Summary: Cathepsin C exclusion domain

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Wikipedia: Cathepsin C
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Cathepsin C Edit Wikipedia article

Cathepsin C

PDB rendering based on 1k3b.

Available structures

PDB

Ortholog search: PDBe, RCSB

List of PDB id codes
1K3B, 1K3B, 1K3B, 2DJF, 2DJF, 2DJF, 2DJG, 2DJG, 2DJG, 3PDF

Identifiers

Symbols

CTSC; CPPI; DPP-I; DPP1; DPPI; HMS; JP; JPD; PALS; PLS

External IDs

OMIM: 602365 MGI: 109553 HomoloGene: 1373 GeneCards: CTSC Gene

EC number

3.4.14.1

Gene Ontology
Molecular function	• cysteine-type endopeptidase activity • peptidase activity • cysteine-type peptidase activity • chloride ion binding • identical protein binding • protein self-association
Cellular component	• lysosome • endoplasmic reticulum • Golgi apparatus
Biological process	• proteolysis • immune response • aging • response to organic substance
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 11:
88.03 – 88.07 Mb

Chr 7:
95.43 – 95.46 Mb

PubMed search

[1]

[2]

Cathepsin C exclusion domain

re-determination of the native structure of human dipeptidyl peptidase i (cathepsin c)

Identifiers

Symbol

CathepsinC_exc

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

Cathepsin C (CTSC) also known as dipeptidyl peptidase I (DPP-I) is a lysosomal exo-cysteine protease belonging to the peptidase C1 family. In humans, it is encoded by the CTSC gene.^[1]^[2]

[edit] Function

Cathepsin C appears to be a central coordinator for activation of many serine proteases in immune/inflammatory cells.

Cathepsin C catalyses excision of dipeptides from the N-terminus of protein and peptide substrates, except if (i) the amino group of the N-terminus is blocked, (ii) the site of cleavage is on either side of a proline residue, (iii) the N-terminal residue is lysine or arginine, or (iv) the structure of the peptide or protein prevents further digestion from the N-terminus.

[edit] Structure

The cDNAs encoding rat, human, murine, bovine, dog and two Schistosome cathepsin Cs have been cloned and sequenced and show that the enzyme is highly conserved.^[3] The human and rat cathepsin C cDNAs encode precursors (prepro-cathepsin C) comprising signal peptides of 24 residues, pro-regions of 205 (rat cathepsin C) or 206 (human cathepsin C) residues and catalytic domains of 233 residues which contain the catalytic residues and are 30-40% identical to the mature amino acid sequences of papain and a number of other cathepsins including cathepsins, B, H, K, L, and S.^[4]

The translated prepro-cathepsin C is processed into the mature form by at least four cleavages of the polypeptide chain. The signal peptide is removed during translocation or secretion of the pro-enzyme (pro-cathepsin C) and a large N-terminal proregion fragment (also known as the exclusion domain),^[5] which is retained in the mature enzyme, is separated from the catalytic domain by excision of a minor C-terminal part of the pro-region, called the activation peptide. A heavy chain of about 164 residues and a light chain of about 69 residues are generated by cleavage of the catalytic domain.

Unlike the other members of the papain family, mature cathepsin C consists of four subunits, each composed of the N-terminal proregion fragment, the heavy chain and the light chain. Both the pro-region fragment and the heavy chain are glycosylated.

[edit] Clinical significance

Defects in the encoded protein have been shown to be a cause of Papillon-Lefevre disease,^[6]^[7] an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis.

Cathepsin C functions as a key enzyme in the activation of granule serine peptidases in inflammatory cells, such as elastase and cathepsin G in neutrophils cells and chymase and tryptase in mast cells. In many inflammatory diseases, such as Rheumatoid Arthritis, Chronic Obstructive Pulmonary Disease (COPD), Inflammatory Bowel Disease, Asthma, Sepsis and Cystic Fibrosis, a significant part of the pathogenesis is caused by increased activity of some of these inflammatory proteases. Once activated by cathepsin C, the proteases are capable of degrading various extracellular matrix components, which can lead to tissue damage and chronic inflammation.

