Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Binds heparin. May play a role in dentinogenesis and/or maintenance of dentin and dental pulp (By similarity). Ligand for CD36 mediating antiangiogenic properties. Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors (By similarity). (updated: April 1, 2015)

Protein identification was indicated in the following studies:

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

Publication	Identification ¹	Uniprot mapping ²	Not mapped / Obsolete	TrEMBL	Swiss-Prot
Goodman (2013)	2289 (gene list)	2278	53	20599	2269
Lange (2014)	1234	1234	7	28	1224
Hegedus (2015)	2638	2622	0	235	2387
Wilson (2016)	1658	1528	170	291	1068
d'Alessandro (2017)	1826	1817	2	0	1815
Bryk (2017)	2090	2060	10	108	1942
Chu (2018)	1853	1804	55	362	1387

¹ as available in the article and/or in supplementary material
² uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Protein sequence (FASTA)

Protein coevolution profile (FreeContact)

Multiple Sequence Alignment (Muscle)

Total structural coverage: 71%

Model score: 77

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Variant	Description
	dbSNP:rs41515347
	dbSNP:rs2292305
	dbSNP:rs2228262

Biological Process

Activation of MAPK activity

Behavioral response to pain

Blood coagulation

Cell adhesion

Cell cycle arrest

Cell migration

Cellular protein metabolic process

Cellular response to growth factor stimulus

Cellular response to heat

Cellular response to nitric oxide

Cellular response to tumor necrosis factor

Chronic inflammatory response

Endocardial cushion development

Engulfment of apoptotic cell

Extracellular matrix organization

Growth plate cartilage development

Immune response

Inflammatory response

Negative regulation of angiogenesis

Negative regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II

Negative regulation of apoptotic process

Negative regulation of blood vessel endothelial cell migration

Negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis

Negative regulation of cell migration involved in sprouting angiogenesis

Negative regulation of cell-matrix adhesion

Negative regulation of cGMP-mediated signaling

Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Negative regulation of dendritic cell antigen processing and presentation

Negative regulation of endothelial cell chemotaxis

Negative regulation of endothelial cell migration

Negative regulation of endothelial cell proliferation

Negative regulation of extrinsic apoptotic signaling pathway

Negative regulation of fibrinolysis

Negative regulation of fibroblast growth factor receptor signaling pathway

Negative regulation of focal adhesion assembly

Negative regulation of interleukin-12 production

Negative regulation of long-chain fatty acid import across plasma membrane

Negative regulation of nitric oxide mediated signal transduction

Negative regulation of plasminogen activation

Negative regulation of sprouting angiogenesis

Obsolete regulation of cGMP metabolic process

Outflow tract morphogenesis

Peptide cross-linking

Platelet activation

Platelet degranulation

Positive regulation of angiogenesis

Positive regulation of blood coagulation

Positive regulation of blood vessel endothelial cell migration

Positive regulation of cell migration

Positive regulation of cell population proliferation

Positive regulation of cell-substrate adhesion

Positive regulation of chemotaxis

Positive regulation of endothelial cell apoptotic process

Positive regulation of endothelial cell migration

Positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

Positive regulation of fibroblast migration

Positive regulation of macrophage activation

Positive regulation of macrophage chemotaxis

Positive regulation of phosphorylation

Positive regulation of protein kinase B signaling

Positive regulation of reactive oxygen species metabolic process

Positive regulation of smooth muscle cell proliferation

Positive regulation of transforming growth factor beta receptor signaling pathway

