ライフサイエンスコーパス: factor XI

1 quired for hepatocyte-specific expression of factor XI.

2 weight kininogen (HK31-mer) can also bind to factor XI.

3 the gene for the blood coagulation protease factor XI.

4 K(m) 35-fold greater than that of wild-type factor XI.

5 with HK for binding to the Apple 1 domain of factor XI.

6 agonists in the absence of detectable plasma factor XI.

7 activation-dependent expression of platelet factor XI.

8 5,000 reduced) different from that of plasma factor XI.

9 these exons was identical to that of plasma factor XI.

10 mpared its properties with human recombinant factor XI.

11 f 624 amino acids with 78% homology to human factor XI.

12 bstrate of the intrinsic coagulation pathway factor XI.

13 AIS compared to those with normal levels of factor XI.

14 for an increased prekallikrein and decreased factor XI.

15 ogical significance of the dimeric nature of factor XI.

16 ntity and a domain structure very similar to factor XI.

17 nt-like Apetela 2 (AP2) domain transcription factor XI-3 (AP2XI-3), not present in human cells, was c

18 iltered platelets promoted the activation of factor XI (60 nm) by thrombin (0.02-10 nm, EC(50) approx

19 A12 and 11AE) that recognize epitopes on the factor XI A3 domain were potent inhibitors of factor IX

20 , factor IX, in an interaction requiring the factor XI A3 domain.

21 hysiological concentration of prekallikrein, factor XI abrogates HK binding to HUVEC in a concentrati

22 The maximum rates of factor XI activation achieved in the presence of activat

23 port that polyphosphate potently accelerates factor XI activation by alpha-thrombin, beta-thrombin, a

24 ompared with dextran sulfate as surfaces for factor XI activation by factor XIIa, factor XIa, or thro

25 ion of fibrinogen (9.0 micrometer) inhibited factor XI activation by thrombin (but not by factor XIIa

26 Activated gel-filtered platelets promoted factor XI activation by thrombin at initial rates 2-5-fo

27 ical concentrations of HK (636 nM) inhibited factor XI activation by thrombin in a concentration-depe

28 binding to lipid rafts, and initial rates of factor XI activation by thrombin on activated platelets

29 estigated whether glycocalicin could promote factor XI activation by thrombin, another GP Ibalpha lig

30 mers and surfaces have been shown to enhance factor XI activation by thrombin, the physiologic cofact

31 brin clot structure, and greatly accelerates factor XI activation by thrombin.

32 that polyphosphate is a natural cofactor for factor XI activation in plasma that may help explain the

33 ons (360 nm), the rate of thrombin-catalyzed factor XI activation in the presence of glycocalicin was

34 ts and platelet-mediated, thrombin-catalyzed factor XI activation in the presence of prothrombin and

35 n in the factor XI experiment indicates that factor XI activation occurs exclusively by thrombin.

36 romoting optimal rates of thrombin-catalyzed factor XI activation on the platelet surface, thereby in

37 act pathway and amplified thrombin-dependent factor XI activation.

38 sulfate as a surface for thrombin-catalyzed factor XI activation.

39 tors XIIa and XIa, thrombin is the preferred factor XI activator, and activated platelets are a relev

40 All adults tested for factor XI activity between 2002 and 2014 were included i

41 Factor XI activity was classified into 3 categories: nor

42 tor VIII antigen with AIS/CES; and increased factor XI activity with AIS/CES).

43 3 included patients, 8958 (88.9%) had normal factor XI activity, 690 (6.8%) had mild deficiency, and

44 Coagulation factor XI, alpha-1-antichymotrypsin, ficolin-2, 14-3-3 p

45 ied thrombin as the most likely activator of factor XI, although this reaction is slow in solution.

46 ids are located in the third apple domain of factor XI, an area implicated in binding interactions wi

47 n of the naturally occurring complex between factor XI and HK by the addition of a 31-amino acid pept

48 atelets by the recombinant Apple 3 domain of factor XI and inhibition by unlabeled factor XI were ide

49 cimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precurso

50 n at various concentrations exposed platelet factor XI and PAC1 antibody binding in parallel.

