Summary: Zinc finger, C2H2 type

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

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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.

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

Boehm S, Frishman D, Mewes HW; , Nucleic Acids Res 1997;25:2464-2469.: Variations of the C2H2 zinc finger motif in the yeast genome and classification of yeast zinc finger proteins. PUBMED:9171100 EPMC:9171100
Marco E, Garcia-Nieto R, Gago F; , J Mol Biol 2003;328:9-32.: Assessment by molecular dynamics simulations of the structural determinants of DNA-binding specificity for transcription factor Sp1. PUBMED:12683994 EPMC:12683994

Internal database links

SCOOP:	BolA BTB C1_1 C1_4 DZR FOXP-CC GAGA HVO_2753_ZBP HypA NOA36 TF_Zn_Ribbon TFIIA zf-BED zf-C2H2_11 zf-C2H2_2 zf-C2H2_3rep zf-C2H2_4 zf-C2H2_6 zf-C2H2_8 zf-C2H2_aberr zf-C2H2_jaz zf-C2HC_2 zf-C2HE zf-Di19 zf-H2C2_2 zf-H2C2_5 zf-met zf-TRAF Zn-ribbon_8 Zn_ribbon_SprT
Similarity to PfamA using HHSearch:	zf-BED zf-Di19 zf-C2H2_jaz zf-C2H2_2 zf-met zf-H2C2_2 zf-C2H2_4 zf-H2C2_5 zf-C2H2_6 zf-C2HC_2 zf-C2HE zf-C2H2_9 zf-C2H2_11 Zn-C2H2_12 zf_UBZ

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_12

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...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

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You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

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 (159)	Full (1201914)	Representative proteomes				UniProt (1783352)
	Seed (159)	Full (1201914)	RP15 (155577)	RP35 (362801)	RP55 (822960)	RP75 (1209189)	UniProt (1783352)
Jalview	View	View	View	View	View	View	View
HTML	View
PP/heatmap	₁

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (159)	Full (1201914)	Representative proteomes				UniProt (1783352)
	Seed (159)	Full (1201914)	RP15 (155577)	RP35 (362801)	RP55 (822960)	RP75 (1209189)	UniProt (1783352)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	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 (159)	Full (1201914)	Representative proteomes				UniProt (1783352)
	Seed (159)	Full (1201914)	RP15 (155577)	RP35 (362801)	RP55 (822960)	RP75 (1209189)	UniProt (1783352)
Raw Stockholm	Download		Download	Download	Download
Gzipped	Download		Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM 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

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

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	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Selections

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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...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

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Tree controls

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

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
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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.

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
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

Showing 40 matches

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Family: zf-C2H2 (PF00096)

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