04.004. PMID 15963892.
^ Brown RS (February 2005). "Zinc finger proteins: getting a grip on RNA". Current Opinion in Structural Biology. 15 (1): 94–8. doi:10.1016/j.sbi.2005.01.006. PMID 15718139.
^ Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, Mackay JP (February 2007). "Sticky fingers: zinc-fingers as protein-recognition motifs". Trends in Biochemical Sciences. 32 (2): 63–70. doi:10.1016/j.tibs.2006.12.007. PMID 17210253.
^ Matthews JM, Sunde M (December 2002). "Zinc fingers--folds for many occasions". IUBMB Life. 54 (6): 351–5. doi:10.1080/15216540216035. PMID 12665246.
^ Laity JH, Lee BM, Wright PE (February 2001). "Zinc finger proteins: new insights into structural and functional diversity". Current Opinion in Structural Biology. 11 (1): 39–46. doi:10.1016/S0959-440X(00)00167-6. PMID 11179890.
^ a b Krishna SS, Majumdar I, Grishin NV (January 2003). "Structural classification of zinc fingers: survey and summary". Nucleic Acids Research. 31 (2): 532–50. doi:10.1093/nar/gkg161. PMC 140525. PMID 12527760.
^ a b Pabo CO, Peisach E, Grant RA (2001). "Design and selection of novel Cys2His2 zinc finger proteins". Annual Review of Biochemistry. 70: 313–40. doi:10.1146/annurev.biochem.70.1.313. PMID 11395410.
^ a b c Jamieson AC, Miller JC, Pabo CO (May 2003). "Drug discovery with engineered zinc-finger proteins". Nature Reviews. Drug Discovery. 2 (5): 361–8. doi:10.1038/nrd1087. PMID 12750739.
^ Liu Q, Segal DJ, Ghiara JB, Barbas CF (May 1997). "Design of polydactyl zinc-finger proteins for unique addressing within complex genomes". Proceedings of the National Academy of Sciences of the United States of America. 94 (11): 5525–30. Bibcode:1997PNAS...94.5525L. doi:10.1073/pnas.94.11.5525. PMC 20811. PMID 9159105.
^ a b Shukla VK, Doyon Y, Miller JC, DeKelver RC, Moehle EA, Worden SE, Mitchell JC, Arnold NL, Gopalan S, Meng X, Choi VM, Rock JM, Wu YY, Katibah GE, Zhifang G, McCaskill D, Simpson MA, Blakeslee B, Greenwalt SA, Butler HJ, Hinkley SJ, Zhang L, Rebar EJ, Gregory PD, Urnov FD (May 2009). "Precise genome modification in the crop species Zea mays using zinc-finger nucleases". Nature. 459 (7245): 437–41. Bibcode:2009Natur.459..437S. doi:10.1038/nature07992. PMID 19404259.
^ Reynolds IJ, Miller RJ (December 1988). "[3H]MK801 binding to the N-methyl-D-aspartate receptor reveals drug interactions with the zinc and magnesium binding sites". The Journal of Pharmacology and Experimental Therapeutics. 247 (3): 1025–31. PMID 2849655.
^ Carroll D (November 2008). "Progress and prospects: zinc-finger nucleases as gene therapy agents". Gene Therapy. 15 (22): 1463–8. doi:10.1038/gt.2008.145. PMC 2747807. PMID 18784746.
^ Geurts AM, Cost GJ, Freyvert Y, Zeitler B, Miller JC, Choi VM, Jenkins SS, Wood A, Cui X, Meng X, Vincent A, Lam S, Michalkiewicz M, Schilling R, Foeckler J, Kalloway S, Weiler H, Ménoret S, Anegon I, Davis GD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Jacob HJ, Buelow R (July 2009). "Knockout rats via embryo microinjection of zinc-finger nucleases". Science. 325 (5939): 433. Bibcode:2009Sci...325..433G. doi:10.1126/science.1172447. PMC 2831805. PMID 19628861.
^ Tebas P, Stein D (2009). "Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-728 for HIV". ClinicalTrials.gov.