51 fective as the recombinant Apple 3 domain of factor XI and unlabeled factor XI in inhibiting [(125)I]

52 kallikrein, high-molecular weight kininogen, factor XI, and factor XII were decreased in the disease-

53 The zymogen, factor XI, and the enzyme, factor XIa, interact specific

54 Flow cytometry with an affinity-purified factor XI antibody, with PAC1 antibody (to the GPIIb/III

55 erse side effects were found for coagulation factor XI, apolipoprotein(a), and SCARA5.

56 Both recombinant murine and human factor XI are 160 kD homodimers comprised of two 80 kD p

57 tion, those with genetically lower levels of factor XI are at reduced risk of AIS compared to those w

58 results indicate that two forms of activated factor XI are generated during coagulation, and that eac

59 site of synthesis and the nature of platelet factor XI are not known.

60 Plateletcrit and factor XI are potentially tractable new targets for seco

61 in fragment 2 binds to the Apple 1 domain of factor XI at or near the site where high molecular weigh

62 Only activated platelets supported factor XI binding in the presence of HK and zinc (K(D) =

63 Here, we provide evidence that the factor XI binding site on platelets is in the glycoprote

64 tide analogue of this sequence inhibits both factor XI binding to activated platelets and platelet-me

65 Inhibition of [(125)I]factor XI binding to activated platelets by the recombin

66 nd unlabeled factor XI in inhibiting [(125)I]factor XI binding to activated platelets.

67 c peptides were used to compete with [(125)I]factor XI binding to activated platelets.

68 Apple 3 domain of factor XI, which mediates factor XI binding to platelets, also completely displace

69 kininogen (and Zn2+), which are required for factor XI binding to platelets.

70 M), and CaCl2 (2 mM), conditions optimal for factor XI binding to platelets.

71 located in the Apple 3 domain which mediates factor XI binding to platelets.

72 y) and bovine von Willebrand factor, inhibit factor XI binding to platelets; 3) by surface plasmon re

73 An antibody to GPIb (SZ-2) that disrupts factor XI binding to the GPIb-IX-V complex also disrupte

74 ed in von Willebrand's factor secretion, but factor XI binding was not observed.

75 elets, lacking the complex, are deficient in factor XI binding; 2) two GP Ibalpha ligands, SZ-2 (a mo

76 ion of a 31-amino acid peptide mimicking the factor XI-binding site on HK restored HK binding to HUVE

77 Factor XI binds to activated platelets where it is effic

78 Factor XI binds to high affinity sites on the surface of

79 In microtiter wells factor XI binds to more sites in the absence of HUVEC (1

80 Thus, factor XI binds to the GP Ib-IX-V complex, promoting its

81 platelets; 3) by surface plasmon resonance, factor XI bound specifically to glycocalicin (the extrac

82 Interestingly, zymogen factor XI bound SPGG with high affinity, suggesting its

83 xpressed approximately 40% of total platelet factor XI but no PAC1 binding sites.

84 n, because ADP and collagen exposed platelet factor XI but no S12 binding sites.

85 prekallikrein is structurally homologous to factor XI, but activated factor IX poorly.

86 ccelerate thrombin activation of coagulation factor XI by a template mechanism.

87 is important for promoting the activation of factor XI by thrombin on the platelet surface.

88 tease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a cr

89 Factor XI cDNA was cloned from a megakaryocyte library a

90 Factor XI circulates as a homodimer, and the presence of

91 ficiency in FXII substrate factor XI or FXII/factor XI co-deficiency similarly exacerbated S. aureus

92 terminus of the A3 domain markedly decreased factor XI coagulant activity.

93 rence: elevated plasma levels of coagulation factor XI, coagulation factor VIII, von Willebrand facto

94 Variants of factor XI containing Gln226 to Arg (Q226 to R) and Ser24

95 This study showed that factor XI contributes to postoperative venous thromboemb

96 Platelets from four patients with plasma factor XI deficiency (<0.04 U/mL) had normal constitutiv

97 The incidence of VTE was lower in those with factor XI deficiency (activity <50%) compared with those

98 Factor XI deficiency (MIM 264900) is an autosomal bleedi

99 a 9-year-old boy (the propositus) with mild factor XI deficiency and his mother.

