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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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
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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
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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
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.
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
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_12Alignments
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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Seed (159) |
Full (1201914) |
Representative proteomes | UniProt (1783352) |
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RP15 (155577) |
RP35 (362801) |
RP55 (822960) |
RP75 (1209189) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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Seed (159) |
Full (1201914) |
Representative proteomes | UniProt (1783352) |
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RP15 (155577) |
RP35 (362801) |
RP55 (822960) |
RP75 (1209189) |
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Raw Stockholm | |||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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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
Seed source: | Boehm S |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Bateman A |
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
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 23 | ||||||||||||
Family (HMM) version: | 29 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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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-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.