ID TSP1_HUMAN Reviewed; 1170 AA. AC P07996; A8K6H4; B4E3J7; B9EGH6; Q15667; Q59E99; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 260. DE RecName: Full=Thrombospondin-1; DE AltName: Full=Glycoprotein G {ECO:0000303|PubMed:6777381}; DE Flags: Precursor; GN Name=THBS1 {ECO:0000312|HGNC:HGNC:11785}; Synonyms=TSP, TSP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION. RC TISSUE=Endothelial cell; RX PubMed=2430973; DOI=10.1083/jcb.103.5.1635; RA Lawler J., Hynes R.O.; RT "The structure of human thrombospondin, an adhesive glycoprotein with RT multiple calcium-binding sites and homologies with several different RT proteins."; RL J. Cell Biol. 103:1635-1648(1986). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-523. RX PubMed=2918029; DOI=10.1083/jcb.108.2.729; RA Hennessy S.W., Frazier B.A., Kim D.D., Deckwerth T.L., Baumgartel D.M., RA Rotwein P., Frazier W.A.; RT "Complete thrombospondin mRNA sequence includes potential regulatory sites RT in the 3' untranslated region."; RL J. Cell Biol. 108:729-736(1989). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP ALA-523. RC TISSUE=Placenta, and Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-700. RC TISSUE=Aortic endothelium; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-397 (ISOFORM 1). RX PubMed=3030396; DOI=10.1021/bi00374a014; RA Kobayashi S., Eden-Mccutchan F., Framson P., Bornstein P.; RT "Partial amino acid sequence of human thrombospondin as determined by RT analysis of cDNA clones: homology to malarial circumsporozoite proteins."; RL Biochemistry 25:8418-8425(1986). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-374 (ISOFORM 1). RX PubMed=3461443; DOI=10.1073/pnas.83.15.5449; RA Dixit V.M., Hennessy S.W., Grant G.A., Rotwein P., Frazier W.A.; RT "Characterization of a cDNA encoding the heparin and collagen binding RT domains of human thrombospondin."; RL Proc. Natl. Acad. Sci. U.S.A. 83:5449-5453(1986). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-166. RX PubMed=2544587; DOI=10.1016/s0021-9258(18)60452-1; RA Laherty C.D., Gierman T.M., Dixit V.M.; RT "Characterization of the promoter region of the human thrombospondin gene. RT DNA sequences within the first intron increase transcription."; RL J. Biol. Chem. 264:11222-11227(1989). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1028-1170 (ISOFORM 1). RA la Fleur M., Jobin C., Gauthier J., Kreis C.G.; RT "Expression of thrombospondin in chronic inflammation: neutrophils from RT synovial fluids synthesize a novel 3.9 kb TSP mRNA."; RL Submitted (DEC-1992) to the EMBL/GenBank/DDBJ databases. RN [11] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=101549; DOI=10.1016/s0021-9258(17)34336-3; RA Lawler J.W., Slayter H.S., Coligan J.E.; RT "Isolation and characterization of a high molecular weight glycoprotein RT from human blood platelets."; RL J. Biol. Chem. 253:8609-8616(1978). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=6777381; DOI=10.1016/s0021-9258(19)70174-4; RA Phillips D.R., Jennings L.K., Prasanna H.R.; RT "Ca2+-mediated association of glycoprotein G (thrombin-sensitive protein, RT thrombospondin) with human platelets."; RL J. Biol. Chem. 255:11629-11632(1980). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=6341993; DOI=10.1073/pnas.80.4.998; RA Jaffe E.A., Ruggiero J.T., Leung L.K., Doyle M.J., McKeown-Longo P.J., RA Mosher D.F.; RT "Cultured human fibroblasts synthesize and secrete thrombospondin and RT incorporate it into extracellular matrix."; RL Proc. Natl. Acad. Sci. U.S.A. 80:998-1002(1983). RN [14] RP FUNCTION, AND INTERACTION WITH FIBRONECTIN AND FIBRINOGEN. RX PubMed=6489349; DOI=10.1111/j.1432-1033.1984.tb08534.x; RA Lahav J., Lawler J., Gimbrone M.A.; RT "Thrombospondin interactions with fibronectin and fibrinogen. Mutual RT inhibition in binding."; RL Eur. J. Biochem. 145:151-156(1984). RN [15] RP INTERACTION WITH TYPE V COLLAGEN AND LAMININ. RX PubMed=6693501; DOI=10.1083/jcb.98.2.646; RA Mumby S.M., Raugi G.J., Bornstein P.; RT "Interactions of thrombospondin with extracellular matrix proteins: RT selective binding to type V collagen."; RL J. Cell Biol. 98:646-652(1984). RN [16] RP INTERACTION WITH INTEGRIN RECEPTOR. RX PubMed=2478219; RA Lawler J., Hynes R.O.; RT "An integrin receptor on normal and thrombasthenic platelets that binds RT thrombospondin."; RL Blood 74:2022-2027(1989). RN [17] RP FUNCTION, AND INTERACTION WITH CD36. RX PubMed=1371676; DOI=10.1016/0006-291x(92)91860-s; RA Asch A.S., Silbiger S., Heimer E., Nachman R.L.; RT "Thrombospondin sequence motif (CSVTCG) is responsible for CD36 binding."; RL Biochem. Biophys. Res. Commun. 