TSP1

Thrombospondin type 1 repeats
TSP1
SMART accession number:SM00209
Description: Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.
Interpro abstract (IPR000884):

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 organisation. The subgroup A proteins TSP-1 and -2 contain an N-terminal domain, a VWFC domain, three TSP1 repeats, three EGF-like domains, TSP3 repeats and a C-terminal domain. 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 [(PUBMED:11687483)]. EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.

This repeat was first described in 1986 by Lawler and Hynes [(PUBMED:2430973)]. It was found in the thrombospondin protein where it is repeated 3 times. Now a number of proteins involved in the complement pathway (properdin, C6, C7, C8A, C8B, C9) [(PUBMED:2459396)] as well as extracellular matrix protein like mindin, F-spondin [(PUBMED:10409509)], SCO-spondin and even the circumsporozoite surface protein 2 and TRAP proteins of Plasmodium [(PUBMED:10508153), (PUBMED:1501644)] contain one or more instance of this repeat. It has been involved in cell-cell interaction, inhibition of angiogenesis [(PUBMED:10500044)] and apoptosis [(PUBMED:9135017)].

The intron-exon organisation of the properdin gene confirms the hypothesis that the repeat might have evolved by a process involving exon shuffling [(PUBMED:1417780)]. A study of properdin structure provides some information about the structure of the thrombospondin type I repeat [(PUBMED:1868073)].

Family alignment:
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There are 42499 TSP1 domains in 10861 proteins in SMART's nrdb database.

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