Summary: ArsC family

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Wikipedia: Ars operon
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This is the Wikipedia entry entitled "Ars operon". More...

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Ars operon Edit Wikipedia article

Anion-transporting ATPase

Identifiers

Symbol

ArsA_ATPase

Pfam clan

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

ArsB

Identifiers

Symbol

ArsB

Pfam clan

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

ArsC

yffb (pa3664) protein

Identifiers

Symbol

ArsC

Pfam clan

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

ArsD

Identifiers

Symbol

ArsD

Pfam clan

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

In molecular biology, the ars operon is an operon found in several bacterial taxon. It is required for the detoxification of arsenate, arsenite, and antimonite.^[1] This system transports arsenite and antimonite out of the cell. The pump is composed of two polypeptides, the products of the arsA and arsB genes. This two-subunit enzyme produces resistance to arsenite and antimonite. Arsenate, however, must first be reduced to arsenite before it is extruded. A third gene, arsC, expands the substrate specificity to allow for arsenate pumping and resistance. ArsC is an approximately 150-residue arsenate reductase that uses reduced glutathione (GSH) to convert arsenate to arsenite with a redox active cysteine residue in the active site. ArsC forms an active quaternary complex with GSH, arsenate, and glutaredoxin 1 (Grx1). The three ligands must be present simultaneously for reduction to occur.^[2]

ArsA and ArsB

ArsA and ArsB form an anion-translocating ATPase.^[3] The ArsB protein is distinguished by its overall hydrophobic character, in keeping with its role as a membrane-associated channel. Sequence analysis reveals the presence of 13 putative transmembrane (TM) regions.

ArsC

The arsC protein structure has been solved.^[4] It belongs to the thioredoxin superfamily fold which is defined by a beta-sheet core surrounded by alpha-helices. The active cysteine residue of ArsC is located in the loop between the first beta-strand and the first helix, which is also conserved in the Spx protein and its homologues.

The arsC family also comprises the Spx proteins which are Gram-positive bacterial transcription factors that regulate the transcription of multiple genes in response to disulphide stress.^[5]

ArsD and ArsR

ArsD is a trans-acting repressor of the arsRDABC operon that confers resistance to arsenicals and antimonials in Escherichia coli. It possesses two-pairs of vicinal cysteine residues, Cys(12)-Cys(13) and Cys(112)-Cys(113), that potentially form separate binding sites for the metalloids that trigger dissociation of ArsD from the operon. However, as a homodimer it has four vicinal cysteine pairs.^[6] The ArsD family consists of several bacterial arsenical resistance operon trans-acting repressor ArsD proteins.

ArsR is a trans-acting regulatory protein. It acts as a repressor on the arsRDABC operon when no arsenic is present in the cell. When arsenic is present in the cell ArsR will lose affinity for the operator and RNA polymerase can transcribe the arsDCAB genes.^[7]^[8] ArsD and ArsR work together to regulate the ars operon.^[9]

References

^ Carlin A, Shi W, Dey S, Rosen BP (February 1995). "The ars operon of Escherichia coli confers arsenical and antimonial resistance". J. Bacteriol. 177 (4): 981–6. PMC 176692. PMID 7860609.
^ Liu J, Rosen BP (August 1997). "Ligand interactions of the ArsC arsenate reductase". J. Biol. Chem. 272 (34): 21084–9. doi:10.1074/jbc.272.34.21084. PMID 9261111.
^ Rosen BP (1990). "The plasmid-encoded arsenical resistance pump: an anion-translocating ATPase.". Res Microbiol 141 (3): 336–41. doi:10.1016/0923-2508(90)90008-e. PMID 1704144.
^ Martin P, DeMel S, Shi J, Gladysheva T, Gatti DL, Rosen BP, Edwards BF (November 2001). "Insights into the structure, solvation, and mechanism of ArsC arsenate reductase, a novel arsenic detoxification enzyme". Structure 9 (11): 1071–81. doi:10.1016/S0969-2126(01)00672-4. PMID 11709171.
^ Zuber P (April 2004). "Spx-RNA polymerase interaction and global transcriptional control during oxidative stress". J. Bacteriol. 186 (7): 1911–8. doi:10.1128/jb.186.7.1911-1918.2004. PMC 374421. PMID 15028674.
^ Li S, Rosen BP, Borges-Walmsley MI, Walmsley AR (July 2002). "Evidence for cooperativity between the four binding sites of dimeric ArsD, an As(III)-responsive transcriptional regulator". J. Biol. Chem. 277 (29): 25992–6002. doi:10.1074/jbc.M201619200. PMID 11980902.
^ http://www.springerimages.com/Images/RSS/1-10.1007_s00216-009-2785-x-0
^ http://www.ncbi.nlm.nih.gov/pubmed/9188467?dopt=Abstract
^ http://www.jbc.org/content/272/22/14257.long

This article incorporates text from the public domain Pfam and InterPro IPR006660

This article incorporates text from the public domain Pfam and InterPro IPR000802

This article incorporates text from the public domain Pfam and InterPro IPR010712

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.

