1857:
1586:
335:
312:
4613:
234:
209:
586:
341:
240:
46:
4598:
6440:
1812:(TNF-α). Activated leukocytes release these inflammatory mediators during inflammation, inhibiting the creation of both thrombomodulin and EPCR, and inducing their shedding from the endothelial surface. Both of these actions down-regulate protein C activation. Thrombin itself may also have an effect on the levels of EPCR. In addition, proteins released from cells can impede protein C activation, for example
1736:. Activated protein C is found at levels approximately 2000 times lower than this. Mild protein C deficiency corresponds to plasma levels above 20 IU/dL, but below the normal range. Moderately severe deficiencies describe blood concentrations between 1 and 20 IU/dL; severe deficiencies yield levels of protein C that are below 1 IU/dL or are undetectable. Protein C levels in a healthy
1760:, with two main classes of functions: anticoagulation and cytoprotection (its direct effect on cells). Which function protein C performs depends on whether or not APC remains bound to EPCR after it is activated; the anticoagulative effects of APC occur when it does not. In this case, protein C functions as an anticoagulant by irreversibly proteolytically inactivating
1717:). Because of the accelerating effect of thrombomodulin on the activation of protein C, the protein may be said to be activated not by thrombin but the thrombin–thrombomodulin (or even thrombin–thrombomodulin–EPCR) complex. Once in active form, APC may or may not remain bound to EPCR, to which it has approximately the same affinity as the protein zymogen.
2020:
Treatment of cells with APC demonstrates that its gene expression modulation effectively controls major pathways for inflammatory and apoptotic behaviour. There are about 20 genes that are up-regulated by protein C, and 20 genes that are down-regulated: the former are generally anti-inflammatory
2117:
Several studies have indicated that the proteolytic activity of APC contributes to the observed cytoprotective properties of APC, but variants that are proteolytically inactive also are able to regulate formation of PAR-activators thrombin and factor Xa and express cytoprotective properties in vitro
2280:
Drotrecogin alfa-activated was the subject of significant controversy while it was approved for clinical use as it was found to increase bleeding and not to reduce mortality. In
October 2011 rhAPC (Xigris) was withdrawn from the market by Eli Lilly due to a higher mortality in a trial among adults.
2016:
When APC is bound to EPCR, it performs a number of important cytoprotective (i.e. cell-protecting) functions, most of which are known to require EPCR and PAR-1. These include regulating gene expression, anti-inflammatory effects, antiapoptotic effects and protecting endothelial barrier function.
1969:, and though the first of these sites is slow to be cleaved, it is entirely necessary to the functioning of Factor V. Protein S aids this process by catalysing the proteolysis at Arg, in which the A2 domain of Factor V is dissociated from the rest of the protein. Protein S also binds to Factor X
2182:
occurs when APC is unable to perform its functions. This disease has similar symptoms to protein C deficiency. The most common mutation leading to activated protein C resistance among
Caucasians is at the cleavage site in Factor V for APC. There, Arg is replaced with Gln, producing
2219:
targeting Factor V, and dysfunction of any of APC's cofactors. Also, some acquired conditions may reduce the efficacy of APC in performing its anticoagulative functions. Studies suggest that between 20% and 60% of thrombophilic patients suffer from some form of APC resistance.
72:
1616:-like serine protease domain (212–450). The light chain contains the Gla- and EGF-like domains and the aromatic segment. The heavy chain contains the protease domain and the activation petide. It is in this form that 85–90% of protein C circulates in the plasma as a
2234:
when warfarin is used to treat deep vein thrombosis associated with cancer. In these situations, warfarin may be restarted at a low dosage to ensure that the protein C deficiency does not present before the vitamin K coagulation factors II, IX and X are suppressed.
2174:
The frequency of protein C deficiency among asymptomatic individuals is between 1 in 200 and 1 in 500. In contrast, significant symptoms of the deficiency are detectable in 1 in 20,000 individuals. No racial nor ethnic biases have been detected.
1389:, which measure global clotting function. Soon after this, Seegers recognised Stenflo's discovery was identical with his own. Activated protein C was discovered later that year, and in 1977 it was first recognised that APC inactivates Factor V
2021:
and antiapoptotic pathways, while the latter tend to be proinflammatory and proapoptotic. APC's mechanisms for altering gene expression profiles are not well understood, but it is believed that they at least partly involve an inhibitory effect on
2158:
in the womb; this is very severe and usually fatal. Deletion of the protein C gene in mice causes fetal death around the time of birth. Fetal mice with no protein C develop normally at first, but experience severe bleeding,
4084:
Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G (June 2008). "Pharmacology and management of the vitamin K antagonists: American
College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)".
