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.
82  structures 1581  species 0  interactions 56235  sequences 2128  architectures

Family: zf-CCHC (PF00098)

Summary: Zinc knuckle

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Zinc finger". More...

Zinc finger Edit Wikipedia article

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.

History

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]

Domain

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.

Classes

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 PDB 1zaa EBI.jpg Two ligands from a knuckle and two more from the c terminus of a helix.
Gag knuckle PDB 1ncp EBI.jpg 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 PDB 1pft EBI.jpg Two ligands each from two knuckles.
Zn2/Cys6 PDB 1d66 EBI.jpg 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
Identifiers
Symbolzf-C2H2
PfamPF00096
Pfam clanCL0361
InterProIPR007087
PROSITEPS00028

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
Identifiers
Symbolzf-CCHC
PfamPF00098
InterProIPR001878
SMARTSM00343
PROSITEPS50158

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
Identifiers
SymbolTF_Zn_Ribbon
PfamPF08271
Pfam clanZn_Beta_Ribbon
InterProIPR013137
PROSITEPS51134

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
Identifiers
SymbolZn_clus
PfamPF00172
InterProIPR001138
SMARTGAL4
PROSITEPS00463
CDDcd00067

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
PDB 1pxe EBI.jpg
solution structure of a cchhc domain of neural zinc finger factor-1
Identifiers
Symbolzf-C2HC
PfamPF01530
InterProIPR002515
zf-C2HC5
Identifiers
Symbolzf-C2HC5
PfamPF06221
InterProIPR009349

Miscellaneous

zf-C2HC
PDB 1pxe EBI.jpg
solution structure of a cchhc domain of neural zinc finger factor-1
Identifiers
Symbolzf-C2HC
PfamPF01530
InterProIPR002515
zf-C2HC5
Identifiers
Symbolzf-C2HC5
PfamPF06221
InterProIPR009349

Applications

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.

Examples

This entry represents the CysCysHisCys (C2HC) type zinc finger domain found in eukaryotes. Proteins containing these domains include:

See also

References

  1. ^ 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.
  2. ^ 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.
  3. ^ 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.
  4. ^ 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. â€“ via Annual Reviews (subscription required)
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ Matthews JM, Sunde M (December 2002). "Zinc fingers--folds for many occasions". IUBMB Life. 54 (6): 351–5. doi:10.1080/15216540216035. PMID 12665246.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ 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.
  24. ^ 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.
  25. ^ Tebas P, Stein D (2009). "Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-728 for HIV". ClinicalTrials.gov.
  26. ^ 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.
  27. ^ 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.
  28. ^ 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.
  29. ^ 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.
  30. ^ 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.
  31. ^ 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.
  32. ^ 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.
  33. ^ 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.
  34. ^ 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.
  35. ^ 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.
  36. ^ 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.
  37. ^ 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.
  38. ^ 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.
  39. ^ 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.
  40. ^ 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.
  41. ^ 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.
  42. ^ 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.
  43. ^ 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.
  44. ^ 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.
  45. ^ 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.

External links

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 knuckle Provide feedback

The zinc knuckle is a zinc binding motif composed of the the following CX2CX4HX4C where X can be any amino acid. The motifs are mostly from retroviral gag proteins (nucleocapsid). Prototype structure is from HIV. Also contains members involved in eukaryotic gene regulation, such as C. elegans GLH-1. Structure is an 18-residue zinc finger.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001878

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 CysCysHisCys (CCHC) type zinc finger domains, and have the sequence:

C-X2-C-X4-H-X4-C

where X can be any amino acid, and number indicates the number of residues. These 18 residues CCHC zinc finger domains are mainly found in the nucleocapsid protein of retroviruses. It is required for viral genome packaging and for early infection process [ PUBMED:17416621 , PUBMED:17202191 , PUBMED:17029416 ]. It is also found in eukaryotic proteins involved in RNA binding or single-stranded DNA binding [ PUBMED:15937226 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan Retroviral_zf (CL0511), which has the following description:

This superfamily has zinc-finger domains from GAG proteins, HIV nucleocapsids, nucleocapsid proteins from mason-pfizer monkey virus, and from other nucleic-acid binding proteins. Sometimes the domains appears in duplicate.

The clan contains the following 8 members:

CLIP1_ZNF eIF3g zf-CCHC zf-CCHC_2 zf-CCHC_3 zf-CCHC_4 zf-CCHC_5 zf-CCHC_6

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(79)
Full
(56235)
Representative proteomes UniProt
(195734)
RP15
(13338)
RP35
(31018)
RP55
(47576)
RP75
(61056)
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, x not generated, not available.

