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5  structures 115  species 0  interactions 2347  sequences 87  architectures

Clan: CLIP (CL0678)


CLIP domain superfamily Add an annotation

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 spätzle 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 [1].

This clan contains 4 families and the total number of domains in the clan is 2347. The clan was built by S El-Gebali.

Literature references

  1. 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:


Domain organisation

Below is a listing of the unique domain organisations or architectures from this clan. More...

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The table below shows the number of occurrences of each domain throughout the sequence database. More...

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

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Family relationships

This diagram shows the relationships between members of this clan. More...

Species distribution

Tree controls


This tree shows the occurrence of the domains in this clan across different species. More...



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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