182:1208-1217(1992). RN [18] RP FUNCTION, AND INTERACTION WITH CD47. RX PubMed=8550562; DOI=10.1074/jbc.271.1.21; RA Gao A.G., Lindberg F.P., Finn M.B., Blystone S.D., Brown E.J., RA Frazier W.A.; RT "Integrin-associated protein is a receptor for the C-terminal domain of RT thrombospondin."; RL J. Biol. Chem. 271:21-24(1996). RN [19] RP FUNCTION, AND INTERACTION WITH CD36. RX PubMed=10613822; DOI=10.1038/71517; RA Jimenez B., Volpert O.V., Crawford S.E., Febbraio M., Silverstein R.L., RA Bouck N.; RT "Signals leading to apoptosis-dependent inhibition of neovascularization by RT thrombospondin-1."; RL Nat. Med. 6:41-48(2000). RN [20] RP GLYCOSYLATION AT TRP-385; SER-394; TRP-438; TRP-441; THR-450; TRP-498 AND RP THR-507. RC TISSUE=Platelet; RX PubMed=11067851; DOI=10.1074/jbc.m008073200; RA Hofsteenge J., Huwiler K.G., Macek B., Hess D., Lawler J., Mosher D.F., RA Peter-Katalinic J.; RT "C-mannosylation and O-fucosylation of the thrombospondin type 1 module."; RL J. Biol. Chem. 276:6485-6498(2001). RN [21] RP FUNCTION, AND INTERACTION WITH HRG. RX PubMed=11134179; DOI=10.1172/jci9061; RA Simantov R., Febbraio M., Crombie R., Asch A.S., Nachman R.L., RA Silverstein R.L.; RT "Histidine-rich glycoprotein inhibits the antiangiogenic effect of RT thrombospondin-1."; RL J. Clin. Invest. 107:45-52(2001). RN [22] RP DISULFIDE BONDS IN THROMBOSPONDIN DOMAIN. RX PubMed=12450399; DOI=10.1021/bi026463u; RA Huwiler K.G., Vestling M.M., Annis D.S., Mosher D.F.; RT "Biophysical characterization, including disulfide bond assignments, of the RT anti-angiogenic type 1 domains of human thrombospondin-1."; RL Biochemistry 41:14329-14339(2002). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY PROSTAGLANDIN E2, AND TISSUE RP SPECIFICITY. RX PubMed=14568985; DOI=10.1084/jem.20030705; RA Doyen V., Rubio M., Braun D., Nakajima T., Abe J., Saito H., Delespesse G., RA Sarfati M.; RT "Thrombospondin 1 is an autocrine negative regulator of human dendritic RT cell activation."; RL J. Exp. Med. 198:1277-1283(2003). RN [24] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-248 AND ASN-1067. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [25] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1067. RC TISSUE=Saliva; RX PubMed=16740002; DOI=10.1021/pr050492k; RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.; RT "Identification of N-linked glycoproteins in human saliva by glycoprotein RT capture and mass spectrometry."; RL J. Proteome Res. 5:1493-1503(2006). RN [26] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-248. RC TISSUE=Platelet; RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200; RA Lewandrowski U., Moebius J., Walter U., Sickmann A.; RT "Elucidation of N-glycosylation sites on human platelet proteins: a RT glycoproteomic approach."; RL Mol. Cell. Proteomics 5:226-233(2006). RN [27] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-926 AND RP 1019-ASP--ASP-1021. RX PubMed=18285447; DOI=10.1242/jcs.021006; RA Adams J.C., Bentley A.A., Kvansakul M., Hatherley D., Hohenester E.; RT "Extracellular matrix retention of thrombospondin 1 is controlled by its RT conserved C-terminal region."; RL J. Cell Sci. 121:784-795(2008). RN [28] RP INTERACTION WITH FN1. RX PubMed=18042364; DOI=10.1016/j.matbio.2007.10.003; RA Kuznetsova S.A., Mahoney D.J., Martin-Manso G., Ali T., Nentwich H.A., RA Sipes J.M., Zeng B., Vogel T., Day A.J., Roberts D.D.; RT "TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin RT and increases fibronectin matrix assembly."; RL Matrix Biol. 27:201-210(2008). RN [29] RP FUNCTION, AND INTERACTION WITH CD47. RX PubMed=19004835; DOI=10.1074/jbc.m804860200; RA Isenberg J.S., Annis D.S., Pendrak M.L., Ptaszynska M., Frazier W.A., RA Mosher D.F., Roberts D.D.; RT "Differential interactions of thrombospondin-1, -2, and -4 with CD47 and RT effects on cGMP signaling and ischemic injury responses."; RL J. Biol. Chem. 284:1116-1125(2009). RN [30] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1067. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [32] RP FUNCTION, AND INTERACTION WITH SIRPA. RX PubMed=24511121; DOI=10.1681/asn.2013040433; RA Yao M., Rogers N.M., Csanyi G., Rodriguez A.I., Ross M.A., St Croix C., RA Knupp H., Novelli E.M., Thomson A.W., Pagano P.J., Isenberg J.S.; RT "Thrombospondin-1 activation of signal-regulatory protein-alpha stimulates RT reactive oxygen species production and promotes renal ischemia reperfusion RT injury."; RL J. Am. Soc. Nephrol. 25:1171-1186(2014). RN [33] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [34] 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 [35] RP FUNCTION, AND INDUCTION. 