Format an alignment

  Seed
(79)
Full
(56235)
Representative proteomes UniProt
(195734)
RP15
(13338)
RP35
(31018)
RP55
(47576)
RP75
(61056)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(79)
Full
(56235)
Representative proteomes UniProt
(195734)
RP15
(13338)
RP35
(31018)
RP55
(47576)
RP75
(61056)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   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 logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Overington and HMM_iterative_training
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Eddy SR
Number in seed: 79
Number in full: 56235
Average length of the domain: 17.70 aa
Average identity of full alignment: 43 %
Average coverage of the sequence by the domain: 5.46 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.8 16.7
Trusted cut-off 20.8 16.7
Noise cut-off 20.7 16.6
Model length: 18
Family (HMM) version: 25
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

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...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

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.

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the zf-CCHC domain has been found. There are 82 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
A0A0G2JUE8 View 3D Structure Click here
A0A0G2JZ04 View 3D Structure Click here
A0A0G2JZ04 View 3D Structure Click here
A0A0G2L234 View 3D Structure Click here
A0A0G2L234 View 3D Structure Click here
A0A0P0V1S7 View 3D Structure Click here
A0A0P0XGU7 View 3D Structure Click here
A0A0P0XKJ7 View 3D Structure Click here
A0A0P0XR38 View 3D Structure Click here
A0A0P0XSQ0 View 3D Structure Click here
A0A0P0Y3R0 View 3D Structure Click here
A0A0P0Y3R0 View 3D Structure Click here
A0A0P0YB17 View 3D Structure Click here
A0A0R0E8P4 View 3D Structure Click here
A0A0R0EFT0 View 3D Structure Click here
A0A0R0EIY4 View 3D Structure Click here
A0A0R0F0U3 View 3D Structure Click here
A0A0R0F5I7 View 3D Structure Click here
A0A0R0F8M0 View 3D Structure Click here
A0A0R0F9J4 View 3D Structure Click here
A0A0R0FBM4 View 3D Structure Click here
A0A0R0FS92 View 3D Structure Click here
A0A0R0G440 View 3D Structure Click here
A0A0R0G483 View 3D Structure Click here
A0A0R0G9G9 View 3D Structure Click here
A0A0R0GBX8 View 3D Structure Click here
A0A0R0GC44 View 3D Structure Click here
A0A0R0GDR6 View 3D Structure Click here
A0A0R0GEV9 View 3D Structure Click here
A0A0R0GPQ8 View 3D Structure Click here
A0A0R0HGG0 View 3D Structure Click here
A0A0R0HHA3 View 3D Structure Click here
A0A0R0HHW1 View 3D Structure Click here
A0A0R0HHY3 View 3D Structure Click here
A0A0R0HUG5 View 3D Structure Click here
A0A0R0I6T9 View 3D Structure Click here
A0A0R0ITV8 View 3D Structure Click here
A0A0R0JKW9 View 3D Structure Click here
A0A0R0JL31 View 3D Structure Click here
A0A0R0JU30 View 3D Structure Click here
A0A0R0JYQ1 View 3D Structure Click here
A0A0R0JZ47 View 3D Structure Click here
A0A0R0K893 View 3D Structure Click here
A0A0R0KHL4 View 3D Structure Click here
A0A0R0KNT4 View 3D Structure Click here
A0A0R0KS55 View 3D Structure Click here
A0A0R0L9J5 View 3D Structure Click here
A0A0R4IBT0 View 3D Structure Click here
A0A0R4ID65 View 3D Structure Click here
A0A0R4IRA3 View 3D Structure Click here
A0A1D6DVT0 View 3D Structure Click here
A0A1D6E4V9 View 3D Structure Click here
A0A1D6E4V9 View 3D Structure Click here
A0A1D6ED98 View 3D Structure Click here
A0A1D6F6X8 View 3D Structure Click here
A0A1D6F6X8 View 3D Structure Click here
A0A1D6F6X8 View 3D Structure Click here
A0A1D6F8W7 View 3D Structure Click here
A0A1D6FVH3 View 3D Structure Click here