[edit] References

^ "Entrez Gene: CTSC cathepsin C". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1075.
^ Paris A, Strukelj B, Pungercar J, Renko M, Dolenc I, Turk V (August 1995). "Molecular cloning and sequence analysis of human preprocathepsin C". FEBS Letters 369 (2–3): 326–30. doi:10.1016/0014-5793(95)00777-7. PMID 7649281.
^ Hola-Jamriska L, Tort JF, Dalton JP, Day SR, Fan J, Aaskov J, Brindley PJ (August 1998). "Cathepsin C from Schistosoma japonicum--cDNA encoding the preproenzyme and its phylogenetic relationships". European Journal of Biochemistry / FEBS 255 (3): 527–34. doi:10.1046/j.1432-1327.1998.2550527.x. PMID 9738890.
^ Kominami E, Ishido K, Muno D, Sato N (July 1992). "The primary structure and tissue distribution of cathepsin C". Biological Chemistry Hoppe-Seyler 373 (7): 367–73. PMID 1515062.
^ Turk, D.; Janjić, V.; Stern, I.; Podobnik, M.; Lamba, D.; Dahl, S. W.; Lauritzen, C.; Pedersen, J. et al (2001). "Structure of human dipeptidyl peptidase I (cathepsin C): Exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases". The EMBO Journal 20 (23): 6570–6582. doi:10.1093/emboj/20.23.6570. PMC 125750. PMID 11726493. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125750. edit
^ Wani AA, Devkar N, Patole MS, Shouche YS (2006). "Description of two new cathepsin C gene mutations in patients with Papillon-Lefèvre syndrome". J. Periodontol. 77 (2): 233–7. doi:10.1902/jop.2006.050124. PMID 16460249.
^ Meade JL, de Wynter EA, Brett P, Sharif SM, Woods CG, Markham AF, Cook GP (2006). "A family with Papillon-Lefevre syndrome reveals a requirement for cathepsin C in granzyme B activation and NK cell cytolytic activity". Blood 107 (9): 3665–3668. doi:10.1182/blood-2005-03-1140. PMID 16410452.

[edit] Further reading

McGuire MJ, Lipsky PE, Thiele DL (1992). "Purification and characterization of dipeptidyl peptidase I from human spleen". Arch. Biochem. Biophys. 295 (2): 280–8. doi:10.1016/0003-9861(92)90519-3. PMID 1586157.
Paris A, Strukelj B, Pungercar J, et al. (1995). "Molecular cloning and sequence analysis of human preprocathepsin C". FEBS Lett. 369 (2–3): 326–30. doi:10.1016/0014-5793(95)00777-7. PMID 7649281.
Dolenc I, Turk B, Pungercic G, et al. (1995). "Oligomeric structure and substrate induced inhibition of human cathepsin C". J. Biol. Chem. 270 (37): 21626–31. doi:10.1074/jbc.270.37.21626. PMID 7665576.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Rao NV, Rao GV, Hoidal JR (1997). "Human dipeptidyl-peptidase I. Gene characterization, localization, and expression". J. Biol. Chem. 272 (15): 10260–5. doi:10.1074/jbc.272.15.10260. PMID 9092576.
Fischer J, Blanchet-Bardon C, Prud'homme JF, et al. (1997). "Mapping of Papillon-Lefevre syndrome to the chromosome 11q14 region". Eur. J. Hum. Genet. 5 (3): 156–60. PMID 9272739.
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 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Cigić B, Krizaj I, Kralj B, et al. (1998). "Stoichiometry and heterogeneity of the pro-region chain in tetrameric human cathepsin C". Biochim. Biophys. Acta 1382 (1): 143–50. doi:10.1016/S0167-4838(97)00173-8. PMID 9507095.
Toomes C, James J, Wood AJ, et al. (1999). "Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis". Nat. Genet. 23 (4): 421–4. doi:10.1038/70525. PMID 10581027.
Hart TC, Hart PS, Bowden DW, et al. (2000). "Mutations of the cathepsin C gene are responsible for Papillon-Lefèvre syndrome". J. Med. Genet. 36 (12): 881–7. doi:10.1136/jmg.36.12.881. PMC 1734286. PMID 10593994. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1734286.
Hart TC, Hart PS, Michalec MD, et al. (2000). "Haim-Munk syndrome and Papillon-Lefèvre syndrome are allelic mutations in cathepsin C". J. Med. Genet. 37 (2): 88–94. doi:10.1136/jmg.37.2.88. PMC 1734521. PMID 10662807. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1734521.
Hart TC, Hart PS, Michalec MD, et al. (2000). "Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation". J. Med. Genet. 37 (2): 95–101. doi:10.1136/jmg.37.2.95. PMC 1734516. PMID 10662808. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1734516.
Suzuki Y, Ishihara D, Sasaki M, et al. (2000). "Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries". Genomics 64 (3): 286–97. doi:10.1006/geno.2000.6076. PMID 10756096.
Cigić B, Dahl SW, Pain RH (2000). "The residual pro-part of cathepsin C fulfills the criteria required for an intramolecular chaperone in folding and stabilizing the human proenzyme". Biochemistry 39 (40): 12382–90. doi:10.1021/bi0008837. PMID 11015218.
Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948.
Hart PS, Zhang Y, Firatli E, et al. (2001). "Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients". J. Med. Genet. 37 (12): 927–32. doi:10.1136/jmg.37.12.927. PMC 1734492. PMID 11106356. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1734492.
Zhang Y, Lundgren T, Renvert S, et al. (2001). "Evidence of a founder effect for four cathepsin C gene mutations in Papillon-Lefèvre syndrome patients". J. Med. Genet. 38 (2): 96–101. doi:10.1136/jmg.38.2.96. PMC 1734811. PMID 11158173. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1734811.
Nakano A, Nomura K, Nakano H, et al. (2001). "Papillon-Lefèvre syndrome: mutations and polymorphisms in the cathepsin C gene". J. Invest. Dermatol. 116 (2): 339–43. doi:10.1046/j.1523-1747.2001.01244.x. PMID 11180012.
Allende LM, García-Pérez MA, Moreno A, et al. (2001). "Cathepsin C gene: First compound heterozygous patient with Papillon-Lefèvre syndrome and a novel symptomless mutation". Hum. Mutat. 17 (2): 152–3. doi:10.1002/1098-1004(200102)17:2<152::AID-HUMU10>3.0.CO;2-#. PMID 11180601.
Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=311072.

