Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

THBS1 (thrombospondin-1)

Written2005-05David D Roberts
Biochemical Pathology Section, Laboratory of Pathology, CCR, NCI, Bethesda, Maryland 20892, USA
Updated2019-10Jeffrey S. Isenberg, David D. Roberts
Jeffrey S. Isenberg, Radiation Control Technologies, Inc., Loudonville, NY, USA; tsp1cd47@gmail.com (JSI); Biochemical Pathology Section, Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland 20892, USA; droberts@helix.nih.gov (DDR)

Abstract Thrombospondins are encoded in vertebrates by a family of 5 THBS genes. THBS1 is infrequently mutated in most cancers, but its expression is positively regulated by several tumor suppressor genes and negatively regulated by activated oncogenes and promoter hypermethylation. Consequently, loss of thrombospondin-1 expression is frequently lost during oncogenesis and is correlated with a poor prognosis for some cancers. Thrombospondin-1 is a secreted protein that acts in the tumor microenvironment to inhibit angiogenesis, regulate antitumor immunity, stimulate tumor cell migration, and regulate the activities of extracellular proteases and growth factors. Differential effects of thrombospondin-1 on the sensitivity of normal versus malignant cells to ischemic and genotoxic stress also regulate the responses to tumors to therapeutic radiation and chemotherapy.

Keywords thrombospondin-1, matricellular, tumor angiogenesis, metastasis, resistance to genotoxic therapy

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)TSP1
THBS
TSP
THBS-1
TSP-1
Other aliasplatelet glycoprotein G
HGNC (Hugo) THBS1
LocusID (NCBI) 7057
Atlas_Id 42548
Location 15q14  [Link to chromosome band 15q14]
Location_base_pair Starts at 39581079 and ends at 39598921 bp from pter ( according to hg19-Feb_2009)  [Mapping THBS1.png]
Local_order Telomeric to FLJ39531, centromeric to FSIP1 (fibrous sheath interacting protein 1)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CIDEC (3p25.3) / THBS1 (15q14)CWC22 (2q31.3) / THBS1 (15q14)DHCR24 (1p32.3) / THBS1 (15q14)
SEPT9 (17q25.2) / THBS1 (15q14)SGCB (4q12) / THBS1 (15q14)SUN2 (22q13.1) / THBS1 (15q14)
THBS1 (15q14) / AGBL1 (15q25.3)THBS1 (15q14) / AKAP2 (9q31.3)THBS1 (15q14) / NRG1 (8p12)
THBS1 (15q14) / PRPF8 (17p13.3)THBS1 (15q14) / THBS1 (15q14)THBS1 (15q14) / ZNF587 (19q13.43)
TSPYL2 (Xp11.22) / THBS1 (15q14)ZMIZ2 (7p13) / THBS1 (15q14)

DNA/RNA

 
  Exon/intron organization of the THBS1 gene.
Description The THBS1 gene is 16,393 bases in size and is composed of 22 exons. Exons 2-21 encode the 5729 b mRNA.
Transcription Egr-1 and Sp1 sites function in the transcription of THBS1 stimulated in most cell types by culture in the presence of serum (Shingu and Bornstein, 1994). Transcription is regulated by JUN (c_jun orAP1) in cooperation with the repressor Yin Yang-1 (YY1) and by TP53. USF2 and the aryl hydrocarbon receptor ( AHR) mediate glucose-induced THBS1 transcription (Wang et al., 2004; Dabir et al., 2008). ID1 represses THBS1 transcription (Volpert et al., 2002). The ATF1 transcription factor also down-regulates transcription of THBS1 through an ATF/cAMP-responsive element-binding protein binding site (Ghoneim et al., 2007). In contrast, MYC increases turnover of thrombospondin-1 mRNA (Janz et al., 2000). Transcription of THBS1 in some human cancers is suppressed through hypermethylation (Li et al., 1999; Yang et al., 2003). THBS1 expression is also regulated post-transcriptionally by micro-RNAs including MIR17HG (miR-17-92), MIR18A, MIR19A, MIR27B, MIR98, miR-194, MIR221, and MIRLET7I (let-7i-5p) (van Almen et al., 2011; Sundaram et al.,, 2011; Italiano et al., 2012; Yang et al., 2019; Miao et al., 2018; Farberov and Meidan 2018; Chen et al., 2017).
Pseudogene None identified.

Protein

 
  Domain organization and localization of selected ligand binding sites in THBS1. THBS1 is a homotrimer linked via disulfide bonds.
Description The THBS1 precursor contains 1170 amino acids; 129,412 Da. The mature secreted protein comprises residues 19-1170 after removal of the N-terminal signal peptide and assembles into a disulfide linked homotrimer. Secreted THBS1 is a glycoprotein with a molecular mass of 150-180 kDa that contains approximately 12 Asn-linked mono-, bi- tri-, and tetraantennary complex oligosaccharides and variable numbers of C-mannosylated Trp residues in the type 1 repeats, and O-fucosylation (Furukawa et al., 1989; Hofsteenge et al., 2001).
Expression THBS1 is expressed in many tissues during embryonic development but has limited expression in the healthy adult. THBS1 is the most abundant protein in alpha granules of platelets, but normal plasma levels are very low (typically 100-200 ng/ml). Expression in other cell types and tissues is induced by wounding, ischemia, ischemia reperfusion, during tissue remodeling, in atherosclerotic lesions, rheumatoid synovium, glomerulonephritis, in response to high glucose and fat, and in the stroma of many tumors. THBS1 expression increases with aging and in age-related conditions including type 2 diabetes and cardiovascular disease. THBS1 may also play a role in hematologic conditions such as sickle cell disease. Conversely, most but not all malignant cells in tumors exhibit loss of THBS1 expression during malignant progression (Isenberg et al., 2009). This loss is due to diminished positive regulation of the THBS1 gene by suppressor genes such as TP53 and NME1 and increased negative regulation by oncogenes including RAS and MYC. THBS1 expression is induced by TGF-beta, vitamin A, progesterone, and retinoids and suppressed by nickel, ID1, and HGF (hepatocyte growth factor).
Localisation THBS1 is secreted by many cell types in response to injury or specific cytokines, THBS1 is and present transiently in extracellular matrix but is rapidly internalized for degradation by fibroblasts and endothelial cells. THBS1 is abundant in megakaryocytes and platelets and is constitutively expressed at the dermal-epidermal boundary in skin and in subendothelial matrix of some blood vessels. However, THBS1 levels are generally low or undetectable in most healthy adult tissues.
Function THBS1 binds to extracellular matrix ligands including fibrinogen, fibronectin, some collagens, latent and active TGFB1 (transforming growth factor-beta-1), TNFAIP6 (TSG6), heparin, plasmin, CTSG (cathepsin G), ELANE (neutrophil elastase), some MMPs, tissue factor pathway inhibitor, and heparan sulfate proteoglycans (Resovi et al., 2014). THBS1 binds to cell surface receptors including CD36, CD47, some syndecans, LRP1 (LDL receptor-related protein-1) (via CALR (calreticulin)) and the integrins ITGA5/ ITGB3 (al pha-5/beta-3), THBS1 in a context-dependent and cell-specific manner stimulates or inhibits cell adhesion, proliferation, motility, and survival. THBS1 is a potent inhibitor of angiogenesis, but N-terminal proteolytic and recombinant parts of THBS1 have clear pro-angiogenic activities mediated by beta-1 integrins. In the immune system, THBS1 is a potent inhibitor of T cell and dendritic cell activation and mediates clearance of apoptotic cells by phagocytes (Soto-Pantoja et al., 2015). In the CNS, THBS1 secreted by astrocytes promotes synaptogenesis (Risher and Eroglu, 2012).
Based on studies of Thbs1 null mice, platelet THBS1 is not essential for platelet aggregation, but THBS1 null mice have impaired excisional but improved ischemic wound repair, increased retinal angiogenesis, and are hyper-responsive to several inflammatory stimuli (Soto-Pantoja et al., 2015). time stimulates pathologic production of reactive oxygen species (ROS) by targeting NOX1. Mitochondria from CD47 null mice produce less ROS. Inhibition of H2S signaling contributes to the inhibition of T cell activation by THBS1 mediated through the CD47 receptor (Miller et al., 2015).
THBS1 through interacting with CD47, plays a broader role in primary non-cancer and cancer tissue survival of genotoxic damage caused by ionizing radiation and chemotherapy (Soto-Pantoja et al., 2015; Feliz-Mosquea et al., 2018). Animals lacking either THBS1 or CD47 tolerated high-dose regional radiation with minimal soft-tissue injury or loss of bone marrow (Isenberg et al., 2008). Suppressing THBS1-CD47 signaling renders non-cancer cells and tissues resistant to radiation- and chemotherapy-mediated injury by promoting protective autophagy and enhancing anabolic metabolic repair pathways (Soto-Pantoja et al., 2012; Miller et al., 2015). Blocking the THBS1-CD47 axis also enhanced survival to lethal whole-body radiation (Soto-Pantoja et al., 2013). Conversely, interruption of THBS1-CD47 signaling increases radiation- and chemotherapy-mediated killing of cancers (Maxhimer et al., 2009; Feliz-Mosquea et al., 2018). This latter effect is mediated through activation of T and NK cell killing of tumors (Soto-Pantoja et al., 2014; Nath et al., 2019).
THBS1 is also a proximate inhibitor of stem cell self-renewal (Kaur et al., 2013). Acting via its cell surface receptor CD47, THBS1 limits the expression of important self-renewal transcription factors including POU5F1 (Oct3/4), SOX2, KLF4, and MYC in nonmalignant cells (Kaur et al., 2013). However, the ability of THBS1 to limit stem cell self-renewal is lost in cancer cells where MYC is amplified or dysregulated, and loss of CD47 expression or function consequently can suppress cancer stem cells (Kaur et al., 2013; Lee et al., 2014; Kaur and Roberts, 2016).
Homology THBS1 is a member of the thrombospondin family that also contains THBS2, THBS3, THBS4, and COMP (cartilage oligomeric matrix protein) which arose from gene duplication of a single primordial thrombospondin in insects (Adams and Lawler, 2012). The central type 1 repeats are also known as thrombospondin-repeats (TSRs) and are shared with the larger thrombospondin/properdin repeat superfamily (Adams and Tucker, 2000; Apte 2009; deLau et al., 2012). Orthologs of THBS1 are widely conserved in mammals and have also been identified in birds (Gallus gallus NP_001186382.1), amphibians (Xenopus tropicalis XP_002937245.1) and fish (Dania rerio XP_005160819.1).