100 Factor XI deficiency is associated with a bleeding diath

101 In summary, factor XI deficiency is associated with decreased incide

102 Factor XI deficiency is one of the rare inherited coagul

103 The data demonstrate that factor XI deficiency results in significantly delayed cl

104 preparation for developing a mouse model of factor XI deficiency to facilitate investigations into t

105 died 39 consecutively referred patients with factor XI deficiency to identify the molecular defect.

106 ns at the FXI locus, which cause coagulation factor XI deficiency, have high frequencies in Jewish po

107 tudies have shown the causative mutations of factor XI deficiency, outside the Ashkenazi Jewish popul

108 e gene deletion as the causative mutation of factor XI deficiency, the result of unequal homologous r

109 rlying cardiovascular benefit may exist with factor XI deficiency.

110 CI, 0.35-0.93) in those with moderate-severe factor XI deficiency.

111 the reaction was more strongly influenced by factor XI deficiency.

112 ion in a patient with subsequently diagnosed factor XI deficiency.

113 actor XI shortens the clotting time of human factor XI deficient plasma in an activated partial throm

114 At the same level of TF in factor XI-deficient blood (XI:C <2%), only minor differe

115 lease of platelet osteonectin were slower in factor XI-deficient blood than in normal blood.

116 Well-washed platelets from normal and from factor XI-deficient donors incubated with low concentrat

117 lood from normal, factor VIII-deficient, and factor XI-deficient donors.

118 ilar to fibrin(ogen)-deficient mice, whereas factor XI-deficient mice show wild-type levels of resist

119 corrected the clotting defect observed with factor XI-deficient plasma.

120 Factor XI did not bind to HUVEC or to HEK293 cell monola

121 In the absence of coagulation inhibitors, factor XI did not influence thrombin generation initiate

122 Murine factor XI differs from human factor XI in that it underg

123 nts, reviews the data on the factor XII- and factor XI-directed anticoagulants under development, des

124 Because factor XI displays both procoagulant and antifibrinolyti

125 These results, consistent with previous factor XI domain analyses, suggest that the active site

126 actor XIa generation by added hirudin in the factor XI experiment indicates that factor XI activation

127 , we cloned the complementary DNA for murine factor XI, expressed the protein in a mammalian expressi

128 Activated factor XI (factor XIa) participates in blood coagulation

129 Activated coagulation factor XI (factor XIa) proteolytically cleaves its subst

130 their mean values for prothrombin, factor X, factor XI, factor IX, factor VII, factor VIII, factor V,

131 Genes for the "contact system" factors (factor XI, factor XII, and prekallikrein) could not be i

132 ding to platelets, also completely displaces factor XI from membrane rafts.

133 In this study, we tested the hypothesis that factor XI (FXI) activation occurs in plasma following ac

134 h both proteins bind, we examined binding of factor XI (FXI) and FXIa to heparin.

135 Thrombin, generated through activation of factor XI (FXI) and/or tissue factor (TF)-factor VIIa, i

136 Mice lacking factor XII (fXII) or factor XI (fXI) are resistant to experimentally-induced

137 Factor XI (FXI) binds specifically and reversibly to hig

138 We have previously shown that the zymogen factor XI (FXI) binds to activated platelets but not to

139 on thrombin production of the activation of factor XI (fXI) by thrombin and of the activation of fac

140 Activation of factor XI (FXI) by thrombin on stimulated platelets play

141 teases factor XII (FXII), prekallikrein, and factor XI (FXI) can trigger coagulation and inflammatory

142 The blood coagulation protein factor XI (FXI) consists of a pair of disulfide-linked c

143 The plasma zymogens factor XII (fXII) and factor XI (fXI) contribute to thrombosis in a variety of

144 Factor XI (FXI) contributes substantially to pathologica

145 Individuals with Factor XI (FXI) deficiency have a variable bleeding tend

146 Factor XI (FXI) deficiency is a rare bleeding disorder t

147 Factor XI (FXI) deficiency is an autosomal bleeding diso

148 leeding diathesis associated with hereditary factor XI (fXI) deficiency is prevalent in Ashkenazi Jew

149 The bleeding disorder associated with factor XI (fXI) deficiency is typically inherited as an

150 Coagulation factor XI (FXI) has become increasingly interesting for

151 Coagulation factor XI (FXI) has emerged as a promising target for th

152 Inhibition of factor XI (FXI) has emerged as a strategy with the poten

153 nces several reactions involving coagulation factor XI (FXI) including activation of FXI by factor XI