A0A1D6FVH3 View 3D Structure Click here
A0A1D6GDY8 View 3D Structure Click here
A0A1D6GE70 View 3D Structure Click here
A0A1D6GFM9 View 3D Structure Click here
A0A1D6GKH5 View 3D Structure Click here
A0A1D6HMW8 View 3D Structure Click here
A0A1D6IB14 View 3D Structure Click here
A0A1D6IHC6 View 3D Structure Click here
A0A1D6JZP0 View 3D Structure Click here
A0A1D6L6V1 View 3D Structure Click here
A0A1D6L6V1 View 3D Structure Click here
A0A1D6L6V1 View 3D Structure Click here
A0A1D6L9V3 View 3D Structure Click here
A0A1D6L9V3 View 3D Structure Click here
A0A1D6L9V3 View 3D Structure Click here
A0A1D6L9V3 View 3D Structure Click here
A0A1D6L9V3 View 3D Structure Click here
A0A1D6L9V3 View 3D Structure Click here
A0A1D6LAB7 View 3D Structure Click here
A0A1D6LG97 View 3D Structure Click here
A0A1D6LH52 View 3D Structure Click here
A0A1D6LH52 View 3D Structure Click here
A0A1D6LHJ8 View 3D Structure Click here
A0A1D6LHJ8 View 3D Structure Click here
A0A1D6LHJ8 View 3D Structure Click here
A0A1D6LHJ8 View 3D Structure Click here
A0A1D6LHJ8 View 3D Structure Click here
A0A1D6LHJ8 View 3D Structure Click here
A0A1D6LHJ8 View 3D Structure Click here
A0A1D6LPV5 View 3D Structure Click here
A0A1D6LYS2 View 3D Structure Click here
A0A1D6LYS2 View 3D Structure Click here
A0A1D6MX03 View 3D Structure Click here
A0A1D6NTG8 View 3D Structure Click here
A0A1D6NVB4 View 3D Structure Click here
A0A1I9LR82 View 3D Structure Click here
A0A1P8AUP0 View 3D Structure Click here
A0A1P8BEI2 View 3D Structure Click here
A4HTZ3 View 3D Structure Click here
A4IBI7 View 3D Structure Click here
A4IDA7 View 3D Structure Click here
A4IDA7 View 3D Structure Click here
A4IDA7 View 3D Structure Click here
A4IDD1 View 3D Structure Click here
A4IDD1 View 3D Structure Click here
A4IDD1 View 3D Structure Click here
A4IDD1 View 3D Structure Click here
A4IDD1 View 3D Structure Click here
A4IDD2 View 3D Structure Click here
A4IDD2 View 3D Structure Click here
A4IDD2 View 3D Structure Click here
A4IDD2 View 3D Structure Click here
A4IDD2 View 3D Structure Click here
A4IDD4 View 3D Structure Click here
A4IDD4 View 3D Structure Click here
A4IDD4 View 3D Structure Click here
A4IDD4 View 3D Structure Click here
A4IDD4 View 3D Structure Click here
A4IDD4 View 3D Structure Click here
A4IDD5 View 3D Structure Click here
A4IDD5 View 3D Structure Click here
A4IDD5 View 3D Structure Click here
A4IDD5 View 3D Structure Click here
A4IDD5 View 3D Structure Click here
A4IDD5 View 3D Structure Click here
A4IDD5 View 3D Structure Click here
A4IDD5 View 3D Structure Click here
A4IDD5 View 3D Structure Click here
B0V0Y9 View 3D Structure Click here
B1AX39 View 3D Structure Click here
B1AX39 View 3D Structure Click here
B1WC15 View 3D Structure Click here
B1WC15 View 3D Structure Click here
B2RX14 View 3D Structure Click here
B2RX14 View 3D Structure Click here
B4F7Z5 View 3D Structure Click here
B4FG21 View 3D Structure Click here
B4FGF8 View 3D Structure Click here
B4FGF8 View 3D Structure Click here
B4FGF8 View 3D Structure Click here
B4FKN3 View 3D Structure Click here
B4FKN3 View 3D Structure Click here
B4FKN3 View 3D Structure Click here
B4FKN3 View 3D Structure Click here
B4FKN3 View 3D Structure Click here
B4FKN3 View 3D Structure Click here
B4FKN3 View 3D Structure Click here
B4FKN3 View 3D Structure Click here
B4FLG4 View 3D Structure Click here
B4FLG4 View 3D Structure Click here
B4FLG4 View 3D Structure Click here
B4FLG4 View 3D Structure Click here
B4FLG4 View 3D Structure Click here
B4FLG4 View 3D Structure Click here
B4FLG4 View 3D Structure Click here
B4FLG4 View 3D Structure Click here
B6THC3 View 3D Structure Click here
