Summary: Cofilin/tropomyosin-type actin-binding protein

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Wikipedia: ADF-H domain
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This is the Wikipedia entry entitled "ADF-H domain". More...

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ADF-H domain Edit Wikipedia article

Cofilin_ADF

crystal structure of adf1 from arabidopsis thaliana

Identifiers

Symbol

Cofilin_ADF

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

In molecular biology, ADF-H domain (actin-depolymerising factor homology domain) is an approximately 150 amino acid motif that is present in three phylogenetically distinct classes of eukaryotic actin-binding proteins.^[1]^[2]^[3]

ADF/cofilins, which include ADF, cofilin, destrin, actophorin, coactosin, depactin and glia maturation factors (GMFs) beta and gamma. ADF/cofilins are small actin-binding proteins composed of a single ADF-H domain. They bind both actin-monomers and filaments and promote rapid filament turnover in cells by depolymerising/fragmenting actin filaments. ADF/cofilins bind ADP-actin with higher affinity than ATP-actin and inhibit the spontaneous nucleotide exchange on actin monomers
Twinfilins, which are actin monomer-binding proteins that are composed of two ADF-H domains
Abp1/Drebrins, which are relatively large proteins composed of an N-terminal ADF-H domain followed by a variable region and a C-terminal SH3 domain. Abp1/Drebrins interact only with actin filaments and do not promote filament depolymerisation or fragmentation. Although these proteins are biochemically distinct and play different roles in actin dynamics, they all appear to use the ADF-H domain for their interactions with actin.

The ADF-H domain consists of a six-stranded mixed beta-sheet in which the four central strands (beta2-beta5) are anti-parallel and the two edge strands (beta1 and beta6) run parallel with the neighbouring strands. The sheet is surrounded by two alpha-helices on each side .^[1]^[2]^[4]

References

^ ^a ^b Lappalainen P, Kessels MM, Cope MJ, Drubin DG (August 1998). "The ADF homology (ADF-H) domain: a highly exploited actin-binding module". Mol. Biol. Cell. 9 (8): 1951–9. doi:10.1091/mbc.9.8.1951. PMC 25446. PMID 9693358.
^ ^a ^b Paavilainen VO, Merckel MC, Falck S, Ojala PJ, Pohl E, Wilmanns M, Lappalainen P (November 2002). "Structural conservation between the actin monomer-binding sites of twinfilin and actin-depolymerizing factor (ADF)/cofilin". J. Biol. Chem. 277 (45): 43089–95. doi:10.1074/jbc.M208225200. PMID 12207032.
^ Liu LX, Xu H, Weller PF, Shi A, Debnath I (February 1997). "Structure and expression of a novel filarial gene for glia maturation factor". Gene. 186 (1): 1–5. doi:10.1016/S0378-1119(96)00585-9. PMID 9047337.
^ Liu L, Wei Z, Wang Y, Wan M, Cheng Z, Gong W (November 2004). "Crystal structure of human coactosin-like protein". J. Mol. Biol. 344 (2): 317–23. doi:10.1016/j.jmb.2004.09.036. PMID 15522287.

This article incorporates text from the public domain Pfam and InterPro IPR002108

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.

Cofilin/tropomyosin-type actin-binding protein Provide feedback

Severs actin filaments and binds to actin monomers.

Literature references

Fedorov AA, Lappalainen P, Fedorov EV, Drubin DG, Almo SC; , Nat Struct Biol 1997;4:366-369.: Structure determination of yeast cofilin. PUBMED:9145106 EPMC:9145106
Leonard SA, Gittis AG, Petrella EC, Pollard TD, Lattman EE; , Nat Struct Biol 1997;4:369-373.: Crystal structure of the actin-binding protein actophorin from Acanthamoeba. PUBMED:9145107 EPMC:9145107
Jiang CJ, Weeds AG, Khan S, Hussey PJ; , Proc Natl Acad Sci U S A 1997;94:9973-9978.: F-actin and G-actin binding are uncoupled by mutation of conserved tyrosine residues in maize actin depolymerizing factor. PUBMED:9275236 EPMC:9275236
Lappalainen P, Drubin DG; , Nature 1997;388:78-82.: Cofilin promotes rapid actin filament turnover in vivo. PUBMED:9214506 EPMC:9214506

External database links

HOMSTRAD:	ADF
PROSITE:	PDOC00297
SCOP:	2prf
SMART:	ADF

This tab holds annotation information from the InterPro database.