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 [36] 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). RN [37] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 434-546, DISULFIDE BONDS, AND RP GLYCOSYLATION AT THR-450 AND THR-507. RX PubMed=12391027; DOI=10.1083/jcb.200206062; RA Tan K., Duquette M., Liu J.-H., Dong Y., Zhang R., Joachimiak A., RA Lawler J., Wang J.-H.; RT "Crystal structure of the TSP-1 type 1 repeats: a novel layered fold and RT its biological implication."; RL J. Cell Biol. 159:373-382(2002). RN [38] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 834-1170 IN COMPLEX WITH CALCIUM RP IONS, DISULFIDE BONDS, MUTAGENESIS OF ASN-1067, GLYCOSYLATION AT ASN-1067, RP CELL ATTACHMENT SITE, AND FUNCTION. RX PubMed=15014436; DOI=10.1038/sj.emboj.7600166; RA Kvansakul M., Adams J.C., Hohenester E.; RT "Structure of a thrombospondin C-terminal fragment reveals a novel calcium RT core in the type 3 repeats."; RL EMBO J. 23:1223-1233(2004). RN [39] RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 19-233 IN COMPLEX WITH SYNTHETIC RP PENTAMERIC HEPARIN, AND DISULFIDE BOND. RX PubMed=16407063; DOI=10.1016/j.str.2005.09.017; RA Tan K., Duquette M., Liu J.-H., Zhang R., Joachimiak A., Wang J.-H., RA Lawler J.; RT "The structures of the thrombospondin-1 N-terminal domain and its complex RT with a synthetic pentameric heparin."; RL Structure 14:33-42(2006). RN [40] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 19-257 IN COMPLEXES WITH HEPARIN, RP IDENTIFICATION BY MASS SPECTROMETRY, AND GLYCOSYLATION AT ASN-248. RX PubMed=18065761; DOI=10.1074/jbc.m705203200; RA Tan K., Duquette M., Liu J.-H., Shanmugasundaram K., Joachimiak A., RA Gallagher J.T., Rigby A.C., Wang J.-H., Lawler J.; RT "Heparin-induced cis- and trans-dimerization modes of the thrombospondin-1 RT N-terminal domain."; RL J. Biol. Chem. 283:3932-3941(2008). CC -!- FUNCTION: Adhesive glycoprotein that mediates cell-to-cell and cell-to- CC matrix interactions (PubMed:2430973, PubMed:6489349, PubMed:15014436, CC PubMed:18285447). Multifunctional, involved in inflammation, CC angiogenesis, wound healing, reactive oxygen species (ROS) signaling, CC nitrous oxide (NO) signaling, apoptosis, senescence, aging, cellular CC self-renewal, stemness, and cardiovascular and metabolic homeostasis CC (PubMed:14568985, PubMed:1371676, PubMed:10613822, PubMed:11134179, CC PubMed:24511121, PubMed:29042481, PubMed:32679764). Negatively CC modulates dendritic cell activation and cytokine release, as part of an CC autocrine feedback loop, contributing to the resolution of inflammation CC and immune homeostasis (PubMed:14568985). Ligand for receptor CD47 CC (PubMed:8550562, PubMed:19004835). Modulates nitrous oxide (NO) CC signaling via CD47, hence playing a role as a pressor agent, supporting CC blood pressure (By similarity). Plays a role in endothelial cell CC senescence, acting via CD47, by increasing the abundance and activation CC of NADPH oxidase NOX1, and so generating excess ROS (PubMed:29042481). CC Inhibits stem cell self-renewal, acting via CD47 signaling, probably by CC regulation of the stem cell transcription factors POU5F1/OCT4, SOX2, CC MYC/c-Myc and KLF4 (By similarity). Negatively modulates wound healing, CC acting via CD47 (By similarity). Ligand for receptor CD36 CC (PubMed:1371676, PubMed:10613822, PubMed:11134179). Involved in CC inducing apoptosis in podocytes in response to elevated free fatty CC acids, acting via CD36 (By similarity). Plays a role in suppressing CC angiogenesis, acting, depending on context, via CD36 or CD47 CC (PubMed:1371676, PubMed:10613822, PubMed:32679764, PubMed:11134179). CC Promotes cellular senescence in a TP53-CDKN1A-RB1 signaling-dependent CC manner (PubMed:29042481). Ligand for immunoglobulin-like cell surface CC receptor SIRPA (PubMed:24511121). Involved in ROS signaling in non- CC phagocytic cells, stimulating NADPH oxidase-derived ROS production, CC acting via interaction with SIRPA (PubMed:24511121). Plays a role in CC metabolic dysfunction in diet-induced obesity, perhaps acting by CC exacerbating adipose inflammatory activity; its effects may be CC mediated, at least in part, through enhanced adipocyte proliferation CC (By similarity). Plays a role in ER stress response, via its CC interaction with the activating transcription factor 6 alpha (ATF6) CC which produces adaptive ER stress response factors (By similarity). May CC be involved in age-related conditions, including metabolic CC dysregulation, during normal aging (PubMed:29042481, PubMed:32679764). CC {ECO:0000250|UniProtKB:P35441, ECO:0000269|PubMed:10613822, CC ECO:0000269|PubMed:11134179, ECO:0000269|PubMed:1371676, CC ECO:0000269|PubMed:14568985, ECO:0000269|PubMed:15014436, CC ECO:0000269|PubMed:18285447, ECO:0000269|PubMed:19004835, CC ECO:0000269|PubMed:2430973, ECO:0000269|PubMed:24511121, CC ECO:0000269|PubMed:29042481, ECO:0000269|PubMed:32679764, CC ECO:0000269|PubMed:6489349, ECO:0000269|PubMed:8550562}. CC -!