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76  structures 5292  species 0  interactions 25686  sequences 640  architectures

Family: CAP (PF00188)

Summary: Cysteine-rich secretory protein family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "CAP superfamily". More...

CAP superfamily Edit Wikipedia article

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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 [2] and non-vertebrate eukaryotes [3] 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 [4]. The Ca++-chelating function [3] 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.

Literature references

  1. Fernandez C, Szyperski T, Bruyere T, Ramage P, Mosinger E, Wuthrich K; , J Mol Biol 1997;266:576-593.: NMR solution structure of the pathogenesis-related protein P14a. PUBMED:9067611 EPMC:9067611

  2. Yeats C, Bentley S, Bateman A; , BMC Microbiol 2003;3:3-3.: New Knowledge from Old: In silico discovery of novel protein domains in Streptomyces coelicolor. PUBMED:12625841 EPMC:12625841

  3. 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

  4. 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

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 ].

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.

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 CAP (CL0659), which has the following description:

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) [1].

The clan contains the following 2 members:

ASPRs CAP

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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
(94)
Full
(25686)
Representative proteomes UniProt
(64831)
RP15
(6537)
RP35
(14010)
RP55
(23704)
RP75
(33010)
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PP/heatmap 1            

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

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(94)
Full
(25686)
Representative proteomes UniProt
(64831)
RP15
(6537)
RP35
(14010)
RP55
(23704)
RP75
(33010)
Alignment:
Format:
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Sequence:
Gaps:
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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
(94)
Full
(25686)
Representative proteomes UniProt
(64831)
RP15
(6537)
RP35
(14010)
RP55
(23704)
RP75
(33010)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Yeats C
Previous IDs: SCP;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Yeats C
Number in seed: 94
Number in full: 25686
Average length of the domain: 122.10 aa
Average identity of full alignment: 17 %
Average coverage of the sequence by the domain: 45.35 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.1 21.1
Trusted cut-off 21.1 21.1
Noise cut-off 21.0 21.0
Model length: 126
Family (HMM) version: 28
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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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 CAP domain has been found. There are 76 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0B4JCT2 View 3D Structure Click here
A0A0B4K7N3 View 3D Structure Click here
A0A0B4KFH2 View 3D Structure Click here
A0A0B4LGE9 View 3D Structure Click here
A0A0K3AST9 View 3D Structure Click here
A0A0K3AST9 View 3D Structure Click here
A0A0N7KMW0 View 3D Structure Click here
A0A0P0VIW1 View 3D Structure Click here
A0A0P0VIY0 View 3D Structure Click here
A0A0P0VQE6 View 3D Structure Click here
A0A0P0WW96 View 3D Structure Click here
A0A0P0X1X8 View 3D Structure Click here
A0A0P0X260 View 3D Structure Click here
A0A0P0X4B6 View 3D Structure Click here
A0A0R0FIW9 View 3D Structure Click here
A0A0R0JCN7 View 3D Structure Click here
A0A0R0JCN7 View 3D Structure Click here
A0A0R4IVU8 View 3D Structure Click here
A0A143ZVI9 View 3D Structure Click here
A0A1D6EDD4 View 3D Structure Click here
A0A1D6F6J1 View 3D Structure Click here
A0A1D6HMS1 View 3D Structure Click here
A0A1D6HMS4 View 3D Structure Click here
A0A1D6HRU2 View 3D Structure Click here