B6THC3 View 3D Structure Click here
B6TJ91 View 3D Structure Click here
B6TN55 View 3D Structure Click here
B6U3A0 View 3D Structure Click here
B6U4N8 View 3D Structure Click here
B8A500 View 3D Structure Click here
C0P2Q6 View 3D Structure Click here
C0PLI2 View 3D Structure Click here
C0PLI2 View 3D Structure Click here
C0PLI2 View 3D Structure Click here
C0PLI2 View 3D Structure Click here
C0PP56 View 3D Structure Click here
C0PP56 View 3D Structure Click here
C4JAE0 View 3D Structure Click here
C6SVE9 View 3D Structure Click here
C6TJJ8 View 3D Structure Click here
D3ZH95 View 3D Structure Click here
D3ZIK1 View 3D Structure Click here
D3ZIK1 View 3D Structure Click here
D3ZKR9 View 3D Structure Click here
D3ZKR9 View 3D Structure Click here
D3ZKR9 View 3D Structure Click here
D3ZUL8 View 3D Structure Click here
D3ZZ10 View 3D Structure Click here
D3ZZA6 View 3D Structure Click here
D4A5W5 View 3D Structure Click here
D5MCP3 View 3D Structure Click here
D5MCP3 View 3D Structure Click here
E7F3W9 View 3D Structure Click here
E7F8R0 View 3D Structure Click here
E7FCQ0 View 3D Structure Click here
E7FCQ0 View 3D Structure Click here
E7FCQ0 View 3D Structure Click here
E7FCQ0 View 3D Structure Click here
E7FCQ0 View 3D Structure Click here
E7FCQ0 View 3D Structure Click here
E9QES1 View 3D Structure Click here
E9QIC4 View 3D Structure Click here
F1LSC3 View 3D Structure Click here
F1Q6Z5 View 3D Structure Click here
F1Q6Z5 View 3D Structure Click here
F1Q6Z5 View 3D Structure Click here
F1Q6Z5 View 3D Structure Click here
F1Q6Z5 View 3D Structure Click here
F1Q6Z5 View 3D Structure Click here
F1Q6Z5 View 3D Structure Click here
F1Q7F8 View 3D Structure Click here
F1Q949 View 3D Structure Click here
F1QE26 View 3D Structure Click here
F1QE26 View 3D Structure Click here
F1QE26 View 3D Structure Click here
F1QLJ5 View 3D Structure Click here
F1QLY2 View 3D Structure Click here
F2Z4T3 View 3D Structure Click here
F6NKN9 View 3D Structure Click here
F6P4J7 View 3D Structure Click here
G5EF97 View 3D Structure Click here
I1JPG3 View 3D Structure Click here
I1JPG3 View 3D Structure Click here
I1JPG4 View 3D Structure Click here
I1JPG4 View 3D Structure Click here
I1JQZ9 View 3D Structure Click here
I1JRB6 View 3D Structure Click here
I1JRL0 View 3D Structure Click here
I1JSF3 View 3D Structure Click here
I1JSF3 View 3D Structure Click here
I1JZ92 View 3D Structure Click here
I1JZ92 View 3D Structure Click here
I1KA68 View 3D Structure Click here
I1KA68 View 3D Structure Click here
I1KXH3 View 3D Structure Click here
I1L0M7 View 3D Structure Click here
I1LAW9 View 3D Structure Click here
I1LIR6 View 3D Structure Click here
I1LPI5 View 3D Structure Click here
I1LPN7 View 3D Structure Click here
I1LPN7 View 3D Structure Click here
I1LXY7 View 3D Structure Click here
I1LXY7 View 3D Structure Click here
I1LXY7 View 3D Structure Click here
I1LXY7 View 3D Structure Click here
I1M9U2 View 3D Structure Click here
I1MC52 View 3D Structure Click here
I1MGB1 View 3D Structure Click here
I1MI74 View 3D Structure Click here
I1NA27 View 3D Structure Click here
I1NA27 View 3D Structure Click here
I1NA32 View 3D Structure Click here
I1NA32 View 3D Structure Click here
I1NBL1 View 3D Structure Click here
I1NC68 View 3D Structure Click here
I1NE34 View 3D Structure Click here
I1NE34 View 3D Structure Click here
I1NE34 View 3D Structure Click here
I1NES2 View 3D Structure Click here
I1NFF9 View 3D Structure Click here
I1NIU2 View 3D Structure Click here
K7K299 View 3D Structure Click here
K7K3K9 View 3D Structure Click here
K7K6H1 View 3D Structure Click here
K7K6H1 View 3D Structure Click here
K7K6H1 View 3D Structure Click here
