Summary: Scavenger mRNA decapping enzyme C-term binding

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Wikipedia: DCPS (gene)
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DCPS (gene) Edit Wikipedia article

Decapping enzyme, scavenger

PDB rendering based on 1st0.

Available structures

PDB

Ortholog search: PDBe, RCSB

List of PDB id codes
1ST0, 1ST4, 1XML, 1XMM, 3BL7, 3BL9, 3BLA

Identifiers

Symbols

DCPS; HINT-5; HSL1

External IDs

OMIM: 610534 MGI: 1916555 HomoloGene: 32202 GeneCards: DCPS Gene

Gene Ontology
Molecular function	protein binding hydrolase activity
Cellular component	nucleus nucleolus cytoplasm mitochondrion cytosol
Biological process	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay deadenylation-dependent decapping of nuclear-transcribed mRNA gene expression RNA metabolic process mRNA metabolic process exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 11:
126.17 126.22 Mb

Chr 9:
34.93 34.98 Mb

PubMed search

[1]

[2]

Scavenger mRNA decapping enzyme (DcpS) N-terminal

crystal structure of mrna decapping enzyme (dcps) from mus musculus at 1.83 a resolution

Identifiers

Symbol

DcpS

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

Scavenger mRNA decapping enzyme C-term binding

Identifiers

Symbol

DcpS_C

Pfam clan

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

Scavenger mRNA-decapping enzyme DcpS is a protein that in humans is encoded by the DCPS gene.^[1]^[2]^[3]

The scavenger mRNA decapping enzymes include Dcp2 and DcpS. DcpS is a scavenger pyrophosphatase that hydrolyses the residual cap structure following 3' to 5' mRNA degradation. DcpS uses cap dinucleotides or capped oligonucleotides as substrates to release m(7)GMP (N7-methyl GMP), while Dcp2 uses capped mRNA as a substrate in order to hydrolyse the cap to release m(7)GDP (N7-methyl GDP).^[4] The association of DcpS with 3' to 5' exonuclease exosome components suggests that these two activities are linked and there is a coupled exonucleolytic decay-dependent decapping pathway. The family contains a histidine triad (HIT) sequence in its C-terminal domain, with three histidines separated by hydrophobic residues.^[5] The central histidine within the DcpS HIT motif is critical for decapping activity and defines the HIT motif as a new mRNA decapping domain, making DcpS the first member of the HIT family of proteins with a defined biological function.

[edit] References

^ Liu H, Rodgers ND, Jiao X, Kiledjian M (Aug 2002). "The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases". EMBO J 21 (17): 46994708. doi:10.1093/emboj/cdf448. PMC 126188. PMID 12198172. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=126188.
^ van Dijk E, Le Hir H, Seraphin B (Oct 2003). "DcpS can act in the 5'-3' mRNA decay pathway in addition to the 3'-5' pathway". Proc Natl Acad Sci U S A 100 (21): 1208112086. doi:10.1073/pnas.1635192100. PMC 218716. PMID 14523240. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=218716.
^ "Entrez Gene: DCPS decapping enzyme, scavenger". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=28960.
^ Liu H, Kiledjian M (February 2006). "Decapping the message: a beginning or an end". Biochem. Soc. Trans. 34 (Pt 1): 358. doi:10.1042/BST20060035. PMID 16246173.
^ Han GW, Schwarzenbacher R, McMullan D, Abdubek P, Ambing E, Axelrod H, Biorac T, Canaves JM, Chiu HJ, Dai X, Deacon AM, DiDonato M, Elsliger MA, Godzik A, Grittini C, Grzechnik SK, Hale J, Hampton E, Haugen J, Hornsby M, Jaroszewski L, Klock HE, Koesema E, Kreusch A, Kuhn P, Lesley SA, McPhillips TM, Miller MD, Moy K, Nigoghossian E, Paulsen J, Quijano K, Reyes R, Spraggon G, Stevens RC, van den Bedem H, Velasquez J, Vincent J, White A, Wolf G, Xu Q, Hodgson KO, Wooley J, Wilson IA (September 2005). "Crystal structure of an Apo mRNA decapping enzyme (DcpS) from Mouse at 1.83 A resolution". Proteins 60 (4): 797802. doi:10.1002/prot.20467. PMID 16001405.

