Summary

A20-like zinc finger

The A20 Zn-finger of bovine/human Rabex5/rabGEF1 is a Ubiquitin Binding Domain [5-6]. The zinc finger mediates self-association in A20. These fingers also mediate IL-1-induced NF-kappa B activation.

Literature references

Heyninck K, Beyaert R; , FEBS Lett 1999;442:147-150.: The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF- kappaB activation at the level of TRAF6. PUBMED:9928991
De Valck D, Heyninck K, Van Criekinge W, Contreras R, Beyaert R, Fiers W; , FEBS Lett 1996;384:61-64.: A20, an inhibitor of cell death, self-associates by its zinc finger domain. PUBMED:8797804
Song HY, Rothe M, Goeddel DV; , Proc Natl Acad Sci U S A 1996;93:6721-6725.: The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. PUBMED:8692885
Opipari AW Jr, Boguski MS, Dixit VM; , J Biol Chem 1990;265:14705-14708.: The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. PUBMED:2118515
Penengo L, Mapelli M, Murachelli AG, Confalonieri S, Magri L, Musacchio A, Di Fiore PP, Polo S, Schneider TR;, Cell. 2006;124:1183-1195.: Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin. PUBMED:16499958
Lee S, Tsai YC, Mattera R, Smith WJ, Kostelansky MS, Weissman AM, Bonifacino JS, Hurley JH;, Nat Struct Mol Biol. 2006;13:264-271.: Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5. PUBMED:16462746

InterPro entry IPR002653

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 zinc finger domain found in A20. A20 is an inhibitor of cell death that inhibits NF-kappaB activation via the tumour necrosis factor receptor associated factor pathway PUBMED:17449604. The zinc finger domains appear to mediate self-association in A20. These fingers also mediate IL-1-induced NF-kappa B activation.

More information about these proteins can be found at Protein of the Month: Zinc Fingers PUBMED:.

Gene Ontology

Molecular function	DNA binding (GO:0003677)
	zinc ion binding (GO:0008270)

External database links

PANDIT:	PF01754
SMART:	ZnF_A20
SYSTERS:	zf-A20

Domain organisation

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

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (56) Full (368) NCBI (687) Metagenomics
Viewer:

Formatting options

Alignment:	Seed (56) Full (368)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (56) Full (368) NCBI (687) Metagenomics
Full length sequences	Full-sequences (368)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER2.

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. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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:

SMART

Previous IDs:

none

Type:

Family

Author:

SMART

Number in seed:

56

Number in full:

368

Average length of the domain:

24.90 aa

Average identity of full alignment:

47 %

Average coverage of the sequence by the domain:

7.20 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	21.6	21.6
Trusted cut-off	22.4	21.8
Noise cut-off	21.4	20.6

Model length:

25

Family (HMM) version:

9

Download:

download the raw HMM for this family

Species distribution

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
save a plain text representation of the tree

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Interactions

There are 2 interactions for this family. More...

ubiquitin zf-A20

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 MSD 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-A20 domain has been found.

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Family: zf-A20 (PF01754)

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