154 Coagulation factor XI (FXI) inhibitors are a promising and novel cla

155 Coagulation factor XI (FXI) inhibitors can reduce the incidence of t

156 Coagulation factor XI (FXI) is a covalent homodimer consisting of tw

157 Factor XI (FXI) is a homodimeric blood coagulation prote

158 Factor XI (FXI) is a homodimeric plasma zymogen that is

159 Factor XI (fXI) is a homodimeric zymogen that is convert

160 Human coagulation factor XI (FXI) is a plasma serine protease composed of

161 The serine protease factor XI (FXI) is a prominent drug target as it holds p

162 Factor XI (FXI) is the zymogen of an enzyme (FXIa) that

163 Factor XI (FXI) is the zymogen of FXIa, which cleaves FI

164 sis associated with congenital deficiency of factor XI (FXI) is variable and correlates poorly with s

165 in humans and animals suggests that reducing factor XI (FXI) levels has the potential to effectively

166 Activation of coagulation factor XI (FXI) may play a role in hemostasis.

167 Coagulation factor XI (FXI) plays a regulatory role in inflammation.

168 Coagulation factor XI (FXI) plays an important part in both venous a

169 vitro, activated factor XII (fXIIa) converts factor XI (fXI) to fXIa.

170 ions between immobilized SkM and coagulation factor XI (FXI) using biolayer interferometry (K(d) = 0.

171 eficiency of the coagulation serine protease factor XI (FXI) was reported to be homozygous for a Gly(

172 The Apple 4 (A4) domain of human plasma factor XI (FXI) was used to investigate the process of F

173 -Willebrand-factor antigen and activity, and factor XI (FXI) were measured in all patients; further t

174 eeding may be possible through inhibition of factor XI (FXI), a component of the intrinsic coagulatio

175 d strains of mice predicted that coagulation factor XI (FXI), a liver-derived protein, protects again

176 ligonucleotides (ASOs) targeting coagulation factor XI (FXI), a member of the intrinsic coagulation p

177 ease-activated receptors (PARs), fibrinogen, factor XI (fXI), and other substrates, and a negative re

178 Since the mechanism of coagulation factor XI (FXI)-dependent thrombus growth remains unclea

179 ) and thrombin in the Apple 1 (A1) domain of factor XI (FXI).

180 ar weight kininogen (HK) in the A1 domain of factor XI (FXI).

181 wn to bind to ligands, including coagulation factor XI (FXI).

182 hepatic mRNA encoding the hemostatic enzyme factor XI (FXI).

183 Since heparin potentiates activated factor XI (FXIa) inhibition by protease nexin-2 by provi

184 Activated factor XI (FXIa) inhibitors are promising novel anticoag

185 Activated coagulation factor XI (FXIa) is a highly attractive antithrombotic t

186 Activated Factor XI (FXIa) is a key enzyme in the amplification ph

187 I is an alternatively spliced product of the factor XI gene expressed specifically within megakaryocy

188 Previously reported mutations in the factor XI gene seem to cause deficiency primarily by red

189 presence of mutations in both alleles of the factor XI gene suggests that his bleeding disorder is ca

190 d approximately 2600 base pairs of the human factor XI gene upstream of exon one, identified transcri

191 XI is an alternative splicing product of the factor XI gene, localized to platelets and megakaryocyte

192 allikrein gene and the closely related human factor XI gene, the human KLKB1 gene contains 15 exons a

193 is considerable genetic heterogeneity in the factor XI gene.

194 We report on the genetic analysis of the factor XI genes of two African American patients: a 9-ye

195 ant FXI/G326C in which the Gly326 residue of factor XI has been mutated to Cys326, reasoning that Cys

196 Factor XII and factor XI have emerged as targets for new anticoagulants

197 The studies show that murine and human factor XI have similar structural and enzymatic properti

198 proximately 3.5 nM), whereas the recombinant factor XI heavy chain did not, demonstrating that the pl

199 ions reside in the third apple domain of the factor XI heavy chain, an area that has been shown to co

200 tor IX-binding exosites on the non-catalytic factor XI heavy chain.