- SUBUNIT: Homotrimer; disulfide-linked (PubMed:101549, PubMed:18285447). CC Can bind to fibrinogen, fibronectin, laminin, type V collagen and CC integrins alpha-V/beta-1, alpha-V/beta-3 and alpha-IIb/beta-3 CC (PubMed:6489349, PubMed:6693501, PubMed:2478219). Binds heparin CC (PubMed:101549, PubMed:16407063, PubMed:18065761). Interacts (via the CC C-terminal domain) with CD47 (PubMed:8550562, PubMed:19004835). CC Interacts (via the TSP type I repeats) with CD36; the interaction CC conveys an antiangiogenic effect (PubMed:1371676, PubMed:10613822). CC Interacts (via the TSP type I repeats) with HRG; the interaction blocks CC the antiangiogenic effect of THBS1 with CD36 (PubMed:11134179). CC Interacts with ATF6 (via lumenal domain) (By similarity). Interacts CC with FN1; this interaction is enhanced by TNFAIP6, which may act as a CC bridging molecule between FN1 and THBS1 (PubMed:18042364). Interacts CC with SIRPA; the interaction stimulates phosphorylation of SIRPA CC (PubMed:24511121). {ECO:0000250|UniProtKB:P35441, CC ECO:0000269|PubMed:101549, ECO:0000269|PubMed:10613822, CC ECO:0000269|PubMed:11134179, ECO:0000269|PubMed:1371676, CC ECO:0000269|PubMed:16407063, ECO:0000269|PubMed:18042364, CC ECO:0000269|PubMed:18065761, ECO:0000269|PubMed:18285447, CC ECO:0000269|PubMed:19004835, ECO:0000269|PubMed:24511121, CC ECO:0000269|PubMed:2478219, ECO:0000269|PubMed:6489349, CC ECO:0000269|PubMed:6693501, ECO:0000269|PubMed:8550562}. CC -!- INTERACTION: CC P07996; P02751: FN1; NbExp=2; IntAct=EBI-2530274, EBI-1220319; CC P07996; Q15113: PCOLCE; NbExp=3; IntAct=EBI-2530274, EBI-8869614; CC P07996; P01137: TGFB1; NbExp=2; IntAct=EBI-2530274, EBI-779636; CC PRO_0000035842; P16671: CD36; NbExp=2; IntAct=EBI-13915509, EBI-2808214; CC PRO_0000035842; Q92743: HTRA1; NbExp=2; IntAct=EBI-13915509, EBI-352256; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:101549, CC ECO:0000269|PubMed:14568985, ECO:0000269|PubMed:6777381}. Cell surface CC {ECO:0000269|PubMed:6777381}. Secreted, extracellular space, CC extracellular matrix {ECO:0000269|PubMed:18285447, CC ECO:0000269|PubMed:6341993}. Endoplasmic reticulum CC {ECO:0000250|UniProtKB:P35441}. Sarcoplasmic reticulum CC {ECO:0000250|UniProtKB:P35441}. Note=Secreted by thrombin-activated CC platelets and binds to the cell surface in the presence of CC extracellular Ca(2+) (PubMed:6777381, PubMed:101549). Incorporated into CC the extracellular matrix (ECM) of fibroblasts (PubMed:6341993). The C- CC terminal region in trimeric form is required for retention in the ECM CC (PubMed:18285447). Also detected in the endoplasmic reticulum and CC sarcoplasmic reticulum where it plays a role in the ER stress response CC (By similarity). {ECO:0000250|UniProtKB:P35441, CC ECO:0000269|PubMed:6341993, ECO:0000269|PubMed:6777381}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P07996-1; Sequence=Displayed; CC Name=2; CC IsoId=P07996-2; Sequence=VSP_055757; CC -!- TISSUE SPECIFICITY: Expressed by platelets (at protein level) CC (PubMed:101549). Expressed by monocyte-derived immature and mature CC dendritic cells (at protein level) (PubMed:14568985). CC {ECO:0000269|PubMed:101549, ECO:0000269|PubMed:14568985}. CC -!- INDUCTION: Expression is induced by PGE2, S.aureus and CC lipopolysaccharide (PubMed:14568985). Induced in arteries and lung CC parenchyma following injury or stress (PubMed:27742621). Expression in CC vasculature, including arteries, increases in normal aging CC (PubMed:32679764, PubMed:29042481). {ECO:0000269|PubMed:14568985, CC ECO:0000269|PubMed:27742621, ECO:0000269|PubMed:29042481, CC ECO:0000269|PubMed:32679764}. CC -!- SIMILARITY: Belongs to the thrombospondin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD93149.