K7K6H1 View 3D Structure Click here
K7K6H1 View 3D Structure Click here
K7K9P1 View 3D Structure Click here
K7KDX6 View 3D Structure Click here
K7KHH1 View 3D Structure Click here
K7KHH1 View 3D Structure Click here
K7KHH1 View 3D Structure Click here
K7KHH1 View 3D Structure Click here
K7KHH1 View 3D Structure Click here
K7KHH1 View 3D Structure Click here
K7KHH1 View 3D Structure Click here
K7KHH1 View 3D Structure Click here
K7KN36 View 3D Structure Click here
K7KP22 View 3D Structure Click here
K7KSE0 View 3D Structure Click here
K7KSE0 View 3D Structure Click here
K7KSE0 View 3D Structure Click here
K7KSE0 View 3D Structure Click here
K7KSE0 View 3D Structure Click here
K7KSE0 View 3D Structure Click here
K7KSE0 View 3D Structure Click here
K7KSE0 View 3D Structure Click here
K7KV90 View 3D Structure Click here
K7KYG5 View 3D Structure Click here
K7L5F9 View 3D Structure Click here
K7LC71 View 3D Structure Click here
K7LF83 View 3D Structure Click here
K7LF83 View 3D Structure Click here
K7LHY8 View 3D Structure Click here
K7LL23 View 3D Structure Click here
K7M6P8 View 3D Structure Click here
K7MC34 View 3D Structure Click here
K7MH03 View 3D Structure Click here
K7MH03 View 3D Structure Click here
K7MH03 View 3D Structure Click here
K7MH03 View 3D Structure Click here
K7MH03 View 3D Structure Click here
K7MLZ7 View 3D Structure Click here
K7MQK2 View 3D Structure Click here
K7MRK3 View 3D Structure Click here
K7MRN2 View 3D Structure Click here
K7MRY5 View 3D Structure Click here
K7MVQ0 View 3D Structure Click here
K7MX92 View 3D Structure Click here
K7N1H4 View 3D Structure Click here
K7N3Q9 View 3D Structure Click here
K7N3Q9 View 3D Structure Click here
K7U5B6 View 3D Structure Click here
K7V3Q2 View 3D Structure Click here
K7V3Q2 View 3D Structure Click here
K7V3Q2 View 3D Structure Click here
M0R4K3 View 3D Structure Click here
M0R729 View 3D Structure Click here
M0R729 View 3D Structure Click here
M0R729 View 3D Structure Click here
M0R729 View 3D Structure Click here
M0R729 View 3D Structure Click here
M0R729 View 3D Structure Click here
M0R729 View 3D Structure Click here
O01836 View 3D Structure Click here
O01836 View 3D Structure Click here
O16635 View 3D Structure Click here
O22703 View 3D Structure Click here
O65639 View 3D Structure Click here
O65639 View 3D Structure Click here
O65639 View 3D Structure Click here
O65639 View 3D Structure Click here
O65639 View 3D Structure Click here
O65639 View 3D Structure Click here
O65639 View 3D Structure Click here
O74555 View 3D Structure Click here
O74555 View 3D Structure Click here
O76743 View 3D Structure Click here
O76743 View 3D Structure Click here
O76743 View 3D Structure Click here
O76743 View 3D Structure Click here
O76743 View 3D Structure Click here
O81126 View 3D Structure Click here
O81127 View 3D Structure Click here
O95639 View 3D Structure Click here
P34689 View 3D Structure Click here
P34689 View 3D Structure Click here
P34689 View 3D Structure Click here
P34689 View 3D Structure Click here
P36627 View 3D Structure Click here
P36627 View 3D Structure Click here
P36627 View 3D Structure Click here
P36627 View 3D Structure Click here
P36627 View 3D Structure Click here
P36627 View 3D Structure Click here
P36627 View 3D Structure Click here
P40507 View 3D Structure Click here
P40507 View 3D Structure Click here
P40507 View 3D Structure Click here
P53849 View 3D Structure Click here
P53849 View 3D Structure Click here
P53849 View 3D Structure Click here
P53849 View 3D Structure Click here
P53849 View 3D Structure Click here
P53849 View 3D Structure Click here
P53849 View 3D Structure Click here