Positive regulation of transforming growth factor beta1 production

Positive regulation of translation

Positive regulation of tumor necrosis factor biosynthetic process

Positive regulation of tumor necrosis factor production

Post-translational protein modification

Protein O-linked fucosylation

Protein O-linked glycosylation

Regulation of megakaryocyte differentiation

Response to calcium ion

Response to drug

Response to endoplasmic reticulum stress

Response to glucose

Response to hypoxia

Response to magnesium ion

Response to mechanical stimulus

Response to progesterone

Response to testosterone

Response to unfolded protein

Sprouting angiogenesis

Cellular Component

Cell surface

Collagen-containing extracellular matrix

Endoplasmic reticulum

Endoplasmic reticulum lumen

External side of plasma membrane

Extracellular exosome

Extracellular matrix

Extracellular region

Extracellular space

Fibrinogen complex

Platelet alpha granule

Platelet alpha granule lumen

Sarcoplasmic reticulum

Secretory granule

Molecular Function

Calcium ion binding

Collagen V binding

Extracellular matrix structural constituent

Fibrinogen binding

Fibroblast growth factor binding

Fibronectin binding

Glycoprotein binding

Heparin binding

Identical protein binding

Integrin binding

Laminin binding

Low-density lipoprotein particle binding

Phosphatidylserine binding

Proteoglycan binding

Transforming growth factor beta binding

The reference OMIM entry for this protein is 188060

Thrombospondin i; thbs1
Tsp1

DESCRIPTION

Thrombospondin I is a multimodular secreted protein that associates with the extracellular matrix and possesses a variety of biologic functions, including a potent antiangiogenic activity. Other thrombospondin genes include thrombospondins II (THBS2; 188061), III (THBS3; 188062), and IV (THBS4; 600715).

CLONING

Thrombospondin (THBS) is a homotrimeric glycoprotein with disulfide-linked subunits of 180 kD. THBS was first described as a component of the alpha-granule of platelets, released on platelet activation. It is associated with the platelet membrane in the presence of divalent cations and has a role in platelet aggregation. THBS is not limited to platelets, however. It is synthesized and secreted for incorporation into the extracellular matrix by a variety of cells including endothelial cells, fibroblasts, smooth muscle cells, and type II pneumocytes. THBS binds heparin, sulfatides, fibrinogen, fibronectin, plasminogen, and type V collagen. Dixit et al. (1986) reported characterization of a cDNA encoding the N-terminal 376 amino acid residues of human THBS. Asch et al. (1987) identified an 88-kD glycoprotein which they concluded functions as the cellular THBS receptor. Frazier (1987) reviewed the molecular structure of thrombospondin. Using real-time RT-PCR, Hirose et al. (2008) detected specific and high expression levels of both THBS1 and THBS2 in human intervertebral disc tissue.

GENE FUNCTION

De Fraipont et al. (2000) measured the cytosolic concentrations of 3 proteins involved in angiogenesis, namely, platelet-derived endothelial cell growth factor (PDECGF; 131222), VEGFA (192240), and THBS1 in a series of 43 human sporadic adrenocortical tumors. The tumors were classified as adenomas, transitional tumors, or carcinomas. PDECGF/thymidine phosphorylase levels were not significantly different among these 3 groups. One hundred percent of the adenomas and 73% of the transitional tumors showed VEGFA concentrations under the threshold value of 107 ng/g protein, whereas 75% of the carcinomas had VEGFA concentrations above this threshold value. Similarly, 89% of the adenomas showed THBS1 concentrations above the threshold value of 57 microg/g protein, whereas only 25% of the carcinomas and 33% of the transitional tumor samples did so. IGF2 (147470) overexpression, a common genetic alteration of adrenocortical carcinomas, was significantly correlated with higher VEGFA and lower THBS1 concentrations. The authors concluded that a decrease in THBS1 expression is an event that precedes an increase in VEGFA expression during adrenocortical tumor progression. The population of premalignant tumors with low THBS1 and normal VEGFA levels could represent a selective target for antiangiogenic therapies. Natural inhibitors of angiogenesis are able to block pathologic neovascularization without harming the preexisting vasculature. Volpert et al. (2002) demonstrated that 2 such inhibitors, thrombospondin I and pigment epithelium-derived factor (172860), derive specificity for remodeling vessels from their dependence on Fas/Fas ligand (134637; 134638)-mediated apoptosis to block angiogenesis. Both inhibitors upregulated FasL on endothelial cells. Expression of the essential partner of FasL, Fas receptor, was low on quiescent endothelial cells and vessels but greatly enhanced by inducers of angiogenesis, thereby specifically sensitizing the stimulated cells to apoptosis by inhibitor-generated FasL. The antia ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 188060 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed

Thrombospondin-1 (THBS1)