Mutations

 
  Identified mutations in thrombospondin-1 in human cancers include 187 missense (green), 41 truncating nonsense (black), 3 inframe (brown), and 2 other (purple). Data is from The Cancer Genome Atlas (TCGA) using cBioPortal tools to analyze data from 10,953 patients.
 
Epigenetics Most down-regulation of THBS1 in cancers is epigenetic, resulting from promoter hypermethylation (Yang et al., 2003), altered expression of regulatory noncoding RNAs (van Almen et al., 2011; Sundaram et al., 2011; Italiano et al., 2012; Yang et al., 2019; Miao et al., 2018; Farberov and Meidan 2018; Chen et al., 2017), or altered levels of oncogenic transcription factor. Epigenetic silencing of THBS1 is associated with a poor prognosis in several cancers (Guerrero et al., 2008; Isenberg et al., 2009).
Germinal Deep exon sequencing of THBS1 from 60,706 humans identified 4 putative loss of function mutations, which was significantly below the 37.6 expected loss of function mutations for a non-essential gene of this size (Lek et al., 2016). The resulting calculated probability that THBS1 is loss intolerant (pLI =1.0) exceeds the pLI > 0.9 cut-off, which predicts a strong selective pressure against inactivation of this gene. The basis for this apparent selective pressure against loss of THBS1 in humans remains unclear. Thbs1-/- mice are viable and fertile but exhibit defects in inflammatory responses and wound repair that may compromise their viability outside a protected laboratory environment (Lawler et al., 1998; Crawford et al., 1998; Lamy et al., 2007; Qu et al., 2018). Coding polymorphisms in THBS1 associated with altered disease risk in humans include a2210g (Asn700Ser), which is associated with premature familial myocardial infarction and small for gestational age infants. This mutation alters calcium binding to THBS1 and protein stability (Carlson et al., 2008; Hannah et al., 2004). The coding polymorphism g1678a (Thr523Ser) was identified as a genetic risk factor of cerebral thrombosis in a Chinese population (Liu et al., 2004). Several noncoding SNPs in THBS1 have been associated with cancer risk as detailed below.
Somatic The frequency of somatic THBS1 mutation in human cancers is low. Somatic mutations have been identified at a frequency of 1.9% in The Cancer Genome Atlas (cbioprortal.org). A total of 233 mutations have been identified, most of which are missense or nonsense. However, the random distribution of these mutations indicates a lack of cancer-specific mutation hotspots. THBS1 is most frequently mutated in cutaneous melanomas (12%) followed by uterine cancers (7%), but rare or absent in other cancer types. The higher mutation rate of THBS1 in melanomas may simply reflect the high overall mutation burden of this malignancy.

Implicated in

Note
  
Entity Gastric carcinoma
Disease THBS1 rs1478605 T>C
Carriers of the CC genotype exhibited a decreased risk of developing gastric cancer compared to the carriers of the CT and TT genotypes [adjusted OR, 0.56; 95% confidence interval (CI), 0.39-0.79; P=0.001] (Hong et al., 2015). The CC genotype of rs1478605 was negatively associated with gastric cancer lymph node metastasis (OR, 0.41; 95% CI, 0.23-0.71; P=0.001) and was associated with a reduced risk of lymph node metastasis in male patients (OR, 0.27; 95% CI, 0.14-0.52; P<0.001). The THBS1 CT haplotype was associated with a reduced risk of developing gastric cancer (OR, 0.56; 95% CI, 0.33-0.93; P=0.02).
THBS1 rs2292305 T>C, rs1478604 A>G
Significant association was found between the homozygous CC variant of THBS1 (rs2292305 T>C) and development of highly differentiated gastric carcinoma (Lin et al., 2012). The rs1478604 A>G variant was associated with invasion and lymph node metastasis in gastric cancer. Based on logistic regression and stratification analysis, rs1478604 A>G was more strongly associated with lymph node metastasis in highly differentiated gastric cancer.
Oncogenesis The mechanism by which this polymorphism regulates carcinogenesis remains to be determined.
  
  
Entity Bladder cancer
Disease THBS1 696 C/T polymorphism (rs2664139)
Compared with the CT/TT genotypes, the CC genotype was associated with a significantly increased risk of bladder cancer (adjusted odds ratio [OR] 1.43, 95% CI 1.01-2.04) (Gu et al., 2014).
Oncogenesis The mechanism by which this polymorphism regulates carcinogenesis remains to be determined.
  