P53996 View 3D Structure Click here
P53996 View 3D Structure Click here
P53996 View 3D Structure Click here
P53996 View 3D Structure Click here
P53996 View 3D Structure Click here
P53996 View 3D Structure Click here
P53996 View 3D Structure Click here
P62633 View 3D Structure Click here
P62633 View 3D Structure Click here
P62633 View 3D Structure Click here
P62633 View 3D Structure Click here
P62633 View 3D Structure Click here
P62633 View 3D Structure Click here
P62633 View 3D Structure Click here
P62634 View 3D Structure Click here
P62634 View 3D Structure Click here
P62634 View 3D Structure Click here
P62634 View 3D Structure Click here
P62634 View 3D Structure Click here
P62634 View 3D Structure Click here
P62634 View 3D Structure Click here
P62684 View 3D Structure Click here
P63128 View 3D Structure Click here
P63145 View 3D Structure Click here
P91223 View 3D Structure Click here
P91223 View 3D Structure Click here
P91223 View 3D Structure Click here
P92186 View 3D Structure Click here
Q0DL70 View 3D Structure Click here
Q0DL70 View 3D Structure Click here
Q0DM51 View 3D Structure Click here
Q0J8A6 View 3D Structure Click here
Q10BE5 View 3D Structure Click here
Q10BE5 View 3D Structure Click here
Q10BE5 View 3D Structure Click here
Q10BE5 View 3D Structure Click here
Q10BE5 View 3D Structure Click here
Q10N19 View 3D Structure Click here
Q10N19 View 3D Structure Click here
Q12186 View 3D Structure Click here
Q12476 View 3D Structure Click here
Q12476 View 3D Structure Click here
Q12476 View 3D Structure Click here
Q15637 View 3D Structure Click here
Q18244 View 3D Structure Click here
Q21278 View 3D Structure Click here
Q2PE14 View 3D Structure Click here
Q2QNI2 View 3D Structure Click here
Q2R072 View 3D Structure Click here
Q2R2A2 View 3D Structure Click here
Q2R394 View 3D Structure Click here
Q2R394 View 3D Structure Click here
Q2R6R8 View 3D Structure Click here
Q2R6R8 View 3D Structure Click here
Q2R6R8 View 3D Structure Click here
Q38896 View 3D Structure Click here
Q38896 View 3D Structure Click here
Q41188 View 3D Structure Click here
Q41188 View 3D Structure Click here
Q45KJ6 View 3D Structure Click here
Q45KJ6 View 3D Structure Click here
Q498S6 View 3D Structure Click here
Q499V6 View 3D Structure Click here
Q4CLS4 View 3D Structure Click here
Q4CLS4 View 3D Structure Click here
Q4CLS4 View 3D Structure Click here
Q4CLS4 View 3D Structure Click here
Q4CLS4 View 3D Structure Click here
Q4CLS4 View 3D Structure Click here
Q4CLS4 View 3D Structure Click here
Q4CLS4 View 3D Structure Click here
Q4CM27 View 3D Structure Click here
Q4D488 View 3D Structure Click here
Q4D6T7 View 3D Structure Click here
Q4D6T7 View 3D Structure Click here
Q4D6T7 View 3D Structure Click here
Q4D6T7 View 3D Structure Click here
Q4D6T7 View 3D Structure Click here
Q4D6T8 View 3D Structure Click here
Q4D6T8 View 3D Structure Click here
Q4D6T8 View 3D Structure Click here
Q4D6T8 View 3D Structure Click here
Q4D6T8 View 3D Structure Click here
Q4D6T8 View 3D Structure Click here
Q4D6T8 View 3D Structure Click here
Q4D6T9 View 3D Structure Click here
Q4D6T9 View 3D Structure Click here
Q4D6T9 View 3D Structure Click here
Q4D6T9 View 3D Structure Click here
Q4D6T9 View 3D Structure Click here
Q4D6T9 View 3D Structure Click here
Q4D6T9 View 3D Structure Click here
Q4D6T9 View 3D Structure Click here
Q4D7B2 View 3D Structure Click here
Q4D7B2 View 3D Structure Click here
Q4D8U5 View 3D Structure Click here
Q4D8U5 View 3D Structure Click here
Q4D8U5 View 3D Structure Click here
Q4D8U5 View 3D Structure Click here
Q4D8U5 View 3D Structure Click here
Q4D8U5 View 3D Structure Click here