A0A1D6HRU4 View 3D Structure Click here
A0A1D6HX47 View 3D Structure Click here
A0A1D6K5Y8 View 3D Structure Click here
A0A1D6L369 View 3D Structure Click here
A0A1D6MEI0 View 3D Structure Click here
A0A1D6MV60 View 3D Structure Click here
A0A1W2P7V2 View 3D Structure Click here
A0A1W2Q642 View 3D Structure Click here
A0A286Y9K7 View 3D Structure Click here
A0A2R8QR25 View 3D Structure Click here
A0A2R8QT26 View 3D Structure Click here
A0A2R8QTE4 View 3D Structure Click here
A0A368UIM9 View 3D Structure Click here
A1Z959 View 3D Structure Click here
A2A5I3 View 3D Structure Click here
A2CF32 View 3D Structure Click here
A2CF32 View 3D Structure Click here
A2CF32 View 3D Structure Click here
A5D8T8 View 3D Structure Click here
A8WHB7 View 3D Structure Click here
B4FQY0 View 3D Structure Click here
B4FQY1 View 3D Structure Click here
B4FVP5 View 3D Structure Click here
B5DFM5 View 3D Structure Click here
B6EU60 View 3D Structure Click here
B6UG61 View 3D Structure Click here
C6SY84 View 3D Structure Click here
C6SZJ3 View 3D Structure Click here
C6T1N0 View 3D Structure Click here
D3ZBM0 View 3D Structure Click here
D3ZI91 View 3D Structure Click here
E7EZY0 View 3D Structure Click here
E7F689 View 3D Structure Click here
E7F9U0 View 3D Structure Click here
E7FB91 View 3D Structure Click here
E9PTT8 View 3D Structure Click here
E9PVG4 View 3D Structure Click here
F1M2W7 View 3D Structure Click here
F1M5V2 View 3D Structure Click here
F1QAW7 View 3D Structure Click here
F1QHW4 View 3D Structure Click here
F1QW68 View 3D Structure Click here
F4I4X9 View 3D Structure Click here
F4JZQ4 View 3D Structure Click here
G3V9T1 View 3D Structure Click here
G5EF50 View 3D Structure Click here
I1JCU3 View 3D Structure Click here
I1KL97 View 3D Structure Click here
I1LVT9 View 3D Structure Click here
I1ME52 View 3D Structure Click here
I1ME53 View 3D Structure Click here
I1ME54 View 3D Structure Click here
I1ME56 View 3D Structure Click here
I1ME57 View 3D Structure Click here
I1MNJ7 View 3D Structure Click here
K7L2K1 View 3D Structure Click here
K7LHG3 View 3D Structure Click here
K7M1T8 View 3D Structure Click here
K7M9X3 View 3D Structure Click here
K7MK81 View 3D Structure Click here
K7U9G0 View 3D Structure Click here
K7VTQ5 View 3D Structure Click here
M0R4P4 View 3D Structure Click here
M0RCW2 View 3D Structure Click here
M9PBI0 View 3D Structure Click here
O16575 View 3D Structure Click here
O43692 View 3D Structure Click here
O45790 View 3D Structure Click here
O53976 View 3D Structure Click here
O61870 View 3D Structure Click here
O62507 View 3D Structure Click here
O62508 View 3D Structure Click here
O76663 View 3D Structure Click here
O81888 View 3D Structure Click here
O81889 View 3D Structure Click here
O88205 View 3D Structure Click here
P12020 View 3D Structure Click here
P16562 View 3D Structure Click here
P16563 View 3D Structure Click here
P33154 View 3D Structure Click here
P36110 View 3D Structure Click here
P47032 View 3D Structure Click here
P47033 View 3D Structure Click here
P48060 View 3D Structure Click here
P54107 View 3D Structure Click here
P54108 View 3D Structure Click here
Q00008 View 3D Structure Click here
Q03401 View 3D Structure Click here
Q03402 View 3D Structure Click here
Q09566 View 3D Structure Click here
Q0DFE6 View 3D Structure Click here
Q0DWY7 View 3D Structure Click here
Q0JED8 View 3D Structure Click here
Q17625 View 3D Structure Click here
Q18538 View 3D Structure Click here
Q18539 View 3D Structure Click here
Q18540 View 3D Structure Click here
Q18543 View 3D Structure Click here
Q20603 View 3D Structure Click here
Q20608 View 3D Structure Click here
Q20609 View 3D Structure Click here
Q22421 View 3D Structure Click here
Q22930 View 3D Structure Click here
Q2FYU2 View 3D Structure Click here
Q2FZG1 View 3D Structure Click here
Q2PDZ4 View 3D Structure Click here
Q2QLQ1 View 3D Structure Click here
Q39186 View 3D Structure Click here
Q39187 View 3D Structure Click here