  
Entity Colorectal cancer
Note Cancer progression associated with loss of THBS1 expression in the absence of known gene mutations.
Prognosis Mutation of THBS1 is rare in most cancers, but loss of THBS1 expression due to hypermethylation, transcriptional regulation by oncogenes or tumor suppressor genes, or altered mRNA stability is commonly reported (Isenberg et al., 2009). Decreased THBS1 expression has been correlated with malignant progression and decreased survival in several cancers (Isenberg et al., 2009). To date, the strongest data is for colorectal carcinomas. Multiple independent studies have shown significant association of reduced THBS1 expression with increased invasion, microvascular densities, and poor prognosis (Miyanaga et al., 2002; Maeda et al., 2001; Isenberg et al., 2009; Teraoku et al., 2016). Increased circulating levels of THBS1 were also a favourable prognostic marker in patients with colon cancer (HR 0.43, p = 0.007) (Marisi et al., 2018).
Oncogenesis The specific role of THBS1 in colorectal oncogenesis has been studied in the APCMin/+ mouse model. Mice lacking THBS1 on the ApcMin/+ background exhibited increased intestinal adenoma formation with increased vascularization compared to Thbs1+/+: ApcMin/+ mice, consistent with the known anti-angiogenic activity of THBS1 (Gutierrez et al., 2003). Lack of THBS1 also decreased colorectal carcinogenesis in mice exposed to the carcinogen azoxymethane in combination with oral administration of dextran sulfate to induce intestinal inflammation (Lopez-Dee, et al., 2015). Again, angiogenesis was increased in the lesions formed in the Thbs1-/- mice. However, the protective role of THBS1 expression to limit colorectal carcinogenesis was lost when ApcMin/+ mice were fed a high fat Western diet, and metabolomic analysis identified systemic alterations including in eicosanoid metabolism that may mediate this effect (Soto-Pantoja et al., 2016).
  
  
Entity Various cancers
Disease Cancer progression associated with loss of THBS1 expression in the absence of known gene mutations.
Prognosis Studies have shown associations of decreased THBS1 with poor prognosis in various cancers including non-small cell lung carcinoma (Rouanne et al., 2016), pancreatic adenocarcinoma, gastric (Nakao, et al., 2011), invasive cervical carcinoma, and oral squamous cell carcinomas (Isenberg et al., 2009). Reports are mixed regarding THBS1 as a prognostic factor in breast cancers (Rice et al., 2002). Stromal THBS1 expression in breast cancer was inversely related to lymph node involvement (Ioachim et al., 2012). Evidence indicates that the failure of THBS1 to protect in breast cancer is due to an escape mechanism involving increased VEGFA expression (Fontana et al., 2005). Hypermethylation of THBS1 was associated with a poor prognosis in prostate cancers (Guerrero et al., 2008). However, THBS1 was positively correlated with invasion in hepatocellular carcinomas (Poon et al 2004). Evidence is mixed regarding the clinical significance of THBS1 expression in prostate cancer, , and urothelial cancer (Miyata and Sakai, 2013).
Oncogenesis Several transgenic mouse models support an indirect tumor suppressor activity of THBS1. Mice lacking THBS1 developed tumors earlier in a tp53 null background (Lawler et al., 2001). Loss of THBS1 expression was associated with local invasive behavior, tumor neovascularization, and metastasis. A study of UVB-induced skin carcinogenesis in wildtype versus Thbs1-/- hairless SKH1 mice found that the protective activity of the flavone apigenin was lost in the absence of THBS1 (Mirzoeva et al., 2018). The protective role of THBS1 to limit carcinogenesis in skin was associated with decreased levels of circulating inflammatory cytokines and infiltrating macrophages and neutrophils.
Conversely, transgenic mice overexpressing THBS1 in skin or mammary tissue were resistant to chemical or oncogene-driven carcinogenesis (Streit et al., 1999; Rodriguez-Manzaneque et al., 2001). In addition to inhibiting the angiogenic switch required for tumor growth and hematologic metastasis, over-expression of THBS1 in tumor cells was associated with increased M1 polarization of tumor-associated macrophages in xenograft tumors, and THBS1 treatment increased superoxide production and killing of tumor cells by macrophages in vitro (Martin-Manos et al., 2008).
  
  
Entity Familial pulmonary artery hypertension
Disease THBS1 missense mutant Asp362Asn
The THBS1 missense mutation (Asp362Asn) alters a residue in the first type 1 repeat of THBS1 (Maloney et al., 2012). The Asp362Asn THBS1 mutant had less than half of the ability of wild-type THBS1 to activate latent TGFB1. Mutant 362Asn THBS1 also lost the ability to inhibit growth of pulmonary arterial smooth muscle cells and was over three-fold less effective at inhibiting endothelial cell growth.
The mutation was found in two unrelated probands from 60 familial pulmonary arterial hypertension (PAH) kindreds but not in any healthy or chronic disease control cohorts. Several affected family members carried a mutation in BMPR2, which is known to be associated with PAH risk, and one family member with the THBS1 mutation but lacking the BMPR2 mutation was not diagnosed with PAH. Therefore, the THBS1 mutation alone may not be sufficient to cause PAH, and THBS1 was proposed to be a modifier gene for familial PAH. The frequency of other common THBS1 polymorphisms did not differ between PAH and control cohorts.
THBS1 intronic mutation (IVS8+255 G/A)
THBS1 intronic mutation (IVS8+255 G/A) was identified in a proband with familial pulmonary hypertension (Maloney et al., 2012). This mutation decreased and/or eliminated local binding of the transcription factors SP1 and MAZ in aortic smooth muscle cells. The mutation was confirmed to not alter splicing of THBS1 mRNA but is predicted to alter gene expression.
The mutation was found in multiple members of the single proband family with nine members diagnosed with PAH but absent in healthy and chronic disease control cohorts. Some of the affected family members were known to have BMPR2 mutations that are associated with PAH risk, and two family members with the THBS1 mutation but lacking the BMPR2 mutation were not diagnosed with PAH. Therefore, THBS1 was proposed to be a modifier gene. Because only one family was reported to date, the relative risk associated with this mutation remains to be determined.
  
  
Entity Post-refractive surgery chronic ocular surface inflammation
Disease THBS1 SNPs (rs1478604 T >?C, rs2228262 missense AAT> AGT, rs2292305 missense ACA> GCA)
Increased risk for developing chronic inflammation in patients undergoing refractive eye surgery or receiving corneal allografts.
Prognosis Patients with the minor alleles were more susceptible to developing chronic keratoconjunctivitis (rs1478604: odds ratio [OR], 2.5; 95% confidence interval [CI], 1.41-4.47; P = 2.5 × 10-3; rs2228262 and rs2292305: OR, 1.9; 95% CI, 1.05-3.51; P = 4.8 × 10-2. The rs1478604 A SNP was significantly associated with increased risk of corneal allograft rejection (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.02-2.45; P = 0.04) (Contreras-Ruiz et al., 2014; Winton et al., 2014
  
  
Entity Familial premature myocardial infarction, Small for gestational age (SGA) infants
Disease THBS1 variant A2210G (Ser700Asn)
The THBS1 S700N variant is a significant risk factor for familial premature myocardial infarction in both homozygous and heterozygous carriers of the variant allele (Topol et al., 2001; Zwicker et al., 2006; Stenina et al., 2004). Paternal and neonatal THBS1 A2210G was also associated with small gestational age. Maternal THBS1 A2210G was associated with reduced maternal birth weight adjusted for gestational age at delivery (P = 0.03) (Andraweera et al., 2011).
Prognosis The THBS1 S700N variant may be a general risk factor for vascular disorders throughout life.
  
  
Entity Sickle cell disease
Disease THBS1 SNPs (rs1478605 T > C and rs1478604 T > C)
The THBS1 SNPs rs1478604 (minor allele frequencies (MAF) 0.291) and rs1478605 (MAF 0.286) were negatively associated [OR 0.45 (95% CI 0.19, 1.08; p=0.069) and OR 0.33 (95% CI 0.12, 0.88; p=0.017, respectively)] with tricuspid regurgitant velocity (TRV) ≥2.5 in sickle cell disease patients (Jacob et al., 2017). Elevated TRV is a marker of pulmonary dysfunction. Of note, rs1478605 and rs1478604 are proximal to the THBS1 transcription start site and may alter THBS1 expression in patients with sickle cell disease.
  

