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586  structures 1648  species 0  interactions 1201914  sequences 14182  architectures

Family: zf-C2H2 (PF00096)

Summary: Zinc finger, C2H2 type

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

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.

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].

Literature references

  1. 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

  2. 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.

Domain organisation

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

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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...

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

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Representative proteomes UniProt

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

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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...


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: 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: 23.1 aa
Average identity of full alignment: 41 %
Average coverage of the sequence by the domain: 20.45 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
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

Species distribution

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Colour assignments

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


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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.

Protein Predicted structure External Information
A0A044QQ42 View 3D Structure Click here
A0A044QTR4 View 3D Structure Click here
A0A044R058 View 3D Structure Click here
A0A044R0L0 View 3D Structure Click here
A0A044R2C0 View 3D Structure Click here
A0A044R8X9 View 3D Structure Click here
A0A044R9E9 View 3D Structure Click here
A0A044RBR4 View 3D Structure Click here
A0A044RF22 View 3D Structure Click here
A0A044RHT5 View 3D Structure Click here
A0A044RKS3 View 3D Structure Click here
A0A044RPZ8 View 3D Structure Click here
A0A044RX86 View 3D Structure Click here
A0A044RXZ3 View 3D Structure Click here
A0A044RZL8 View 3D Structure Click here
A0A044S992 View 3D Structure Click here
A0A044SBM8 View 3D Structure Click here
A0A044SDQ5 View 3D Structure Click here
A0A044SF40 View 3D Structure Click here
A0A044SN26 View 3D Structure Click here
A0A044SPQ3 View 3D Structure Click here
A0A044SS33 View 3D Structure Click here
A0A044SS66 View 3D Structure Click here
A0A044SS72 View 3D Structure Click here
A0A044STF7 View 3D Structure Click here
A0A044SV19 View 3D Structure Click here
A0A044T639 View 3D Structure Click here
A0A044TC32 View 3D Structure Click here
A0A044TCB9 View 3D Structure Click here
A0A044TGX1 View 3D Structure Click here
A0A044THN7 View 3D Structure Click here
A0A044THP6 View 3D Structure Click here
A0A044TMB8 View 3D Structure Click here
A0A044TQV9 View 3D Structure Click here
A0A044TU78 View 3D Structure Click here
A0A044U1Q6 View 3D Structure Click here
A0A044U2F9 View 3D Structure Click here
A0A044U747 View 3D Structure Click here
A0A044UK99 View 3D Structure Click here
A0A044UPW0 View 3D Structure Click here