ID TSP1_MOUSE Reviewed; 1170 AA. AC P35441; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 04-NOV-2026, entry version 199. DE RecName: Full=Thrombospondin-1; DE AltName: Full=Glycoprotein G {ECO:0000250|UniProtKB:P07996}; DE Flags: Precursor; GN Name=Thbs1; Synonyms=Tsp1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1774063; DOI=10.1016/0888-7543(91)90066-n; RA Lawler J., Duquette M., Ferro P., Copeland N.G., Gilbert D.J., RA Jenkins N.A.; RT "Characterization of the murine thrombospondin gene."; RL Genomics 11:587-600(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1371115; DOI=10.1016/s0021-9258(19)50727-x; RA Laherty C.D., O'Rourke K., Wolf F.W., Katz R., Seldin M.F., Dixit V.M.; RT "Characterization of mouse thrombospondin 2 sequence and expression during RT cell growth and development."; RL J. Biol. Chem. 267:3274-3281(1992). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-490. RX PubMed=2398070; DOI=10.1016/s0021-9258(17)46276-4; RA Bornstein P., Alfi D., Devarayalu S., Framson P., Li P.; RT "Characterization of the mouse thrombospondin gene and evaluation of the RT role of the first intron in human gene expression."; RL J. Biol. Chem. 265:16691-16698(1990). RN [4] RP PROTEIN SEQUENCE OF 19-37. RX PubMed=8654563; DOI=10.1016/0014-5793(96)00460-7; RA Chen H., Aeschlimann D., Nowlen J., Mosher D.F.; RT "Expression and initial characterization of recombinant mouse RT thrombospondin 1 and thrombospondin 3."; RL FEBS Lett. 387:36-41(1996). RN [5] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=18156939; DOI=10.1097/sla.0b013e31815685dc; RA Isenberg J.S., Pappan L.K., Romeo M.J., Abu-Asab M., Tsokos M., Wink D.A., RA Frazier W.A., Roberts D.D.; RT "Blockade of thrombospondin-1-CD47 interactions prevents necrosis of full RT thickness skin grafts."; RL Ann. Surg. 247:180-190(2008). RN [6] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1067. RC TISSUE=Myoblast; RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200; RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D., RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.; RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome: RT identification, glycosite occupancy, and membrane orientation."; RL Mol. Cell. Proteomics 8:2555-2569(2009). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [8] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=20610415; DOI=10.1093/cvr/cvq218; RA Bauer E.M., Qin Y., Miller T.W., Bandle R.W., Csanyi G., Pagano P.J., RA Bauer P.M., Schnermann J., Roberts D.D., Isenberg J.S.; RT "Thrombospondin-1 supports blood pressure by limiting eNOS activation and RT endothelial-dependent vasorelaxation."; RL Cardiovasc. Res. 88:471-481(2010). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ATF6. RX PubMed=22682248; DOI=10.1016/j.cell.2012.03.050; RA Lynch J.M., Maillet M., Vanhoutte D., Schloemer A., Sargent M.A., RA Blair N.S., Lynch K.A., Okada T., Aronow B.J., Osinska H., Prywes R., RA Lorenz J.N., Mori K., Lawler J., Robbins J., Molkentin J.D.; RT "A thrombospondin-dependent pathway for a protective ER stress response."; RL Cell 149:1257-1268(2012). RN [10] RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE. RX PubMed=23757408; DOI=10.1152/ajpendo.00006.2013; RA Kong P., Gonzalez-Quesada C., Li N., Cavalera M., Lee D.W., RA Frangogiannis N.G.; RT "Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet- RT induced obesity enhancing adipose inflammation and stimulating adipocyte RT proliferation."; RL Am. J. Physiol. 