Bibliography

The thrombospondins
Adams JC, Lawler J
Cold Spring Harb Perspect Biol 2011 Oct 1;3(10):a009712
PMID 21875984
 
The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development
Adams JC, Tucker RP
Dev Dyn 2000 Jun;218(2):280-99
PMID 10842357
 
A functional variant in the thrombospondin-1 gene and the risk of small for gestational age infants
Andraweera PH, Dekker GA, Thompson SD, North RA, McCowan LM, Roberts CT; Scope Consortium
J Thromb Haemost 2011 Nov;9(11):2221-8
PMID 21883885
 
A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms
Apte SS
J Biol Chem 2009 Nov 13;284(46):31493-7
PMID 19734141
 
Novel integrin antagonists derived from thrombospondins
Calzada MJ, Roberts DD
Curr Pharm Des 2005;11(7):849-66
PMID 15777239
 
Influences of the N700S thrombospondin-1 polymorphism on protein structure and stability
Carlson CB, Liu Y, Keck JL, Mosher DF
J Biol Chem 2008 Jul 18;283(29):20069-76
PMID 18499674
 
MicroRNA-98 interferes with thrombospondin 1 expression in peripheral B cells of patients with asthma
Chen L, Xu J, Chu X, Ju C
Biosci Rep 2017 Aug 30;37(4)
PMID 28760845
 
Polymorphism in THBS1 gene is associated with post-refractive surgery chronic ocular surface inflammation
Contreras-Ruiz L, Ryan DS, Sia RK, Bower KS, Dartt DA, Masli S
Ophthalmology 2014 Jul;121(7):1389-97
PMID 24679443
 
Thrombospondin-1 is a major activator of TGF-beta1 in vivo
Crawford SE, Stellmach V, Murphy-Ullrich JE, Ribeiro SM, Lawler J, Hynes RO, Boivin GP, Bouck N
Cell 1998 Jun 26;93(7):1159-70
PMID 9657149
 
Aryl hydrocarbon receptor is activated by glucose and regulates the thrombospondin-1 gene promoter in endothelial cells
Dabir P, Marinic TE, Krukovets I, Stenina OI
Circ Res 2008 Jun 20;102(12):1558-65
PMID 18515748
 
Fibroblast growth factor-2 and transforming growth factor-beta1 oppositely regulate miR-221 that targets thrombospondin-1 in bovine luteal endothelial cells
Farberov S, Meidan R
Biol Reprod 2018 Mar 1;98(3):366-375
PMID 29228113
 
Combination of anthracyclines and anti-CD47 therapy inhibit invasive breast cancer growth while preventing cardiac toxicity by regulation of autophagy
Feliz-Mosquea YR, Christensen AA, Wilson AS, Westwood B, Varagic J, Meléndez GC, Schwartz AL, Chen QR, Mathews Griner L, Guha R, Thomas CJ, Ferrer M, Merino MJ, Cook KL, Roberts DD, Soto-Pantoja DR
Breast Cancer Res Treat 2018 Nov;172(1):69-82
 
Human breast tumors override the antiangiogenic effect of stromal thrombospondin-1 in vivo
Fontana A, Filleur S, Guglielmi J, Frappart L, Bruno-Bossio G, Boissier S, Cabon F, Clézardin P
Int J Cancer 2005 Sep 20;116(5):686-91
PMID 15838828
 
Structural study of the sugar chains of human platelet thrombospondin
Furukawa K, Roberts DD, Endo T, Kobata A
Arch Biochem Biophys 1989 Apr;270(1):302-12
PMID 2930192
 
Activating transcription factor-1-mediated hepatocyte growth factor-induced down-regulation of thrombospondin-1 expression leads to thyroid cancer cell invasion
Ghoneim C, Soula-Rothhut M, Blanchevoye C, Martiny L, Antonicelli F, Rothhut B
J Biol Chem 2007 May 25;282(21):15490-7
PMID 17409099
 
CpG island methylation of tumor-related genes in three primary central nervous system lymphomas in immunocompetent patients
Gonzalez-Gomez P, Bello MJ, Arjona D, Alonso ME, Lomas J, Amiñoso C, de Campos JM, Sarasa JL, Gutierrez M, Rey JA
Cancer Genet Cytogenet 2003 Apr 1;142(1):21-4
PMID 12660028
 
Effects of TSP-1-696 C/T polymorphism on bladder cancer susceptibility and clinicopathologic features
Gu J, Tao J, Yang X, Li P, Yang X, Qin C, Cao Q, Cai H, Zhang Z, Wang M, Gu M, Lu Q, Yin C
Cancer Genet 2014 Jun;207(6):247-52
PMID 25150583
 
Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma
Guerrero D, Guarch R, Ojer A, Casas JM, Ropero S, Mancha A, Pesce C, Lloveras B, Garcia-Bragado F, Puras A
BJU Int 2008 Sep;102(6):747-55
PMID 18336597
 
A polymorphism in thrombospondin-1 associated with familial premature coronary artery disease alters Ca2+ binding
Hannah BL, Misenheimer TM, Pranghofer MM, Mosher DF
J Biol Chem 2004 Dec 10;279(50):51915-22
PMID 15456750
 
C-mannosylation and O-fucosylation of the thrombospondin type 1 module
Hofsteenge J, Huwiler KG, Macek B, Hess D, Lawler J, Mosher DF, Peter-Katalinic J
J Biol Chem 2001 Mar 2;276(9):6485-98
PMID 11067851
 
Association of THBS1 rs1478605 T>C in 5'-untranslated regions with the development and progression of gastric cancer
Hong BB, Chen SQ, Qi YL, Zhu JW, Lin JY
Biomed Rep 2015 Mar;3(2):207-214
PMID 26075074
 
Thrombospondin-1 expression in breast cancer: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components
Ioachim E, Damala K, Tsanou E, Briasoulis E, Papadiotis E, Mitselou A, Charhanti A, Doukas M, Lampri L, Arvanitis DL
Histol Histopathol 2012 Feb;27(2):209-16
PMID 22207555
 
Regulation of nitric oxide signalling by thrombospondin 1: implications for anti-angiogenic therapies
Isenberg JS, Martin-Manso G, Maxhimer JB, Roberts DD
Nat Rev Cancer 2009 Mar;9(3):182-94
PMID 19194382
 
The miR-17-92 cluster and its target THBS1 are differentially expressed in angiosarcomas dependent on MYC amplification
Italiano A, Thomas R, Breen M, Zhang L, Crago AM, Singer S, Khanin R, Maki RG, Mihailovic A, Hafner M, Tuschl T, Antonescu CR
Genes Chromosomes Cancer 2012 Jun;51(6):569-78
PMID 22383169
 
Thrombospondin-1 gene polymorphism is associated with estimated pulmonary artery pressure in patients with sickle cell anemia
Jacob SA, Novelli EM, Isenberg JS, Garrett ME, Chu Y, Soldano K, Ataga KI, Telen MJ, Ashley-Koch A, Gladwin MT, Zhang Y, Kato GJ
Am J Hematol 2017 Mar;92(3):E31-E34
PMID 28033687
 
Activation of the myc oncoprotein leads to increased turnover of thrombospondin-1 mRNA
Janz A, Sevignani C, Kenyon K, Ngo CV, Thomas-Tikhonenko A
Nucleic Acids Res 2000 Jun 1;28(11):2268-75
PMID 10871348
 
Divergent modulation of normal and neoplastic stem cells by thrombospondin-1 and CD47 signaling
Kaur S, Roberts DD
Int J Biochem Cell Biol 2016 Dec;81(Pt A):184-194
PMID 27163531
 
Thrombospondin-1 signaling through CD47 inhibits self-renewal by regulating c-Myc and other stem cell transcription factors
Kaur S, Soto-Pantoja DR, Stein EV, Liu C, Elkahloun AG, Pendrak ML, Nicolae A, Singh SP, Nie Z, Levens D, Isenberg JS, Roberts DD
Sci Rep 2013;3:1673
PMID 23591719
 
Thrombospondin-1 gene expression affects survival and tumor spectrum of p53-deficient mice
Lawler J, Miao WM, Duquette M, Bouck N, Bronson RT, Hynes RO
Am J Pathol 2001 Nov;159(5):1949-56
PMID 11696456
 
Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia
Lawler J, Sunday M, Thibert V, Duquette M, George EL, Rayburn H, Hynes RO
J Clin Invest 1998 Mar 1;101(5):982-92
PMID 9486968
 
Blockade of CD47-mediated cathepsin S/protease-activated receptor 2 signaling provides a therapeutic target for hepatocellular carcinoma
Lee TK, Cheung VC, Lu P, Lau EY, Ma S, Tang KH, Tong M, Lo J, Ng IO
Hepatology 2014 Jul;60(1):179-91
PMID 24523067
 
Analysis of protein-coding genetic variation in 60,706 humans
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG; Exome Aggregation Consortium
Nature 2016 Aug 18;536(7616):285-91
PMID 27535533
 
Methylation and silencing of the Thrombospondin-1 promoter in human cancer
Li Q, Ahuja N, Burger PC, Issa JP
Oncogene 1999 May 27;18(21):3284-9
PMID 10359534
 
Polymorphism of THBS1 rs1478604 A>G in 5-untranslated region is associated with lymph node metastasis of gastric cancer in a Southeast Chinese population
Lin XD, Chen SQ, Qi YL, Zhu JW, Tang Y, Lin JY
DNA Cell Biol 2012 Apr;31(4):511-9
PMID 22011138
 
Thrombospondin-1 expression in relation to p53 status and VEGF expression in human breast cancers
Linderholm B, Karlsson E, Klaar S, Lindahl T, Borg AL, Elmberger G, Bergh J
Eur J Cancer 2004 Nov;40(16):2417-23
PMID 15519514
 
[Correlation of thrombospondin-1 G1678A polymorphism to stroke: a study in Chinese population]
Liu XN, Song L, Wang DW, Liao YH, Ma AQ, Zhu ZM, Zhao BR, Zhao JZ, Hui RT
Zhonghua Yi Xue Za Zhi 2004 Dec 2;84(23):1959-62
PMID 15730804
 
Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis
Lopez-Dee ZP, Chittur SV, Patel H, Chinikaylo A, Lippert B, Patel B, Lawler J, Gutierrez LS
PLoS One 2015 Oct 13;10(10):e0139918
PMID 26461935
 
Expression of thrombospondin-1 inversely correlated with tumor vascularity and hematogenous metastasis in colon cancer
Maeda K, Nishiguchi Y, Kang SM, Yashiro M, Onoda N, Sawada T, Ishikawa T, Hirakawa K
Oncol Rep 2001 Jul-Aug;8(4):763-6
PMID 11410779
 
Loss-of-function thrombospondin-1 mutations in familial pulmonary hypertension
Maloney JP, Stearman RS, Bull TM, Calabrese DW, Tripp-Addison ML, Wick MJ, Broeckel U, Robbins IM, Wheeler LA, Cogan JD, Loyd JE
Am J Physiol Lung Cell Mol Physiol 2012 Mar 15;302(6):L541-54
PMID 22198906
 
IL-8 and thrombospondin-1 as prognostic markers in patients with metastatic colorectal cancer receiving bevacizumab
Marisi G, Scarpi E, Passardi A, Nanni O, Pagan F, Valgiusti M, Casadei Gardini A, Neri LM, Frassineti GL, Amadori D, Ulivi P
Cancer Manag Res 2018 Nov 14;10:5659-5666
PMID 30532588
 
Thrombospondin 1 promotes tumor macrophage recruitment and enhances tumor cell cytotoxicity of differentiated U937 cells
Martin-Manso G, Galli S, Ridnour LA, Tsokos M, Wink DA, Roberts DD
Cancer Res 2008 Sep 1;68(17):7090-9
PMID 18757424
 
Radioprotection in normal tissue and delayed tumor growth by blockade of CD47 signaling
Maxhimer JB, Soto-Pantoja DR, Ridnour LA, Shih HB, Degraff WG, Tsokos M, Wink DA, Isenberg JS, Roberts DD
Sci Transl Med 2009 Oct 21;1(3):3ra7
PMID 20161613
 
Thrombin-reduced miR-27b attenuates platelet angiogenic activities in vitro via enhancing platelet synthesis of anti-angiogenic thrombospondin-1
Miao X, Rahman MF, Jiang L, Min Y, Tan S, Xie H, Lee L, Wang M, Malmström RE, Lui WO, Li N
J Thromb Haemost 2018 Apr;16(4):791-801
PMID 29442415
 
Thrombospondin-1 is a CD47-dependent endogenous inhibitor of hydrogen sulfide signaling in T cell activation
Miller TW, Kaur S, Ivins-O'Keefe K, Roberts DD
Matrix Biol 2013 Aug 8;32(6):316-24
PMID 23499828
 
CD47 Receptor Globally Regulates Metabolic Pathways That Control Resistance to Ionizing Radiation
Miller TW, Soto-Pantoja DR, Schwartz AL, Sipes JM, DeGraff WG, Ridnour LA, Wink DA, Roberts DD
J Biol Chem 2015 Oct 9;290(41):24858-74
 
Apigenin Inhibits UVB-Induced Skin Carcinogenesis: The Role of Thrombospondin-1 as an Anti-Inflammatory Factor
Mirzoeva S, Tong X, Bridgeman BB, Plebanek MP, Volpert OV
Neoplasia 2018 Sep;20(9):930-942
PMID 30118999
 
Expression and role of thrombospondin-1 in colorectal cancer
Miyanaga K, Kato Y, Nakamura T, Matsumura M, Amaya H, Horiuchi T, Chiba Y, Tanaka K
Anticancer Res 2002 Nov-Dec;22(6C):3941-8
PMID 12553016
 
Thrombospondin-1 in urological cancer: pathological role, clinical significance, and therapeutic prospects
Miyata Y, Sakai H
Int J Mol Sci 2013 Jun 7;14(6):12249-72
PMID 23749112
 
Thrombospondin-1 regulation of latent TGF-β activation: A therapeutic target for fibrotic disease
Murphy-Ullrich JE, Suto MJ
Matrix Biol 2018 Aug;68-69:28-43
PMID 29288716
 
Expression of thrombospondin-1 and Ski are prognostic factors in advanced gastric cancer
Nakao T, Kurita N, Komatsu M, Yoshikawa K, Iwata T, Utsunomiya T, Shimada M
Int J Clin Oncol 2011 Apr;16(2):145-52
PMID 21107877
 
Natural Killer Cell Recruitment and Activation Are Regulated by CD47 Expression in the Tumor Microenvironment
Nath PR, Pal-Nath D, Mandal A, Cam MC, Schwartz AL, Roberts DD
Cancer Immunol Res 2019 Sep;7(9):1547-1561
PMID 31362997
 
Vascular TSP1-CD47 signaling promotes sickle cell-associated arterial vasculopathy and pulmonary hypertension in mice
Novelli EM, Little-Ihrig L, Knupp HE, Rogers NM, Yao M, Baust JJ, Meijles D, St Croix CM, Ross MA, Pagano PJ, DeVallance ER, Miles G, Potoka KP, Isenberg JS, Gladwin MT
Am J Physiol Lung Cell Mol Physiol 2019 Jun 1;316(6):L1150-L1164
PMID 30892078
 
Clinical significance of thrombospondin 1 expression in hepatocellular carcinoma
Poon RT, Chung KK, Cheung ST, Lau CP, Tong SW, Leung KL, Yu WC, Tuszynski GP, Fan ST
Clin Cancer Res 2004 Jun 15;10(12 Pt 1):4150-7
PMID 15217952
 
Thrombospondin-1 protects against pathogen-induced lung injury by limiting extracellular matrix proteolysis
Qu Y, Olonisakin T, Bain W, Zupetic J, Brown R, Hulver M, Xiong Z, Tejero J, Shanks RM, Bomberger JM, Cooper VS, Zegans ME, Ryu H, Han J, Pilewski J, Ray A, Cheng Z, Ray P, Lee JS
JCI Insight 2018 Feb 8;3(3)
PMID 29415890
 