ArsC family Provide feedback

This family is related to glutaredoxins PF00462.

Internal database links

SCOOP:	Y_phosphatase3C HSDR_N
Similarity to PfamA using HHSearch:	Glutaredoxin

External database links

PANDIT:	PF03960
Pseudofam:	PF03960
SCOP:	1i9d
SYSTERS:	ArsC

This tab holds annotation information from the InterPro database.

InterPro entry IPR006660

Several bacterial taxon have a chromosomal resistance system, encoded by the ars operon, for the detoxification of arsenate, arsenite, and antimonite [PUBMED:7860609]. This system transports arsenite and antimonite out of the cell. The pump is composed of two polypeptides, the products of the arsA and arsB genes. This two-subunit enzyme produces resistance to arsenite and antimonite. Arsenate, however, must first be reduced to arsenite before it is extruded. A third gene, arsC, expands the substrate specificity to allow for arsenate pumping and resistance. ArsC is an approximately 150-residue arsenate reductase that uses reduced glutathione (GSH) to convert arsenate to arsenite with a redox active cysteine residue in the active site. ArsC forms an active quaternary complex with GSH, arsenate, and glutaredoxin 1 (Grx1). The three ligands must be present simultaneously for reduction to occur [PUBMED:9261111].

The arsC family also comprises the Spx proteins which are GRAM-positive bacterial transcription factors that regulate the transcription of multiple genes in response to disulphide stress [PUBMED:15028674].

The arsC protein structure has been solved [PUBMED:11709171]. It belongs to the thioredoxin superfamily fold which is defined by a beta-sheet core surrounded by alpha-helices. The active cysteine residue of ArsC is located in the loop between the first beta-strand and the first helix, which is also conserved in the Spx protein and its homologues.

Domain organisation

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

Loading domain graphics...

Pfam Clan

This family is a member of clan Thioredoxin (CL0172), which has the following description:

This clan contains families related to the thioredoxin family. Thioredoxins are small enzymes that are involved in redox reactions via the reversible oxidation of an active centre disulfide bond. The thioredoxin fold consists of a 3 layer alpha/beta/alpha sandwich and a central beta sheet.

The clan contains the following 45 members:

2Fe-2S_thioredx AhpC-TSA AhpC-TSA_2 ArsC ArsD Calsequestrin DIM1 DSBA DUF1525 DUF1687 DUF2703 DUF4174 DUF836 DUF899 DUF953 ERp29_N Glutaredoxin GSHPx GST_N GST_N_2 GST_N_3 HyaE KaiB MRP-S23 MRP-S25 OST3_OST6 Phosducin Redoxin SCO1-SenC SelP_N SH3BGR T4_deiodinase Thioredox_DsbH Thioredoxin Thioredoxin_2 Thioredoxin_3 Thioredoxin_4 Thioredoxin_5 Thioredoxin_6 Thioredoxin_7 Thioredoxin_8 Thioredoxin_9 Tom37 TraF YtfJ_HI0045

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics 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.
Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

Reformatting

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

Selex
Stockholm
FASTA
MSF

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 (36)	Full (7591)	Representative proteomes				NCBI (4303)	Meta (1099)
	Seed (36)	Full (7591)	RP15 (315)	RP35 (718)	RP55 (1014)	RP75 (1253)	NCBI (4303)	Meta (1099)
Jalview	View	View	View	View	View	View	View	View
HTML	View		View	View	View	View
PP/heatmap	₁		View	View	View	View
Pfam viewer	View	View

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

Key: available, not generated, — not available.

Format an alignment

	Seed (36)	Full (7591)	Representative proteomes				NCBI (4303)	Meta (1099)
	Seed (36)	Full (7591)	RP15 (315)	RP35 (718)	RP55 (1014)	RP75 (1253)	NCBI (4303)	Meta (1099)
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 (36)	Full (7591)	Representative proteomes				NCBI (4303)	Meta (1099)
	Seed (36)	Full (7591)	RP15 (315)	RP35 (718)	RP55 (1014)	RP75 (1253)	NCBI (4303)	Meta (1099)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	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.

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 HMMER3.

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:

COG1393

Previous IDs:

none

Type:

Family

Author:

Bateman A

Number in seed:

36

Number in full:

7591

Average length of the domain:

107.40 aa

Average identity of full alignment:

26 %

Average coverage of the sequence by the domain:

86.65 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	21.0	21.0
Trusted cut-off	21.0	21.0
Noise cut-off	20.9	20.9

Model length:

110

Family (HMM) version:

10

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Show

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.

Loading sunburst data...

Tree controls

Hide

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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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There is 1 interaction for this family. More...

RNA_pol_A_CTD

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 ArsC domain has been found. There are 24 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 seqence.

Loading structure mapping...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: ArsC (PF03960)

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Summary: ArsC family

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Ars operon Edit Wikipedia article

Contents

ArsA and ArsB

ArsC

ArsD and ArsR

References

ArsC family Provide feedback

Internal database links

External database links

InterPro entry IPR006660

Domain organisation

Pfam Clan

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures