Summary: Cysteine-rich secretory protein family
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This is the Wikipedia entry entitled "CAP superfamily". More...
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CAP superfamily Edit Wikipedia article
crystal structure of golgi-associated pr-1 protein
crystal structure of stecrisp, a member of crisp family from trimeresurus stejnegeri refined at 1.6 angstroms resolution: structural relationship of the two domains
The CAP superfamily (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP)) is a large superfamily of secreted proteins that are produced by a wide range of organisms, including prokaryotes and non-vertebrate eukaryotes.
The nine subfamilies of the mammalian CAP superfamily include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. Members are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumour suppressor or pro-oncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilisation. The overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters the target specificity and, thus, the biological consequences. The calcium-chelating function would fit with the various signalling processes (e.g. the CRISP proteins) that members of this family are involved in, and also the sequence and structural evidence of a conserved pocket containing two histidines and a glutamate.
Many of these proteins contain a Crisp domain. This domain is found in the mammalian reproductive tract and the venom of reptiles, and has been shown to regulate ryanodine receptor calcium signalling. It contains 10 conserved cysteines which are all involved in disulphide bonds and is structurally related to the ion channel inhibitor toxins BgK and ShK.
- Yeats, C.; Bentley, S.; Bateman, A. (2003). "New knowledge from old: In silico discovery of novel protein domains in Streptomyces coelicolor". BMC Microbiology. 3: 3. PMC . PMID 12625841.
- Milne, T. J.; Abbenante, G.; Tyndall, J. D.; Halliday, J.; Lewis, R. J. (2003). "Isolation and Characterization of a Cone Snail Protease with Homology to CRISP Proteins of the Pathogenesis-related Protein Superfamily". Journal of Biological Chemistry. 278 (33): 31105–31110. doi:10.1074/jbc.M304843200. PMID 12759345.
- Gibbs, G. M.; Roelants, K.; O'Bryan, M. K. (2008). "The CAP Superfamily: Cysteine-Rich Secretory Proteins, Antigen 5, and Pathogenesis-Related 1 Proteins--Roles in Reproduction, Cancer, and Immune Defense". Endocrine Reviews. 29 (7): 865–897. doi:10.1210/er.2008-0032. PMID 18824526.
- Semb, B. K.; Halvorsen, J. F.; Fossdal, J. E. (1977). "Acute gastric volvulus with necrosis of the stomach and the left lower pulmonary lobe". Acta chirurgica Scandinavica. 143 (4): 256–258. PMID 906761.
- Gibbs GM, Scanlon MJ, Swarbrick J, Curtis S, Gallant E, Dulhunty AF, O'Bryan MK (February 2006). "The cysteine-rich secretory protein domain of Tpx-1 is related to ion channel toxins and regulates ryanodine receptor Ca2+ signaling". J. Biol. Chem. 281 (7): 4156–63. doi:10.1074/jbc.M506849200. PMID 16339766.
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.
Cysteine-rich secretory protein family Provide feedback
This is a large family of cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) that are found in a wide range of organisms, including prokaryotes  and non-vertebrate eukaryotes  The nine subfamilies of the mammalian CAP 'super'family include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. Members are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumour suppressor or pro-oncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilisation. The overall protein structural conservation within the CAP 'super'family results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters the target specificity and, thus, the biological consequences . The Ca++-chelating function  would fit with the various signalling processes (e.g. the CRISP proteins) that members of this family are involved in, and also the sequence and structural evidence of a conserved pocket containing two histidines and a glutamate. It also may explain how Q91055 blocks the Ca++ transporting ryanodine receptors.
Milne TJ, Abbenante G, Tyndall JD, Halliday J, Lewis RJ; , J Biol Chem 2003;278:31105-31110.: Isolation and characterization of a cone snail protease with homology to CRISP proteins of the pathogenesis-related protein superfamily. PUBMED:12759345 EPMC:12759345
Gibbs GM, Roelants K, O'Bryan MK;, Endocr Rev. 2008;29:865-897.: The CAP superfamily: cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins--roles in reproduction, cancer, and immune defense. PUBMED:18824526 EPMC:18824526
Internal database links
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR014044
The cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) superfamily proteins are found in a wide range of organisms, including prokaryotes [PUBMED:12625841] and non-vertebrate eukaryotes [PUBMED:12759345], The nine subfamilies of the mammalian CAP superfamily include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. Members are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumour suppressor or pro-oncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilisation. The overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters the target specificity and, thus, the biological consequences [PUBMED:18824526]. The Ca++-chelating function [PUBMED:12759345] would fit with the various signalling processes (e.g. the CRISP proteins) that members of this family are involved in, and also the sequence and structural evidence of a conserved pocket containing two histidines and a glutamate. It also may explain how SWISSPROT blocks the Ca++ transporting ryanodine receptors.
This entry represents the CAP domain common to all members of the CAP superfamily. The CAP domain forms a unique 3 layer alpha-beta-alpha fold with some, though not all, of the structural elements found in proteases [PUBMED:18824526].
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
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This is a highly evolutionary diversified protein superfamily whose members share specific sequence motifs. For the mammalian members, roles in reproduction, development, immune function and several pathologies have been proposed. Ant and wasp allergens, snake venom toxins and plant antifungal proteins are included in this superfamily data suggest that CAP proteins participate in various biological activities across phyla. Several signature sequences characterize mammalian members of the superfamily: CAP1-2 and CAP3-4, variable Cys-rich hinge regions and Ct extensions. Mammalian CAPs include nine subfamilies: cysteine rich secretory proteins (CRISPs), glioma pathogenesis related-1 (GLIPR1), glioma pathogenesis related-2 (GLIPR2)/Golgi, associated pathogenesis related-1 (GAPR1), peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), CRISP LCCL domain containing 1 and 2 (CRISPLD1/CAPLD1 and CRISPLD2/CAPLD2), mannose receptor-like/CP domain, CTL domain containing (CAPCL) and the R3H domain-like protein (R3HMDL). CRISP (cysteine rich secretory proteins) proteins (venom-related proteins, and proteins produced by reproductive organs and cells) and plant-derived pathogenesis related proteins are the best characterized. Helminth parasite proteins of this superfamily were first reported in hookworms and later in related nematodes and platyhelminths. While nematodes' CAP proteins are known as Ancylostoma secreted proteins (ASPs), platyhelminths' CAP are known as venom allergen-like (VAL) proteins. Some of these proteins have been studied as vaccine candidates due to their immunogenic and protective properties (e.g. Na-ASP-2, Ov-Asp1, Oo-ASP-1) .
The clan contains the following 2 members:ASPRs CAP
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, the UniProtKB sequence database, 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.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- 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
- 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.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
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.
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.
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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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...
If you find these logos useful in your own work, please consider citing the following article:
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.
|Seed source:||Yeats C|
|Author:||Finn RD , Yeats C|
|Number in seed:||94|
|Number in full:||20748|
|Average length of the domain:||122.80 aa|
|Average identity of full alignment:||17 %|
|Average coverage of the sequence by the domain:||44.84 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||26|
|Download:||download the raw HMM for this family|
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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 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:
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".
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.
The tree shows the occurrence of this domain across different species. More...
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.
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
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.
There are 3 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 CAP domain has been found. There are 75 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.
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