Thrombospondins are secreted proteins with antiangiogenic abilities. TSP was discovered by Nancy L. Baenziger.

Types

The thrombospondins (TSP) are a family of multifunctional proteins. The family consists of thrombospondins 1-5 and can be divided into 2 subgroups: A, which contains TSP-1 and -2, and B, which contains TSP-3, -4 and -5 (also designated cartilage oligomeric protein

Cartilage oligomeric matrix protein

Cartilage oligomeric matrix protein is a protein that in humans is encoded by the COMP gene.COMP is a marker of cartilage turnover.-Further reading:-External links:* *...

 or COMP). TSP-1 and -2 are homotrimers, consisting of three identical subunits, whereas TSP-3, -4 and -5 are homopentamers.

TSP-1 and TSP-2 are produced by immature astrocyte

Astrocyte

Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...

s during brain development, which promotes the development of new synapse

Synapse

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

s.

Thrombospondin 1

Thrombospondin 1 (TSP-1) is encoded by THBS1. It was first isolated from platelets that had been stimulated with thrombin, and so was designated 'thrombin-sensitive protein'. Since its first recognition, functions for TSP-1 have been found in multiple biological processes including angiogenesis, apoptosis, activation of TGF-beta and Immune regulation. As such, TSP-1 is designated a multifunctional protein.

TSP-1 has multiple receptors, among which CD36

CD36

CD36 is an integral membrane protein found on the surface of many cell types in vertebrate animals and is also known as FAT, SCARB3, GP88, glycoprotein IV and glycoprotein IIIb . CD36 is a member of the class B scavenger receptor family of cell surface proteins...

, CD47

CD47

CD47 is a protein that in humans is encoded by the CD47 gene.- Function :CD47 is a membrane protein, which is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to extracellular matrix...

 and integrins are of particular note.

TSP-1 is an antiangiogenic, inhibiting the proliferation and migration of endothelial cells by interactions with CD36 expressed on their surface of these cells. Inhibitory peptides and fragments of TSP1 bind to CD36

CD36

CD36 is an integral membrane protein found on the surface of many cell types in vertebrate animals and is also known as FAT, SCARB3, GP88, glycoprotein IV and glycoprotein IIIb . CD36 is a member of the class B scavenger receptor family of cell surface proteins...

, leading to the expression of FAS ligand

FAS ligand

Fas ligand is a type-II transmembrane protein that belongs to the tumor necrosis factor family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer.- Structure :Fas ligand or...

 (FasL), which activates its specific, ubiquitous receptor, Fas

Fas receptor

The FAS receptor also known as apoptosis antigen 1 , cluster of differentiation 95 or tumor necrosis factor receptor superfamily member 6 is a protein that in humans is encoded by the TNFRSF6 gene....

. This leads to the activation of caspase

Caspase

Caspases, or cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases are a family of cysteine proteases that play essential roles in apoptosis , necrosis, and inflammation....

s and apoptosis

Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 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. Because TSP1 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 from TSP1 are being tested. One analog, ABT-510

ABT-510

ABT-510 is a molecular therapeutic drug used to treat cancer. According to the Journal of Clinical Oncology, ABT-510 is a "subcutaneously administered nonapeptide thrombospondin analogue in phase 2 clinical development for treatment of advanced malignancies."ABT-510 is a new Abbott Laboratories...

, exhibits potent proapoptotic activity in cultured cells, while clinically it is very well tolerated with therapeutic benefits reported against several malignancies. ABT-510 is being evaluated in phase II clinical trials for the treatment of several types of cancer.

Human proteins containing this domain

ADAMTS1

ADAMTS1

A disintegrin and metalloproteinase with thrombospondin motifs 1 is an enzyme that in humans is encoded by the ADAMTS1 gene.-Interactions:ADAMTS1 has been shown to interact with Vascular endothelial growth factor A.-External Links:...

; ADAMTS10

ADAMTS10

A disintegrin and metalloproteinase with thrombospondin motifs 10 is an enzyme that in humans is encoded by the ADAMTS10 gene.-External Links:* * The MEROPS online database for peptidases and their inhibitors:...

; ADAMTS12

ADAMTS12

A disintegrin and metalloproteinase with thrombospondin motifs 12 is an enzyme that in humans is encoded by the ADAMTS12 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...

; ADAMTS13

ADAMTS13

ADAMTS13 —also known as von Willebrand factor-cleaving protease —is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor , a large protein involved in blood clotting...

; ADAMTS14; ADAMTS15; ADAMTS16; ADAMTS17;
ADAMTS18; ADAMTS19; ADAMTS2

ADAMTS2

A disintegrin and metalloproteinase with thrombospondin motifs 2 also known as procollagen I N-proteinase is an enzyme that in humans is encoded by the ADAMTS2 gene.- Gene :...

; ADAMTS20; ADAMTS3

ADAMTS3

A disintegrin and metalloproteinase with thrombospondin motifs 3 is an enzyme that in humans is encoded by the ADAMTS3 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...