^ Christy B, Nathans D (November 1989). "DNA binding site of the growth factor-inducible protein Zif268". Proceedings of the National Academy of Sciences of the United States of America. 86 (22): 8737–41. Bibcode:1989PNAS...86.8737C. doi:10.1073/pnas.86.22.8737. PMC 298363. PMID 2510170.
^ Rebar EJ, Pabo CO (February 1994). "Zinc finger phage: affinity selection of fingers with new DNA-binding specificities". Science. 263 (5147): 671–3. Bibcode:1994Sci...263..671R. doi:10.1126/science.8303274. PMID 8303274.
^ Jamieson AC, Kim SH, Wells JA (May 1994). "In vitro selection of zinc fingers with altered DNA-binding specificity". Biochemistry. 33 (19): 5689–95. doi:10.1021/bi00185a004. PMID 8180194.
^ Choo Y, Klug A (November 1994). "Toward a code for the interactions of zinc fingers with DNA: selection of randomized fingers displayed on phage". Proceedings of the National Academy of Sciences of the United States of America. 91 (23): 11163–7. Bibcode:1994PNAS...9111163C. doi:10.1073/pnas.91.23.11163. PMC 45187. PMID 7972027.
^ Wu H, Yang WP, Barbas CF (January 1995). "Building zinc fingers by selection: toward a therapeutic application". Proceedings of the National Academy of Sciences of the United States of America. 92 (2): 344–8. Bibcode:1995PNAS...92..344W. doi:10.1073/pnas.92.2.344. PMC 42736. PMID 7831288.
^ Kim JS, Lee HJ, Carroll D (February 2010). "Genome editing with modularly assembled zinc-finger nucleases". Nature Methods. 7 (2): 91, author reply 91–2. doi:10.1038/nmeth0210-91a. PMC 2987589. PMID 20111032.
^ Joung JK, Voytas DF, Cathomen T (February 2010). "Reply to "Genome editing with modularly assembled zinc-finger nucleases"". Nat. Methods. 7 (2): 91–2. doi:10.1038/nmeth0210-91b. PMC 2987589.
^ Segal DJ, Dreier B, Beerli RR, Barbas CF (March 1999). "Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5'-GNN-3' DNA target sequences". Proceedings of the National Academy of Sciences of the United States of America. 96 (6): 2758–63. Bibcode:1999PNAS...96.2758S. doi:10.1073/pnas.96.6.2758. PMC 15842. PMID 10077584.
^ Dreier B, Fuller RP, Segal DJ, Lund CV, Blancafort P, Huber A, Koksch B, Barbas CF (October 2005). "Development of zinc finger domains for recognition of the 5'-CNN-3' family DNA sequences and their use in the construction of artificial transcription factors". The Journal of Biological Chemistry. 280 (42): 35588–97. doi:10.1074/jbc.M506654200. PMID 16107335.
^ Dreier B, Beerli RR, Segal DJ, Flippin JD, Barbas CF (August 2001). "Development of zinc finger domains for recognition of the 5'-ANN-3' family of DNA sequences and their use in the construction of artificial transcription factors". The Journal of Biological Chemistry. 276 (31): 29466–78. doi:10.1074/jbc.M102604200. PMID 11340073.
^ Bae KH, Kwon YD, Shin HC, Hwang MS, Ryu EH, Park KS, Yang HY, Lee DK, Lee Y, Park J, Kwon HS, Kim HW, Yeh BI, Lee HW, Sohn SH, Yoon J, Seol W, Kim JS (March 2003). "Human zinc fingers as building blocks in the construction of artificial transcription factors". Nature Biotechnology. 21 (3): 275–80. doi:10.1038/nbt796. PMID 12592413.
^ Ramirez CL, Foley JE, Wright DA, Müller-Lerch F, Rahman SH, Cornu TI, Winfrey RJ, Sander JD, Fu F, Townsend JA, Cathomen T, Voytas DF, Joung JK (May 2008). "Unexpected failure rates for modular assembly of engineered zinc fingers". Nature Methods. 5 (5): 374–5. doi:10.1038/nmeth0508-374. PMID 18446154.
^ Kim HJ, Lee HJ, Kim H, Cho SW, Kim JS (July 2009). "Targeted genome editing in human cells with zinc finger nucleases constructed via modular assembly". Genome Research. 19 (7): 1279–88. doi:10.1101/gr.089417.108. PMC 2704428. PMID 19470664.
