| Description | The TSP1 precursor contains 1170 amino acids; 129,412 Da. The mature secreted protein comprises residues 19-1170 and assembles into a disulfide linked homotrimer. Secreted TSP1 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. |
| Expression | TSP1 is expressed in many tissues during embryonic development but has limited expression in the healthy adult. TSP1 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 is induced by wounding, during tissue remodeling, in atherosclerotic lesions, rheumatoid synovium, glomerulonephritis, and in stroma of many tumors. Conversely, most but not all malignant cells in tumors exhibit loss of TSP1 expression during malignant progression. This loss is due to diminished positive regulation of the THBS1 gene by suppressor genes such as p53 and NM23 and increased negative regulation by oncogenes including Ras and Myc. TSP1 expression is induced by TGF-beta, vitamin A, progesterone, and retinoids and suppressed by nickel, Id1, and hepatocyte growth factor. TSP1 expression in the epidermis of skin is suppressed following exposure to UV irradiation. |
| Localisation | TSP1 is secreted and present transiently in extracellular matrix but is rapidly internalized for degradation by fibroblasts and endothelial cells. TSP1 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. |
| Function | TSP1 binds to extracellular matrix ligands including fibrinogen, fibronectin, some collagens, latent and active transforming growth factor-beta-1, TSG6, heparin, plasmin, cathepsin G, neutrophil elastase, some MMPs, tissue factor pathway inhibitor, and heparan sulfate proteoglycans. TSP1 binds to cell surface receptors including CD36, CD47, some syndecans, LDL receptor-related protein-1 (via calreticulin) and the integrins alpha-V/beta-3, alpha-3/beta-1, alpha-4/beta-1, and alpha-6/beta-1. TSP1 is a slow tight inhibitor of plasmin, cathepsin G, and neutrophil elastase. TSP1 directly binds and activates latent TGF-beta-1.
TSP1 in a context-dependent and cell-specific manner stimulates or inhibits cell adhesion, proliferation, motility, and survival. TSP1 is a potent inhibitor of angiogenesis, but N-terminal proteolytic and recombinant parts of TSP1 have clear pro-angiogenic activities mediated by beta-1 integrins. In the immune system, TSP1 is a potent inhibitor of T cell and dendritic cell activation and mediates clearance of apoptotic cells by phagocytes. In the CNS, TSP1 secreted by astrocytes promotes synaptogenesis.
Based on studies of TSP1 null mice, platelet TSP1 is not essential for platelet aggregation, but TSP1 null mice have impaired wound repair, increased retinal angiogenesis, and are hyper-responsive to several inflammatory stimuli. |
| Homology | TSP1 is a member of the thrombospondin family that also contains thrombospondin-2, -3, -4, and cartilage oligomeric matrix protein (COMP). The central type 1 repeats are also known as thrombospondin-repeats and are shared with the larger thrombospondin/properdin repeat superfamily. |
| Nomenclature | | Hugo | THBS1 |
| GDB | THBS1 |
| Entrez_Gene | THBS1 7057 thrombospondin 1 |
| Cards |
|---|
| Atlas | THBS1ID42548ch15q15 |
| GeneCards | THBS1 |
| Ensembl | THBS1 [Search_View] ENSG00000137801 [Gene_View] |
| Genatlas | THBS1 |
| GeneLynx | THBS1 |
| eGenome | THBS1 |
| euGene | 7057 |
| Genomic and cartography |
|---|
| GoldenPath | THBS1 - 15q15 chr15:37660572-37676959 + 15q15 (hg18-Mar_2006) |
| Ensembl | THBS1 - 15q15 [CytoView] |
| NCBI | Mapview |
| OMIM | Disease map [OMIM] |
| HomoloGene | THBS1 |
| Gene and transcription | | Genbank | AB209912 [ ENTREZ ] |
