PROSITE documentation PDOC51234
Thrombospondin type-3 (TSP3) repeat profile


Thrombospondins are multimeric multidomain glycoproteins that function at cell surfaces and in the extracellular matrix milieu. They act as regulators of cell interactions in vertebrates. They are divided into two subfamilies, A and B, according to their overall molecular organization. The subgroup A proteins TSP-1 and -2 contain an N-terminal domain, a VWFC domain (see <PDOC00928>), three TSP1 repeats (see <PDOC50092>), three EGF-like domains (see <PDOC00021>), TSP3 repeats and a C-terminal domain (see <PDOC51236>). They are assembled as trimer. The subgroup B thrombospondins, designated TSP-3, -4, and COMP (cartilage oligomeric matrix protein, also designated TSP-5) are distinct in that they contain unique N-terminal regions, lack the VWFC domain and TSP1 repeats, contain four copies of EGF-like domains, and are assembled as pentamers [1]. EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.

The calcium-binding TSP3 repeats are a tandem of aspartic acid-rich motifs, which resembles EF hands in the acidic side chains. But unlike EF hands, the calcium-binding loops of the TSP3 repeats are not flanked by secondary structure elements. The structure of the TSP3 repeats has been solved (see for example <PDB:1YO8>) [2,3]. They form a wire draped around the calcium ions. The individual calcium-binding repeats are linked by disulfide bonds to each other.

The profile we developed covers the entire TSP3 repeat.

Last update:

March 2007 / First entry.


Technical section

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

TSP3, PS51234; Thrombospondin type-3 (TSP3) repeat profile  (MATRIX)


1AuthorsAdams J.C.
TitleThrombospondins: multifunctional regulators of cell interactions.
SourceAnnu. Rev. Cell Dev. Biol. 17:25-51(2001).
PubMed ID11687483

2AuthorsKvansakul M. Adams J.C. Hohenester E.
TitleStructure of a thrombospondin C-terminal fragment reveals a novel calcium core in the type 3 repeats.
SourceEMBO J. 23:1223-1233(2004).
PubMed ID15014436

3AuthorsCarlson C.B. Bernstein D.A. Annis D.S. Misenheimer T.M. Hannah B.L. Mosher D.F. Keck J.L.
TitleStructure of the calcium-rich signature domain of human thrombospondin-2.
SourceNat. Struct. Mol. Biol. 12:910-914(2005).
PubMed ID16186819

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