^ Sander JD, Dahlborg EJ, Goodwin MJ, Cade L, Zhang F, Cifuentes D, Curtin SJ, Blackburn JS, Thibodeau-Beganny S, Qi Y, Pierick CJ, Hoffman E, Maeder ML, Khayter C, Reyon D, Dobbs D, Langenau DM, Stupar RM, Giraldez AJ, Voytas DF, Peterson RT, Yeh JR, Joung JK (January 2011). "Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA)". Nature Methods. 8 (1): 67–9. doi:10.1038/nmeth.1542. PMC 3018472. PMID 21151135.
^ Greisman HA, Pabo CO (January 1997). "A general strategy for selecting high-affinity zinc finger proteins for diverse DNA target sites". Science. 275 (5300): 657–61. doi:10.1126/science.275.5300.657. PMID 9005850.
^ Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM, Eichtinger M, Jiang T, Foley JE, Winfrey RJ, Townsend JA, Unger-Wallace E, Sander JD, Müller-Lerch F, Fu F, Pearlberg J, Göbel C, Dassie JP, Pruett-Miller SM, Porteus MH, Sgroi DC, Iafrate AJ, Dobbs D, McCray PB, Cathomen T, Voytas DF, Joung JK (July 2008). "Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification". Molecular Cell. 31 (2): 294–301. doi:10.1016/j.molcel.2008.06.016. PMC 2535758. PMID 18657511.
^ Smith AT, Tucker-Samaras SD, Fairlamb AH, Sullivan WJ (December 2005). "MYST family histone acetyltransferases in the protozoan parasite Toxoplasma gondii". Eukaryotic Cell. 4 (12): 2057–65. doi:10.1128/EC.4.12.2057-2065.2005. PMC 1317489. PMID 16339723.
^ Akhtar A, Becker PB (February 2001). "The histone H4 acetyltransferase MOF uses a C2HC zinc finger for substrate recognition". EMBO Reports. 2 (2): 113–8. doi:10.1093/embo-reports/kve022. PMC 1083818. PMID 11258702.
^ Kim JG, Armstrong RC, v Agoston D, Robinsky A, Wiese C, Nagle J, Hudson LD (October 1997). "Myelin transcription factor 1 (Myt1) of the oligodendrocyte lineage, along with a closely related CCHC zinc finger, is expressed in developing neurons in the mammalian central nervous system". Journal of Neuroscience Research. 50 (2): 272–90. doi:10.1002/(SICI)1097-4547(19971015)50:2<272::AID-JNR16>3.0.CO;2-A. PMID 9373037.
^ Jandrig B, Seitz S, Hinzmann B, Arnold W, Micheel B, Koelble K, Siebert R, Schwartz A, Ruecker K, Schlag PM, Scherneck S, Rosenthal A (December 2004). "ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2". Oncogene. 23 (57): 9295–302. doi:10.1038/sj.onc.1208131. PMID 15489893.
C2H2 family at PlantTFDB: Plant Transcription Factor Database
McDowall J. "Protein of the Month: Zinc Fingers". European Molecular Biology Laboratory - European Bioinformatics Institute (EMBL-EBI). Retrieved 2008-01-13.
Goodsell DS. "Molecule of the Month: Zinc Fingers". Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB). Retrieved 2008-01-13.
