G3DSA:2.20.100.10

Thrombospondin type-1 (TSP1) repeat

CATH-Gene3D entry
Member databaseCATH-Gene3D
CATH-Gene3D typehomologous superfamily

Description
Imported from IPR036383

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
[7]
. 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
[2]
. 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)
[1]
as well as extracellular matrix protein like mindin, F-spondin
[8]
, SCO-spondin and even the circumsporozoite surface protein 2 and TRAP proteins of Plasmodium
[3, 4]
contain one or more instance of this repeat. It has been involved in cell-cell interaction, inhibition of angiogenesis
[10]
and apoptosis
[9]
.

The intron-exon organisation of the properdin gene confirms the hypothesis that the repeat might have evolved by a process involving exon shuffling
[5]
. A study of properdin structure provides some information about the structure of the thrombospondin type I repeat
[6]
.

The TSP1 repeat structure has a disulfide-rich fold with all-beta sheets, each with three antiparallel strands.

References
Imported from IPR036383

1.Detecting distant homologies of mosaic proteins. Analysis of the sequences of thrombomodulin, thrombospondin complement components C9, C8 alpha and C8 beta, vitronectin and plasma cell membrane glycoprotein PC-1. Patthy L. J. Mol. Biol. 202, 689-96, (1988). View articlePMID: 2459396

2.The structure of human thrombospondin, an adhesive glycoprotein with multiple calcium-binding sites and homologies with several different proteins. Lawler J, Hynes RO. J. Cell Biol. 103, 1635-48, (1986). View articlePMID: 2430973

3.The A-domain and the thrombospondin-related motif of Plasmodium falciparum TRAP are implicated in the invasion process of mosquito salivary glands. Wengelnik K, Spaccapelo R, Naitza S, Robson KJ, Janse CJ, Bistoni F, Waters AP, Crisanti A. EMBO J. 18, 5195-204, (1999). View articlePMID: 10508153

4.Characterization of the gene encoding sporozoite surface protein 2, a protective Plasmodium yoelii sporozoite antigen. Rogers WO, Rogers MD, Hedstrom RC, Hoffman SL. Mol. Biochem. Parasitol. 53, 45-51, (1992). View articlePMID: 1501644

5.Characterization of the human properdin gene. Nolan KF, Kaluz S, Higgins JM, Goundis D, Reid KB. Biochem. J. 287 ( Pt 1), 291-7, (1992). View articlePMID: 1417780

6.Neutron and X-ray scattering studies on the human complement protein properdin provide an analysis of the thrombospondin repeat. Smith KF, Nolan KF, Reid KB, Perkins SJ. Biochemistry 30, 8000-8, (1991). View articlePMID: 1868073

7.Thrombospondins: multifunctional regulators of cell interactions. Adams JC. Annu. Rev. Cell Dev. Biol. 17, 25-51, (2001). View articlePMID: 11687483

8.F-spondin and mindin: two structurally and functionally related genes expressed in the hippocampus that promote outgrowth of embryonic hippocampal neurons. Feinstein Y, Borrell V, Garcia C, Burstyn-Cohen T, Tzarfaty V, Frumkin A, Nose A, Okamoto H, Higashijima S, Soriano E, Klar A. Development 126, 3637-48, (1999). View articlePMID: 10409509

9.Thrombospondin 1 and type I repeat peptides of thrombospondin 1 specifically induce apoptosis of endothelial cells. Guo N, Krutzsch HC, Inman JK, Roberts DD. Cancer Res. 57, 1735-42, (1997). View articlePMID: 9135017

10.Inhibition of angiogenesis by thrombospondin-1 is mediated by 2 independent regions within the type 1 repeats. Iruela-Arispe ML, Lombardo M, Krutzsch HC, Lawler J, Roberts DD. Circulation 100, 1423-31, (1999). View articlePMID: 10500044

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.