[edit] External links

The MEROPS online database for peptidases and their inhibitors: C01.070
MeSH Cathepsin+C

PDB gallery

1k3b: Crystal Structure of Human Dipeptidyl Peptidase I (Cathepsin C): Exclusion Domain Added to an Endopeptidase Framework Creates the Machine for Activation of Granular Serine Proteases

2djf: Crystal Structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2

2djg: Re-determination of the native structure of human dipeptidyl peptidase I (cathepsin C)

Proteases: cysteine proteases (EC 3.4.22)

Caspase

Caspase 1 · Caspase 2 · Caspase 3 · Caspase 4 · Caspase 5 · Caspase 6 · Caspase 7 · Caspase 8 · Caspase 9 · Caspase 10 · Caspase 12 · Caspase 13 · Caspase 14

Fruit-derived

Papain · Ficain · Bromelain · Actinidain

Calpain

CAPN1 · CAPN2 · CAPN3 · CAPN5 · CAPN6 · CAPN7 · CAPN8 · CAPN9 · CAPN10 · CAPN11 · CAPN12 · CAPN13 · CAPN14 · CAPNS1 · CAPNS2

Cathepsin

B · C · F · H · K · L1/L2 · O · S · W · Z

Other

Clostripain · Cancer procoagulant · Separase · Autophagin · Cruzipain

B
enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
2.7.10
2.7.11-12
3.1
- 2
- 3
- 4
- 5
- 6
- 7
3.1.3.48
3.4.21
- 22
- 23
- 24
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

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.

Cathepsin C exclusion domain Provide feedback

Cathepsin C (dipeptidyl peptidase I) is the physiological activator of a group of serine proteases. This domain corresponds to the exclusion domain whose structure excludes the approach of a polypeptide apart from its termini. It forms an enclosed beta barrel structure composed from 8 anti-parallel beta strands [1]. Based on a structural comparison and interaction data, it is suggested that the exclusion domain originates from a metallo-protease inhibitor [1].

Literature references

Turk D, Janjic V, Stern I, Podobnik M, Lamba D, Dahl SW, Lauritzen C, Pedersen J, Turk V, Turk B; , EMBO J. 2001;20:6570-6582.: Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. PUBMED:11726493 EPMC:11726493

External database links

PANDIT:	PF08773
Pseudofam:	PF08773
SCOP:	1k3b
SYSTERS:	CathepsinC_exc

This tab holds annotation information from the InterPro database.

InterPro entry IPR014882

Cathepsin C (dipeptidyl peptidase I) is the physiological activator of a group of serine proteases. This protein corresponds to the exclusion domain whose structure excludes the approach of a polypeptide apart from its termini. It forms an enclosed beta barrel structure composed from 8 anti-parallel beta strands [PUBMED:11726493]. Based on a structural comparison and interaction data, it is suggested that the exclusion domain originates from a metallo-protease inhibitor [PUBMED:11726493].

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

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:

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Stockholm
FASTA
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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 (10)	Full (167)	Representative proteomes				NCBI (178)	Meta (1)
	Seed (10)	Full (167)	RP15 (42)	RP35 (50)	RP55 (67)	RP75 (92)	NCBI (178)	Meta (1)
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 (10)	Full (167)	Representative proteomes				NCBI (178)	Meta (1)
	Seed (10)	Full (167)	RP15 (42)	RP35 (50)	RP55 (67)	RP75 (92)	NCBI (178)	Meta (1)
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 (10)	Full (167)	Representative proteomes				NCBI (178)	Meta (1)
	Seed (10)	Full (167)	RP15 (42)	RP35 (50)	RP55 (67)	RP75 (92)	NCBI (178)	Meta (1)
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:

pdb_1k3b

Previous IDs:

none

Type:

Domain

Author:

Mistry J

Number in seed:

10

Number in full:

167

Average length of the domain:

106.90 aa

Average identity of full alignment:

39 %

Average coverage of the sequence by the domain:

23.58 %

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	20.2	20.2
Trusted cut-off	20.8	20.5
Noise cut-off	19.1	19.7

Model length:

118

Family (HMM) version:

6

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.

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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
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 are 2 interactions for this family. More...

CathepsinC_exc Peptidase_C1

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 CathepsinC_exc domain has been found. There are 5 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.

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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: CathepsinC_exc (PF08773)

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