The double helix between the zinc finger
Zinc Finger Tools design and information site
Human KZNF Gene Catalog
Zinc finger C2H2-type domain in PROSITE
Entry for zinc finger class C2H2 in the SMART database
The Zinc Finger Consortium
ZiFiT- Zinc Finger Design Tool
Zinc Finger Consortium Materials from Addgene
Predicting DNA-binding Specificities for C2H2 Zinc Finger Proteins
Protein domains
BZIP
ENTH
Kringle
PDZ
Pyrin
zinc finger
Transcription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
Activating transcription factor
AATF
c-Fos
FOSB
FOSL1
JDP2
c-Jun
JUNB
BATF
BLZF1
C/EBP
α
β
γ
ε
ζ
CREB
DDIT3
GABPA
GCN4
NFIL3
XBP1
(1.2) Basic helix-loop-helix (bHLH)
AHRR
ARNT
ASCL1
BHLH
ARNTL
ARNTL2
HES1
LYL1
MYCL1
MYCN
Myogenic regulatory factors
MyoD
Myogenin
Neurogenins
NeuroD
OLIG
Scleraxis
USF1
(1.3) bHLH-ZIP
MLX
MLXIPL
MXI1
Myc
SREBP
(1.4) NF-1
R-SMAD
I-SMAD
(1.5) RF-X
ANK
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
Thyroid hormone
β/δ
PXR
Rev-ErbA
COUP-TF
Ear-2
HNF4
Testicular receptor
Steroid hormone
Androgen
Glucocorticoid
Mineralocorticoid
Estrogen related
NGFIB
NOR1
NURR1
LRH-1
GCNF
(2.2) Other Cys4
(2.3) Cys2His2
General transcription factors
TFIIA
TFIIB
TFIID
TFIIE
TFIIF
TFIIH
ATBF1
E4F1
ERV3
GLI-Krüppel family
YY1
HIVEP
IKZF
KLF
MTF1
OSR1
TSHZ3
Zbtb7
ZBTB
(2.4) Cys6
HIVEP1
(2.5) Alternating composition
DIDO1
GRLF1
JARID
JMJD1B
(2.6) WRKY
WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
protoHOX
ParaHox
Xlox
extended Hox: Evx1
Evx2
MEOX1
Homeobox
GBX1
MNX1
metaHOX
BARHL1
BARX1
HHEX
HLX
LBX1
NANOG
NKX
TLX1
CUTL1
FHL
HOPX
IRX
LMX
PITX
POU domain
PIT-1
BRN-3: A
Octamer transcription factor: 1
OTX
SHOX2
(3.2) Paired box
PRRX
(3.3) Fork head / winged helix
E2F
FOX proteins
(3.4) Heat shock factors
(3.5) Tryptophan clusters
SPIB
Interferon regulatory factors
MYB
MYBL2
(3.6) TEA domain
transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
NF-κB
NFAT
(4.2) STAT
(4.3) p53
TBX
TBR1
MYRF
(4.4) MADS box
Mef2
(4.6) TATA-binding proteins
TBP
TBPL1
(4.7) High-mobility group
BBX
HMGB
HMGN
HNF
LEF1
SRY
SSRP1
(4.9) Grainyhead
TFCP2
(4.10) Cold-shock domain
YBX1
(4.11) Runt
CBFA2T2
RUNX1T1
(0) Other transcription factors
(0.2) HMGI(Y)
HMGA
HBP1
(0.3) Pocket domain
RBL1
(0.5) AP-2/EREBP-related factors
Apetala 2
EREBP
(0.6) Miscellaneous
MLL
MNDA
NFY
Rho/Sigma
see also transcription factor/coregulator deficiencies
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.
Zinc finger, C2H2 type Provide feedback
The C2H2 zinc finger is the classical zinc finger domain. The two conserved cysteines and histidines co-ordinate a zinc ion. The following pattern describes the zinc finger. #-X-C-X(1-5)-C-X3-#-X5-#-X2-H-X(3-6)-[H/C] Where X can be any amino acid, and numbers in brackets indicate the number of residues. The positions marked # are those that are important for the stable fold of the zinc finger. The final position can be either his or cys. The C2H2 zinc finger is composed of two short beta strands followed by an alpha helix. The amino terminal part of the helix binds the major groove in DNA binding zinc fingers. The accepted consensus binding sequence for Sp1 is usually defined by the asymmetric hexanucleotide core GGGCGG but this sequence does not include, among others, the GAG (=CTC) repeat that constitutes a high-affinity site for Sp1 binding to the wt1 promoter [2].