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42548/THBS1"; 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; X04665; CAA28370.1; -; mRNA. DR EMBL; X14787; CAA32889.1; -; mRNA. DR EMBL; AK291639; BAF84328.1; -; mRNA. DR EMBL; AK304754; BAG65509.1; -; mRNA. DR EMBL; AB209912; BAD93149.1; ALT_INIT; mRNA. DR EMBL; AC037198; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC136469; AAI36470.1; -; mRNA. DR EMBL; BC136470; AAI36471.1; -; mRNA. DR EMBL; M25631; AAA36741.1; -; mRNA. DR EMBL; M14326; AAA61237.1; ALT_SEQ; mRNA. DR EMBL; J04835; AAA61178.1; -; Genomic_DNA. DR EMBL; M99425; AAB59366.1; -; mRNA. DR CCDS; CCDS32194.1; -. [P07996-1] DR PIR; A26155; TSHUP1. DR RefSeq; NP_003237.2; NM_003246.3. [P07996-1] DR PDB; 1LSL; X-ray; 1.90 A; A=434-546. DR PDB; 1UX6; X-ray; 1.90 A; A=834-1170. DR PDB; 1Z78; X-ray; 1.80 A; A=19-233. DR PDB; 1ZA4; X-ray; 1.90 A; A=19-257. DR PDB; 2ERF; X-ray; 1.45 A; A=25-233. DR PDB; 2ES3; X-ray; 1.85 A; A/B=25-233. DR PDB; 2OUH; X-ray; 2.40 A; A/B=19-257. DR PDB; 2OUJ; X-ray; 1.90 A; A=19-257. DR PDB; 3R6B; X-ray; 2.40 A; A=434-547. DR PDB; 5FOE; X-ray; 1.98 A; A/B=378-429. DR PDB; 7YYK; X-ray; 2.60 A; A=378-547. DR PDBsum; 1LSL; -. DR PDBsum; 1UX6; -. DR PDBsum; 1Z78; -. DR PDBsum; 1ZA4; -. DR PDBsum; 2ERF; -. DR PDBsum; 2ES3; -. DR PDBsum; 2OUH; -. DR PDBsum; 2OUJ; -. DR PDBsum; 3R6B; -. DR PDBsum; 5FOE; -. DR PDBsum; 7YYK; -. DR AlphaFoldDB; P07996; -. DR SMR; P07996; -. DR BioGRID; 112915; 116. DR ComplexPortal; CPX-1785; Thrombospondin 1 complex. DR CORUM; P07996; -. DR DIP; DIP-1037N; -. DR IntAct; P07996; 30. DR MINT; P07996; -. DR STRING; 9606.ENSP00000260356; -. DR BindingDB; P07996; -. DR ChEMBL; CHEMBL4630810; -. DR GlyConnect; 594; 88 N-Linked glycans (6 sites), 1 O-Fuc glycan (1 site), 1 O-Linked glycan (3 sites). DR GlyCosmos; P07996; 15 sites, 94 glycans. DR GlyGen; P07996; 21 sites, 1 C-linked glycan (5 sites), 90 N-linked glycans (6 sites), 4 O-linked glycans (11 sites). DR iPTMnet; P07996; -. DR MetOSite; P07996; -. DR PhosphoSitePlus; P07996; -. DR SwissPalm; P07996; -. DR BioMuta; THBS1; -. DR DMDM; 117949802; -. DR OGP; P07996; -. DR CPTAC; non-CPTAC-1162; -. DR EPD; P07996; -. DR jPOST; P07996; -. DR MassIVE; P07996; -. DR MaxQB; P07996; -. DR PaxDb; 9606-ENSP00000260356; -. DR PeptideAtlas; P07996; -. DR ProteomicsDB; 52058; -. [P07996-1] DR Pumba; P07996; -. DR ABCD; P07996; 6 sequenced antibodies. DR Antibodypedia; 9950; 768 antibodies from 38 providers. DR DNASU; 7057; -. DR Ensembl; ENST00000260356.6; ENSP00000260356.5; ENSG00000137801.11. [P07996-1] DR GeneID; 7057; -. DR KEGG; hsa:7057; -. DR MANE-Select; ENST00000260356.6; ENSP00000260356.5; NM_003246.4; NP_003237.2. DR UCSC; uc001zkh.4; human. [P07996-1] DR AGR; HGNC:11785; -. DR CTD; 7057; -. DR DisGeNET; 7057; -. DR GeneCards; THBS1; -. DR HGNC; HGNC:11785; THBS1. DR HPA; ENSG00000137801; Low tissue specificity. DR MIM; 188060; gene. DR neXtProt; NX_P07996; -. DR OpenTargets; ENSG00000137801; -. DR PharmGKB; PA36497; -. DR VEuPathDB; HostDB:ENSG00000137801; -. DR eggNOG; ENOG502QRK8; Eukaryota. DR GeneTree; ENSGT00940000155832; -. DR HOGENOM; CLU_009257_0_0_1; -. DR InParanoid; P07996; -. DR OMA; AVPDDKF; -. DR OrthoDB; 5345349at2759; -. DR PhylomeDB; P07996; -. DR TreeFam; TF324917; -. DR PathwayCommons; P07996; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-186797; Signaling by PDGF. DR Reactome; R-HSA-216083; Integrin cell surface interactions. DR Reactome; R-HSA-3000170; Syndecan interactions. DR Reactome; R-HSA-5083635; Defective B3GALTL causes PpS. DR Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins. DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function. DR SignaLink; P07996; -. DR SIGNOR; P07996; -. DR BioGRID-ORCS; 7057; 10 hits in 1076 CRISPR screens. DR ChiTaRS; THBS1; human. DR EvolutionaryTrace; P07996; -. DR GeneWiki; Thrombospondin_1; -. DR GenomeRNAi; 7057; -. DR Pharos; P07996; Tchem. DR PRO; PR:P07996; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; P07996; Protein. DR Bgee; ENSG00000137801; Expressed in stromal cell of endometrium and 190 other cell types or tissues. DR ExpressionAtlas; P07996; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0005577; C:fibrinogen complex; IDA:BHF-UCL. DR GO; GO:0031091; C:platelet alpha granule; IDA:BHF-UCL. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0016529; C:sarcoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0030141; C:secretory granule; IDA:BHF-UCL. DR GO; GO:0005509; F:calcium ion binding; NAS:BHF-UCL. DR GO; GO:0070052; F:collagen V binding; IDA:BHF-UCL. DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:BHF-UCL. DR GO; GO:0005201; F:extracellular matrix structural constituent; HDA:BHF-UCL. DR GO; GO:0070051; F:fibrinogen binding; IDA:BHF-UCL. DR GO; GO:0017134; F:fibroblast growth factor binding; IDA:BHF-UCL. DR GO; GO:0001968; F:fibronectin binding; IDA:UniProtKB. DR GO; GO:0008201; F:heparin binding; IDA:BHF-UCL. DR GO; GO:0005178; F:integrin binding; IMP:BHF-UCL. DR GO; GO:0043236; F:laminin binding; IDA:BHF-UCL. DR GO; GO:0030169; F:low-density lipoprotein particle binding; IDA:BHF-UCL. DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB. DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL. DR GO; GO:0043394; F:proteoglycan binding; TAS:BHF-UCL. DR GO; GO:0050431; F:transforming growth factor beta binding; ISS:BHF-UCL. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0048266; P:behavioral response to pain; ISS:UniProtKB. DR GO; GO:0007155; P:cell adhesion; NAS:BHF-UCL. DR GO; GO:0016477; P:cell migration; IDA:BHF-UCL. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl. DR GO; GO:0034605; P:cellular response to heat; NAS:BHF-UCL. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0002544; P:chronic inflammatory response; IEP:BHF-UCL. DR GO; GO:0043652; P:engulfment of apoptotic cell; IDA:BHF-UCL. DR GO; GO:0006955; P:immune response; IEP:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; IDA:CACAO. DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0002581; P:negative regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II; IDA:BHF-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:BHF-UCL. DR GO; GO:1903588; P:negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IMP:BHF-UCL. DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IMP:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; IDA:MGI. DR GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; IDA:BHF-UCL. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0002605; P:negative regulation of dendritic cell antigen processing and presentation; IDA:BHF-UCL. DR GO; GO:2001027; P:negative regulation of endothelial cell chemotaxis; IDA:MGI. DR GO; GO:0010596; P:negative regulation of endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IDA:MGI. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; TAS:BHF-UCL. DR GO; GO:0051918; P:negative regulation of fibrinolysis; IDA:BHF-UCL. DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; TAS:BHF-UCL. DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IDA:BHF-UCL. DR GO; GO:0010748; P:negative regulation of long-chain fatty acid import across plasma membrane; IDA:BHF-UCL. DR GO; GO:0010751; P:negative regulation of nitric oxide mediated signal transduction; IDA:MGI. DR GO; GO:0010757; P:negative regulation of plasminogen activation; IDA:BHF-UCL. DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; IGI:BHF-UCL. DR GO; GO:0018149; P:peptide cross-linking; IDA:BHF-UCL. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL. DR GO; GO:0030194; P:positive regulation of blood coagulation; IDA:BHF-UCL. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0050921; P:positive regulation of chemotaxis; IDA:BHF-UCL. DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IDA:UniProtKB. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:BHF-UCL. DR GO; GO:1902043; P:positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; IDA:BHF-UCL. DR GO; GO:0010763; P:positive regulation of fibroblast migration; IDA:BHF-UCL. DR GO; GO:0043032; P:positive regulation of macrophage activation; IDA:BHF-UCL. DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISS:BHF-UCL. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IMP:BHF-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:0042327; P:positive regulation of phosphorylation; IMP:BHF-UCL. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA:BHF-UCL. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL. DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0032914; P:positive regulation of transforming growth factor beta1 production; ISS:BHF-UCL. DR GO; GO:0045727; P:positive regulation of translation; IDA:BHF-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB. DR GO; GO:0051592; P:response to calcium ion; IDA:BHF-UCL. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB. DR GO; GO:0009749; P:response to glucose; IDA:BHF-UCL. DR GO; GO:0001666; P:response to hypoxia; NAS:BHF-UCL. DR GO; GO:0032026; P:response to magnesium ion; IDA:BHF-UCL. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0032570; P:response to progesterone; TAS:BHF-UCL. DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl. DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:UniProtKB. DR GO; GO:0002040; P:sprouting angiogenesis; IMP:BHF-UCL. DR CDD; cd00054; EGF_CA; 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; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR024731; EGF_dom. 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; PF12947; EGF_3; 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; SM00181; EGF; 3. 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. DR Genevisible; P07996; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Angiogenesis; Apoptosis; Calcium; KW Cell adhesion; 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 CHAIN 19..1170 FT /note="Thrombospondin-1" FT /id="PRO_0000035842" FT DOMAIN 65..