305:E439-E450(2013). RN [11] RP FUNCTION. RX PubMed=23591719; DOI=10.1038/srep01673; RA Kaur S., Soto-Pantoja D.R., Stein E.V., Liu C., Elkahloun A.G., RA Pendrak M.L., Nicolae A., Singh S.P., Nie Z., Levens D., Isenberg J.S., RA Roberts D.D.; RT "Thrombospondin-1 signaling through CD47 inhibits self-renewal by RT regulating c-Myc and other stem cell transcription factors."; RL Sci. Rep. 3:1673-1673(2013). RN [12] RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE. RX PubMed=25835637; DOI=10.1016/j.bbadis.2015.03.010; RA Cui W., Maimaitiyiming H., Zhou Q., Norman H., Zhou C., Wang S.; RT "Interaction of thrombospondin1 and CD36 contributes to obesity-associated RT podocytopathy."; RL Biochim. Biophys. Acta 1852:1323-1333(2015). RN [13] RP INDUCTION. RX PubMed=27742621; DOI=10.1093/cvr/cvw218; RA Rogers N.M., Sharifi-Sanjani M., Yao M., Ghimire K., Bienes-Martinez R., RA Mutchler S.M., Knupp H.E., Baust J., Novelli E.M., Ross M., St Croix C., RA Kutten J.C., Czajka C.A., Sembrat J.C., Rojas M., Labrousse-Arias D., RA Bachman T.N., Vanderpool R.R., Zuckerbraun B.S., Champion H.C., Mora A.L., RA Straub A.C., Bilonick R.A., Calzada M.J., Isenberg J.S.; RT "TSP1-CD47 signaling is upregulated in clinical pulmonary hypertension and RT contributes to pulmonary arterial vasculopathy and dysfunction."; RL Cardiovasc. Res. 113:15-29(2017). RN [14] RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE. RX PubMed=29042481; DOI=10.1126/scisignal.aaj1784; RA Meijles D.N., Sahoo S., Al Ghouleh I., Amaral J.H., Bienes-Martinez R., RA Knupp H.E., Attaran S., Sembrat J.C., Nouraie S.M., Rojas M.M., RA Novelli E.M., Gladwin M.T., Isenberg J.S., Cifuentes-Pagano E., RA Pagano P.J.; RT "The matricellular protein TSP1 promotes human and mouse endothelial cell RT senescence through CD47 and Nox1."; RL Sci. Signal. 10:0-0(2017). RN [15] RP FUNCTION, AND INDUCTION. RX PubMed=32679764; DOI=10.3390/cells9071695; RA Ghimire K., Li Y., Chiba T., Julovi S.M., Li J., Ross M.A., Straub A.C., RA O'Connell P.J., Rueegg C., Pagano P.J., Isenberg J.S., Rogers N.M.; RT "CD47 Promotes Age-Associated Deterioration in Angiogenesis, Blood Flow and RT Glucose Homeostasis."; RL Cells 9:0-0(2020). CC -!- FUNCTION: Adhesive glycoprotein that mediates cell-to-cell and cell-to- CC matrix interactions (By similarity). Multifunctional, involved in CC inflammation, angiogenesis, wound healing, reactive oxygen species CC (ROS) signaling, nitrous oxide (NO) signaling, apoptosis, senescence, CC aging, cellular self-renewal, stemness, and cardiovascular and CC metabolic homeostasis (By similarity). Negatively modulates dendritic CC cell activation and cytokine release, as part of an autocrine feedback CC loop, contributing to the resolution of inflammation and immune CC homeostasis (By similarity). Ligand for receptor CD47 (By similarity). CC Modulates nitrous oxide (NO) signaling via CD47, hence playing a role CC as a pressor agent, supporting blood pressure (PubMed:20610415). Plays CC a role in endothelial cell senescence, acting via CD47, by increasing CC the abundance and activation of NADPH oxidase NOX1, and so generating CC excess ROS (PubMed:29042481). Inhibits stem cell self-renewal, acting CC via CD47 signaling, probably by regulation of the stem cell CC transcription factors POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 CC (PubMed:23591719). Negatively modulates wound healing, acting via CD47 CC (PubMed:18156939). Ligand for receptor CD36 (By similarity). Involved CC in inducing apoptosis in podocytes in response to elevated free fatty CC acids, acting via CD36 (PubMed:25835637). Plays a role in suppressing CC angiogenesis, acting, depending on context, via CD36 or CD47 (By CC similarity). Promotes cellular senescence in a TP53-CDKN1A-RB1 CC signaling-dependent manner (PubMed:29042481). Ligand for CC immunoglobulin-like cell surface receptor SIRPA (By similarity). CC Involved in ROS signaling in non-phagocytic cells, stimulating NADPH CC oxidase-derived ROS production, acting via interaction with SIRPA (By CC similarity). Plays a role in metabolic dysfunction in diet-induced CC obesity, perhaps acting by exacerbating adipose inflammatory activity; CC its effects may be mediated, at least in part, through enhanced CC adipocyte proliferation (PubMed:23757408). Plays a role in ER stress CC response, via its interaction with the activating transcription factor CC 6 alpha (ATF6) which produces adaptive ER stress response factors CC (PubMed:22682248). May be involved in age-related conditions, including CC metabolic dysregulation, during normal aging (PubMed:29042481, CC PubMed:32679764). {ECO:0000250|UniProtKB:P07996, CC ECO:0000269|PubMed:18156939, ECO:0000269|PubMed:20610415, CC ECO:0000269|PubMed:22682248, ECO:0000269|PubMed:23591719, CC ECO:0000269|PubMed:23757408, ECO:0000269|PubMed:25835637, CC ECO:0000269|PubMed:29042481, ECO:0000269|PubMed:32679764}. CC -!- SUBUNIT: Homotrimer; disulfide-linked (By similarity). Can bind to CC fibrinogen, fibronectin, laminin, type V collagen and integrins alpha- CC V/beta-1, alpha-V/beta-3 and alpha-IIb/beta-3 (By similarity). Binds CC heparin (By similarity). Interacts (via the C-terminal domain) with CC CD47 (By similarity). Interacts (via the TSP type I repeats) with CD36; CC the interaction conveys an antiangiogenic effect (By similarity). CC Interacts (via the TSP type I repeats) with HRG; the interaction blocks CC the antiangiogenic effect of THBS1 with CD36 (By similarity). Interacts CC with ATF6 (via lumenal domain) (PubMed:22682248). Interacts with FN1; CC this interaction is enhanced by TNFAIP6, which may act as a bridging CC molecule between FN1 and THBS1 (By similarity). Interacts with SIRPA; CC the interaction stimulates phosphorylation of SIRPA (By similarity). CC {ECO:0000250|UniProtKB:P07996, ECO:0000269|PubMed:22682248}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P07996}. Cell CC surface {ECO:0000250|UniProtKB:P07996}. Secreted, extracellular space, CC extracellular matrix {ECO:0000250|UniProtKB:P07996}. Endoplasmic CC reticulum {ECO:0000269|PubMed:22682248}. Sarcoplasmic reticulum CC {ECO:0000269|PubMed:22682248}. Note=Secreted by thrombin-activated CC platelets and binds to the cell surface in the presence of CC extracellular Ca(2+) (By similarity). Incorporated into the CC extracellular matrix (ECM) of fibroblasts (By similarity). The C- CC terminal region in trimeric form is required for retention in the ECM CC (By similarity). Also detected in the endoplasmic reticulum and CC sarcoplasmic reticulum where it plays a role in the ER stress response CC (PubMed:22682248). {ECO:0000250|UniProtKB:P07996, CC ECO:0000269|PubMed:22682248}. CC -!- INDUCTION: Expression increases in lungs following short-term hypoxia CC (PubMed:27742621). Expression increases in kidney podocytes in response CC to elevated free fatty acids (PubMed:25835637). Expression in CC vasculature, including arteries, increases in normal aging CC (PubMed:29042481, PubMed:32679764). Expression increases in adipose CC tissue in diet-induced obesity (PubMed:23757408). CC {ECO:0000269|PubMed:23757408, ECO:0000269|PubMed:25835637, CC ECO:0000269|PubMed:27742621, ECO:0000269|PubMed:29042481, CC ECO:0000269|PubMed:32679764}. CC -!