Q4D8U5 View 3D Structure Click here
Q4D8U6 View 3D Structure Click here
Q4D8U6 View 3D Structure Click here
Q4D8U6 View 3D Structure Click here
Q4D8U6 View 3D Structure Click here
Q4D8U6 View 3D Structure Click here
Q4DJB8 View 3D Structure Click here
Q4DJB8 View 3D Structure Click here
Q4DJB8 View 3D Structure Click here
Q4DNR6 View 3D Structure Click here
Q4DNR6 View 3D Structure Click here
Q4DNR6 View 3D Structure Click here
Q4DT61 View 3D Structure Click here
Q4DVP5 View 3D Structure Click here
Q4DVP5 View 3D Structure Click here
Q4E420 View 3D Structure Click here
Q4V8Q5 View 3D Structure Click here
Q54AM7 View 3D Structure Click here
Q54BY8 View 3D Structure Click here
Q54BY8 View 3D Structure Click here
Q54BY8 View 3D Structure Click here
Q54BY8 View 3D Structure Click here
Q54BY8 View 3D Structure Click here
Q54PX3 View 3D Structure Click here
Q54VI2 View 3D Structure Click here
Q54VI2 View 3D Structure Click here
Q54Y39 View 3D Structure Click here
Q55CA3 View 3D Structure Click here
Q55CA3 View 3D Structure Click here
Q55EN4 View 3D Structure Click here
Q59YJ9 View 3D Structure Click here
Q59YJ9 View 3D Structure Click here
Q59YJ9 View 3D Structure Click here
Q59YJ9 View 3D Structure Click here
Q59YJ9 View 3D Structure Click here
Q59YJ9 View 3D Structure Click here
Q59YJ9 View 3D Structure Click here
Q5AED9 View 3D Structure Click here
Q5APC1 View 3D Structure Click here
Q5BLK4 View 3D Structure Click here
Q5BLK4 View 3D Structure Click here
Q5BLK4 View 3D Structure Click here
Q5FVR7 View 3D Structure Click here
Q5RG88 View 3D Structure Click here
Q5SP50 View 3D Structure Click here
Q5TAX3 View 3D Structure Click here
Q5TAX3 View 3D Structure Click here
Q5VYS8 View 3D Structure Click here
Q5VYS8 View 3D Structure Click here
Q5VYS8 View 3D Structure Click here
Q5XII6 View 3D Structure Click here
Q5XII6 View 3D Structure Click here
Q5XII6 View 3D Structure Click here
Q5ZCD9 View 3D Structure Click here
Q5ZCD9 View 3D Structure Click here
Q64213 View 3D Structure Click here
Q64LC9 View 3D Structure Click here
Q64MA5 View 3D Structure Click here
Q64MA5 View 3D Structure Click here
Q653M6 View 3D Structure Click here
Q65XV7 View 3D Structure Click here
Q65XV7 View 3D Structure Click here
Q65XV7 View 3D Structure Click here
Q69KL9 View 3D Structure Click here
Q69ZB8 View 3D Structure Click here
Q6F378 View 3D Structure Click here
Q6F3B9 View 3D Structure Click here
Q6F3B9 View 3D Structure Click here
Q6F3B9 View 3D Structure Click here
Q6IQ97 View 3D Structure Click here
Q6K4N0 View 3D Structure Click here
Q6K9C3 View 3D Structure Click here
Q6NZY4 View 3D Structure Click here
Q6P1Y1 View 3D Structure Click here
Q6Q151 View 3D Structure Click here
Q6R9A9 View 3D Structure Click here
Q6YUR8 View 3D Structure Click here
Q6YUR8 View 3D Structure Click here
Q6YUR8 View 3D Structure Click here
Q6YUR8 View 3D Structure Click here
Q6Z6G7 View 3D Structure Click here
Q6ZN17 View 3D Structure Click here
Q6ZN17 View 3D Structure Click here
Q75IR8 View 3D Structure Click here
Q75IR8 View 3D Structure Click here
Q75LJ7 View 3D Structure Click here
Q75NR7 View 3D Structure Click here
Q7Y008 View 3D Structure Click here
Q7YTG9 View 3D Structure Click here
Q803L0 View 3D Structure Click here
Q84UR8 View 3D Structure Click here
Q84UR8 View 3D Structure Click here
Q8BPK2 View 3D Structure Click here
Q8BQZ5 View 3D Structure Click here
Q8C7Q4 View 3D Structure Click here
Q8GXC5 View 3D Structure Click here
Q8GXC5 View 3D Structure Click here
Q8GXC5 View 3D Structure Click here
Q8GXC5 View 3D Structure Click here
Q8GXC5 View 3D Structure Click here
Q8GXC5 View 3D Structure Click here
Q8H335 View 3D Structure Click here