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 REGION 531..1152 FT /note="Involved in retention in extracellular matrix (ECM); FT involved in trimer formation" FT /evidence="ECO:0000269|PubMed:18285447" FT REGION 839..934 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 926..928 FT /note="Cell attachment site" FT /evidence="ECO:0000305" FT COMPBIAS 841..868 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 883..897 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 903..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:0000305|PubMed:16263699, FT ECO:0000305|PubMed:16335952, ECO:0000305|PubMed:18065761" 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:0000269|PubMed:11067851" FT /id="CAR_000205" FT CARBOHYD 394 FT /note="O-linked (Fuc...) serine" FT /evidence="ECO:0000269|PubMed:11067851" FT /id="CAR_000206" FT CARBOHYD 438 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000269|PubMed:11067851" FT /id="CAR_000207" FT CARBOHYD 441 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000269|PubMed:11067851" FT /id="CAR_000208" FT CARBOHYD 450 FT /note="O-linked (Fuc...) threonine" FT /evidence="ECO:0000269|PubMed:11067851, FT ECO:0000269|PubMed:12391027" FT /id="CAR_000209" FT CARBOHYD 498 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000269|PubMed:11067851" FT /id="CAR_000210" FT CARBOHYD 507 FT /note="O-linked (Fuc...) threonine" FT /evidence="ECO:0000269|PubMed:11067851, FT ECO:0000269|PubMed:12391027" FT /id="CAR_000211" 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:15014436, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16740002, FT ECO:0000269|PubMed:19159218" FT DISULFID 171..232 FT /evidence="ECO:0000269|PubMed:16407063, FT ECO:0000269|PubMed:18065761, ECO:0007744|PDB:1Z78, FT ECO:0007744|PDB:2ERF, ECO:0007744|PDB:2ES3, FT ECO:0007744|PDB:2OUH, ECO:0007744|PDB:2OUJ" 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 DISULFID 395..428 FT DISULFID 406..413 FT DISULFID 447..484 FT /evidence="ECO:0000269|PubMed:12391027, FT ECO:0007744|PDB:1LSL" FT DISULFID 451..489 FT /evidence="ECO:0000269|PubMed:12391027, FT ECO:0007744|PDB:1LSL" FT DISULFID 462..474 FT /evidence="ECO:0000269|PubMed:12391027, FT ECO:0007744|PDB:1LSL" FT DISULFID 504..541 FT /evidence="ECO:0000269|PubMed:12391027, FT ECO:0007744|PDB:1LSL" FT DISULFID 508..546 FT /evidence="ECO:0000269|PubMed:12391027, FT ECO:0007744|PDB:1LSL" FT DISULFID 519..531 FT /evidence="ECO:0000269|PubMed:12391027, FT ECO:0007744|PDB:1LSL" 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:0000269|PubMed:15014436, FT ECO:0007744|PDB:1UX6" FT DISULFID 874..894 FT /evidence="ECO:0000269|PubMed:15014436, FT ECO:0007744|PDB:1UX6" FT DISULFID 910..930 FT /evidence="ECO:0000269|PubMed:15014436, FT ECO:0007744|PDB:1UX6" FT DISULFID 946..1167 FT /evidence="ECO:0000269|PubMed:15014436, FT ECO:0007744|PDB:1UX6" FT VAR_SEQ 17..101 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055757" FT VARIANT 24 FT /note="S -> A (in dbSNP:rs41515347)" FT /id="VAR_052657" FT VARIANT 523 FT /note="T -> A (in dbSNP:rs2292305)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:2918029" FT /id="VAR_028938" FT VARIANT 700 FT /note="N -> S (in dbSNP:rs2228262)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_028939" FT MUTAGEN 926 FT /note="R->V: Reduces attachment to cells and retention in FT extracellular matrix (ECM); retention in ECM partially FT dependent on beta-1 integrin." FT /evidence="ECO:0000269|PubMed:18285447" FT MUTAGEN 1019..1021 FT /note="DDD->AAA: Reduces attachment to cells and retention FT in extracellular matrix." FT /evidence="ECO:0000269|PubMed:18285447" FT MUTAGEN 1067 FT /note="N->K: Loss of N-glycosylation site." FT /evidence="ECO:0000269|PubMed:15014436" FT CONFLICT 4 FT /note="A -> S (in Ref. 3; BAG65509)" FT /evidence="ECO:0000305" FT CONFLICT 84 FT /note="A -> T (in Ref. 1; CAA28370 and 9; AAA61178)" FT /evidence="ECO:0000305" FT CONFLICT 431 FT /note="R -> I (in Ref. 3; BAG65509)" FT /evidence="ECO:0000305" FT CONFLICT 451 FT /note="C -> R (in Ref. 3; BAG65509)" FT /evidence="ECO:0000305" FT CONFLICT 546 FT /note="C -> Y (in Ref. 3; BAF84328)" FT /evidence="ECO:0000305" FT CONFLICT 812 FT /note="N -> D (in Ref. 3; BAG65509)" FT /evidence="ECO:0000305" FT CONFLICT 1008 FT /note="F -> S (in Ref. 3; BAF84328)" FT /evidence="ECO:0000305" FT STRAND 30..32 FT /evidence="ECO:0007829|PDB:2ERF" FT HELIX 33..37 FT /evidence="ECO:0007829|PDB:2ERF" FT TURN 38..41 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 44..49 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 58..62 FT /evidence="ECO:0007829|PDB:2ERF" FT HELIX 64..66 FT /evidence="ECO:0007829|PDB:2ERF" FT HELIX 72..85 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 87..96 