PROSITE documentation PDOC51888
Clip domain profile


Some biological processes such as blood coagulation in mammals or development and immune responses in invertebrates occur after the amplification of a recognition signal by serine proteases (SP) (see <PDOC00124>) that are organized in cascades. These SPs are characterized by a modular organization comprising a C-terminal catalytic domain and one or several N-terminal domains (CUB, EGF-like, LDL, CCP, or clip) and are activated in a very specific order. Clip-domain SP (see <PDOC00124>) is an important SP family involved in many biological processes, which is only found in invertebrates. Clip domain SPs are the essential components of extracellular signaling cascades in various biological processes, especially in the immune response of invertebrates. The SPs and SP homologs (SPHs are SPs where the catalytic triad is mutated) that contain one or more clip domains are called clip-SPs and clip-SPHs. The clip domain, which is found in the N-terminal position, consists of 35-55 residues including six strictly conserved cysteines arranged in three disulfide bonds. The clip and the catalytic domains are connected by a linker containing at least one cysteine, which is involved in an interdomain disulfide bond with a cysteine of the SP domain. The SPs in the clip domain family are synthesized as zymogens and are activated by a specific proteolytic cleavage. The activation site of clip-SPs is located between the linker and the catalytic domain. After activation of the zymogen, the clip and SP domains remain linked by the interdomain disulfide bond. The clip domain, named according to the schematic form of a paper clip, may be involved in protein-protein interactions, regulation of the protease activity, and even antimicrobial activity. Although the functions of clip domains are not completely clear, the clip domain in arthropods has been demonstrated to act in the regulation of proteinase activity, protein-protein interaction and bactericidal activities [1,2,3,4,5,6].

The clip domain adopts an α/β mixed fold consisting of two helices and an antiparallel distorted β-sheet made of four strands (see <PDB:2XXL>). The two helices are antiparallel and are almost perpendicular to the β-sheet. Three disulfide bridges (C1-C5, C2-C4, C3-C6) stabilize the β-sheet, C3 being the only cysteine that is not located on a β-strand. The clip domain is located opposite the activation loop and contacts the C-terminal α-helix of the SP domain [1].

The profile we developed covers the entire clip domain.

Last update:

March 2019 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

CLIP, PS51888; Clip domain profile  (MATRIX)


1AuthorsKellenberger C. Leone P. Coquet L. Jouenne T. Reichhart J.-M. Roussel A.
TitleStructure-function analysis of grass clip serine protease involved in Drosophila Toll pathway activation.
SourceJ. Biol. Chem. 286:12300-12307(2011).
PubMed ID21310954

2AuthorsLin C.-Y. Hu K.-Y. Ho S.-H. Song Y.-L.
TitleCloning and characterization of a shrimp clip domain serine protease homolog (c-SPH) as a cell adhesion molecule.
SourceDev. Comp. Immunol. 30:1132-1144(2006).
PubMed ID16701896

3AuthorsJiang H. Kanost M.R.
TitleThe clip-domain family of serine proteinases in arthropods.
SourceInsect. Biochem. Mol. Biol. 30:95-105(2000).
PubMed ID10696585

4AuthorsKanost M.R. Jiang H.
TitleClip-domain serine proteases as immune factors in insect hemolymph.
SourceCurr. Opin. Insect. Sci. 11:47-55(2015).
PubMed ID26688791

5AuthorsSun W. Li Z. Wang S. Wan W. Wang S. Wen X. Zheng H. Zhang Y. Li S.
TitleIdentification of a novel clip domain serine proteinase (Sp-cSP) and its roles in innate immune system of mud crab Scylla paramamosain.
SourceFish. Shellfish. Immunol. 47:15-27(2015).
PubMed ID26272638

6AuthorsJia Z. Wang M. Zhang H. Wang X. Lv Z. Wang L. Song L.
TitleIdentification of a clip domain serine proteinase involved in immune defense in Chinese mitten crab Eriocheir sinensis.
SourceFish. Shellfish. Immunol. 74:332-340(2018).
PubMed ID29305333

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