| Genbank | AI290070 [ ENTREZ ] |
| Genbank | AK291639 [ ENTREZ ] |
| Genbank | AU117102 [ ENTREZ ] |
| Genbank | AU279999 [ ENTREZ ] |
| RefSeq | NM_003246 [ SRS ] NM_003246 [ ENTREZ ] |
| RefSeq | AC_000058 [ SRS ] AC_000058 [ ENTREZ ] |
| RefSeq | NC_000015 [ SRS ] NC_000015 [ ENTREZ ] |
| RefSeq | NT_010194 [ SRS ] NT_010194 [ ENTREZ ] |
| RefSeq | NW_925840 [ SRS ] NW_925840 [ ENTREZ ] |
| AceView | THBS1 AceView - NCBI |
| Unigene | Hs.164226 [ SRS ] Hs.164226 [ NCBI ]
HS164226 [ spliceNest ] |
| Fast-db | 1969 (alternative variants) |
| Protein : pattern, domain, 3D structure |
|---|
| SwissProt | P07996 [ SRS] P07996 [ EXPASY ] P07996 [ INTERPRO ] |
| Prosite | PS00022 EGF_1 [ SRS ] PS00022 EGF_1 [ Expasy ] |
| Prosite | PS01186 EGF_2 [ SRS ] PS01186 EGF_2 [ Expasy ] |
| Prosite | PS50026 EGF_3 [ SRS ] PS50026 EGF_3 [ Expasy ] |
| Prosite | PS50092 TSP1 [ SRS ] PS50092 TSP1 [ Expasy ] |
| Prosite | PS51234 TSP3 [ SRS ] PS51234 TSP3 [ Expasy ] |
| Prosite | PS51236 TSP_CTER [ SRS ] PS51236 TSP_CTER [ Expasy ] |
| Prosite | PS01208 VWFC_1 [ SRS ] PS01208 VWFC_1 [ Expasy ] |
| Prosite | PS50184 VWFC_2 [ SRS ] PS50184 VWFC_2 [ Expasy ] |
| Interpro | IPR013320 ConA_like_subgrp [ SRS ] IPR013320 ConA_like_subgrp [ EBI ] |
| Interpro | IPR006210 EGF [ SRS ] IPR006210 EGF [ EBI ] |
| Interpro | IPR000742 EGF_3 [ SRS ] IPR000742 EGF_3 [ EBI ] |
| Interpro | IPR006209 EGF_like [ SRS ] IPR006209 EGF_like [ EBI ] |
| Interpro | IPR013032 EGF_like_reg_CS [ SRS ] IPR013032 EGF_like_reg_CS [ EBI ] |
| Interpro | IPR003129 Laminin_G_TSP_N [ SRS ] IPR003129 Laminin_G_TSP_N [ EBI ] |
| Interpro | IPR003367 Thrombospondin_3 [ SRS ] IPR003367 Thrombospondin_3 [ EBI ] |
| Interpro | IPR000884 TSP1 [ SRS ] IPR000884 TSP1 [ EBI ] |
| Interpro | IPR008085 TSP_1 [ SRS ] IPR008085 TSP_1 [ EBI ] |
| Interpro | IPR008859 TSP_C [ SRS ] IPR008859 TSP_C [ EBI ] |
| Interpro | IPR001007 VWF_C [ SRS ] IPR001007 VWF_C [ EBI ] |
| CluSTr | P07996 |
| Pfam | PF00008 EGF [ SRS ] PF00008 EGF [ Sanger ] pfam00008 [ NCBI-CDD ] |
| Pfam | PF00090 TSP_1 [ SRS ] PF00090 TSP_1 [ Sanger ] pfam00090 [ NCBI-CDD ] |
| Pfam | PF02412 TSP_3 [ SRS ] PF02412 TSP_3 [ Sanger ] pfam02412 [ NCBI-CDD ] |
| Pfam | PF05735 TSP_C [ SRS ] PF05735 TSP_C [ Sanger ] pfam05735 [ NCBI-CDD ] |
| Pfam | PF00093 VWC [ SRS ] PF00093 VWC [ Sanger ] pfam00093 [ NCBI-CDD ] |
| Smart | SM00181 EGF [EMBL] |
| Smart | SM00209 TSP1 [EMBL] |
| Smart | SM00210 TSPN [EMBL] |
| Smart | SM00214 VWC [EMBL] |
| Blocks | P07996 |
| PDB | 1LSL [ SRS ] 1LSL [ PdbSum ], 1LSL [ IMB ] 1LSL [ RSDB ] |
| PDB | 1UX6 [ SRS ] 1UX6 [ PdbSum ], 1UX6 [ IMB ] 1UX6 [ RSDB ] |
| PDB | 1Z78 [ SRS ] 1Z78 [ PdbSum ], 1Z78 [ IMB ] 1Z78 [ RSDB ] |
| PDB | 1ZA4 [ SRS ] 1ZA4 [ PdbSum ], 1ZA4 [ IMB ] 1ZA4 [ RSDB ] |
| PDB | 2ERF [ SRS ] 2ERF [ PdbSum ], 2ERF [ IMB ] 2ERF [ RSDB ] |
| PDB | 2ES3 [ SRS ] 2ES3 [ PdbSum ], 2ES3 [ IMB ] 2ES3 [ RSDB ] |
| HPRD | 01765 |
| Protein Interaction databases |
|---|
| DIP | P07996 |
| IntAct | P07996 |
| Polymorphism : SNP, mutations, diseases |
|---|
| OMIM | 188060 [ map ] |
| GENECLINICS | 188060 |
| SNP | THBS1 [dbSNP-NCBI] |
| SNP | NM_003246 [SNP-NCI] |
| SNP | THBS1 [GeneSNPs - Utah] THBS1] [HGBASE - SRS] |
| HAPMAP | THBS1 [HAPMAP] |
| COSMIC | THBS1 [Somatic mutation (COSMIC-CGP-Sanger)] |
| HGMD | THBS1 |
| General knowledge |
|---|
| Family Browser | THBS1 [UCSC Family Browser] |
| SOURCE | NM_003246 |
| SMD | Hs.164226 |
| SAGE | Hs.164226 |
| GO | endopeptidase inhibitor activity [Amigo] endopeptidase inhibitor activity |
| GO | signal transducer activity [Amigo] signal transducer activity |
