{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:48:01Z","timestamp":1790826481188,"version":"4.1.0"},"reference-count":213,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Eb177\/13-1"],"award-info":[{"award-number":["Eb177\/13-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Snake venoms contain an astounding variety of different proteins. Among them are numerous C-type lectin family members, which are grouped into classical Ca2+- and sugar-binding lectins and the non-sugar-binding snake venom C-type lectin-related proteins (SV-CLRPs), also called snaclecs. Both groups share the robust C-type lectin domain (CTLD) fold but differ in a long loop, which either contributes to a sugar-binding site or is expanded into a loop-swapping heterodimerization domain between two CLRP subunits. Most C-type lectin (-related) proteins assemble in ordered supramolecular complexes with a high versatility of subunit numbers and geometric arrays. Similarly versatile is their ability to inhibit or block their target molecules as well as to agonistically stimulate or antagonistically blunt a cellular reaction triggered by their target receptor. By utilizing distinct interaction sites differentially, SV-CLRPs target a plethora of molecules, such as distinct coagulation factors and receptors of platelets and endothelial cells that are involved in hemostasis, thrombus formation, inflammation and hematogenous metastasis. Because of their robust structure and their high affinity towards their clinically relevant targets, SV-CLRPs are and will potentially be valuable prototypes to develop new diagnostic and therapeutic tools in medicine, provided that the molecular mechanisms underlying their versatility are disclosed.<\/jats:p>","DOI":"10.3390\/toxins11030136","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T05:45:36Z","timestamp":1551678336000},"page":"136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Structurally Robust and Functionally Highly Versatile\u2014C-Type Lectin (-Related) Proteins in Snake Venoms"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-2137","authenticated-orcid":false,"given":"Johannes A.","family":"Eble","sequence":"first","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, University of M\u00fcnster, Waldeyerstr. 15, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0304-4165(02)00308-2","article-title":"Animal lectins: A historical introduction and overview","volume":"1572","author":"Kilpatrick","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1111\/j.1742-4658.2005.05031.x","article-title":"The C-type lectin-like domain superfamily","volume":"272","author":"Zelensky","year":"2005","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0959-440X(99)00009-3","article-title":"C-type lectin-like domains","volume":"9","author":"Drickamer","year":"1999","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/prot.10626","article-title":"Comparative analysis of structural properties of the C-type-lectin-like domain (CTLD)","volume":"52","author":"Zelensky","year":"2003","journal-title":"Proteins"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/S0092-8674(00)80151-8","article-title":"Solution structure of the link module: A hyaluronan-binding domain involved in extracellular matrix stability and cell migration","volume":"86","author":"Kohda","year":"1996","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1126\/science.286.5438.291","article-title":"Crystal structure of invasin: A bacterial integrin-binding protein","volume":"286","author":"Hamburger","year":"1999","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/7545","article-title":"Structure of the cell-adhesion fragment of intimin from enteropathogenic Escherichia coli","volume":"6","author":"Kelly","year":"1999","journal-title":"Nat. Struct. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2174\/156720106775197475","article-title":"Bacterial invasin: Structure, function, and implication for targeted oral gene delivery","volume":"3","author":"Palumbo","year":"2006","journal-title":"Curr. Drug Deliv."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/BF01887396","article-title":"Knowledge-based model building of the tertiary structures for lectin domains of the selectin family","volume":"15","author":"Chou","year":"1996","journal-title":"J. Protein Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/367532a0","article-title":"Insight into E-selectin\/ligand interaction from the crystal structure and mutagenesis of the lec\/EGF domains","volume":"367","author":"Graves","year":"1994","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1002\/bies.950141210","article-title":"The selectin family of carbohydrate-binding proteins: Structure and importance of carbohydrate ligands for cell adhesion","volume":"14","author":"Cummings","year":"1992","journal-title":"Bioessays"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.matbio.2015.02.003","article-title":"Proteoglycan form and function: A comprehensive nomenclature of proteoglycans","volume":"42","author":"Iozzo","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxicon.2004.07.028","article-title":"Molecular diversity and accelerated evolution of C-type lectin-like proteins from snake venom","volume":"45","author":"Ogawa","year":"2005","journal-title":"Toxicon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nsb0697-438","article-title":"Structure of coagulation factors IX\/X-binding protein, a heterodimer of C-type lectin domains","volume":"4","author":"Mizuno","year":"1997","journal-title":"Nat. Struct. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0378-1119(97)00024-3","article-title":"Structures of genes encoding phospholipase A2 inhibitors from the serum of Trimeresurus flavoviridis snake","volume":"191","author":"Nobuhisa","year":"1997","journal-title":"Gene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1111\/j.1432-1033.1997.00838.x","article-title":"Characterization and evolution of a gene encoding a Trimeresurus flavoviridis serum protein that inhibits basic phospholipase A2 isozymes in the snake\u2019s venom","volume":"249","author":"Nobuhisa","year":"1997","journal-title":"Eur. J. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.biocel.2018.09.011","article-title":"Snake venom components in medicine: From the symbolic rod of Asclepius to tangible medical research and application","volume":"104","author":"Johanningmeier","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17063","DOI":"10.1038\/nrdp.2017.63","article-title":"Snakebite envenoming","volume":"3","author":"Gutierrez","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/j.toxicon.2010.03.011","article-title":"Snaclecs (snake C-type lectins) that inhibit or activate platelets by binding to receptors","volume":"56","author":"Clemetson","year":"2010","journal-title":"Toxicon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0014-5793(80)80902-1","article-title":"Thrombolectin: A lectin isolated from Bothrops atrox venom","volume":"117","author":"Gartner","year":"1980","journal-title":"FEBS Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.toxicon.2014.02.018","article-title":"A lectin from Bothrops leucurus snake venom raises cytosolic calcium levels and promotes B16-F10 melanoma necrotic cell death via mitochondrial permeability transition","volume":"82","author":"Rossato","year":"2014","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ijbiomac.2012.11.018","article-title":"Biochemical and functional characterization of a C-type lectin (BpLec) from Bothrops pauloensis snake venom","volume":"54","author":"Castanheira","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jprot.2007.10.004","article-title":"Snake venomics of the South and Central American Bushmasters. Comparison of the toxin composition of Lachesis muta gathered from proteomic versus transcriptomic analysis","volume":"71","author":"Sanz","year":"2008","journal-title":"J. Proteomics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cbpb.2006.11.022","article-title":"Amino acid sequence and characterization of C-type lectin purified from the snake venom of Crotalus ruber","volume":"146","author":"Hamako","year":"2007","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jchromb.2006.02.036","article-title":"Simple affinity chromatographic procedure to purify \u03b2-galactoside binding lectins","volume":"838","author":"Netto","year":"2006","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2004.08.018","article-title":"Cloning, characterization, and structural analysis of a C-type lectin from Bothrops insularis (BiL) venom","volume":"432","author":"DL","year":"2004","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1016\/S0021-9258(18)52246-8","article-title":"Complete primary structure of a galactose-specific lectin from the venom of the rattlesnake Crotalus atrox. Homologies with Ca2(+)-dependent-type lectins","volume":"266","author":"Hirabayashi","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1093\/oxfordjournals.jbchem.a121848","article-title":"Isolation and characterization of lactose-binding lectins from the venoms of the snakes Lachesis muta and Dendroaspis jamesonii","volume":"100","author":"Ogilvie","year":"1986","journal-title":"J. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1042\/bj3410733","article-title":"Cloning of a galactose-binding lectin from the venom of Trimeresurus stejnegeri","volume":"341","author":"Xu","year":"1999","journal-title":"Biochem. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1021\/bi035871a","article-title":"X-ray crystal structure of a galactose-specific C-type lectin possessing a novel decameric quaternary structure","volume":"43","author":"Walker","year":"2004","journal-title":"Biochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.toxicon.2016.12.007","article-title":"Structural and binding studies of a C-type galactose-binding lectin from Bothrops jararacussu snake venom","volume":"126","author":"Sartim","year":"2017","journal-title":"Toxicon"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.toxicon.2006.08.006","article-title":"Structure-function inferences based on molecular modeling, sequence-based methods and biological data analysis of snake venom lectins","volume":"48","author":"Abreu","year":"2006","journal-title":"Toxicon"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1016\/S0041-0101(01)00172-6","article-title":"Cloning of cDNAs encoding C-type lectins from Elapidae snakes Bungarus fasciatus and Bungarus multicinctus","volume":"39","author":"Zha","year":"2001","journal-title":"Toxicon"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.toxicon.2018.11.309","article-title":"A C-type lectin from Bothrops leucurus snake venom forms amyloid-like aggregates in RPMI medium and are efficiently phagocytosed by peritoneal macrophages","volume":"157","author":"Lorena","year":"2019","journal-title":"Toxicon"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1006\/bbrc.2000.2693","article-title":"Expression of isolated C-type carbohydrate recognition domains","volume":"271","author":"Xu","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/S0041-0101(98)00239-6","article-title":"Primary structure and biological activity of snake venom lectin (APL) from Agkistrodon p. piscivorus (Eastern cottonmouth)","volume":"37","author":"Komori","year":"1999","journal-title":"Toxicon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1006\/abbi.1994.1043","article-title":"C-type galactoside-binding lectin from Bothrops jararaca venom: Comparison of its structure and function with those of botrocetin","volume":"308","author":"Ozeki","year":"1994","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.biochi.2010.11.006","article-title":"Characterisation of a mannose-binding C-type lectin from Oxyuranus scutellatus snake venom","volume":"93","author":"Earl","year":"2011","journal-title":"Biochimie"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1600-065X.2009.00789.x","article-title":"Mannose-binding lectin and innate immunity","volume":"230","author":"Ip","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Van Asbeck, E.C., Hoepelman, A.I., Scharringa, J., Herpers, B.L., and Verhoef, J. (2008). Mannose binding lectin plays a crucial role in innate immunity against yeast by enhanced complement activation and enhanced uptake of polymorphonuclear cells. BMC Microbiol., 8.","DOI":"10.1186\/1471-2180-8-229"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S440","DOI":"10.1086\/431987","article-title":"The role of the mannose-binding lectin in innate immunity","volume":"41","author":"Takahashi","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.tiv.2017.02.003","article-title":"Effect of BjcuL, a lectin isolated from Bothrops jararacussu, on human peripheral blood mononuclear cells","volume":"41","author":"Pires","year":"2017","journal-title":"Toxicol. In Vitro"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Elifio-Esposito, S., Tomazeli, L., Schwartz, C., Gimenez, A.P., Fugii, G.M., Fernandes, L.C., Zishler, L.F., Stuelp-Campelo, P.M., and Moreno, A.N. (2011). Human neutrophil migration and activation by BJcuL, a galactose binding lectin purified from Bothrops jararacussu venom. BMC Immunol., 12.","DOI":"10.1186\/1471-2172-12-10"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ijbiomac.2017.04.012","article-title":"Angiogenenic effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom","volume":"102","author":"Castanheira","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Klein, R.C., Fabres-Klein, M.H., de Oliveira, L.L., Feio, R.N., Malouin, F., and Ribon Ade, O. (2015). A C-type lectin from Bothrops jararacussu venom disrupts Staphylococcal biofilms. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120514"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1093\/molbev\/msh091","article-title":"Assembling an arsenal: Origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences","volume":"21","author":"Fry","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Junqueira-de-Azevedo, I.L., Campos, P.F., Ching, A.T., and Mackessy, S.P. (2016). Colubrid Venom Composition: An -Omics Perspective. Toxins, 8.","DOI":"10.3390\/toxins8080230"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.toxicon.2005.02.022","article-title":"Snake venom C-type lectins interacting with platelet receptors. Structure-function relationships and effects on haemostasis","volume":"45","author":"Lu","year":"2005","journal-title":"Toxicon"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.toxicon.2005.02.021","article-title":"Structures and functions of snake venom CLPs (C-type lectin-like proteins) with anticoagulant-, procoagulant-, and platelet-modulating activities","volume":"45","author":"Morita","year":"2005","journal-title":"Toxicon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1021\/bi992134z","article-title":"Crystal structure of flavocetin-A, a platelet glycoprotein Ib-binding protein, reveals a novel cyclic tetramer of C-type lectin-like heterodimers","volume":"39","author":"Fukuda","year":"2000","journal-title":"Biochemistry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1160\/TH03-02-0072","article-title":"A tetrameric glycoprotein Ib-binding protein, agglucetin, from Formosan pit viper: Structure and interaction with human platelets","volume":"90","author":"Wang","year":"2003","journal-title":"Thromb. Haemost."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1055\/s-0037-1616536","article-title":"A novel tetrameric venom protein, agglucetin from Agkistrodon acutus, acts as a glycoprotein Ib agonist","volume":"86","author":"Wang","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1042\/bj20031507","article-title":"Crystal structure of a platelet-agglutinating factor isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus)","volume":"378","author":"Huang","year":"2004","journal-title":"Biochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1021\/bi801820q","article-title":"Convulxin forms a dimer in solution and can bind eight copies of glycoprotein VI: Implications for platelet activation","volume":"48","author":"Horii","year":"2009","journal-title":"Biochemistry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.biomaterials.2018.03.028","article-title":"The spatial molecular pattern of integrin recognition sites and their immobilization to colloidal nanobeads determine \u03b12\u03b21 integrin-dependent platelet activation","volume":"167","author":"Lima","year":"2018","journal-title":"Biomaterials"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/jth.12235","article-title":"Platelet receptors activated via mulitmerization: Glycoprotein VI, GPIb-IX-V, and CLEC-2","volume":"11","author":"Ozaki","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1111\/j.1538-7836.2006.01874.x","article-title":"Effect of multimer size and a natural dimorphism on the binding of convulxin to platelet glycoprotein (GP)VI","volume":"4","author":"Kato","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.bbrc.2003.09.032","article-title":"Crystal structure of the platelet activator convulxin, a disulfide-linked \u03b14\u03b24 cyclic tetramer from the venom of Crotalus durissus terrificus","volume":"310","author":"Murakami","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1107\/S0907444903021620","article-title":"Structure of the snake-venom toxin convulxin","volume":"60","author":"Batuwangala","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1159\/000092414","article-title":"Snake C-type lectin-like proteins and platelet receptors","volume":"34","author":"Clemetson","year":"2005","journal-title":"Pathophysiol. Haemost. Thromb."},{"key":"ref_61","first-page":"148","article-title":"Multifunctional snake C-type lectins affecting platelets","volume":"31","author":"Clemetson","year":"2001","journal-title":"Haemostasis"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1159\/000092415","article-title":"Structure-function relationships of C-type lectin-related proteins","volume":"34","author":"Morita","year":"2005","journal-title":"Pathophysiol. Haemost. Thromb."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.toxicon.2012.03.001","article-title":"C-type lectin-like proteins from snake venoms","volume":"60","author":"Arlinghaus","year":"2012","journal-title":"Toxicon"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.thromres.2011.11.002","article-title":"Blood platelet biochemistry","volume":"129","author":"Broos","year":"2012","journal-title":"Thromb. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1177\/0192623310389474","article-title":"Continuing education course #2: Current understanding of hemostasis","volume":"39","author":"Gale","year":"2011","journal-title":"Toxicol. Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1111\/j.1538-7836.2005.01358.x","article-title":"Snake venoms and hemostasis","volume":"3","author":"Lu","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.toxicon.2011.01.006","article-title":"Haemostatically active proteins in snake venoms","volume":"57","author":"Sajevic","year":"2011","journal-title":"Toxicon"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1016\/j.jprot.2011.03.026","article-title":"Key events in microvascular damage induced by snake venom hemorrhagic metalloproteinases","volume":"74","author":"Escalante","year":"2011","journal-title":"J. Proteomics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/0014-4800(92)90004-U","article-title":"Ultrastructural alterations in mouse capillary blood vessels after experimental injection of venom from the snake Bothrops asper (Terciopelo)","volume":"57","author":"Moreira","year":"1992","journal-title":"Exp. Mol. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.bcmd.2006.03.001","article-title":"Blood cells as targets of snake toxins","volume":"36","author":"Du","year":"2006","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/978-3-319-49674-0_13","article-title":"Fibrin formation, structure and properties","volume":"82","author":"Weisel","year":"2017","journal-title":"Subcell. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.toxicon.2012.09.004","article-title":"Snake venom metalloproteinases","volume":"62","author":"Markland","year":"2013","journal-title":"Toxicon"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.toxicon.2012.09.003","article-title":"The long road of research on snake venom serine proteinases","volume":"62","author":"Serrano","year":"2013","journal-title":"Toxicon"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Takeda, S. (2016). ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview. Toxins, 8.","DOI":"10.3390\/toxins8050155"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.ijbiomac.2018.03.164","article-title":"Thrombin-like enzymes from snake venom: Structural characterization and mechanism of action","volume":"114","author":"Ullah","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"14109","DOI":"10.1016\/S0021-9258(19)49685-3","article-title":"Coagulation factor X activating enzyme from Russell\u2019s viper venom (RVV-X). A novel metalloproteinase with disintegrin (platelet aggregation inhibitor)-like and C-type lectin-like domains","volume":"267","author":"Takeya","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5200","DOI":"10.1074\/jbc.271.9.5200","article-title":"Isolation and characterization of carinactivase, a novel prothrombin activator in Echis carinatus venom with a unique catalytic mechanism","volume":"271","author":"Yamada","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"10794","DOI":"10.1021\/bi00091a034","article-title":"Bothrojaracin, a new thrombin inhibitor isolated from Bothrops jararaca venom: Characterization and mechanism of thrombin inhibition","volume":"32","author":"Zingali","year":"1993","journal-title":"Biochemistry"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1006\/bbrc.1999.1297","article-title":"Allosteric changes of thrombin catalytic site induced by interaction of bothrojaracin with anion-binding exosites I and II","volume":"262","author":"Monteiro","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/abbi.2000.2006","article-title":"Inhibition of prothrombin activation by bothrojaracin, a C-type lectin from Bothrops jararaca venom","volume":"382","author":"Monteiro","year":"2000","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5264","DOI":"10.1021\/bi952520q","article-title":"Functional and sequence characterization of coagulation factor IX\/factor X-binding protein from the venom of Echis carinatus leucogaster","volume":"35","author":"Chen","year":"1996","journal-title":"Biochemistry"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/jb\/mvn145","article-title":"Anticoagulant mechanism of factor IX\/factor X-binding protein isolated from the venom of Trimeresurus flavoviridis","volume":"145","author":"Ishikawa","year":"2009","journal-title":"J. Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"7230","DOI":"10.1073\/pnas.131179698","article-title":"Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X","volume":"98","author":"Mizuno","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1006\/jmbi.1999.2756","article-title":"Crystal structure of coagulation factor IX-binding protein from habu snake venom at 2.6 A: Implication of central loop swapping based on deletion in the linker region","volume":"289","author":"Mizuno","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"357","DOI":"10.2174\/1568006043335916","article-title":"C-type lectin-related proteins from snake venoms","volume":"4","author":"Morita","year":"2004","journal-title":"Curr. Drug Targets Cardiovasc. Haematol. Disord."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"10043","DOI":"10.1021\/bi00031a028","article-title":"Role of calcium(II) ions in the recognition of coagulation factors IX and X by IX\/X-bp, an anticoagulant from snake venom","volume":"34","author":"Sekiya","year":"1995","journal-title":"Biochemistry"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/S0041-0101(02)00091-0","article-title":"Characterization and cDNA cloning of halyxin, a heterogeneous three-chain anticoagulant protein from the venom of Agkistrodon halys brevicaudus","volume":"40","author":"Koo","year":"2002","journal-title":"Toxicon"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"17361","DOI":"10.1021\/bi981177x","article-title":"Coagulation factor X-binding protein from Deinagkistrodon acutus venom is a Gla domain-binding protein","volume":"37","author":"Atoda","year":"1998","journal-title":"Biochemistry"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.toxicon.2012.03.006","article-title":"Anticoagulation factor I, a snaclec (snake C-type lectin) from Agkistrodon acutus venom binds to FIX as well as FX: Ca2+ induced binding data","volume":"59","author":"Zhang","year":"2012","journal-title":"Toxicon"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1107\/S0907444903002191","article-title":"Purification, crystallization and preliminary crystallographic analysis of AHP IX-bp, a zinc ion and pH-dependent coagulation factor IX binding protein from Agkistrodon halys Pallas venom","volume":"59","author":"Zang","year":"2003","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1532\/IJH97.03172","article-title":"Use of snake venom inhibitors in studies of the function and tertiary structure of coagulation factors","volume":"79","author":"Morita","year":"2004","journal-title":"Int. J. Hematol."},{"key":"ref_92","first-page":"211","article-title":"Diagnostic uses of snake venom","volume":"31","author":"Marsh","year":"2001","journal-title":"Haemostasis"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.toxicon.2012.09.008","article-title":"Non-enzymatic proteins from snake venoms: A gold mine of pharmacological tools and drug leads","volume":"62","author":"McCleary","year":"2013","journal-title":"Toxicon"},{"key":"ref_94","first-page":"388","article-title":"Determination of plasma prothrombin level by Ca2+-dependent prothrombin activator (CA-1) during warfarin anticoagulation","volume":"10","author":"Iwahashi","year":"2001","journal-title":"J. Heart Valve Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0049-3848(98)00212-6","article-title":"CA-1 method, a novel assay for quantification of normal prothrombin using a Ca2+ -dependent prothrombin activator, carinactivase-1","volume":"94","author":"Yamada","year":"1999","journal-title":"Thromb. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1055\/s-2002-36698","article-title":"Prothrombin levels in newborn infants by the carinactivase-1 method","volume":"28","author":"Fukushima","year":"2002","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_97","first-page":"225","article-title":"Snake venom activators of factor X: An overview","volume":"31","author":"Tans","year":"2001","journal-title":"Haemostasis"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"891","DOI":"10.12669\/pjms.293.3497","article-title":"Platelet receptors; an instrumental of platelet physiology","volume":"29","author":"Saboor","year":"2013","journal-title":"Pak. J. Med. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.thromres.2004.07.020","article-title":"Platelet physiology and thrombosis","volume":"114","author":"Andrews","year":"2004","journal-title":"Thromb. Res."},{"key":"ref_100","first-page":"a004978","article-title":"The collagen family","volume":"3","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/jcp.25887","article-title":"A biophysical view on von Willebrand factor activation","volume":"233","author":"Lof","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/joic.12478","article-title":"Von Willebrand factor revisited","volume":"31","author":"Yasar","year":"2018","journal-title":"J. Interv. Cardiol."