InterPro entry IPR002108

The actin-depolymerising factor homology (ADF-H) domain is an ~150-amino acid motif that is present in three phylogenetically distinct classes of eukaryotic actin-binding proteins [ PUBMED:9693358 , PUBMED:12207032 , PUBMED:9047337 ]:

ADF/cofilins, which include ADF, cofilin, destrin, actophorin, coactosin, depactin and glia maturation factors (GMFs) beta and gamma. ADF/cofilins are small actin-binding proteins composed of a single ADF-H domain. They bind both actin-monomers and filaments and promote rapid filament turnover in cells by depolymerising/fragmenting actin filaments. ADF/cofilins bind ADP-actin with higher affinity than ATP-actin and inhibit the spontaneous nucleotide exchange on actin monomers
Twinfilins, which are actin monomer-binding proteins that are composed of two ADF-H domains
Abp1/Drebrins, which are relatively large proteins composed of an N-terminal ADF-H domain followed by a variable region and a C-terminal SH3 domain. Abp1/Drebrins interact only with actin filaments and do not promote filament depolymerisation or fragmentation

Although these proteins are biochemically distinct and play different roles in actin dynamics, they all appear to use the ADF-H domain for their interactions with actin.

The ADF-H domain consists of a six-stranded mixed beta-sheet in which the four central strands (beta2-beta5) are anti-parallel and the two edge strands (beta1 and beta6) run parallel with the neighbouring strands. The sheet is surrounded by two alpha-helices on each side [ PUBMED:9693358 , PUBMED:12207032 , PUBMED:15522287 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function

actin binding (GO:0003779)

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 ADF (CL0092), which has the following description:

For motile cells such as Amoeba to move, there must be the rapid recycling of their actin cytoskeleton to enable a dynamic change in their shape. Gelsolin (PFAM:PF00626) and Cofilin (PFAM:PF00241) are two key domain families in this process. Both of these domain are structural and functional similar [1,2]. In particular, the beta sheet found at the core of the domain is structurally well conserved, with the helices that surround this sheet less conserved[2].

The clan contains the following 2 members:

Cofilin_ADF Gelsolin

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:

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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 (445)	Full (11908)	Representative proteomes				UniProt (20562)
	Seed (445)	Full (11908)	RP15 (2011)	RP35 (5192)	RP55 (9397)	RP75 (12744)	UniProt (20562)
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 (445)	Full (11908)	Representative proteomes				UniProt (20562)
	Seed (445)	Full (11908)	RP15 (2011)	RP35 (5192)	RP55 (9397)	RP75 (12744)	UniProt (20562)
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 (445)	Full (11908)	Representative proteomes				UniProt (20562)
	Seed (445)	Full (11908)	RP15 (2011)	RP35 (5192)	RP55 (9397)	RP75 (12744)	UniProt (20562)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	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:

Prosite; SMART;

Previous IDs:

cofilin_ADF;

Type:

Domain

Sequence Ontology:

SO:0000417

Author:

Ponting CP

, Schultz J, Bork P

, Finn RD

Number in seed:

445

Number in full:

11908

Average length of the domain:

119.90 aa

Average identity of full alignment:

20 %

Average coverage of the sequence by the domain:

48.25 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	22.4	22.4
Trusted cut-off	22.4	22.4
Noise cut-off	22.3	22.3

Model length:

125

Family (HMM) version:

22

Download:

download the raw HMM for this family

Species distribution

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Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
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Viroids	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...

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:

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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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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:

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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 Cofilin_ADF domain has been found. There are 102 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...

Family: Cofilin_ADF (PF00241)

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