Current understanding of the thrombospondin-1 interactome
Resovi A, Pinessi D, Chiorino G, Taraboletti G
Matrix Biol 2014 Jul;37:83-91
PMID 24476925
 
Thrombospondin 1 protein expression relates to good prognostic indices in ductal carcinoma in situ of the breast
Rice AJ, Steward MA, Quinn CM
J Clin Pathol 2002 Dec;55(12):921-5
PMID 12461058
 
Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor
Rodriguez-Manzaneque JC, Lane TF, Ortega MA, Hynes RO, Lawler J, Iruela-Arispe ML
Proc Natl Acad Sci U S A 2001 Oct 23;98(22):12485-90
PMID 11606713
 
Thrombospondin-1 and CD47 regulation of cardiac, pulmonary and vascular responses in health and disease
Rogers NM, Sharifi-Sanjani M, Csányi G, Pagano PJ, Isenberg JS
Matrix Biol 2014 Jul;37:92-101
PMID 24418252
 
Osteopontin and thrombospondin-1 play opposite roles in promoting tumor aggressiveness of primary resected non-small cell lung cancer
Rouanne M, Adam J, Goubar A, Robin A, Ohana C, Louvet E, Cormier J, Mercier O, Dorfmüller P, Fattal S, de Montpreville VT, Lebret T, Dartevelle P, Fadel E, Besse B, Olaussen KA, Auclair C, Soria JC
BMC Cancer 2016 Jul 15;16:483
PMID 27422280
 
Overlapping Egr-1 and Sp1 sites function in the regulation of transcription of the mouse thrombospondin 1 gene
Shingu T, Bornstein P
J Biol Chem 1994 Dec 23;269(51):32551-7
PMID 7798257
 
Dietary fat overcomes the protective activity of thrombospondin-1 signaling in the Apc(Min/+) model of colon cancer
Soto-Pantoja DR, Sipes JM, Martin-Manso G, Westwood B, Morris NL, Ghosh A, Emenaker NJ, Roberts DD
Oncogenesis 2016 May 30;5(5):e230
PMID 27239962
 
Coronary artery disease and the thrombospondin single nucleotide polymorphisms
Stenina OI, Byzova TV, Adams JC, McCarthy JJ, Topol EJ, Plow EF
Int J Biochem Cell Biol 2004 Jun;36(6):1013-30
PMID 15094117
 
Overexpression of thrombospondin-1 decreases angiogenesis and inhibits the growth of human cutaneous squamous cell carcinomas
Streit M, Velasco P, Brown LF, Skobe M, Richard L, Riccardi L, Lawler J, Detmar M
Am J Pathol 1999 Aug;155(2):441-52
PMID 10433937
 
p53-responsive miR-194 inhibits thrombospondin-1 and promotes angiogenesis in colon cancers
Sundaram P, Hultine S, Smith LM, Dews M, Fox JL, Biyashev D, Schelter JM, Huang Q, Cleary MA, Volpert OV, Thomas-Tikhonenko A
Cancer Res 2011 Dec 15;71(24):7490-501
PMID 22028325
 
Role of thrombospondin-1 expression in colorectal liver metastasis and its molecular mechanism
Teraoku H, Morine Y, Ikemoto T, Saito Y, Yamada S, Yoshikawa M, Takasu C, Higashijima J, Imura S, Shimada M
J Hepatobiliary Pancreat Sci 2016 Sep;23(9):565-73
PMID 27404020
 
Single nucleotide polymorphisms in multiple novel thrombospondin genes may be associated with familial premature myocardial infarction
Topol EJ, McCarthy J, Gabriel S, Moliterno DJ, Rogers WJ, Newby LK, Freedman M, Metivier J, Cannata R, O'Donnell CJ, Kottke-Marchant K, Murugesan G, Plow EF, Stenina O, Daley GQ
Circulation 2001 Nov 27;104(22):2641-4
PMID 11723011
 
Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1
Volpert OV, Pili R, Sikder HA, Nelius T, Zaichuk T, Morris C, Shiflett CB, Devlin MK, Conant K, Alani RM
Cancer Cell 2002 Dec;2(6):473-83
PMID 12498716
 
Thrombospondins and synaptogenesis
Wang B, Guo W, Huang Y
Neural Regen Res 2012 Aug 5;7(22):1737-43
PMID 25624796
 
Glucose up-regulates thrombospondin 1 gene transcription and transforming growth factor-beta activity through antagonism of cGMP-dependent protein kinase repression via upstream stimulatory factor 2
Wang S, Skorczewski J, Feng X, Mei L, Murphy-Ullrich JE
J Biol Chem 2004 Aug 13;279(33):34311-22
PMID 15184388
 
Thrombospondin-1 polymorphisms influence risk of corneal allograft rejection
Winton HL, Bidwell JL, Armitage WJ
Invest Ophthalmol Vis Sci 2014 Apr 7;55(4):2115-20
PMID 24618326
 
Structure and chromosomal localization of the human thrombospondin gene
Wolf FW, Eddy RL, Shows TB, Dixit VM
Genomics 1990 Apr;6(4):685-91
PMID 2341158
 
HDAC6 Suppresses Let-7i-5p to Elicit TSP1/CD47-Mediated Anti-Tumorigenesis and Phagocytosis of Hepatocellular Carcinoma
Yang HD, Kim HS, Kim SY, Na MJ, Yang G, Eun JW, Wang HJ, Cheong JY, Park WS, Nam SW
Hepatology 2019 Oct;70(4):1262-1279
PMID 30991448
 
Methylation-associated silencing of the thrombospondin-1 gene in human neuroblastoma
Yang QW, Liu S, Tian Y, Salwen HR, Chlenski A, Weinstein J, Cohn SL
Cancer Res 2003 Oct 1;63(19):6299-310
PMID 14559817
 
The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size
Zwicker JI, Peyvandi F, Palla R, Lombardi R, Canciani MT, Cairo A, Ardissino D, Bernardinelli L, Bauer KA, Lawler J, Mannucci P
Blood 2006 Aug 15;108(4):1280-3
PMID 16684956
 
The R-spondin protein family
de Lau WB, Snel B, Clevers HC
Genome Biol 2012;13(3):242
PMID 22439850
 
MicroRNA-18 and microRNA-19 regulate CTGF and TSP-1 expression in age-related heart failure
van Almen GC, Verhesen W, van Leeuwen RE, van de Vrie M, Eurlings C, Schellings MW, Swinnen M, Cleutjens JP, van Zandvoort MA, Heymans S, Schroen B
Aging Cell 2011 Oct;10(5):769-79
PMID 21501375
 

Citation

This paper should be referenced as such :
Isenberg, JS; Roberts, DD
THBS1 (thrombospondin-1);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/THBS1ID42548ch15q15.html
History of this paper:
Roberts, DD. THBS1 (thrombospondin-1). Atlas Genet Cytogenet Oncol Haematol. 2005;9(3):231-233.
http://documents.irevues.inist.fr/bitstream/handle/2042/38213/05-2005-THBS1ID42548ch15q15.pdf


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 3 ]
  t(1;15)(p32;q14) DHCR24/THBS1
t(2;15)(p23;q14) THBS1/ALK
t(15;15)(q14;q25) THBS1/AGBL1