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 101..109 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 115..122 FT /evidence="ECO:0007829|PDB:2ERF" FT TURN 123..126 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 127..134 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 137..145 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 150..161 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 164..169 FT /evidence="ECO:0007829|PDB:2ERF" FT TURN 170..172 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 173..178 FT /evidence="ECO:0007829|PDB:2ERF" FT HELIX 183..185 FT /evidence="ECO:0007829|PDB:2ERF" FT HELIX 191..194 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 195..200 FT /evidence="ECO:0007829|PDB:2ERF" FT TURN 203..205 FT /evidence="ECO:0007829|PDB:2ERF" FT STRAND 210..218 FT /evidence="ECO:0007829|PDB:2ERF" FT HELIX 223..228 FT /evidence="ECO:0007829|PDB:2ERF" FT TURN 229..231 FT /evidence="ECO:0007829|PDB:2OUH" FT STRAND 394..403 FT /evidence="ECO:0007829|PDB:5FOE" FT TURN 408..410 FT /evidence="ECO:0007829|PDB:5FOE" FT STRAND 417..424 FT /evidence="ECO:0007829|PDB:5FOE" FT STRAND 450..459 FT /evidence="ECO:0007829|PDB:1LSL" FT STRAND 469..471 FT /evidence="ECO:0007829|PDB:7YYK" FT STRAND 478..485 FT /evidence="ECO:0007829|PDB:1LSL" FT STRAND 507..509 FT /evidence="ECO:0007829|PDB:1LSL" FT STRAND 511..516 FT /evidence="ECO:0007829|PDB:1LSL" FT STRAND 535..541 FT /evidence="ECO:0007829|PDB:1LSL" FT TURN 838..840 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 849..852 FT /evidence="ECO:0007829|PDB:1UX6" FT TURN 854..856 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 865..867 FT /evidence="ECO:0007829|PDB:1UX6" FT HELIX 869..871 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 888..890 FT /evidence="ECO:0007829|PDB:1UX6" FT HELIX 892..894 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 901..903 FT /evidence="ECO:0007829|PDB:1UX6" FT HELIX 905..907 FT /evidence="ECO:0007829|PDB:1UX6" FT TURN 909..912 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 924..926 FT /evidence="ECO:0007829|PDB:1UX6" FT HELIX 928..930 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 937..939 FT /evidence="ECO:0007829|PDB:1UX6" FT TURN 941..943 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 961..965 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 986..988 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 995..1014 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1022..1031 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1034..1043 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1051..1053 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1059..1067 FT /evidence="ECO:0007829|PDB:1UX6" FT HELIX 1074..1081 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1082..1084 FT /evidence="ECO:0007829|PDB:1UX6" FT TURN 1087..1089 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1090..1095 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1107..1115 FT /evidence="ECO:0007829|PDB:1UX6" FT TURN 1116..1119 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1120..1127 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1130..1134 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1146..1154 FT /evidence="ECO:0007829|PDB:1UX6" FT STRAND 1156..1167 FT /evidence="ECO:0007829|PDB:1UX6" SQ SEQUENCE 1170 AA; 129383 MW; 74749B2418E0943B CRC64; MGLAWGLGVL FLMHVCGTNR IPESGGDNSV FDIFELTGAA RKGSGRRLVK GPDPSSPAFR IEDANLIPPV PDDKFQDLVD AVRAEKGFLL LASLRQMKKT RGTLLALERK DHSGQVFSVV SNGKAGTLDL SLTVQGKQHV VSVEEALLAT GQWKSITLFV QEDRAQLYID CEKMENAELD VPIQSVFTRD LASIARLRIA KGGVNDNFQG VLQNVRFVFG TTPEDILRNK GCSSSTSVLL TLDNNVVNGS SPAIRTNYIG HKTKDLQAIC GISCDELSSM VLELRGLRTI VTTLQDSIRK VTEENKELAN ELRRPPLCYH NGVQYRNNEE WTVDSCTECH CQNSVTICKK VSCPIMPCSN ATVPDGECCP RCWPSDSADD GWSPWSEWTS CSTSCGNGIQ QRGRSCDSLN NRCEGSSVQT RTCHIQECDK RFKQDGGWSH WSPWSSCSVT CGDGVITRIR LCNSPSPQMN GKPCEGEARE TKACKKDACP INGGWGPWSP WDICSVTCGG GVQKRSRLCN NPTPQFGGKD CVGDVTENQI CNKQDCPIDG CLSNPCFAGV KCTSYPDGSW KCGACPPGYS GNGIQCTDVD ECKEVPDACF NHNGEHRCEN TDPGYNCLPC PPRFTGSQPF GQGVEHATAN KQVCKPRNPC TDGTHDCNKN AKCNYLGHYS DPMYRCECKP GYAGNGIICG EDTDLDGWPN ENLVCVANAT YHCKKDNCPN LPNSGQEDYD KDGIGDACDD DDDNDKIPDD RDNCPFHYNP AQYDYDRDDV GDRCDNCPYN HNPDQADTDN NGEGDACAAD IDGDGILNER DNCQYVYNVD QRDTDMDGVG DQCDNCPLEH NPDQLDSDSD RIGDTCDNNQ DIDEDGHQNN LDNCPYVPNA NQADHDKDGK GDACDHDDDN DGIPDDKDNC RLVPNPDQKD SDGDGRGDAC KDDFDHDSVP DIDDICPENV DISETDFRRF QMIPLDPKGT SQNDPNWVVR HQGKELVQTV NCDPGLAVGY DEFNAVDFSG TFFINTERDD DYAGFVFGYQ SSSRFYVVMW KQVTQSYWDT NPTRAQGYSG LSVKVVNSTT GPGEHLRNAL WHTGNTPGQV RTLWHDPRHI GWKDFTAYRW RLSHRPKTGF IRVVMYEGKK IMADSGPIYD KTYAGGRLGL FVFSQEMVFF SDLKYECRDP //