Boehm S, Frishman D, Mewes HW; , Nucleic Acids Res 1997;25:2464-2469.: Variations of the C2H2 zinc finger motif in the yeast genome and classification of yeast zinc finger proteins. PUBMED:9171100 EPMC:9171100
Marco E, Garcia-Nieto R, Gago F; , J Mol Biol 2003;328:9-32.: Assessment by molecular dynamics simulations of the structural determinants of DNA-binding specificity for transcription factor Sp1. PUBMED:12683994 EPMC:12683994
Internal database links
SCOOP: BolA BTB C1_1 C1_4 DZR FOXP-CC GAGA HVO_2753_ZBP HypA NOA36 TF_Zn_Ribbon TFIIA zf-BED zf-C2H2_11 zf-C2H2_2 zf-C2H2_3rep zf-C2H2_4 zf-C2H2_6 zf-C2H2_8 zf-C2H2_aberr zf-C2H2_jaz zf-C2HC_2 zf-C2HE zf-Di19 zf-H2C2_2 zf-H2C2_5 zf-met zf-TRAF Zn-ribbon_8 Zn_ribbon_SprT
Similarity to PfamA using HHSearch: zf-BED zf-Di19 zf-C2H2_jaz zf-C2H2_2 zf-met zf-H2C2_2 zf-C2H2_4 zf-H2C2_5 zf-C2H2_6 zf-C2HC_2 zf-C2HE zf-C2H2_9 zf-C2H2_11 Zn-C2H2_12 zf_UBZ
HOMSTRAD: zf-CCHH
PRINTS: PR00048
PROSITE: PDOC00028
SCOP: 1zaa
This tab holds annotation information from the InterPro database.
InterPro entry IPR013087
C2H2-type (classical) zinc fingers (Znf) were the first class to be characterised. They contain a short beta hairpin and an alpha helix (beta/beta/alpha structure), where a single zinc atom is held in place by Cys(2)His(2) (C2H2) residues in a tetrahedral array. C2H2 Znf's can be divided into three groups based on the number and pattern of fingers: triple-C2H2 (binds single ligand), multiple-adjacent-C2H2 (binds multiple ligands), and separated paired-C2H2 [ PUBMED:11361095 ]. C2H2 Znf's are the most common DNA-binding motifs found in eukaryotic transcription factors, and have also been identified in prokaryotes [ PUBMED:10664601 ]. Transcription factors usually contain several Znf's (each with a conserved beta/beta/alpha structure) capable of making multiple contacts along the DNA, where the C2H2 Znf motifs recognise DNA sequences by binding to the major groove of DNA via a short alpha-helix in the Znf, the Znf spanning 3-4 bases of the DNA [ PUBMED:10940247 ]. C2H2 Znf's can also bind to RNA and protein targets [ PUBMED:18253864 ].
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [ PUBMED:10529348 , PUBMED:15963892 , PUBMED:15718139 , PUBMED:17210253 , PUBMED:12665246 ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [ PUBMED:11179890 ]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
This entry represents the classical C2H2 zinc finger domain.
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:
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 Gla domain, followed by two consecutive EGF domains, and finally a single Trypsin domain
a link to the page in the Pfam site showing information about the sequence that the graphic describes
the UniProt description of the protein sequence
the number of residues in the sequence
the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
This family is a member of clan C2H2-zf (CL0361), which has the following description:
Superfamily of classical and closely related C2H2 or beta-beta-alpha zinc finger DNA-binding domains.
The clan contains the following 52 members:
ARS2 GAGA Hat1_N Integrase_H2C2 KN17_SH3 Nairovirus_M ROS_MUCR SF3a60_Prp9_C Sgf11 UBZ_FAAP20 Zap1_zf2 zf-AD zf-BED zf-C2H2 zf-C2H2_10 zf-C2H2_11 zf-C2H2_2 zf-C2H2_3 zf-C2H2_3rep zf-C2H2_4 zf-C2H2_6 zf-C2H2_7 zf-C2H2_8 zf-C2H2_9 zf-C2H2_aberr zf-C2H2_jaz zf-C2HC_2 zf-C2HE zf-CRD zf-DBF zf-Di19 zf-H2C2 zf-H2C2_2 zf-H2C2_5 zf-H3C2 zf-LYAR zf-met zf-met2 zf-MYST zf-RAG1 zf-U1 zf-U11-48K zf-WRNIP1_ubi zf_C2H2_10 zf_C2H2_13 zf_C2H2_6 zf_C2H2_ZHX zf_C2HC_14 zf_Hakai zf_UBZ zf_ZIC Zn-C2H2_12
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.
Alignment types
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
RP15/RP35/RP55/RP75
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:
jalview
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
PP/Heatmap
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.