- DISRUPTION PHENOTYPE: Knockout enhances eNOS-dependent arterial CC relaxation in blood vessels (PubMed:20610415). Treating the endothelial CC lining with THBS1 inhibits ACh-stimulated vasorelaxation CC (PubMed:20610415). Mean arterial pressure (MAP) is significantly CC decreased following ACh treatment (PubMed:20610415). Enhanced survival CC of full-thickness skin grafts, with increased numbers of functional CC vessels in wound beds (PubMed:18156939). Significant increase in CC proliferating cell nuclear antigen (PCNA) in middle-aged (8- to 10- CC month-old) lungs (PubMed:29042481). Increases in abundance of other CC senescence-associated markers in middle-aged lungs, including TP53/p53 CC and CDKN1A/p21cip, decrease in RB1, and no change in CDKN2A/p16INK4A CC (PubMed:29042481). Reduces weight gain in animals fed on a high- CC carbohydrate and low-fat diet (HCLFD), or a high-fat diet (HFD); mainly CC due to reduced adiposity, and yet does not affect food intake and CC energy expenditure (PubMed:23757408). Insulin level and estimated CC insulin resistance are both reduced on either HFD or HCLFD, and free CC fatty-acids (FFA) and triglyceride levels are both increased CC (PubMed:23757408). Plasma leptin levels are reduced in animals fed the CC HCLFD but not in animals fed the HFD (PubMed:23757408). No significant CC difference in adipocyte size, nor vascular density in adipose tissue CC (PubMed:23757408). Reduced macrophage infiltration in adipose tissue in CC animals fed HCLFD (PubMed:23757408). Reduced mRNA expression levels of CC TNF, type I collagen COL1A1, and TGF-beta 1 in adipose tissue in CC animals fed HCLFD (PubMed:23757408). Markers of podocyte function, such CC as WT1, nephrin and synaptopodin are decreased in obese wild type, but CC these changes are attenuated in obese knockout animals CC (PubMed:25835637). Fewer apoptotic cells and reduced levels of active CC caspase 3 in glomeruli (PubMed:25835637). {ECO:0000269|PubMed:18156939, CC ECO:0000269|PubMed:20610415, ECO:0000269|PubMed:23757408, CC ECO:0000269|PubMed:25835637, ECO:0000269|PubMed:29042481}. CC -!- SIMILARITY: Belongs to the thrombospondin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M62470; AAA50611.1; -; Genomic_DNA. DR EMBL; M62450; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62451; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62452; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62453; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62454; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62455; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62456; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62457; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62458; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62459; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62460; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62461; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62462; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62463; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62464; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62465; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62466; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62467; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62468; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M62469; AAA50611.1; JOINED; Genomic_DNA. DR EMBL; M87276; AAA53063.1; -; mRNA. DR EMBL; J05606; AAA40431.1; -; Genomic_DNA. DR EMBL; J05605; AAA40431.1; JOINED; Genomic_DNA. DR PIR; A40558; A40558. DR AlphaFoldDB; P35441; -. DR SMR; P35441; -. DR ComplexPortal; CPX-3022; Thrombospondin 1 complex. DR CORUM; P35441; -. DR FunCoup; P35441; 414. DR IntAct; P35441; 6. DR STRING; 10090.ENSMUSP00000044903; -. DR GlyConnect; P35441; 1 N-Linked glycan (1 site). DR GlyCosmos; P35441; 11 sites, 4 glycans. DR