},{"key":"ref_103","first-page":"969","article-title":"Platelet adhesion receptors and (patho)physiological thrombus formation","volume":"16","author":"Andrews","year":"2001","journal-title":"Histol. Histopathol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.toxicon.2005.02.025","article-title":"Snake venom probes of platelet adhesion receptors and their ligands","volume":"45","author":"Wijeyewickrema","year":"2005","journal-title":"Toxicon"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/S1357-2725(02)00280-7","article-title":"Glycoprotein Ib-IX-V","volume":"35","author":"Andrews","year":"2003","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1111\/j.1538-7836.2005.01379.x","article-title":"Platelet GPIb-IX-V-dependent signaling","volume":"3","author":"Ozaki","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1002\/prot.24060","article-title":"Crystal structure of agkisacucetin, a Gpib-binding snake C-type lectin that inhibits platelet adhesion and aggregation","volume":"80","author":"Gao","year":"2012","journal-title":"Proteins"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3904","DOI":"10.1111\/bph.13178","article-title":"A novel snake venom-derived GPIb antagonist, anfibatide, protects mice from acute experimental ischaemic stroke and reperfusion injury","volume":"172","author":"Li","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1006\/bbrc.1995.1684","article-title":"Functional and sequence characterization of agkicetin, a new glycoprotein Ib antagonist isolated from Agkistrodon acutus venom. offf2p4","volume":"210","author":"Chen","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.toxicon.2004.11.017","article-title":"How does agkicetin-C bind on platelet glycoprotein Ib\u03b1 and achieve its platelet effects?","volume":"45","author":"Xu","year":"2005","journal-title":"Toxicon"},{"key":"ref_111","first-page":"372","article-title":"cDNA cloning, sequence analysis, and recombinant expression of akitonin \u03b2, a C-type lectin-like protein from Agkistrodon acutus","volume":"25","author":"Zha","year":"2004","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"10635","DOI":"10.1074\/jbc.271.18.10635","article-title":"Complete amino acid sequence and identification of the platelet glycoprotein Ib-binding site of jararaca GPIb-BP, a snake venom protein isolated from Bothrops jararaca","volume":"271","author":"Kawasaki","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/S0041-0101(03)00067-9","article-title":"Molecular cloning and characterization of a platelet glycoprotein Ib-binding protein from the venom of Trimeresurus stejnegeri","volume":"41","author":"Lee","year":"2003","journal-title":"Toxicon"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0304-4165(95)00052-D","article-title":"Flavocetin-A and -B, two high molecular mass glycoprotein Ib binding proteins with high affinity purified from Trimeresurus flavoviridis venom, inhibit platelet aggregation at high shear stress","volume":"1244","author":"Taniuchi","year":"1995","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1055\/s-0038-1649807","article-title":"Isolation and characterization of jararaca GPIb-BP, a snake venom antagonist specific to platelet glycoprotein Ib","volume":"74","author":"Fujimura","year":"1995","journal-title":"Thromb. Haemost."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S1570-9639(03)00232-2","article-title":"Lebecetin, a potent antiplatelet C-type lectin from Macrovipera lebetina venom","volume":"1651","author":"Sarray","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Navdaev, A., Subramanian, H., Petunin, A., Clemetson, K.J., Gambaryan, S., and Walter, U. (2014). Echicetin coated polystyrene beads: A novel tool to investigate GPIb-specific platelet activation and aggregation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093569"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1006\/bbrc.1994.2630","article-title":"Isolation, characterization and amino acid sequence of echicetin \u03b2 subunit, a specific inhibitor of von Willebrand factor and thrombin interaction with glycoprotein Ib","volume":"205","author":"Peng","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1182\/blood.V81.9.2321.2321","article-title":"Echicetin: A snake venom protein that inhibits binding of von Willebrand factor and alboaggregins to platelet glycoprotein Ib","volume":"81","author":"Peng","year":"1993","journal-title":"Blood"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.toxicon.2011.04.008","article-title":"The rhodocetin \u03b1\u03b2 subunit targets GPIb and inhibits von Willebrand factor induced platelet activation","volume":"57","author":"Navdaev","year":"2011","journal-title":"Toxicon"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1080\/09537100601078232","article-title":"Molecular cloning and sequence analysis of alboaggregin B","volume":"18","author":"Arpijuntarangkoon","year":"2007","journal-title":"Platelets"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1055\/s-0037-1614954","article-title":"Alboaggregins A and B. Structure and interaction with human platelets","volume":"79","author":"Kowalska","year":"1998","journal-title":"Thromb. Haemost."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"11529","DOI":"10.1021\/bi00113a007","article-title":"Alboaggregin-B: A new platelet agonist that binds to platelet membrane glycoprotein Ib","volume":"30","author":"Peng","year":"1991","journal-title":"Biochemistry"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1160\/TH03-12-0747","article-title":"GPIb is involved in platelet aggregation induced by mucetin, a snake C-type lectin protein from Chinese habu (Trimeresurus mucrosquamatus) venom","volume":"91","author":"Lu","year":"2004","journal-title":"Thromb. Haemost."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.toxicon.2010.10.011","article-title":"Jerdonuxin, a novel snaclec (snake C-type lectin) with platelet aggregation activity from Trimeresurus jerdonii venom","volume":"57","author":"Chen","year":"2011","journal-title":"Toxicon"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/nsmb892","article-title":"The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation","volume":"12","author":"Fukuda","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/S0969-2126(02)00787-6","article-title":"Structural basis of von Willebrand factor activation by the snake toxin botrocetin","volume":"10","author":"Fukuda","year":"2002","journal-title":"Structure"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"37777","DOI":"10.1074\/jbc.M305566200","article-title":"Crystal structure of von Willebrand factor A1 domain complexed with snake venom, bitiscetin: Insight into glycoprotein Ib\u03b1 binding mechanism induced by snake venom proteins","volume":"278","author":"Maita","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1055\/s-0037-1615657","article-title":"Characterization of aspercetin, a platelet aggregating component from the venom of the snake Bothrops asper which induces thrombocytopenia and potentiates metalloproteinase-induced hemorrhage","volume":"85","author":"Rucavado","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.toxicon.2005.02.023","article-title":"Structure and function of snake venom toxins interacting with human von Willebrand factor","volume":"45","author":"Matsui","year":"2005","journal-title":"Toxicon"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"13592","DOI":"10.1021\/bi0114933","article-title":"Crystal structure of bitiscetin, a von Willebrand factor-dependent platelet aggregation inducer","volume":"40","author":"Hirotsu","year":"2001","journal-title":"Biochemistry"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-94-017-9153-3_3","article-title":"\u03b12\u03b21 Integrin","volume":"819","author":"Madamanchi","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s00441-009-0834-6","article-title":"Integrins","volume":"339","author":"Barczyk","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Campbell, I.D., and Humphries, M.J. (2011). Integrin structure, activation, and interactions. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a004994"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"867","DOI":"10.2174\/1381612053381738","article-title":"Collagen-binding integrins as pharmaceutical targets","volume":"11","author":"Eble","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1242\/jcs.03098","article-title":"Integrin ligands at a glance","volume":"119","author":"Humphries","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ceb.2018.08.004","article-title":"Signal transduction via integrin adhesion complexes","volume":"56","author":"Humphries","year":"2018","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1146\/annurev.immunol.25.022106.141618","article-title":"Structural basis of integrin regulation and signaling","volume":"25","author":"Luo","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nature09621","article-title":"Nanoscale architecture of integrin-based cell adhesions","volume":"468","author":"Kanchanawong","year":"2010","journal-title":"Nature"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.toxicon.2013.01.001","article-title":"Identification of \u03b12\u03b21 integrin inhibitor VP-i with anti-platelet properties in the venom of Vipera palaestinae","volume":"64","author":"Arlinghaus","year":"2013","journal-title":"Toxicon"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.toxicon.2012.09.005","article-title":"The continuing saga of snake venom disintegrins","volume":"62","author":"Calvete","year":"2013","journal-title":"Toxicon"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"12274","DOI":"10.1074\/jbc.M009338200","article-title":"\u03b12\u03b21 integrin is not recognized by rhodocytin but is the specific, high affinity target of rhodocetin, an RGD-independent disintegrin and potent inhibitor of cell adhesion to collagen","volume":"276","author":"Eble","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"7584","DOI":"10.1021\/bi982132z","article-title":"Rhodocetin, a novel platelet aggregation inhibitor from the venom of Calloselasma rhodostoma (Malayan pit viper): Synergistic and noncovalent interaction between its subunits","volume":"38","author":"Wang","year":"1999","journal-title":"Biochemistry"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"9859","DOI":"10.1021\/bi000428a","article-title":"Isolation and characterization of EMS16, a C-lectin type protein from Echis multisquamatus venom, a potent and selective inhibitor of the \u03b12\u03b21 integrin","volume":"39","author":"Marcinkiewicz","year":"2000","journal-title":"Biochemistry"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/jcp.20935","article-title":"Lebectin, a Macrovipera lebetina venom-derived C-type lectin, inhibits angiogenesis both in vitro and in vivo","volume":"211","author":"Pilorget","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"862","DOI":"10.3390\/toxins4100862","article-title":"Vixapatin (VP12), a C-type lectin-protein from Vipera xantina palestinae venom: Characterization as a novel anti-angiogenic compound","volume":"4","author":"Momic","year":"2012","journal-title":"Toxins"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"26235","DOI":"10.1074\/jbc.M112.381483","article-title":"Rhinocetin, a venom-derived integrin-specific antagonist inhibits collagen-induced platelet and endothelial cell functions","volume":"287","author":"Vaiyapuri","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.taap.2013.03.002","article-title":"Identification of inhibitors of \u03b12\u03b21 integrin, members of C-lectin type proteins, in Echis sochureki venom","volume":"269","author":"Jakubowski","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1096\/fj.08-126763","article-title":"The \u03b12\u03b21 integrin-specific antagonist rhodocetin is a cruciform, heterotetrameric molecule","volume":"23","author":"Eble","year":"2009","journal-title":"FASEB J."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20110584","article-title":"Monoclonal antibodies reveal the alteration of the rhodocetin structure upon \u03b12\u03b21 integrin binding","volume":"440","author":"Bracht","year":"2011","journal-title":"Biochem. J."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1161\/ATVBAHA.112.00006","article-title":"Rhodocetin-\u03b1\u03b2-induced neuropilin-1-cMet association triggers restructuring of matrix contacts in endothelial cells","volume":"33","author":"Niland","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Eble, J.A., McDougall, M., Orriss, G.L., Niland, S., Johanningmeier, B., Pohlentz, G., Meier, M., Karrasch, S., Estevao-Costa, M.I., and Martins Lima, A. (2017). Dramatic and concerted conformational changes enable rhodocetin to block \u03b12\u03b21 integrin selectively. PLoS Biol., 15.","DOI":"10.1371\/journal.pbio.2001492"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1074\/jbc.M112.399618","article-title":"The collagen-binding integrin \u03b12\u03b21 is a novel interaction partner of the Trimeresurus flavoviridis venom protein flavocetin-A","volume":"288","author":"Arlinghaus","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1055\/s-0037-1616062","article-title":"Bilinexin, a snake C-type lectin from Agkistrodon bilineatus venom agglutinates platelets via GPIb and \u03b12\u03b21","volume":"86","author":"Du","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.tips.2012.07.004","article-title":"Platelet GPVI: A target for antithrombotic therapy?!","volume":"33","author":"Dutting","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1182\/blood-2002-12-3882","article-title":"Platelet-collagen interaction: Is GPVI the central receptor?","volume":"102","author":"Nieswandt","year":"2003","journal-title":"Blood"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1172\/JCI122955","article-title":"Functional significance of the platelet immune receptors GPVI and CLEC-2","volume":"129","author":"Rayes","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Marjoram, R.J., Li, Z., He, L., Tollefsen, D.M., Kunicki, T.J., Dickeson, S.K., Santoro, S.A., and Zutter, M.M. (2014). \u03b12\u03b21 integrin, GPVI receptor, and common FcR\u03b3 chain on mouse platelets mediate distinct responses to collagen in models of thrombosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114035"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"5069","DOI":"10.1182\/blood-2010-01-260778","article-title":"Synergism between platelet collagen receptors defined using receptor-specific collagen-mimetic peptide substrata in flowing blood","volume":"115","author":"Pugh","year":"2010","journal-title":"Blood"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"35124","DOI":"10.1074\/jbc.M204372200","article-title":"Ophioluxin, a convulxin-like C-type lectin from Ophiophagus hannah (King cobra) is a powerful platelet activator via glycoprotein VI","volume":"277","author":"Du","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1160\/TH03-05-0269","article-title":"Stejnulxin, a novel snake C-type lectin-like protein from Trimeresurus stejnegeri venom is a potent platelet agonist acting specifically via GPVI","volume":"90","author":"Lee","year":"2003","journal-title":"Thromb. Haemost."