External links

Nomenclature
HGNC (Hugo)THBS1   11785
Cards
AtlasTHBS1ID42548ch15q15
Entrez_Gene (NCBI)THBS1  7057  thrombospondin 1
AliasesTHBS; THBS-1; TSP; TSP-1; 
TSP1
GeneCards (Weizmann)THBS1
Ensembl hg19 (Hinxton)ENSG00000137801 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000137801 [Gene_View]  ENSG00000137801 [Sequence]  chr15:39581079-39598921 [Contig_View]  THBS1 [Vega]
ICGC DataPortalENSG00000137801
TCGA cBioPortalTHBS1
AceView (NCBI)THBS1
Genatlas (Paris)THBS1
WikiGenes7057
SOURCE (Princeton)THBS1
Genetics Home Reference (NIH)THBS1
Genomic and cartography
GoldenPath hg38 (UCSC)THBS1  -     chr15:39581079-39598921 +  15q14   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)THBS1  -     15q14   [Description]    (hg19-Feb_2009)
GoldenPathTHBS1 - 15q14 [CytoView hg19]  THBS1 - 15q14 [CytoView hg38]
ImmunoBaseENSG00000137801
Mapping of homologs : NCBITHBS1 [Mapview hg19]  THBS1 [Mapview hg38]
OMIM188060   
Gene and transcription
Genbank (Entrez)AB209912 AI147670 AI168683 AI290070 AK291639
RefSeq transcript (Entrez)NM_003246
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)THBS1
Cluster EST : UnigeneHs.732539 [ NCBI ]
CGAP (NCI)Hs.732539
Alternative Splicing GalleryENSG00000137801
Gene ExpressionTHBS1 [ NCBI-GEO ]   THBS1 [ EBI - ARRAY_EXPRESS ]   THBS1 [ SEEK ]   THBS1 [ MEM ]
Gene Expression Viewer (FireBrowse)THBS1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7057
GTEX Portal (Tissue expression)THBS1
Human Protein AtlasENSG00000137801-THBS1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP07996   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP07996  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP07996
Splice isoforms : SwissVarP07996
PhosPhoSitePlusP07996
Domaine pattern : Prosite (Expaxy)EGF_2 (PS01186)    EGF_3 (PS50026)    TSP1 (PS50092)    TSP3 (PS51234)    TSP_CTER (PS51236)    VWFC_1 (PS01208)    VWFC_2 (PS50184)   
Domains : Interpro (EBI)ConA-like_dom_sf    EGF-like_Ca-bd_dom    EGF-like_CS    EGF-like_dom    Laminin_G    Thrombospondin    Thrombospondin-1    Thrombospondin_3-like_rpt    Thrombospondin_3_rpt    Thrombospondin_C    TSP1_rpt    TSP1_rpt_sf    TSP_type-3_rpt    VWF_dom   
Domain families : Pfam (Sanger)TSP_1 (PF00090)    TSP_3 (PF02412)    TSP_C (PF05735)    VWC (PF00093)   
Domain families : Pfam (NCBI)pfam00090    pfam02412    pfam05735    pfam00093   
Domain families : Smart (EMBL)EGF (SM00181)  EGF_CA (SM00179)  TSP1 (SM00209)  TSPN (SM00210)  VWC (SM00214)  
Conserved Domain (NCBI)THBS1
DMDM Disease mutations7057
Blocks (Seattle)THBS1
PDB (RSDB)1LSL    1UX6    1Z78    1ZA4    2ERF    2ES3    2OUH    2OUJ    3R6B    5FOE   
PDB Europe1LSL    1UX6    1Z78    1ZA4    2ERF    2ES3    2OUH    2OUJ    3R6B    5FOE   
PDB (PDBSum)1LSL    1UX6    1Z78    1ZA4    2ERF    2ES3    2OUH    2OUJ    3R6B    5FOE   
PDB (IMB)1LSL    1UX6    1Z78    1ZA4    2ERF    2ES3    2OUH    2OUJ    3R6B    5FOE   
Structural Biology KnowledgeBase1LSL    1UX6    1Z78    1ZA4    2ERF    2ES3    2OUH    2OUJ    3R6B    5FOE   
SCOP (Structural Classification of Proteins)1LSL    1UX6    1Z78    1ZA4    2ERF    2ES3    2OUH    2OUJ    3R6B    5FOE   
CATH (Classification of proteins structures)1LSL    1UX6    1Z78    1ZA4    2ERF    2ES3    2OUH    2OUJ    3R6B    5FOE   
SuperfamilyP07996
Human Protein Atlas [tissue]ENSG00000137801-THBS1 [tissue]
Peptide AtlasP07996
HPRD01765
IPIIPI00296099   IPI00909182   IPI00796249   
Protein Interaction databases
DIP (DOE-UCLA)P07996
IntAct (EBI)P07996
FunCoupENSG00000137801
BioGRIDTHBS1
STRING (EMBL)THBS1
ZODIACTHBS1
Ontologies - Pathways
QuickGOP07996
Ontology : AmiGOactivation of MAPK activity  response to hypoxia  phosphatidylserine binding  negative regulation of endothelial cell proliferation  negative regulation of endothelial cell proliferation  negative regulation of cell-matrix adhesion  fibronectin binding  sprouting angiogenesis  chronic inflammatory response  platelet degranulation  negative regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II  negative regulation of dendritic cell antigen processing and presentation  integrin binding  extracellular matrix structural constituent  extracellular matrix structural constituent  extracellular matrix structural constituent  calcium ion binding  protein binding  protein binding  extracellular region  extracellular region  fibrinogen complex  extracellular space  extracellular space  endoplasmic reticulum  endoplasmic reticulum lumen  inflammatory response  immune response  response to unfolded protein  cell cycle arrest  cell adhesion  heparin binding  positive regulation of cell proliferation  response to mechanical stimulus  response to glucose  external side of plasma membrane  cell surface  positive regulation of endothelial cell migration  negative regulation of endothelial cell migration  negative regulation of plasma membrane long-chain fatty acid transport  negative regulation of nitric oxide mediated signal transduction  negative regulation of cGMP-mediated signaling  negative regulation of plasminogen activation  positive regulation of macrophage chemotaxis  positive regulation of fibroblast migration  cell migration  negative regulation of angiogenesis  negative regulation of angiogenesis  negative regulation of angiogenesis  sarcoplasmic reticulum  fibroblast growth factor binding  peptide cross-linking  secretory granule  low-density lipoprotein particle binding  positive regulation of blood coagulation  extracellular matrix organization  positive regulation of cell migration  positive regulation of cell migration  positive regulation of transforming growth factor beta receptor signaling pathway  extracellular matrix  platelet alpha granule  platelet alpha granule lumen  response to magnesium ion  response to progesterone  negative regulation of interleukin-12 production  positive regulation of transforming growth factor beta1 production  response to testosterone  cellular response to heat  response to endoplasmic reticulum stress  negative regulation of fibroblast growth factor receptor signaling pathway  positive regulation of phosphorylation  response to drug  positive regulation of tumor necrosis factor biosynthetic process  identical protein binding  positive regulation of macrophage activation  negative regulation of apoptotic process  negative regulation of cysteine-type endopeptidase activity involved in apoptotic process  laminin binding  proteoglycan binding  positive regulation of blood vessel endothelial cell migration  negative regulation of blood vessel endothelial cell migration  engulfment of apoptotic cell  regulation of megakaryocyte differentiation  positive regulation of translation  positive regulation of angiogenesis  behavioral response to pain  positive regulation of smooth muscle cell proliferation  transforming growth factor beta binding  transforming growth factor beta binding  positive regulation of chemotaxis  response to calcium ion  negative regulation of focal adhesion assembly  positive regulation of protein kinase B signaling  negative regulation of fibrinolysis  collagen-containing extracellular matrix  collagen-containing extracellular matrix  collagen-containing extracellular matrix  collagen-containing extracellular matrix  collagen-containing extracellular matrix  fibrinogen binding  collagen V binding  extracellular exosome  cellular response to tumor necrosis factor  cellular response to growth factor stimulus  negative regulation of cell migration involved in sprouting angiogenesis  positive regulation of extrinsic apoptotic signaling pathway via death domain receptors  negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis  negative regulation of sprouting angiogenesis  positive regulation of endothelial cell apoptotic process  positive regulation of reactive oxygen species metabolic process  negative regulation of endothelial cell chemotaxis  negative regulation of extrinsic apoptotic signaling pathway  