GlyGen; P35441; 12 sites, 5 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; P35441; -. DR PhosphoSitePlus; P35441; -. DR SwissPalm; P35441; -. DR CPTAC; non-CPTAC-3360; -. DR jPOST; P35441; -. DR PaxDb; 10090-ENSMUSP00000044903; -. DR PeptideAtlas; P35441; -. DR ProteomicsDB; 297728; -. DR Pumba; P35441; -. DR AGR; MGI:98737; -. DR MGI; MGI:98737; Thbs1. DR eggNOG; ENOG502QRK8; Eukaryota. DR InParanoid; P35441; -. DR OMA; AATKQVC; -. DR Reactome; R-MMU-114608; Platelet degranulation. DR Reactome; R-MMU-186797; Signaling by PDGF. DR Reactome; R-MMU-216083; Integrin cell surface interactions. DR Reactome; R-MMU-5173214; O-glycosylation of TSR domain-containing proteins. DR PRO; PR:P35441; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; P35441; protein. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; ISO:GO_Central. DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IDA:MGI. DR GO; GO:0005577; C:fibrinogen complex; ISO:GO_Central. DR GO; GO:0140144; C:non-collagenous component of basement membrane; IDA:GO_Central. DR GO; GO:0031091; C:platelet alpha granule; ISO:GO_Central. DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0030141; C:secretory granule; ISO:GO_Central. DR GO; GO:1990341; C:thrombospondin complex; TAS:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0070052; F:collagen V binding; ISO:GO_Central. DR GO; GO:0004866; F:endopeptidase inhibitor activity; ISO:GO_Central. DR GO; GO:0050840; F:extracellular matrix binding; IDA:MGI. DR GO; GO:0005201; F:extracellular matrix structural constituent; IBA:GO_Central. DR GO; GO:0070051; F:fibrinogen binding; ISO:GO_Central. DR GO; GO:0017134; F:fibroblast growth factor binding; ISO:GO_Central. DR GO; GO:0001968; F:fibronectin binding; ISS:UniProtKB. DR GO; GO:0008201; F:heparin binding; ISO:GO_Central. DR GO; GO:0005178; F:integrin binding; ISO:GO_Central. DR GO; GO:0043236; F:laminin binding; ISO:GO_Central. DR GO; GO:0030169; F:low-density lipoprotein particle binding; ISO:GO_Central. DR GO; GO:0001786; F:phosphatidylserine binding; ISO:GO_Central. DR GO; GO:0002020; F:protease binding; ISO:GO_Central. DR GO; GO:0042803; F:protein homodimerization activity; ISO:GO_Central. DR GO; GO:0050431; F:transforming growth factor beta binding; ISO:GO_Central. DR GO; GO:0048266; P:behavioral response to pain; IMP:UniProtKB. DR GO; GO:0072378; P:blood coagulation, fibrin clot formation; ISO:GO_Central. DR GO; GO:0048514; P:blood vessel morphogenesis; IGI:MGI. DR GO; GO:0016477; P:cell migration; ISO:GO_Central. DR GO; GO:0071732; P:cellular response to nitric oxide; IMP:MGI. DR GO; GO:0003197; P:endocardial cushion development; IGI:MGI. DR GO; GO:0071603; P:endothelial cell-cell adhesion; NAS:ComplexPortal. DR GO; GO:0043652; P:engulfment of apoptotic cell; ISO:GO_Central. DR GO; GO:0003417; P:growth plate cartilage development; IMP:MGI. DR GO; GO:0006954; P:inflammatory response; IMP:MGI. DR GO; GO:0070487; P:monocyte aggregation; IMP:MGI. DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:MGI. DR GO; GO:0002581; P:negative regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II; ISO:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:GO_Central. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:GO_Central. DR GO; GO:1903588; P:negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISO:GO_Central. DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; ISO:GO_Central. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:GO_Central. DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; ISO:GO_Central. DR GO; GO:0002605; P:negative regulation of dendritic cell antigen processing and presentation; ISO:GO_Central. DR GO; GO:2001027; P:negative regulation of endothelial cell chemotaxis; ISO:MGI. DR GO; GO:0010596; P:negative regulation of endothelial cell migration; ISO:GO_Central. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:MGI. DR GO; GO:0051918; P:negative regulation of fibrinolysis; ISO:GO_Central. DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; ISO:GO_Central. DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISO:GO_Central. DR GO; GO:0032695; P:negative regulation of interleukin-12 production; ISO:GO_Central. DR GO; GO:0010748; P:negative regulation of long-chain fatty acid import across plasma membrane; ISO:GO_Central. DR GO; GO:0141151; P:negative regulation of nitric oxide-cGMP mediated signal transduction; ISO:GO_Central. DR GO; GO:0010757; P:negative regulation of plasminogen activation; ISO:GO_Central. DR GO; GO:0010754; P:negative regulation of receptor guanylyl cyclase signaling pathway; ISO:GO_Central. DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; ISO:GO_Central. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:GO_Central. DR GO; GO:0038060; P:nitric oxide-cGMP-mediated signaling; ISO:GO_Central. DR GO; GO:0003151; P:outflow tract morphogenesis; IGI:MGI. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:GO_Central. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:GO_Central. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:GO_Central. DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IDA:MGI. DR GO; GO:0050921; P:positive regulation of chemotaxis; ISO:GO_Central. DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:GO_Central. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:GO_Central. DR GO; GO:1902043; P:positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:GO_Central. DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISO:GO_Central. DR GO; GO:0043032; P:positive regulation of macrophage activation; ISO:GO_Central. DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IMP:BHF-UCL. DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:GO_Central. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:GO_Central. DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:GO_Central. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:GO_Central. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:GO_Central. DR GO; GO:0071636; P:positive regulation of transforming growth factor beta production; ISO:GO_Central. DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0045727; P:positive regulation of translation; ISO:GO_Central. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:GO_Central. DR GO; GO:0051592; P:response to calcium ion; ISO:GO_Central. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:UniProtKB. DR GO; GO:0009749; P:response to glucose; ISO:GO_Central. DR GO; GO:0032026; P:response to magnesium ion; ISO:GO_Central. DR GO; GO:0009612; P:response to mechanical stimulus; ISO:GO_Central. DR GO; GO:0002040; P:sprouting angiogenesis; ISO:GO_Central. DR CDD; cd00054; EGF_CA; 1. DR FunFam; 2.20.100.10:FF:000007; Thrombospondin 1; 2. DR FunFam; 2.60.120.200:FF:000009; Thrombospondin 1; 1. DR FunFam; 2.10.25.10:FF:000070; Thrombospondin 2; 1. DR FunFam; 4.10.1080.10:FF:000003; Thrombospondin 2; 1. DR FunFam; 2.10.25.10:FF:000025; Thrombospondin 3; 1. DR FunFam; 2.10.25.10:FF:000027; Thrombospondin 3; 1. DR FunFam; 4.10.1080.10:FF:000001; Thrombospondin 3; 1. DR FunFam; 2.20.100.10:FF:000115; Thrombospondin type-1 domain-containing protein 1; 1. DR FunFam; 2.60.120.200:FF:000041; thrombospondin-1; 1. DR Gene3D; 2.60.120.200; -; 2. DR Gene3D; 6.20.200.20; -; 1. DR Gene3D; 2.10.25.10; Laminin; 3. DR Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 3. DR Gene3D; 4.10.1080.10; TSP type-3 repeat; 2. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR000742; EGF. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR001791; Laminin_G. DR InterPro; IPR003367; Thrombospondin_3-like_rpt. DR InterPro; IPR017897; Thrombospondin_3_rpt. DR InterPro; IPR008859; Thrombospondin_C. DR InterPro; IPR000884; TSP1_rpt. DR InterPro; IPR036383; TSP1_rpt_sf. DR InterPro; IPR028974; TSP_type-3_rpt. DR InterPro; IPR048287; TSPN-like_N. DR InterPro; IPR001007; VWF_dom. DR PANTHER; PTHR10199; THROMBOSPONDIN; 1. DR PANTHER; PTHR10199:SF78; THROMBOSPONDIN-1; 1. DR Pfam; PF02210; Laminin_G_2; 1. DR Pfam; PF00090; TSP_1; 3. DR Pfam; PF02412; TSP_3; 7. DR Pfam; PF05735; TSP_C; 1. DR Pfam; PF00093; VWC; 1. DR PRINTS; PR01705; TSP1REPEAT. DR SMART; SM00179; EGF_CA; 2. DR SMART; SM00209; TSP1; 3. DR SMART; SM00210; TSPN; 1. DR SMART; SM00214; VWC; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 2. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF57603; FnI-like domain; 1. DR SUPFAM; SSF103647; TSP type-3 repeat; 3. DR SUPFAM; SSF82895; TSP-1 type 1 repeat; 3. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50026; EGF_3; 2. DR PROSITE; PS50092; TSP1; 3. DR PROSITE; PS51234; TSP3; 8. DR PROSITE; PS51236; TSP_CTER; 1. DR PROSITE; PS01208; VWFC_1; 1. DR PROSITE; PS50184; VWFC_2; 1. PE 1: Evidence at protein level; KW Angiogenesis; Apoptosis; Calcium; Cell adhesion; Direct protein sequencing; KW Disulfide bond; EGF-like domain; Endoplasmic reticulum; KW Extracellular matrix; Glycoprotein; Heparin-binding; Inflammatory response; KW Reference proteome; Repeat; Sarcoplasmic reticulum; Secreted; Signal; KW Unfolded protein response. FT SIGNAL 1..18 FT /evidence="ECO:0000269|PubMed:8654563" FT CHAIN 19..1170 FT /note="Thrombospondin-1" FT /id="PRO_0000035843" FT DOMAIN 56..270 FT /note="Laminin G-like" FT DOMAIN 316..373 FT /note="VWFC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT DOMAIN 379..429 FT /note="TSP type-1 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DOMAIN 435..490 FT /note="TSP type-1 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DOMAIN 492..547 FT /note="TSP type-1 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DOMAIN 547..587 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 646..690 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REPEAT 691..726 FT /note="TSP type-3 1" FT REPEAT 727..762 FT /note="TSP type-3 2" FT REPEAT 763..785 FT /note="TSP type-3 3" FT REPEAT 786..821 FT /note="TSP type-3 4" FT REPEAT 822..844 FT /note="TSP type-3 5" FT REPEAT 845..882 FT /note="TSP type-3 6" FT REPEAT 883..918 FT /note="TSP type-3 7" FT REPEAT 919..954 FT /note="TSP type-3 8" FT DOMAIN 958..1170 FT /note="TSP C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00635" FT REGION 47..95 FT /note="Heparin-binding" FT /evidence="ECO:0000250" FT REGION 531..1152 FT /note="Involved in retention in extracellular matrix (ECM); FT involved in trimer formation" FT /evidence="ECO:0000250|UniProtKB:P07996" FT REGION 840..934 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 926..928 FT /note="Cell attachment site" FT /evidence="ECO:0000255" FT COMPBIAS 883..894 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 917..934 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 248 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 360 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 385 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000250|UniProtKB:P07996" FT CARBOHYD 438 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000250|UniProtKB:P07996" FT CARBOHYD 441 