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/09537109876708","article-title":"Convulxin-induced platelet adhesion and aggregation: Involvement of glycoproteins VI and IaIIa","volume":"9","author":"Lagrue","year":"1998","journal-title":"Platelets"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"13576","DOI":"10.1074\/jbc.272.21.13576","article-title":"Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62\/GPVI collagen receptor","volume":"272","author":"Polgar","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1055\/s-0037-1613067","article-title":"Alboluxin, a snake C-type lectin from Trimeresurus albolabris venom is a potent platelet agonist acting via GPIb and GPVI","volume":"87","author":"Du","year":"2002","journal-title":"Thromb. Haemost."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"12629","DOI":"10.1021\/bi960704e","article-title":"Binding of a novel 50-kilodalton alboaggregin from Trimeresurus albolabris and related viper venom proteins to the platelet membrane glycoprotein Ib-IX-V complex. Effect on platelet aggregation and glycoprotein Ib-mediated platelet activation","volume":"35","author":"Andrews","year":"1996","journal-title":"Biochemistry"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1182\/blood.V97.4.929","article-title":"Alboaggregin A activates platelets by a mechanism involving glycoprotein VI as well as glycoprotein Ib","volume":"97","author":"Dormann","year":"2001","journal-title":"Blood"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1006\/bbrc.2000.2940","article-title":"Convulxin binding to platelet receptor GPVI: Competition with collagen related peptides","volume":"273","author":"Niedergang","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"39452","DOI":"10.1074\/jbc.M300199200","article-title":"Convulxin binds to native, human glycoprotein Ib\u03b1","volume":"278","author":"Kanaji","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1182\/blood-2005-09-3563","article-title":"Arf6 plays an early role in platelet activation by collagen and convulxin","volume":"107","author":"Choi","year":"2006","journal-title":"Blood"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0014-5793(99)00340-3","article-title":"Phosphatidylinositol 3\u2032-kinase and tyrosine-phosphatase activation positively modulate Convulxin-induced platelet activation. Comparison with collagen","volume":"448","author":"Lagrue","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3390\/toxins5040665","article-title":"The snake venom rhodocytin from Calloselasma rhodostoma- a clinically important toxin and a useful experimental tool for studies of C-type lectin-like receptor 2 (CLEC-2)","volume":"5","author":"Bruserud","year":"2013","journal-title":"Toxins"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/1521-4141(200002)30:2<697::AID-IMMU697>3.0.CO;2-M","article-title":"Molecular characterization of two novel C-type lectin-like receptors, one of which is selectively expressed in human dendritic cells","volume":"30","author":"Colonna","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1349-7006.2007.00634.x","article-title":"Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2","volume":"99","author":"Kato","year":"2008","journal-title":"Cancer Sci."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1182\/blood-2005-05-1994","article-title":"A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2","volume":"107","author":"Fuller","year":"2006","journal-title":"Blood"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"25993","DOI":"10.1074\/jbc.M702327200","article-title":"Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells","volume":"282","author":"Kato","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1110\/ps.035568.108","article-title":"Crystal structure of rhodocytin, a ligand for the platelet-activating receptor CLEC-2","volume":"17","author":"Watson","year":"2008","journal-title":"Protein Sci."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"7831","DOI":"10.1021\/bi800528t","article-title":"The crystal structure of the platelet activator aggretin reveals a novel (\u03b1\u03b2)2 dimeric structure","volume":"47","author":"Hooley","year":"2008","journal-title":"Biochemistry"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"10988","DOI":"10.1021\/bi901427d","article-title":"The platelet receptor CLEC-2 is active as a dimer","volume":"48","author":"Watson","year":"2009","journal-title":"Biochemistry"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1182\/blood-2009-08-237834","article-title":"CLEC-2 activates Syk through dimerization","volume":"115","author":"Hughes","year":"2010","journal-title":"Blood"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1182\/blood-2009-12-257212","article-title":"Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization, secondary mediators, and Rac","volume":"115","author":"Pollitt","year":"2010","journal-title":"Blood"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"5127","DOI":"10.1074\/jbc.M112.411462","article-title":"Critical Role for an acidic amino acid region in platelet signaling by the HemITAM (hemi-immunoreceptor tyrosine-based activation motif) containing receptor CLEC-2 (C-type lectin receptor-2)","volume":"288","author":"Hughes","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1074\/jbc.M110.167502","article-title":"Syk-dependent phosphorylation of CLEC-2: A novel mechanism of hem-immunoreceptor tyrosine-based activation motif signaling","volume":"286","author":"Severin","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"12397","DOI":"10.1074\/jbc.M609558200","article-title":"The C-type lectin receptors CLEC-2 and Dectin-1, but not DC-SIGN, signal via a novel YXXL-dependent signaling cascade","volume":"282","author":"Fuller","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"991","DOI":"10.3390\/toxins3080991","article-title":"Molecular analysis of the interaction of the snake venom rhodocytin with the platelet receptor CLEC-2","volume":"3","author":"Watson","year":"2011","journal-title":"Toxins"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/j.str.2014.09.009","article-title":"A platform of C-type lectin-like receptor CLEC-2 for binding O-glycosylated podoplanin and nonglycosylated rhodocytin","volume":"22","author":"Nagae","year":"2014","journal-title":"Structure"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1074\/jbc.M610383200","article-title":"The crystal structure and mutational binding analysis of the extracellular domain of the platelet-activating receptor CLEC-2","volume":"282","author":"Watson","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"22241","DOI":"10.1074\/jbc.M111.329987","article-title":"Platelet activation receptor CLEC-2 regulates blood\/lymphatic vessel separation by inhibiting proliferation, migration, and tube formation of lymphatic endothelial cells","volume":"287","author":"Osada","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12959-016-0099-8","article-title":"New horizon in platelet function: With special reference to a recently-found molecule, CLEC-2","volume":"14","author":"Ozaki","year":"2016","journal-title":"Thromb. J."