Ontology : EGO-EBIactivation of MAPK activity  response to hypoxia  phosphatidylserine binding  negative regulation of endothelial cell proliferation  negative regulation of endothelial cell proliferation  negative regulation of cell-matrix adhesion  fibronectin binding  sprouting angiogenesis  chronic inflammatory response  platelet degranulation  negative regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II  negative regulation of dendritic cell antigen processing and presentation  integrin binding  extracellular matrix structural constituent  extracellular matrix structural constituent  extracellular matrix structural constituent  calcium ion binding  protein binding  protein binding  extracellular region  extracellular region  fibrinogen complex  extracellular space  extracellular space  endoplasmic reticulum  endoplasmic reticulum lumen  inflammatory response  immune response  response to unfolded protein  cell cycle arrest  cell adhesion  heparin binding  positive regulation of cell proliferation  response to mechanical stimulus  response to glucose  external side of plasma membrane  cell surface  positive regulation of endothelial cell migration  negative regulation of endothelial cell migration  negative regulation of plasma membrane long-chain fatty acid transport  negative regulation of nitric oxide mediated signal transduction  negative regulation of cGMP-mediated signaling  negative regulation of plasminogen activation  positive regulation of macrophage chemotaxis  positive regulation of fibroblast migration  cell migration  negative regulation of angiogenesis  negative regulation of angiogenesis  negative regulation of angiogenesis  sarcoplasmic reticulum  fibroblast growth factor binding  peptide cross-linking  secretory granule  low-density lipoprotein particle binding  positive regulation of blood coagulation  extracellular matrix organization  positive regulation of cell migration  positive regulation of cell migration  positive regulation of transforming growth factor beta receptor signaling pathway  extracellular matrix  platelet alpha granule  platelet alpha granule lumen  response to magnesium ion  response to progesterone  negative regulation of interleukin-12 production  positive regulation of transforming growth factor beta1 production  response to testosterone  cellular response to heat  response to endoplasmic reticulum stress  negative regulation of fibroblast growth factor receptor signaling pathway  positive regulation of phosphorylation  response to drug  positive regulation of tumor necrosis factor biosynthetic process  identical protein binding  positive regulation of macrophage activation  negative regulation of apoptotic process  negative regulation of cysteine-type endopeptidase activity involved in apoptotic process  laminin binding  proteoglycan binding  positive regulation of blood vessel endothelial cell migration  negative regulation of blood vessel endothelial cell migration  engulfment of apoptotic cell  regulation of megakaryocyte differentiation  positive regulation of translation  positive regulation of angiogenesis  behavioral response to pain  positive regulation of smooth muscle cell proliferation  transforming growth factor beta binding  transforming growth factor beta binding  positive regulation of chemotaxis  response to calcium ion  negative regulation of focal adhesion assembly  positive regulation of protein kinase B signaling  negative regulation of fibrinolysis  collagen-containing extracellular matrix  collagen-containing extracellular matrix  collagen-containing extracellular matrix  collagen-containing extracellular matrix  collagen-containing extracellular matrix  fibrinogen binding  collagen V binding  extracellular exosome  cellular response to tumor necrosis factor  cellular response to growth factor stimulus  negative regulation of cell migration involved in sprouting angiogenesis  positive regulation of extrinsic apoptotic signaling pathway via death domain receptors  negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis  negative regulation of sprouting angiogenesis  positive regulation of endothelial cell apoptotic process  positive regulation of reactive oxygen species metabolic process  negative regulation of endothelial cell chemotaxis  negative regulation of extrinsic apoptotic signaling pathway  
Pathways : KEGGRap1 signaling pathway    p53 signaling pathway    Phagosome    PI3K-Akt signaling pathway    TGF-beta signaling pathway    Focal adhesion    ECM-receptor interaction    Malaria    Proteoglycans in cancer    MicroRNAs in cancer    Bladder cancer   
REACTOMEP07996 [protein]
REACTOME PathwaysR-HSA-8936459 [pathway]   
NDEx NetworkTHBS1
Atlas of Cancer Signalling NetworkTHBS1
Wikipedia pathwaysTHBS1
Orthology - Evolution
OrthoDB7057
GeneTree (enSembl)ENSG00000137801
Phylogenetic Trees/Animal Genes : TreeFamTHBS1
HOGENOMP07996
Homologs : HomoloGeneTHBS1
Homology/Alignments : Family Browser (UCSC)THBS1
Gene fusions - Rearrangements
Fusion : MitelmanDHCR24/THBS1 [1p32.3/15q14]  [t(1;15)(p32;q14)]  
Fusion : MitelmanTHBS1/AGBL1 [15q14/15q25.3]  [t(15;15)(q14;q25)]  
Fusion PortalDHCR24 1p32.3 THBS1 15q14 HNSC
Fusion PortalTHBS1 15q14 AGBL1 15q25.3 HNSC
Fusion PortalTHBS1 15q14 NRG1 8p12 HNSC
Fusion : FusionGDB33550    37969    37970    37971    37972    37973    37974    39894    42944    7238    9032    9866   
Fusion : Fusion_HubACTB--THBS1    CIDEC--THBS1    CISD2--THBS1    COL12A1--THBS1    COL1A1--THBS1    CTSB--THBS1    CWC22--THBS1    DHCR24--THBS1    FAF1--THBS1    FAM120AOS--THBS1    FN1--THBS1    PKM--THBS1    SEPT9--THBS1    SGCB--THBS1    SORCS3--THBS1   
SUN2--THBS1    TACC1--THBS1    TAF1D--THBS1    THBS1--ACTG2    THBS1--AGBL1    THBS1--AKAP2    THBS1--AMOTL1    THBS1--ARL6IP4    THBS1--BUB3    THBS1--CALD1    THBS1--COL1A2    THBS1--COL5A1    THBS1--FAM227B    THBS1--FN1    THBS1--FSIP1   
THBS1--HDAC3    THBS1--HNRNPH1    THBS1--ITGB1    THBS1--METTL10    THBS1--NFYC    THBS1--NRG1    THBS1--OAZ1    THBS1--PKM    THBS1--PRPF8    THBS1--RECK    THBS1--SEMA6C    THBS1--TGFBI    THBS1--THBS1    THBS1--TIAL1    THBS1--TNNT2   
THBS1--TSC22D1    THBS1--ZNF587    TSPYL2--THBS1    UBC--THBS1    ZMIZ2--THBS1   
Fusion : QuiverTHBS1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTHBS1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)THBS1
dbVarTHBS1
ClinVarTHBS1
1000_GenomesTHBS1 
Exome Variant ServerTHBS1
ExAC (Exome Aggregation Consortium)ENSG00000137801
GNOMAD BrowserENSG00000137801
Varsome BrowserTHBS1
Genetic variants : HAPMAP7057
Genomic Variants (DGV)THBS1 [DGVbeta]
DECIPHERTHBS1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTHBS1 
Mutations
ICGC Data PortalTHBS1 
TCGA Data PortalTHBS1 
Broad Tumor PortalTHBS1
OASIS PortalTHBS1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTHBS1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DTHBS1
Mutations and Diseases : HGMDTHBS1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch THBS1
DgiDB (Drug Gene Interaction Database)THBS1
DoCM (Curated mutations)THBS1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)THBS1 (select a term)
intoGenTHBS1
NCG5 (London)THBS1
Cancer3DTHBS1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM188060   
Orphanet
DisGeNETTHBS1
MedgenTHBS1
Genetic Testing Registry THBS1
NextProtP07996 [Medical]
TSGene7057
GENETestsTHBS1
Target ValidationTHBS1
Huge Navigator THBS1 [HugePedia]
snp3D : Map Gene to Disease7057
BioCentury BCIQTHBS1
ClinGenTHBS1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7057
Chemical/Pharm GKB GenePA36497
Clinical trialTHBS1
Miscellaneous
canSAR (ICR)THBS1 (select the gene name)
DataMed IndexTHBS1
Other databasehttp://exac.broadinstitute.org/gene/ENSG00000137801
Probes
Litterature
PubMed478 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTHBS1
EVEXTHBS1
GoPubMedTHBS1
iHOPTHBS1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Jan 14 11:20:31 CET 2020

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.