Cartilage oligomeric matrix protein (COMP), or thrombospondin-5 (TSP-5), is a member of the thrombospondin gene familyand is found mainly in the extracellular matrix often associated with cartilage tissue. It plays a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin [, , ]. COMP is involved in human limb development and in the pathogenesis of osteoarthritis [].
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 []. EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.TSP3 may be involved in the regulation of skeletal maturation [].
Thrombospondin-2 (TSP2) is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. It has been shown to inhibit tumour growth and angiogenesis []. 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 []. EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.
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 []. 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 []. 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) []as well as extracellular matrix protein like mindin, F-spondin [], SCO-spondin and even the circumsporozoite surface protein 2 and TRAP proteins of Plasmodium [, ]contain one or more instance of this repeat. It has been involved in cell-cell interaction, inhibition of angiogenesis []and apoptosis [].The intron-exon organisation of the properdin gene confirms the hypothesis that the repeat might have evolved by a process involving exon shuffling []. A study of properdin structure provides some information about the structure of the thrombospondin type I repeat [].
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 []. 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 [, ]. They form a wire draped around the calcium ions. The individual calcium-binding repeats are linked by disulphide bonds to each other.
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 []. EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.The globular C-terminal domain is a beta sandwich of two curved antiparallel β-sheets []. The fold is an elaboration of the jelly role topology, with strand B3-B7, B11 and B14-B15 forming the eight-stranded jelly roll motif. The function of the C-terminal domain is not yet known.
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 []. 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 []. 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) []as well as extracellular matrix protein like mindin, F-spondin [], SCO-spondin and even the circumsporozoite surface protein 2 and TRAP proteins of Plasmodium [, ]contain one or more instance of this repeat. It has been involved in cell-cell interaction, inhibition of angiogenesis []and apoptosis [].The intron-exon organisation of the properdin gene confirms the hypothesis that the repeat might have evolved by a process involving exon shuffling []. A study of properdin structure provides some information about the structure of the thrombospondin type I repeat [].The TSP1 repeat structure has a disulfide-rich fold with all-beta sheets, each with three antiparallel strands.
