| Thrombospondin type 1 domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Thrombospondin-1 | |||||||||
| Identifiers | |||||||||
| Symbol | TSP_1 | ||||||||
| Pfam | PF00090 | ||||||||
| InterPro | IPR000884 | ||||||||
| SMART | SM00209 | ||||||||
| PROSITE | PS50092 | ||||||||
| SCOP2 | 1lsl /SCOPe /SUPFAM | ||||||||
| |||||||||
Thrombospondins (TSPs) are a family of secretedglycoproteins withantiangiogenic functions. Due to their dynamic role within theextracellular matrix they are consideredmatricellular proteins.[1] The first member of the family,thrombospondin 1 (THBS1), was discovered in 1971 by Nancy L. Baenziger.[2]
The thrombospondins are a family of multifunctional proteins. The family consists of thrombospondins 1–5 and can be divided into two subgroups: A, which containsTSP-1 andTSP-2, and B, which containsTSP-3,TSP-4 and TSP-5 (also designatedcartilage oligomeric protein or COMP). TSP-1 and TSP-2 are homotrimers, consisting of three identical subunits, whereas TSP-3, TSP-4 and TSP-5 are homopentamers.
TSP-1 and TSP-2 are produced by immatureastrocytes during brain development, which promotes the development of newsynapses.[3]
Thrombospondin 1 (TSP-1) is encoded byTHBS1. It was first isolated fromplatelets that had been stimulated with thrombin, and so was designated 'thrombin-sensitive protein'.[2] Since its first recognition, functions forTSP-1 have been found in multiple biological processes including angiogenesis, apoptosis, activation ofTGF-beta and Immune regulation. As such, TSP-1 is designated a multifunctional protein.
TSP-1 has multiple receptors, among whichCD36,CD47 andintegrins are of particular note.
TSP-1 isantiangiogenic, inhibiting the proliferation and migration of endothelial cells by interactions with CD36 expressed on their surface of these cells. Inhibitory peptides and fragments ofTSP1 bind toCD36, leading to the expression ofFAS ligand (FasL), which activates its specific, ubiquitous receptor,Fas. This leads to the activation ofcaspases andapoptosis of the cell. Since tumors overexpressing TSP-1 typically grow slower, exhibit less angiogenesis, and have fewer metastases, TSP1 is an attractive target for cancer treatment. BecauseTSP1 is extremely large (~ 120 kDa monomer), not very abundant and exerts multiple actions, its clinical usefulness is questionable. However, small-molecules based on a CD36-binding peptide sequence fromTSP1 are being tested. One analog,ABT-510, exhibits potent proapoptotic activity in cultured cells, while clinically it is very well tolerated with therapeutic benefits reported against several malignancies.[4] In 2005, ABT-510 was evaluated in phase II clinical trials for the treatment of several types of cancer.[5]
ADAMTS1;ADAMTS10;ADAMTS12;ADAMTS13;ADAMTS14;ADAMTS15;ADAMTS16;ADAMTS17;ADAMTS18;ADAMTS19;ADAMTS2;ADAMTS20;ADAMTS3;ADAMTS4;ADAMTS5;ADAMTS6;ADAMTS7;ADAMTS8;ADAMTS9;ADAMTSL1;ADAMTSL2;ADAMTSL3;ADAMTSL4;ADAMTSL5;BAI1;BAI2;BAI3;C6;C7;C8A;C8B;C9;C9orf8;C9orf94;CFP;CILP;CILP2;CTGF;CYR61;HMCN1;LIBC;NOV;PAPLN;RSPO1;RSPO3;SEMA5A;SEMA5B;SPON1;SPON2;SSPO;THBS1;THBS2;THSD1;THSD3;THSD7A;THSD7B;UNC5A;UNC5B;UNC5C;UNC5D;WISP1;WISP2;WISP3;