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1055\/s-0037-1604090","article-title":"Platelet CLEC-2: Roles Beyond Hemostasis","volume":"44","author":"Tsukiji","year":"2018","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Suzuki-Inoue, K. (2018). Roles of the CLEC-2-podoplanin interaction in tumor progression. Platelets, 1\u20137.","DOI":"10.1080\/09537104.2018.1478401"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/jth.13604","article-title":"C-type lectin-like receptor 2 promotes hematogenous tumor metastasis and prothrombotic state in tumor-bearing mice","volume":"15","author":"Shirai","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1182\/blood-2009-10-247296","article-title":"Deadly allies: The fatal interplay between platelets and metastizing cancer cells","volume":"115","author":"Erpenbeck","year":"2010","journal-title":"Blood"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1182\/blood-2004-02-0434","article-title":"Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis","volume":"104","author":"Camerer","year":"2004","journal-title":"Blood"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1111\/jth.13987","article-title":"Functional characterization of recombinant snake venom rhodocytin: Rhodocytin mutant blocks CLEC-2\/podoplanin-dependent platelet aggregation and lung metastasis","volume":"16","author":"Sasaki","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1182\/bloodadvances.2018016261","article-title":"Cobalt hematoporphyrin inhibits CLEC-2-podoplanin interaction, tumor metastasis, and arterial\/venous thrombosis in mice","volume":"2","author":"Tsukiji","year":"2018","journal-title":"Blood Adv."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1042\/BST20110689","article-title":"Neuropilin signalling in angiogenesis","volume":"40","author":"Koch","year":"2012","journal-title":"Biochem. Soc. Trans."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Niland, S., and Eble, J.A. (2019). Neuropilins in the context of tumor vasculature. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030639"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"921","DOI":"10.18632\/oncotarget.626","article-title":"Neuropilins are multifunctional coreceptors involved in tumor initiation, growth, metastasis and immunity","volume":"3","author":"Glinka","year":"2012","journal-title":"Oncotarget"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1365-2613.2012.00810.x","article-title":"Neuropilins: Expression and roles in the epithelium","volume":"93","author":"Wild","year":"2012","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nrm3012","article-title":"MET signalling: Principles and functions in development, organ regeneration and cancer","volume":"11","author":"Trusolino","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.4049\/jimmunol.1801346","article-title":"Signals of the neuropilin-1-MET axis and cues of mechanical force exertion converge to elicit inflammmatory activation in coherent endothelial cells","volume":"202","author":"Rezaei","year":"2019","journal-title":"J. Immunol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"22406","DOI":"10.18632\/oncotarget.25032","article-title":"Rhodocetin-\u03b1\u03b2 selectively breaks the endothelial barrier of the tumor vasculature in HT1080 fibrosarcoma and A431 epidermoid carcinoma tumor models","volume":"9","author":"Niland","year":"2018","journal-title":"Oncotarget"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.2174\/0929867324666170605091546","article-title":"Snake Venom: From Deadly Toxins to Life-saving Therapeutics","volume":"24","author":"Waheed","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.biocel.2013.06.009","article-title":"Applications of snake venom components to modulate integrin activities in cell-matrix interactions","volume":"45","author":"Marcinkiewicz","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1593\/neo.07898","article-title":"Integrins as antimetastatic targets of RGD-independent snake venom components in liver metastasis [corrected]","volume":"10","author":"Rosenow","year":"2008","journal-title":"Neoplasia"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12959-016-0100-6","article-title":"Platelets and platelet adhesion molecules: Novel mechanisms of thrombosis and anti-thrombotic therapies","volume":"14","author":"Xu","year":"2016","journal-title":"Thromb. J."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.2174\/138161207782023702","article-title":"Snake venom proteins affecting platelets and their applications to anti-thrombotic research","volume":"13","author":"Clemetson","year":"2007","journal-title":"Curr. Pharm. Des."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1160\/TH13-06-0490","article-title":"Anfibatide, a novel GPIb complex antagonist, inhibits platelet adhesion and thrombus formation in vitro and in vivo in murine models of thrombosis","volume":"111","author":"Lei","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.bbi.2017.11.019","article-title":"Platelet glycoprotein receptor Ib blockade ameliorates experimental cerebral ischemia-reperfusion injury by strengthening the blood-brain barrier function and anti-thrombo-inflammatory property","volume":"69","author":"Chen","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ejphar.2017.04.002","article-title":"Anfibatide protects against rat cerebral ischemia\/reperfusion injury via TLR4\/JNK\/caspase-3 pathway","volume":"807","author":"Luo","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_211","unstructured":"NIH U.S. National Library of Medicine, ClinicalTrials.gov (2018, December 29). Anfibatide Phase Ib-IIa Clinical Trial, ClinicalTrials.gov Identifier: NCT01585259, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01585259."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1182\/asheducation-2018.1.539","article-title":"Beyond plasma exchange: Novel therapies for thrombotic thrombocytopenic purpura","volume":"2018","author":"Dane","year":"2018","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1182\/bloodadvances.2016000711","article-title":"Therapeutic efficacy of the platelet glycoprotein Ib antagonist anfibatide in murine models of thrombotic thrombocytopenic purpura","volume":"1","author":"Zheng","year":"2016","journal-title":"Blood Adv."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/3\/136\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:35:29Z","timestamp":1760186129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/3\/136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,1]]},"references-count":213,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["toxins11030136"],"URL":"https:\/\/doi.org\/10.3390\/toxins11030136","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,1]]}}}