Family

Thrombospondin-2 (IPR015455)

Short name: Thrombospondin-2

Family relationships

Description

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 [PMID: 11687483]. EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.

The gene encoding thrombospondin 2, THBS2, was originally identified by screening of a human fibroblast library [PMID: 1559694]. The cDNA encoding THBS2 showed close homology to THBS1. In gene disruption studies it has been shown that THBS2 null mice were overtly normal, but actually had a number of altered phenotypes [PMID: 9442117]. These included abnormalities in connective tissue resulting in fragile skin with reduced tensile strength. The tail was unusually flexible and the long bones denser and thicker. Mutant mice also displayed abnormal bleeding times and there was an increase in the number of blood vessels suggesting an antiangiogenic role for THBS2.

Further evidence supporting an inhibitory role for THBS2 in angiogenesis has shown by the injection of squamous cell carcinomas stably expressing THBS2 in the dermis of nude mice, resulting in inhibition of tumour growth [PMID: 10611308]. The areas around the THBS2 expressing tumours were necrotic while the density and number of tumour vessels was reduced.

GO terms

Biological Process

GO:0016525 negative regulation of angiogenesis

Molecular Function

GO:0008201 heparin binding

Cellular Component

GO:0031012 extracellular matrix

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PANTHER