Thrombospondins (TSPs) are a family of secreted

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as g ...

s with

antiangiogenic An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical d ...

functions. Due to their dynamic role within the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide struc ...

they are considered

matricellular proteins A matricellular protein is a dynamically expressed non-structural protein that is present in the extracellular matrix (ECM). Rather than serving as stable structural elements in the ECM, these proteins are rapidly turned over and have regulatory rol ...

. The first member of the family, thrombospondin 1 (THBS1), was discovered in 1971 by Nancy L. Baenziger.

Types

The thrombospondins 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 TSP-2, and B, which contains TSP-3, TSP-4 and TSP-5 (also designated cartilage 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 immature

astrocyte Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of e ...

s during brain development, which promotes the development of new

synapse In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses fr ...

Thrombospondin 1

Thrombospondin 1 (TSP-1) is encoded by THBS1. It was first isolated from

platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...

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 Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other si ...

and Immune regulation. As such, TSP-1 is designated a multifunctional protein. TSP-1 has multiple receptors, among which CD36, CD47 and

integrins Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...

are of particular note. TSP-1 is

, 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, leading to the expression of FAS ligand (FasL), which activates its specific, ubiquitous receptor, Fas. This leads to the activation of

caspase Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cyst ...

s and apoptosis 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, exhibits potent proapoptotic activity in cultured cells, while clinically it is very well tolerated with therapeutic benefits reported against several malignancies. In 2005, ABT-510 was evaluated in phase II clinical trials for the treatment of several types of cancer.

Human proteins containing this domain

ADAMTS1; ADAMTS10; ADAMTS12;

ADAMTS13 ADAMTS13 (''a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13'')—also known as ''von Willebrand factor-cleaving protease'' (VWFCP)—is a zinc-containing metalloprotease enzyme that cleaves von Willebrand facto ...

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

ADAMTS2 A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAM-TS2) also known as procollagen I N-proteinase (PC I-NP) is an enzyme that in humans is encoded by the ''ADAMTS2'' gene. Gene The ADAMTS2 gene is located on the long (q) ...

; ADAMTS20; ADAMTS3; ADAMTS4; ADAMTS5;

ADAMTS6 ADAM metallopeptidase with thrombospondin type 1 motif 6 is a protein that in humans is encoded by the ADAMTS6 gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredit ...

; ADAMTS7; ADAMTS8; ADAMTS9;

ADAMTSL1 ADAMTS-like protein 1 is a protein that in humans is encoded by the ''ADAMTSL1'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ...

; ADAMTSL2; ADAMTSL3; ADAMTSL4; ADAMTSL5;

BAI1 Brain-specific angiogenesis inhibitor 1 is a protein that in humans is encoded by the ''BAI1'' gene. It is a member of the adhesion-GPCR family of receptors. Function Angiogenesis is controlled by a local balance between stimulators and inhib ...

; BAI2; BAI3; C6; C7; C8A; C8B; C9; C9orf8; C9orf94; CFP;

CILP Cartilage intermediate layer protein 1 is a protein that in humans is encoded by the ''CILP'' gene. Major alterations in the composition of the cartilage extracellular matrix occur in joint disease, such as osteoarthrosis. The synthesis of cartil ...

; CILP2; CTGF; CYR61; HMCN1;

LIBC The C standard library or libc is the standard library for the C programming language, as specified in the ISO C standard. ISO/ IEC (2018). '' ISO/IEC 9899:2018(E): Programming Languages - C §7'' Starting from the original ANSI C standard, it wa ...

;

NOV Nov or NOV may refer to: * November, the 11th month of the year in the Julian and Gregorian calendars * Nav, Asalem (also , Nov or Nāv), a village in Gilan Province, Iran * Nov, Golan Heights, an Israeli moshav (a cooperative agricultural communi ...

; PAPLN; RSPO1; RSPO3; SEMA5A; SEMA5B;

SPON1 Spondin-1 (also known as F-spondin) is a protein that in humans is encoded by the ''SPON1'' gene. It is secreted by cells of the floor plate and may be involved in axon guidance Axon guidance (also called axon pathfinding) is a subfield of n ...

; SPON2;

SSPO SCO-spondin is a protein that in humans is encoded by the ''SSPO'' gene. SCO-spondin is secreted by the subcommissural organ, and contributes to commissure, commissural Axon#Development and growth, axon growth and the formation of Reissner's fiber ...

; THBS1; THBS2; THSD1; THSD3; THSD7A; THSD7B; UNC5A; UNC5B; UNC5C; UNC5D;

WISP1 WNT1-inducible-signaling pathway protein 1 (WISP-1), also known as CCN4, is a matricellular protein that in humans is encoded by the ''WISP1'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe ...

; WISP2; WISP3;

References

External links

* * , , , , {{Gene, COMP (also known as "THBS5") Protein domains