[edit] Further reading

Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (12): 171174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (12): 149156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Zhang QH, Ye M, Wu XY et al (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 15461560. doi:10.1101/gr.140200. PMC 310934. PMID 11042152. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310934.
Wang Z, Kiledjian M (2002). "Functional link between the mammalian exosome and mRNA decapping". Cell 107 (6): 751762. doi:10.1016/S0092-8674(01)00592-X. PMID 11747811.
Strausberg RL, Feingold EA, Grouse LH et al (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 1689916903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Kwasnicka DA, Krakowiak A, Thacker C et al (2003). "Coordinate expression of NADPH-dependent flavin reductase, Fre-1, and Hint-related 7meGMP-directed hydrolase, DCS-1". J. Biol. Chem. 278 (40): 3905139058. doi:10.1074/jbc.M306355200. PMC 2556063. PMID 12871939. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2556063.
Ota T, Suzuki Y, Nishikawa T et al (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 4045. doi:10.1038/ng1285. PMID 14702039.
Gu M, Fabrega C, Liu SW et al (2004). "Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity". Mol. Cell 14 (1): 6780. doi:10.1016/S1097-2765(04)00180-7. PMID 15068804.
Liu SW, Jiao X, Liu H et al (2004). "Functional analysis of mRNA scavenger decapping enzymes". RNA 10 (9): 14121422. doi:10.1261/rna.7660804. PMC 1370627. PMID 15273322. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1370627.
Gerhard DS, Wagner L, Feingold EA et al (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 21212127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
Malys N, Carroll K, Miyan J, Tollervey D, McCarthy JE (2004). "The 'scavenger' m7GpppX pyrophosphatase activity of Dcs1 modulates nutrient-induced responses in yeast". Nucleic Acids Res. 32 (12): 35903600. doi:10.1093/nar/gkh687. PMC 484174. PMID 15240832. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=484174.
Chen N, Walsh MA, Liu Y et al (2005). "Crystal structures of human DcpS in ligand-free and m7GDP-bound forms suggest a dynamic mechanism for scavenger mRNA decapping". J. Mol. Biol. 347 (4): 707718. doi:10.1016/j.jmb.2005.01.062. PMID 15769464.
Kwa?nicka-Crawford DA, Vincent SR (2005). "Role of a novel dual flavin reductase (NR1) and an associated histidine triad protein (DCS-1) in menadione-induced cytotoxicity". Biochem. Biophys. Res. Commun. 336 (2): 565571. doi:10.1016/j.bbrc.2005.08.129. PMID 16140270.
Malys N, McCarthy JEG (2006). "Dcs2, a novel stress-induced modulator of m7GpppX pyrophosphatase activity that locates to P bodies". J. Mol. Biol. 363 (2): 370382. doi:10.1016/j.jmb.2006.08.015. PMID 16963086.

PDB gallery

1st0: Structure of DcpS bound to m7GpppG

1st4: Structure of DcpS bound to m7GpppA

1xml: Structure of human Dcps

1xmm: Structure of human Dcps bound to m7GDP

This article incorporates text from the public domain Pfam and InterPro IPR008594

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Scavenger mRNA decapping enzyme C-term binding Provide feedback

This family consists of several scavenger mRNA decapping enzymes (DcpS) and is the C-terminal region. DcpS is a scavenger pyrophosphatase that hydrolyses the residual cap structure following 3' to 5' decay of an mRNA. The association of DcpS with 3' to 5' exonuclease exosome components suggests that these two activities are linked and there is a coupled exonucleolytic decay-dependent decapping pathway. The C-terminal domain contains a histidine triad (HIT) sequence with three histidines separated by hydrophobic residues. The central histidine within the DcpS HIT motif is critical for decapping activity and defines the HIT motif as a new mRNA decapping domain, making DcpS the first member of the HIT family of proteins with a defined biological function.

Literature references

Liu H, Rodgers ND, Jiao X, Kiledjian M; , EMBO J 2002;21:4699-4708.: The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases. PUBMED:12198172 EPMC:12198172

Internal database links

SCOOP:	SICA_alpha
Similarity to PfamA using HHSearch:	CDH HIT

External database links

PANDIT:	PF11969
Pseudofam:	PF11969
SCOP:	1st4
SYSTERS:	DcpS_C

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

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 HIT (CL0265), which contains the following 5 members:

CwfJ_C_1 DcpS_C GalP_UDP_tr_C GalP_UDP_transf HIT

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:

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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.
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:

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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 (99)	Full (1192)	Representative proteomes				NCBI (5559)	Meta (3144)
	Seed (99)	Full (1192)	RP15 (218)	RP35 (363)	RP55 (534)	RP75 (661)	NCBI (5559)	Meta (3144)
Jalview	View	View	View	View	View	View	View	View
HTML	View	View	View	View	View	View
PP/heatmap	₁	View	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 (99)	Full (1192)	Representative proteomes				NCBI (5559)	Meta (3144)
	Seed (99)	Full (1192)	RP15 (218)	RP35 (363)	RP55 (534)	RP75 (661)	NCBI (5559)	Meta (3144)
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 (99)	Full (1192)	Representative proteomes				NCBI (5559)	Meta (3144)
	Seed (99)	Full (1192)	RP15 (218)	RP35 (363)	RP55 (534)	RP75 (661)	NCBI (5559)	Meta (3144)
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.

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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:

Pfam-B_9894 (release 8.0)

Previous IDs:

none

Type:

Family

Author:

Moxon SJ

Number in seed:

99

Number in full:

1192

Average length of the domain:

113.70 aa

Average identity of full alignment:

25 %

Average coverage of the sequence by the domain:

50.60 %

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	20.9	20.9
Trusted cut-off	20.9	20.9
Noise cut-off	20.8	20.8

Model length:

116

Family (HMM) version:

3

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

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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

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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.

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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.

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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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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.

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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 DcpS_C domain has been found. There are 20 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: DcpS_C (PF11969)

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Summary: Scavenger mRNA decapping enzyme C-term binding

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DCPS (gene) Edit Wikipedia article

[edit] References

[edit] Further reading

Scavenger mRNA decapping enzyme C-term binding Provide feedback

Literature references

Internal database links

External database links

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

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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

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Annotation

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Selected sequences

Species trees

Interactive tree

Structures