Q4G1C9 View 3D Structure Click here
Q54DG5 View 3D Structure Click here
Q54J84 View 3D Structure Click here
Q54MB6 View 3D Structure Click here
Q54ME1 View 3D Structure Click here
Q54P01 View 3D Structure Click here
Q556T8 View 3D Structure Click here
Q556Y6 View 3D Structure Click here
Q557J0 View 3D Structure Click here
Q558Y8 View 3D Structure Click here
Q55GD8 View 3D Structure Click here
Q59PV6 View 3D Structure Click here
Q59WG5 View 3D Structure Click here
Q59ZX3 View 3D Structure Click here
Q5AB48 View 3D Structure Click here
Q5AB49 View 3D Structure Click here
Q5FVN7 View 3D Structure Click here
Q5TKF8 View 3D Structure Click here
Q5XJ73 View 3D Structure Click here
Q6ID87 View 3D Structure Click here
Q6K4Q3 View 3D Structure Click here
Q6K4Q5 View 3D Structure Click here
Q6PHC5 View 3D Structure Click here
Q6UWM5 View 3D Structure Click here
Q6UXB8 View 3D Structure Click here
Q6UXF7 View 3D Structure Click here
Q6YSG3 View 3D Structure Click here
Q6YSG4 View 3D Structure Click here
Q6YSG9 View 3D Structure Click here
Q6YSH3 View 3D Structure Click here
Q6YT69 View 3D Structure Click here
Q75JH0 View 3D Structure Click here
Q75JL1 View 3D Structure Click here
Q7EYQ2 View 3D Structure Click here
Q7F2P0 View 3D Structure Click here
Q7T141 View 3D Structure Click here
Q7TSQ1 View 3D Structure Click here
Q7XRQ9 View 3D Structure Click here
Q7XRR1 View 3D Structure Click here
Q7XW57 View 3D Structure Click here
Q7YX44 View 3D Structure Click here
Q84J76 View 3D Structure Click here
Q84J99 View 3D Structure Click here
Q8BS03 View 3D Structure Click here
Q8BZQ2 View 3D Structure Click here
Q8CGD2 View 3D Structure Click here
Q8H5R0 View 3D Structure Click here
Q8IND6 View 3D Structure Click here
Q8INR8 View 3D Structure Click here
Q8IRK1 View 3D Structure Click here
Q8IRL3 View 3D Structure Click here
Q8LMW8 View 3D Structure Click here
Q8MN43 View 3D Structure Click here
Q8MQ79 View 3D Structure Click here
Q8MQ79 View 3D Structure Click here
Q8NCF0 View 3D Structure Click here
Q8T3W8 View 3D Structure Click here
Q8W084 View 3D Structure Click here
Q93192 View 3D Structure Click here
Q93193 View 3D Structure Click here
Q93444 View 3D Structure Click here
Q93746 View 3D Structure Click here
Q93747 View 3D Structure Click here
Q95X90 View 3D Structure Click here
Q9CQ35 View 3D Structure Click here
Q9CWG1 View 3D Structure Click here
Q9CYL5 View 3D Structure Click here
Q9DAG6 View 3D Structure Click here
Q9ET66 View 3D Structure Click here
Q9FJY1 View 3D Structure Click here
Q9FKL1 View 3D Structure Click here
Q9H0B8 View 3D Structure Click here
Q9H336 View 3D Structure Click here
Q9H3Y0 View 3D Structure Click here
Q9H4G4 View 3D Structure Click here
Q9LJM5 View 3D Structure Click here
Q9LPM7 View 3D Structure Click here
Q9LZ12 View 3D Structure Click here
Q9M0C8 View 3D Structure Click here
Q9N3I3 View 3D Structure Click here
Q9N5N3 View 3D Structure Click here
Q9N5N4 View 3D Structure Click here
Q9SF44 View 3D Structure Click here
Q9SL82 View 3D Structure Click here
Q9SL83 View 3D Structure Click here
Q9SV22 View 3D Structure Click here
Q9SW04 View 3D Structure Click here
Q9SW05 View 3D Structure Click here
Q9TZ02 View 3D Structure Click here
Q9VFY2 View 3D Structure Click here
Q9VGQ3 View 3D Structure Click here
Q9VHJ0 View 3D Structure Click here
Q9VI17 View 3D Structure Click here
Q9VI35 View 3D Structure Click here
Q9VIN6 View 3D Structure Click here
Q9VQA2 View 3D Structure Click here
Q9VQA7 View 3D Structure Click here
Q9VT82 View 3D Structure Click here
Q9VT84 View 3D Structure Click here
Q9VY18 View 3D Structure Click here
Q9VY19 View 3D Structure Click here
Q9VY39 View 3D Structure Click here
Q9W129 View 3D Structure Click here
Q9W2H3 View 3D Structure Click here
Q9W2H4 View 3D Structure Click here
Q9XWX3 View 3D Structure Click here
Q9XXP4 View 3D Structure Click here
Q9ZNS4 View 3D Structure Click here
Q9ZPG2 View 3D Structure Click here
X2JAR4 View 3D Structure Click here