Q8K3Y3 View 3D Structure Click here
Q8L7S8 View 3D Structure Click here
Q8N3Z6 View 3D Structure Click here
Q8N567 View 3D Structure Click here
Q8N567 View 3D Structure Click here
Q8N8U3 View 3D Structure Click here
Q8R1J3 View 3D Structure Click here
Q8R1J3 View 3D Structure Click here
Q8RWN5 View 3D Structure Click here
Q8T8R1 View 3D Structure Click here
Q8T8R1 View 3D Structure Click here
Q8T8R1 View 3D Structure Click here
Q8T8R1 View 3D Structure Click here
Q8T8R1 View 3D Structure Click here
Q8T8R1 View 3D Structure Click here
Q8TBF4 View 3D Structure Click here
Q8VE92 View 3D Structure Click here
Q8VIG0 View 3D Structure Click here
Q8VYA5 View 3D Structure Click here
Q8VYA5 View 3D Structure Click here
Q8WW36 View 3D Structure Click here
Q8WW36 View 3D Structure Click here
Q8WW36 View 3D Structure Click here
Q8WW36 View 3D Structure Click here
Q8WYQ9 View 3D Structure Click here
Q940K6 View 3D Structure Click here
Q94901 View 3D Structure Click here
Q94C69 View 3D Structure Click here
Q94C69 View 3D Structure Click here
Q94C69 View 3D Structure Click here
Q94C69 View 3D Structure Click here
Q94C69 View 3D Structure Click here
Q94C69 View 3D Structure Click here
Q94C69 View 3D Structure Click here
Q966I7 View 3D Structure Click here
Q966I7 View 3D Structure Click here
Q966I7 View 3D Structure Click here
Q966I7 View 3D Structure Click here
Q966I7 View 3D Structure Click here
Q966L9 View 3D Structure Click here
Q966L9 View 3D Structure Click here
Q966L9 View 3D Structure Click here
Q966L9 View 3D Structure Click here
Q966L9 View 3D Structure Click here
Q966L9 View 3D Structure Click here
Q9AV38 View 3D Structure Click here
Q9AV38 View 3D Structure Click here
Q9AV38 View 3D Structure Click here
Q9AV38 View 3D Structure Click here
Q9AV38 View 3D Structure Click here
Q9AV38 View 3D Structure Click here
Q9AV38 View 3D Structure Click here
Q9AV38 View 3D Structure Click here
Q9AV38 View 3D Structure Click here
Q9BQ04 View 3D Structure Click here
Q9BWF3 View 3D Structure Click here
Q9C0B9 View 3D Structure Click here
Q9CAE4 View 3D Structure Click here
Q9CYA6 View 3D Structure Click here
Q9CZ96 View 3D Structure Click here
Q9D548 View 3D Structure Click here
Q9D548 View 3D Structure Click here
Q9D548 View 3D Structure Click here
Q9D548 View 3D Structure Click here
Q9D548 View 3D Structure Click here
Q9D548 View 3D Structure Click here
Q9D548 View 3D Structure Click here
Q9FG62 View 3D Structure Click here
Q9FHC2 View 3D Structure Click here
Q9FHC2 View 3D Structure Click here
Q9FQ02 View 3D Structure Click here
Q9FQ03 View 3D Structure Click here
Q9FQ04 View 3D Structure Click here
Q9FYB7 View 3D Structure Click here
Q9FYB7 View 3D Structure Click here
Q9FYD1 View 3D Structure Click here
Q9FYD1 View 3D Structure Click here
Q9FYD1 View 3D Structure Click here
Q9FYD1 View 3D Structure Click here
Q9H9Z2 View 3D Structure Click here
Q9HDB9 View 3D Structure Click here
Q9HFF2 View 3D Structure Click here
Q9LIN3 View 3D Structure Click here
Q9LTX7 View 3D Structure Click here
Q9LU46 View 3D Structure Click here
Q9M1L9 View 3D Structure Click here
Q9M1L9 View 3D Structure Click here
Q9M1L9 View 3D Structure Click here
Q9M1L9 View 3D Structure Click here
Q9M3B8 View 3D Structure Click here
Q9M3B8 View 3D Structure Click here
Q9M3B8 View 3D Structure Click here
Q9NUD5 View 3D Structure Click here
Q9P795 View 3D Structure Click here
Q9P795 View 3D Structure Click here
Q9SJA6 View 3D Structure Click here
Q9SKG2 View 3D Structure Click here
Q9SKG2 View 3D Structure Click here
Q9SKM0 View 3D Structure Click here
Q9VPT8 View 3D Structure Click here
Q9VPT8 View 3D Structure Click here