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000250|UniProtKB:P07996" FT CARBOHYD 450 FT /note="O-linked (Fuc...) threonine" FT /evidence="ECO:0000250|UniProtKB:P07996" FT CARBOHYD 498 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000250|UniProtKB:P07996" FT CARBOHYD 507 FT /note="O-linked (Fuc...) threonine" FT /evidence="ECO:0000250|UniProtKB:P07996" FT CARBOHYD 553 FT /note="O-linked (Xyl) serine" FT /evidence="ECO:0000250|UniProtKB:P07996" FT CARBOHYD 708 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1067 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19656770" FT DISULFID 171..232 FT /evidence="ECO:0000250|UniProtKB:P07996" FT DISULFID 270 FT /note="Interchain" FT /evidence="ECO:0000305" FT DISULFID 274 FT /note="Interchain" FT /evidence="ECO:0000305" FT DISULFID 391..423 FT /evidence="ECO:0000250" FT DISULFID 395..428 FT /evidence="ECO:0000250" FT DISULFID 406..413 FT /evidence="ECO:0000250" FT DISULFID 447..484 FT /evidence="ECO:0000250|UniProtKB:P07996" FT DISULFID 451..489 FT /evidence="ECO:0000250|UniProtKB:P07996" FT DISULFID 462..474 FT /evidence="ECO:0000250|UniProtKB:P07996" FT DISULFID 504..541 FT /evidence="ECO:0000250|UniProtKB:P07996" FT DISULFID 508..546 FT /evidence="ECO:0000250|UniProtKB:P07996" FT DISULFID 519..531 FT /evidence="ECO:0000250|UniProtKB:P07996" FT DISULFID 551..562 FT /evidence="ECO:0000250" FT DISULFID 556..572 FT /evidence="ECO:0000250" FT DISULFID 575..586 FT /evidence="ECO:0000250" FT DISULFID 592..608 FT /evidence="ECO:0000250" FT DISULFID 599..617 FT /evidence="ECO:0000250" FT DISULFID 620..644 FT /evidence="ECO:0000250" FT DISULFID 650..663 FT /evidence="ECO:0000250" FT DISULFID 657..676 FT /evidence="ECO:0000250" FT DISULFID 678..689 FT /evidence="ECO:0000250" FT DISULFID 705..713 FT /evidence="ECO:0000250" FT DISULFID 718..738 FT /evidence="ECO:0000250" FT DISULFID 754..774 FT /evidence="ECO:0000250" FT DISULFID 777..797 FT /evidence="ECO:0000250" FT DISULFID 813..833 FT /evidence="ECO:0000250" FT DISULFID 836..856 FT /evidence="ECO:0000250|UniProtKB:P07996" FT DISULFID 874..894 FT /evidence="ECO:0000250|UniProtKB:P07996" FT DISULFID 910..930 FT /evidence="ECO:0000250|UniProtKB:P07996" FT DISULFID 946..1167 FT /evidence="ECO:0000250|UniProtKB:P07996" FT CONFLICT 1025 FT /note="F -> L (in Ref. 2; AAA53063)" FT /evidence="ECO:0000305" SQ SEQUENCE 1170 AA; 129647 MW; 0443E493615E7F06 CRC64; MELLRGLGVL FLLHMCGSNR IPESGGDNGV FDIFELIGGA RRGPGRRLVK GQDLSSPAFR IENANLIPAV PDDKFQDLLD AVWADKGFIF LASLRQMKKT RGTLLAVERK DNTGQIFSVV SNGKAGTLDL SLSLPGKQQV VSVEEALLAT GQWKSITLFV QEDRAQLYID CDKMESAELD VPIQSIFTRD LASVARLRVA KGDVNDNFQG VLQNVRFVFG TTPEDILRNK GCSSSTNVLL TLDNNVVNGS SPAIRTNYIG HKTKDLQAIC GLSCDELSSM VLELKGLRTI VTTLQDSIRK VTEENRELVS ELKRPPLCFH NGVQYKNNEE WTVDSCTECH CQNSVTICKK VSCPIMPCSN ATVPDGECCP RCWPSDSADD GWSPWSEWTS CSATCGNGIQ QRGRSCDSLN NRCEGSSVQT RTCHIQECDK RFKQDGGWSH WSPWSSCSVT CGDGVITRIR LCNSPSPQMN GKPCEGEARE TKACKKDACP INGGWGPWSP WDICSVTCGG GVQRRSRLCN NPTPQFGGKD CVGDVTENQV CNKQDCPIDG CLSNPCFAGA KCTSYPDGSW KCGACPPGYS GNGIQCKDVD ECKEVPDACF NHNGEHRCKN TDPGYNCLPC PPRFTGSQPF GRGVEHAMAN KQVCKPRNPC TDGTHDCNKN AKCNYLGHYS DPMYRCECKP GYAGNGIICG EDTDLDGWPN ENLVCVANAT YHCKKDNCPN LPNSGQEDYD KDGIGDACDD DDDNDKIPDD RDNCPFHYNP AQYDYDRDDV GDRCDNCPYN HNPDQADTDK NGEGDACAVD IDGDGILNER DNCQYVYNVD QRDTDMDGVG DQCDNCPLEH NPDQLDSDSD LIGDTCDNNQ DIDEDGHQNN LDNCPYVPNA NQADHDKDGK GDACDHDDDN DGIPDDRDNC RLVPNPDQKD SDGDGRGDAC KDDFDHDNVP DIDDICPENF DISETDFRRF QMIPLDPKGT SQNDPNWVVR HQGKELVQTV NCDPGLAVGY DEFNAVDFSG TFFINTERDD DYAGFVFGYQ SSSRFYVVMW KQVTQSYWDT NPTRAQGYSG LSVKVVNSTT GPGEHLRNAL WHTGNTPGQV RTLWHDPRHI GWKDFTAYRW RLSHRPKTGY IRVVMYEGKK IMADSGPIYD KTYAGGRLGL FVFSQEMVFF SDMKYECRDS //