201 FXI/G326C was indistinguishable from plasma factor XI in a plasma-clotting assay and in a factor IX

202 factor XI-N248 were compared with wild-type factor XI in assays for factor IX activation or platelet

203 in plasma that may help explain the role of factor XI in hemostasis and thrombosis.

204 tions, the significant amount of circulating factor XI in his plasma must be comprised entirely of ab

205 nt Apple 3 domain of factor XI and unlabeled factor XI in inhibiting [(125)I]factor XI binding to act

206 l of a small-molecule inhibitor of activated factor XI in patients with atrial fibrillation, asundexi

207 Murine factor XI differs from human factor XI in that it undergoes autoactivation slowly in

208 , Zn(2+) and Ca(2+) ions, thrombin activated factor XI in the presence of glycocalicin at rates compa

209 is without causing bleeding, but the role of factor XI in the prevention of postoperative venous thro

210 regulate the expression of tissue factor and factor XI in vitro and decrease venous thrombus formatio

211 nalysis of the recombinant Apple 3 domain of factor XI indicated that amino acids R(250), K(255), F(2

212 Factor XI inhibition with a single intravenous dose of a

213 Factor XI inhibitors appear safe and hold promise for se

214 x with prekallikrein but not in complex with factor XI, interacts with the endothelium and can mainta

215 Factor XI is a plasma glycoprotein that is required for

216 Congenital deficiency of factor XI is a rare condition associated with a mild to

217 In a purified system, murine factor XI is activated by human factor XIIa and thrombin

218 Thus, platelet factor XI is an alternative splicing product of the fact

219 Platelet factor XI is an alternatively spliced product of the fac

220 Platelet factor XI is associated with the platelet plasma membran

221 Thus, functionally active platelet factor XI is differentially expressed on platelet membra

222 Emerging evidence suggests that factor XI is important for thrombosis but has a minor ro

223 Enhanced membrane exposure of platelet factor XI is independent of alpha-granule secretion, bec

224 We conclude that factor XI is localized to GPIb in membrane rafts and tha

225 of activated platelets, a preformed dimer of factor XI is not required.

226 Factor XI is the zymogen of a dimeric plasma protease, f

227 Factor XI is the zymogen of a plasma protease produced p

228 The recombination directionality factor, Xis, is a DNA bending protein that determines th

229 rypsin (Ki = 11.7 +/- 1.2 mum) and activated factor XI (Ki = 94 +/- 11 mum).

230 Experimental data indicate that reducing factor XI levels attenuates thrombosis without causing b

231 stoperative venous thromboembolism; reducing factor XI levels in patients undergoing elective primary

232 ays (IL-6 signaling, MCP-1/CCL2 levels), and factor XI levels on stroke of undetermined source.

233 Around the time of surgery, the mean (+/-SE) factor XI levels were 0.38+/-0.01 units per milliliter i

234 se oligonucleotide that specifically reduces factor XI levels.

235 olyadenylated messenger RNA show that murine factor XI message is expressed, as expected, primarily i

236 r XI, we used mutant full-length recombinant factor XI molecules in which the platelet binding site i

237 By Northern hybridization, a factor XI mRNA transcript of approximately 1.9 kilobases

238 In situ amplification and hybridization of factor XI mRNA was positive for exon III and negative fo

239 not, indicating that, in normal hemostasis, factor XI must be activated in vivo by a protease other

240 Factor XI-N248 activates factor IX normally in a purifie

241 Iodinated factor XI-N248 binds to activated platelets with a disso

242 Activation of factor XI-N248 by thrombin in the presence of activated

243 Factor XI-N248 is the first factor XI variant described

244 Recombinant factor XI-R226 and factor XI-N248 were compared with wild-type factor XI in

245 surface of growing thrombi, such as platelet factor XI or blood-borne TF, appears essential for rapid

246 Deficiency in FXII substrate factor XI or FXII/factor XI co-deficiency similarly exac

247 se, and (4) the development of inhibitors of factor XI or XII as potentially safer anticoagulants.

248 Inherited deficiency in factor XI or XII or high-molecular-weight kininogen, but

249 igh molecular weight kininogen (P<0.03), and factor XI (P<0.04) in group II vs. group III.