| GO | structural molecule activity [Amigo] structural molecule activity |
| GO | calcium ion binding [Amigo] calcium ion binding |
| GO | protein binding [Amigo] protein binding |
| GO | extracellular region [Amigo] extracellular region |
| GO | extracellular region [Amigo] extracellular region |
| GO | cell motility [Amigo] cell motility |
| GO | cell adhesion [Amigo] cell adhesion |
| GO | multicellular organismal development [Amigo] multicellular organismal development |
| GO | nervous system development [Amigo] nervous system development |
| GO | blood coagulation [Amigo] blood coagulation |
| GO | heparin binding [Amigo] heparin binding |
| BIOCARTA | TSP-1 Induced Apoptosis in Microvascular Endothelial Cell [Genes] |
| KEGG | Cell Communication |
| KEGG | TGF-beta signaling pathway |
| KEGG | Focal adhesion |
| KEGG | ECM-receptor interaction |
| PubGene | THBS1 |
| TreeFam | THBS1 |
| Other databases |
|---|
| Probes |
|---|
| Probe | THBS1 Related clones (RZPD - Berlin) |
| PubMed |
|---|
| PubMed | 159 Pubmed reference(s) in LocusLink |
| Structure and chromosomal localization of the human thrombospondin gene. |
| Wolf FW, Eddy RL, Shows TB, Dixit VM |
| Genomics. 1990 ; 6 (4) : 685-691. |
| PMID 2341158 |
| |
| Coronary artery disease and the thrombospondin single nucleotide polymorphisms. |
| Stenina OI, Byzova TV, Adams JC, McCarthy JJ, Topol EJ, Plow EF |
| The international journal of biochemistry & cell biology. 2004 ; 36 (6) : 1013-1030. |
| PMID 15094117 |
| |
| [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 ; 84 (23) : 1959-1962. |
| PMID 15730804 |
| |
| 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 |
| Oncology reports. 2001 ; 8 (4) : 763-766. |
| PMID 11410779 |
| |
| Thrombospondin 1 protein expression relates to good prognostic indices in ductal carcinoma in situ of the breast. |
| Rice AJ, Steward MA, Quinn CM |
| Journal of clinical pathology. 2002 ; 55 (12) : 921-925. |
| PMID 12461058 |
| |
| 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 research. 2002 ; 22 (6C) : 3941-3948. |
| PMID 12553016 |
| |
| 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, Clˆ©zardin P |
| International journal of cancer. Journal international du cancer. 2005 ; 116 (5) : 686-691. |
| PMID 15838828 |
| |
| 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 |
| Clinical cancer research : an official journal of the American Association for Cancer Research. 2004 ; 10 (12 Pt 1) : 4150-4157. |
| PMID 15217952 |
| |
| 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 |
| European journal of cancer (Oxford, England : 1990). 2004 ; 40 (16) : 2417-2423. |
| PMID 15519514 |
| |
| Methylation and silencing of the Thrombospondin-1 promoter in human cancer. |
| Li Q, Ahuja N, Burger PC, Issa JP |
| Oncogene. 1999 ; 18 (21) : 3284-3289. |
| PMID 10359534 |
| |
| 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 ; 2 (6) : 473-483. |
| PMID 12498716 |
| |
| 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 research. 2003 ; 63 (19) : 6299-6310. |
| PMID 14559817 |
| |
| 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 |
| The American journal of pathology. 2001 ; 159 (5) : 1949-1956. |
| PMID 11696456 |
| |
| Novel integrin antagonists derived from thrombospondins. |
| Calzada MJ, Roberts DD |
| Current pharmaceutical design. 2005 ; 11 (7) : 849-866. |
| PMID 15777239 |
| |
| Functional regulation of T lymphocytes by modulatory extracellular matrix proteins. |
| Kuznetsova SA, Roberts DD |
| The international journal of biochemistry & cell biology. 2004 ; 36 (6) : 1126-1134. |
| PMID 15094127 |
| |
