Summary: Zinc finger, C2H2 type
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Zinc finger Edit Wikipedia article
A zinc finger is part of a protein that can bind to DNA.
Many transcription factors (such as Zif268), regulatory proteins, and other proteins that interact with DNA, all contain zinc fingers.
These proteins possess amino acid sequences that combine with a zinc ion. They typically interact with the major and minor grooves along the double helix of DNA.
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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 .
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
External database links
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...
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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
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Seed source:||Boehm S|
|Author:||Bateman A , Boehm S , Sonnhammer ELL , Gago F|
|Number in seed:||159|
|Number in full:||1201914|
|Average length of the domain:||23.1 aa|
|Average identity of full alignment:||41 %|
|Average coverage of the sequence by the domain:||20.45 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||29|
|Download:||download the raw HMM for this family|
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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.
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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.
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The tree shows the occurrence of this domain across different species. More...
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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.
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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.
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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.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.