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 . 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 .
Averaged secondary structure predictions suggested that the TSP1 has an
elongated structure and contains two amphipathic turn regions and one
hydrophilic β-strand region . 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
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
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
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 .
Vertebrate NOV protein homolog. It is likely to play a role in cell growth
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
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 . TRAP
contains one TSP1.
The profile we developed covers the entire TSP1 domain.
October 2002 / Profile and text revised.
PROSITE method (with tools and information) covered by this documentation:
Lawler J., Hynes R.O.
The structure of human thrombospondin, an adhesive glycoprotein with multiple calcium-binding sites and homologies with several different proteins.
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