250 ivation by wild type factor XIa or the other factor XI/PK chimeras (0.11-0.37 microM).

251 the substitution in the third apple domain (factor XI/PKA3) had <1% of the coagulant activity of wil

252 Factor XI plays a minor role in haemostasis but contribu

253 construct is co-transfected into HeLa cells, factor XI promoter activity is enhanced approximately 10

254 The factor XI promoter functions poorly when transfected int

255 Recombinant factor XI proteins were expressed in which each of the f

256 Factor XI-R226 activates factor IX with a Michaelis-Ment

257 Recombinant factor XI-R226 and factor XI-N248 were compared with wil

258 vestigate the physiological relevance of the factor XI-raft association, the structural integrity of

259 ding to the GPIb-IX-V complex also disrupted factor XI-raft association.

260 To localize the platelet binding site on factor XI, rationally designed, conformationally constra

261 The factor XI receptor is the platelet membrane glycoprotein

262 body mass index and diabetes, only elevated factor XI remained associated with VTE risk: OR 1.8 (95%

263 that for normal (110 nmol/L TAT/min) or with factor XI replacement (119 nmol TAT/L/min).

264 minutes, which shortened to 9.7 minutes with factor XI replacement.

265 Factor XI restored the ability of thrombin to stimulate

266 od group ABO system transferase, coagulation factor XI, scavenger receptor class A5 (SCARA5), and tum

267 prekallikrein A3 sequence was replaced with factor XI sequence to restore factor IX activation.

268 Murine factor XI shortens the clotting time of human factor XI

269 coagulant surface for binding and activating factor XI, thereby initiating the consolidation phase of

270 affinity (Kd approximately 25 nM) binding of factor XI to 947 +/- 150 sites per platelet.

271 and HK31-mer as cofactors in the binding of factor XI to activated platelets.

272 contact activation in plasma, conversion of factor XI to factor XIa proceeds through an intermediate

273 ational transition accompanies conversion of factor XI to factor XIa that conceals the Apple 3 domain

274 Optimal binding of factor XI to membrane rafts required prothrombin (and Ca

275 n (1 microm) as cofactors for the binding of factor XI to the platelet.

276 m) as a cofactor for the specific binding of factor XI to the platelet.

277 Factor XI, unlike other coagulation proteins, is a homod

278 Factor XI-N248 is the first factor XI variant described with a clear functional diff

279 ng these procoagulant factors, only elevated factor XI was a risk factor for VTE.

280 n of prekallikrein was replaced with that of factor XI was as effective as the recombinant Apple 3 do

281 The OR for factor XI was higher: 2.0 (95% CI, 1.4-2.9).

282 In contrast, messenger RNA for human factor XI was identified in liver, pancreas, and kidney.

283 We now show that factor XI was localized to lipid rafts in activated plat

284 Activation of factor XI was observed in plasma in the presence of plat

285 om its binding site on the Apple 1 domain of factor XI, we conclude that the Kringle II domain of pro

286 To localize the platelet binding site on factor XI, we used mutant full-length recombinant factor

287 (all except exon V) coding for mature plasma factor XI were amplified from human platelet mRNA.

288 ain of factor XI and inhibition by unlabeled factor XI were identical, whereas the recombinant Apple

289 The isolated recombinant Apple 3 domain of factor XI, which mediates factor XI binding to platelets

290 in with a Ki of 1.3 +/- 0.2 nm and activated factor XI with a Ki of 5.4 +/- 0.2 mum.

291 The recombinant factor XI with alanine substitutions at positions Ser(24

292 ll molecule that inhibits the active form of factor XI with high affinity and selectivity.

293 have examined the interaction of coagulation factor XI with human umbilical vein endothelial cells (H

294 binding energy mediating the interaction of factor XI with platelets is contained within the C-termi

295 Thus, the interaction of factor XI with platelets is mediated by the amino acid r

296 Ia preferentially cleaving a site on zymogen factor XI within the light chain, rather than the activa

297 Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that

298 relative preference of prekallikrein (PK) or factor XI/XIa (FXI/FXIa) binding to endothelial cells (H

299 Factor XI/XIa (FXI/FXIa) represents a potential target f

300 factor XIa that conceals the Apple 3 domain factor XI (zymogen) platelet binding site and exposes th