PROSITE documentation PDOC50092

Thrombospondin type-1 (TSP1) repeat profile

The thrombospondin type-1 repeat (TSP1) was first identified as an about 55 amino acids long module present in thrombospondin 1 and 2 and in the circumsporozoite (CS) protein of Plasmodium [1]. Since, a number of proteins involved in the complement pathway (properdin, C6, C7, C8A, C8B, C9) as well as extracellular matrix proteins like ADAMTS (see <PDOC50215>), mindin, F-spondin or SCO-spondin and TRAP proteins of Plasmodium have been found to contain one to seven TSP1s. Within these TSP1 modules, the WSXW and CSVTCG motifs are highly conserved although not ubiquitous. TSP1s may bind both protein and glycoconjugate ligands [2].

Averaged secondary structure predictions suggested that the TSP1 has an elongated structure and contains two amphipathic turn regions and one hydrophilic β-strand region [3]. The six cysteines of the second TSP1 module of human thrombospondin 1 have been shown to be connected in a 1-5, 2-6, 3-4 disulfide-bond pattern. It is noteworthy that there are some members of the TSP1 module-family which lack certain pairs of cysteines that form disulfide-bonds [4].

Some proteins known to contain TSP1s are listed below:

• Mammalian ADAMTS, extracellular matrix proteases containing metalloprotease (see <PDOC50215> and disintegrin (see <PDOC00351>) domains and one or more TSP1s.
• Vertebrate C6 (3 TSP1s), C7 (2 TSP1s), C8A (2 TSP1s), C8B (2 TSP1s) and C9 (1 or 2 TSP1s), components of the membrane attack complex of the complement system.
• Vertebrate F-spondin, may contribute to the growth and guidance of axons in both the spinal cord and the PNS. It contains six TSP1s.
• Mammalian properdin, a glycoprotein involved in the positive regulation of the alternative pathway of the complement system of immune defense by binding to and stabilizing the C3/C5-convertase complexes. Properdin contains six TSP1s.
• Mammalian semaphorins 5A and 5B which may act as positive axonal cues. They contain seven TSP1s.
• Vertebrate thrombospondin 1 and 2. Thrombospondins are a class of extracellular adhesive proteins that mediate cell-to-cell and cell-to- matrix interactions. They contain six TSP1s. The anti-angiogenic activity of TSPs has been localized to the second and third TSP1s [5].
• Vertebrate NOV protein homolog. It is likely to play a role in cell growth regulation.
• Mammalian connective tissue growth factor (CTGF). It promotes proliferation and differentiation of chondrocytes.
• Mammalian connective tissue growth factor-like protein (CTGFL).
• Mammalian CYR61 protein. It promotes proliferation, migration and adhesion.
• Chicken CEF-10 protein, a probable secreted regulatory protein induced by v-src.
• Plasmodium circumsporozoite (CS) protein, the immunodominant surface antigen on the sporozoite. The CS protein contains one TSP1.
• Plasmodium thrombospondin-related anonymous protein (TRAP), implicated in the recognition and invasion of salivary glands by the sporozoite [6]. TRAP contains one TSP1.

The profile we developed covers the entire TSP1 domain.