; ADAMTS4

ADAMTS4

A disintegrin and metalloproteinase with thrombospondin motifs 4 is an enzyme that in humans is encoded by the ADAMTS4 gene.-External links:* The MEROPS online database for peptidases and their inhibitors:...

; ADAMTS5

ADAMTS5

A disintegrin and metalloproteinase with thrombospondin motifs 5 also known as ADAMTS5 is an enzyme that in humans is encoded by the ADAMTS5 gene.- Function :...

; ADAMTS6;
ADAMTS7; ADAMTS8

ADAMTS8

A disintegrin and metalloproteinase with thrombospondin motifs 8 is an enzyme that in humans is encoded by the ADAMTS8 gene.- Function :...

; ADAMTS9

ADAMTS9

A disintegrin and metalloproteinase with thrombospondin motifs 9 is an enzyme that in humans is encoded by the ADAMTS9 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...

; ADAMTSL1

ADAMTSL1

ADAMTS-like protein 1 is a protein that in humans is encoded by the ADAMTSL1 gene.-Further reading:...

; ADAMTSL2; ADAMTSL3; ADAMTSL4

ADAMTSL4

ADAMTS-like protein 4 is a protein that in humans is encoded by the ADAMTSL4 gene.-Further reading:...

; ADAMTSL5;
BAI1; BAI2; BAI3; C6

Complement component 6

Complement component 6 is a protein that in humans is encoded by the C6 gene.Complement component 6 is a protein involved in the complement system. It is part of the membrane attack complex which can insert into the cell membrane and cause cell to lyse....

; C7

C7 protein

C7 protein is an engineered zinc finger protein based on the murine ZFP, Zif268 and discovered by Wu et al. in 1994 . It shares the same zinc finger 2 and zinc finger 3 of Zif268, but differs in the sequence of finger 1...

; C8A; C8B; C9

Complement component 9

Complement component 9 is a protein involved in the complement system....

;
C9orf8; C9orf94; CFP; CILP

CILP

Cartilage intermediate layer protein 1 is a protein that in humans is encoded by the CILP gene.-Further reading:...

; CILP2; CTGF

CTGF

CTGF is a cysteine-rich, matrix-associated, heparin-binding protein. In vitro, CTGF mirrors some of the effects of TGF beta on skin fibroblasts, such as stimulation of extracellular matrix production, chemotaxis, proliferation and integrin expression...

; CYR61

CYR61

Protein CYR61 is a protein that in humans is encoded by the CYR61 gene.-Further reading:...

; HMCN1

HMCN1

Hemicentin-1 is a protein that in humans is encoded by the HMCN1 gene.-Further reading:...

;
LIBC; NOV

NOV (gene)

Protein NOV homolog is a protein that in humans is encoded by the NOV gene.-Interactions:NOV has been shown to interact with FBLN1 and NOTCH1.-Further reading:...

; PAPLN

PAPLN

Papilin is a protein that in humans is encoded by the PAPLN gene. Papilin is an extracellular matrix glycoprotein....

; RSPO1

RSPO1

R-spondin-1 is a protein that in humans is encoded by the RSPO1 gene.-Further reading:...

; RSPO3

RSPO3

R-spondin-3 is a protein that in humans is encoded by the RSPO3 gene.-Further reading:...

; SEMA5A

SEMA5A

Semaphorin-5A is a protein that in humans is encoded by the SEMA5A gene.Semaphorine 5A also plays a role in autism, reducing the ability of neurons to form connections with other neurons in certain brain regions.-Further reading:...

; SEMA5B; SPON1;
SPON2; SSPO

SSPO

SCO-spondin is a protein that in humans is encoded by the SSPO gene.-Further reading:...

; THBS1; THBS2

THBS2

Thrombospondin-2 is a protein that in humans is encoded by the THBS2 gene.-Further reading:...

; THSD1

THSD1

Thrombospondin type-1 domain-containing protein 1 is a protein that in humans is encoded by the THSD1 gene.-Further reading:...

; THSD3; THSD7A; THSD7B;
UNC5A

UNC5A

Netrin receptor UNC5A is a protein that in humans is encoded by the UNC5A gene.-Further reading:...

; UNC5B; UNC5C

UNC5C

Netrin receptor UNC5C is a protein that in humans is encoded by the UNC5C gene.-Further reading:...

; UNC5D; WISP1

WISP1

WNT1-inducible-signaling pathway protein 1 is a protein that in humans is encoded by the WISP1 gene.-Further reading:...

; WISP2

WISP2

WNT1-inducible-signaling pathway protein 2 is a protein that in humans is encoded by the WISP2 gene.-Further reading:...

; WISP3

WISP3

WNT1-inducible-signaling pathway protein 3 is a protein that in humans is encoded by the WISP3 gene.-Further reading:...

;

External links

• THBS1, , , , (also known as "THBS5")