CLIP domain superfamily
CLIP proteases are non-digestive serine proteases present in hemolymph of insects and other arthropods. They are composed of one or more amino-terminal clip domains followed by a linker sequence and a carboxyl-terminal S1A family serine protease domain. Infections can stimulate activation of CLIP protease zymogens in hemolymph, with specific cleavage at a site at the amino-terminus of the protease domain, creating a two-chain form active form of the enzyme, in which the clip domain and protease domain remain connected by a disulfide bond. Once CLIP proteases are activated, they participate in cascade pathways to trigger activation of prophenoloxidase (proPO) or the Toll ligand spÃ¤tzle and are regulated by serpin inhibitors in hemolymph plasma. Some members of the CLIP superfamily contain a protease domain with mutations of one or more of the catalytic triad residues (i.e. pseudoproteases), such that they lack proteolytic activity. Such serine protease homologs (SPH) can function as cofactors required for proPO activation by an active CLIP protease, and they can also negatively regulate the melanization response. Clip domain sequences fall into three major groups based on sequence similarity and the distance between certain Cys residues. These clip domain groups are labeled types 1, 2, and 3, with three subgroups identified in type 1 (1a, 1b, 1c). There is a conserved association of certain clip domain types with protease domain types, indicating a co-evolution of distinct combinations of the clip domain and protease domain types. There are conserved Cys1 and Cys5, Cys2 and Cys4, and Cys3 and Cys6 which are predicted to form three disulfide bonds .
This clan contains 4 families and the total number of domains in the clan is 2347. The clan was built by S El-Gebali.
- Kanost MR, Jiang H;, Curr Opin Insect Sci. 2015;11:47-55.: Clip-domain serine proteases as immune factors in insect hemolymph. PUBMED:26688791 EPMC:26688791
This clan contains the following 4 member families:CLIP CLIP_1 CLIP_SPH_mas CLIP_SPH_Scar
Below is a listing of the unique domain organisations or architectures from this clan. 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
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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The table below shows the number of occurrences of each domain throughout the sequence database. More...
In brackets beside each number is the percentage of the total number of sequence hits for the clan that are represented by this domain. The rightmost column provides a link to the alignments tab for each domain. Finally, the last row in the table provides a link to the HTML representation of the alignment for the seed alignments for all members of this clan.
Please note: the clan alignment can be extremely large and the resulting HTML file is often too large to be rendered by web-browsers. Please consider downloading the alignment (by right-clicking the link) rather than viewing it in your browser.
|Pfam family||Num. domains||Alignment|
|CLIP (PF12032)||1123 (47.8%)||View|
|CLIP_SPH_mas (PF18398)||556 (23.7%)||View|
|CLIP_1 (PF18322)||537 (22.9%)||View|
|CLIP_SPH_Scar (PF18399)||131 (5.6%)||View|
|Total: 4||Total: 2347||Clan alignment|
Please note: Clan alignments can be very large and can cause problems for some browsers. Read the note above before viewing.
This diagram shows the relationships between members of this clan. More...
Relationships between families in a clan are determined using HHsearch. Families are deemed to be closely related if their E-value is less than 10-3 and these relationships are shown with a solid line. Less closely related family pairs, with an E-value of between 10-3 and 10-1, are shown with a dashed line.
The E-value for each pair of closely or partially related families is shown next to the line linking the families. You can see the information regarding a Pfam family by clicking on the family box.
This tree shows the occurrence of the domains in this clan across different species. More...
For all of the domain matches in a full alignment we count the number of domains 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.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- 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
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the MSD group, to allow us to map Pfam domains onto UniProt three-dimensional structures. The table below shows the mapping between the Pfam families in this clan, the corresponding UniProt entries, and the region of the three-dimensional structures that are available for that sequence.
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