Reformatting
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
Selex
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.
Representative proteomes
Jalview View View View View View View View
HTML View
PP/heatmap 1
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
Alignment:
Format: Selex Stockholm FASTA MSF
Order: Tree Alphabetical
Sequence: Inserts lower case All upper case
Gaps: Gaps as "." or "-" (mixed) Gaps as "." (dots) Gaps as "-" (dashes) No gaps (unaligned)
Download/view: Download View
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.
Raw Stockholm Download Download Download Download
Gzipped Download Download Download Download
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:
HMM Logos for visualization of protein families: B. Schuster-Böckler, J. Schultz, S. Rahmann BMC Bioinformatics (2004) 5:7
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: Boehm S
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Boehm S , Sonnhammer ELL , Gago F
Number in seed: 159
Number in full: 1201914
Average length of the domain: 23.10 aa
Average identity of full alignment: 41 %
Average coverage of the sequence by the domain: 20.45 %
HMM information
HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Gathering cut-off 25.2 15.8
Trusted cut-off 25.2 15.8
Noise cut-off 25.1 15.7
Model length: 23
Family (HMM) version: 29
Download: download the raw HMM for this family
Sunburst controls
Weight segments by...
number of sequences
Change the size of the sunburst
Colour assignments
Archea Eukaryota
Bacteria Other sequences
Viruses Unclassified
Viroids Unclassified sequence
Align selected sequences to HMM
Generate a FASTA-format file
Storing selection…
0 sequences
0 species
Note: selection tools show results in pop-up windows. Please disable pop-up blockers.
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...
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:
superkingdom
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.
Loading sunburst data...
Tree controls
Fully expand tree
Fully collapse tree
Expand tree...
Hide highlighting of species in seed
Hide summaries
Key: species, sequences, regions
Download tree
Save a text representation
Selected sequences
(Uncheck all)
as an alignment
sequence accessions
sequences in FASTA format
The tree shows the occurrence of this domain across different species. More...
Species trees
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
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 zf-C2H2 domain has been found. There are 586 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.
Predicted structure
A0A087WNP1 View 3D Structure Click here
A0A087WPN2 View 3D Structure Click here
A0A087WQI7 View 3D Structure Click here
A0A087WQW2 View 3D Structure Click here
A0A087WR25 View 3D Structure Click here
A0A087WRH0 View 3D Structure Click here
A0A087WRJ1 View 3D Structure Click here
A0A087WRR7 View 3D Structure Click here
A0A087WS64 View 3D Structure Click here
A0A087WSP8 View 3D Structure Click here
A0A087WUV0 View 3D Structure Click here
A0A096MIX7 View 3D Structure Click here
A0A096MJ70 View 3D Structure Click here
A0A096MJU6 View 3D Structure Click here
A0A096MJV6 View 3D Structure Click here
A0A096MKA8 View 3D Structure Click here
A0A0B4K7S6 View 3D Structure Click here
A0A0F0I5G4 View 3D Structure Click here
A0A0G2JEM5 View 3D Structure Click here
A0A0G2JT46 View 3D Structure Click here
A0A0G2JUC1 View 3D Structure Click here
A0A0G2JUJ1 View 3D Structure Click here
A0A0G2JUN3 View 3D Structure Click here
A0A0G2JUV0 View 3D Structure Click here
A0A0G2JV23 View 3D Structure Click here
A0A0G2JVA9 View 3D Structure Click here
A0A0G2JVD5 View 3D Structure Click here
A0A0G2JVG6 View 3D Structure Click here
A0A0G2JW96 View 3D Structure Click here
A0A0G2JWH7 View 3D Structure Click here
A0A0G2JWU0 View 3D Structure Click here
A0A0G2JWY4 View 3D Structure Click here
A0A0G2JX65 View 3D Structure Click here
A0A0G2JXW3 View 3D Structure Click here
A0A0G2JY97 View 3D Structure Click here
A0A0G2JZA5 View 3D Structure Click here
Showing 40 matches
Pfam is part of the ELIXIR infrastructure
Pfam is an Elixir service Read more
Comments or questions on the site? Send a mail to pfam-help@ebi.ac.uk.
European Molecular Biology Laboratory