The THBS2 gene is 38,261 bases in size and is composed of 23 exons. Exons 3-22 encode the 5,808 base mRNA.

Unlike TSP1, TSP2 is less-to-moderately responsive to serum in mouse NIH3T3 and Swiss 3T3 cells respectively. Transcription of THBS2 in some human cancers is suppressed through hypermethylation. TSP2 mRNA is upregulated by Rac1-induced reactive oxygen species, Hox A5, ACTH, TGFb, cerivastatin and in-vitro, by increasing cell confluency. Downregulation of TSP2 mRNA occurs by inhibiting TGFb-dependent p38 MAPK pathway or perturbing the Smad pathway by dexamethasone, ATF3 overexpression, human papilloma virus positive cells, cytomegalovirus infected cells, tissue factor overexpressing sarcoma cells. The oncogene c-myb affects TSP 2 expression via a post-transcriptional regulation of its mRNA stability. Potential transcription factor binding sites have been described for: NF-kB, NF-Y,p53, Myc-CF1, Sp1, CF-1,GATA and AP-1.

none described

The TSP2 precursor contains 1172 amino acids; 129,955 Da. The mature secreted protein comprises residues 19-1172 and assembles into a disulfide linked homotrimer. Secreted TSP2 is a glycoprotein with a molecular mass of 150-160 kDa that contains approximately 7 potential Asn-linked oligosaccharide attachment sites and variable numbers of C-mannosylated Trp residues in the type 1 repeats. An X-ray crystal structure for the C-terminal regions of TSP2 revealed that the type 3 repeats when replete with Ca wrap around the globular G domain.

TSP2 is expressed in many tissues during embryonic development, in the healthy adult and in various tumor stromal environments. Predominant expression is found in the connective tissue compartment and based on EST profiling, expression is highest in bone. Mice lacking thrombospondin 2 show an atypical pattern of endocortical and periosteal bone formation in response to mechanical loading. Expression is induced during the later stages of wound repair, during tissue remodeling, in rheumatoid synovium, ovarian follicle development, in wound keratocytes, hypertrophied heart, by ACTH, cAMP analogs and adenylate cyclase activators in bovine adrenocortical cells, in aged mice. Downregulation has been observed in fetal Leydig cells of mice overexpressing human chorionic gonadotropin/ luteinizing hormone, herpes simplex 1 infected cells, and in Cyclosporin A-induced gingival overgrowths.
TSP2 expression has been reported in some tumors including invasive breast carcinoma, metastatic malignant melanoma, malignant pleural effusions, cervix of pregnant mice, ischemic brain, aggressive ovarian tumor, gastric cancer, renal cell carcinoma, endometrial cancer, colorectal cancer, chemically-induced skin cancer, osteoclastoma, in ACTH-dependent aldosterone producing adenomas, esophageal cancer. Down regulation of TSP2 was reported in ovarian serous papillary carcinoma, salivary gland carcinoma, invasive cervical cancer, and non-small cell lung cancer.

TSP2 is secreted but is present only transiently in extracellular matrix and is rapidly internalized for degradation by fibroblasts after binding to the cell surface. Degradation is similar to TSP1 removal in that it is LRP- and HSPG-dependent and has similar kinetics. Given its pericellular distribution, TSP2, like TSP1, can modulate cell-matrix interactions and cell behavior.

TSP2 binds to extracellular matrix ligands including, transforming growth factor-beta-1, histidine rich glycoprotein, TSG6, heparin, matrix metalloproteinase-2, and heparan sulfate proteoglycans. TSP2 binds to cell surface receptors including CD36, CD47, LDL receptor-related protein-1 (via calreticulin) and the integrins alpha-V/beta-3, alpha-4/beta-1, and alpha-6/beta-1. In contrast to TSP1, TSP2 does not activate latent TGF-beta-1 but similarly to TSP1, TSP2 contains EGF-like modules that bind calcium in a cooperative manner. TSP2 in a context-dependent and cell-specific manner stimulates or inhibits cell adhesion, proliferation, motility, and survival. TSP2 is a potent inhibitor of angiogenesis mediated by the TSP2 receptor CD36. However, its N-terminal region exhibits pro-angiogenic activities mediated by beta-1 integrins . By way of alpha-4/beta-1, TSP2, like TSP1, modulates T cell behavior in-vitro. TSP2 stimulates chemotaxis, MMP gene expression, and activation-dependent adhesion of T cells. In a model of rheumatoid synovium, cell-based TSP2 therapy had an anti-inflammatory role in-vivo and depleted the tissue of infiltrating T cells. In the CNS, TSP2 secreted by astrocytes promotes synaptogenesis.

TSP2 null mice are viable and fertile but display connective tissue abnormalities associated with a defect in collagen fibrillogenesis that manifests as fragile skin, lax tendons and ligaments. Several defects have been reported in responses of TSP2 null mice to specific stresses. Nulls have an enhanced cutaneous inflammatory response, increased endosteal bone density, increased vascular density in dermis, adipose and thymus, a prolonged bleeding time. Fibroblasts isolated from TSP2 nulls are defective in adhesion. In response-to-injury models, TSP2 null mice have an increased vascularity of wounds with a concomitant increase in activity of MMP2 and MMP9 and demonstrate enhanced wound repair.

TSP2 is a member of the thrombospondin family that also contains thrombospondin-1, thrombospondin-3, thrombospondin-4, and cartilage oligomeric matrix protein (COMP). The central type 1 repeats are also known as thrombospondin-repeats and are shared with the larger thrombospondin/properdin repeat superfamily.

t3949g substitution in the 3-untranslated region is associated with a reduced risk of premature myocardial infarcts

LOH in markers proximal to THBS2 were reported in salivary carcinomas, but disruption of the THBS2 gene has not been confirmed to date.