2288:
injury, after studies showed that in patients with lung injury, reduced APC levels in specific parts of the lungs correlated with worse outcomes. APC also has been considered for use in improving patient outcome in cases of
2230:, which is a vitamin K antagonist and an anticoagulant itself. However, warfarin treatment may produce paradoxical skin lesions similar to those seen in purpura fulminans. A variant of this response presents as venous limb
2199:
mutation carry a risk of venous thrombosis 5–7 times higher than in the general population. Homozygous subjects have a risk 80 times higher. This mutation is also the most common hereditary risk for venous thrombosis among
1334:
found that its use cannot be recommended since it does not improve survival and increases bleeding risk. In
October 2011, Xigris was withdrawn from the market by Eli Lilly due to a higher mortality in a trial among adults.
1705:(cells on the inside of blood vessels). The presence of thrombomodulin accelerates activation by several orders of magnitude, and EPCR speeds up activation by a factor of 20. If either of these two proteins is absent in
1620:, waiting to be activated. The remaining protein C zymogen comprises slightly modified forms of the protein. Activation of the enzyme occurs when a thrombin molecule cleaves away the activation peptide from the
1506:
The biologic instructions for synthesising protein C in humans are encoded in the gene officially named "protein C (inactivator of coagulation factors Va and VIIIa)". The gene's symbol approved by the
2068:. APC inhibits the release of inflammatory-response mediators in leukocytes as well as endothelial cells, by reducing cytokine response, and maybe diminishing systemic inflammatory response, such as is seen in
348:
247:
2316:
Ceprotin was approved for medical used in the
European Union in July 2001. Ceprotin is indicated in purpura fulminans and coumarin-induced skin necrosis in people with severe congenital protein C deficiency.
4612:
2293:, a medical emergency in which arterial blockage deprives a region of brain of oxygen, causing tissue death. Promising studies suggest that APC could be coupled with the only currently approved treatment,
1665:
residues in the protein sequence. This modification event is performed by a vitamin K-dependent microsomal carboxylase. The full complement of Gla is required to give full activity to protein C. (2) beta-
2094:
Activated protein C also provides much protection of endothelial barrier function. Endothelial barrier breakdown, and the corresponding increase in endothelial permeability, are associated with
1740:
average 40 IU/dL. The concentration of protein C increases until six months, when the mean level is 60 IU/dL; the level stays low through childhood until it reaches adult levels after
1417:. Homozygous protein C deficiency and the consequent serious health effects were described in 1984 by several scientists. cDNA cloning of protein C was first performed in 1984 by Beckmann
1950:
thus practically halts the production of thrombin. Factor VIII, on the other hand, is a cofactor in production of activated Factor X, which in turn converts prothrombin into thrombin. Factor VIII
1954:
augments Factor X activation by a factor of around 200,000. Because of its importance in clotting, Factor VIII is also known as anti-haemophilic factor, and deficiencies of Factor VIII cause
3415:
Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, et al. (May 1994). "Mutation in blood coagulation factor V associated with resistance to activated protein C".
3631:
Wildhagen KC, Lutgens E, Loubele ST, ten Cate H, Nicolaes GA (December 2011). "The structure-function relationship of activated protein C. Lessons from natural and engineered mutations".
3358:"Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C"
2378:) on the endothelial surface bind to thrombomodulin and inhibit its participation in the activation of protein C by electrostatic interaction on the surface of thrombomodulin.
2859:
Mammen EF, Thomas WR, Seegers WH (December 1960). "Activation of purified prothrombin to autoprothrombin I or autoprothrombin II (platelet cofactor II or autoprothrombin II-A)".
1291:(EPCRs). Because of EPCR's role, activated protein C is found primarily near endothelial cells (i.e., those that make up the walls of blood vessels), and it is these cells and
2079:
Scientists recognise activated protein C's antiapoptotic effects, but are unclear as to the exact mechanisms by which apoptosis is inhibited. It is known that APC is
1793:. To a degree, APC's anticoagulant properties are independent of its cytoprotective ones, in that expression of one pathway is not affected by the existence of the other.
2064:. This reduces leukocyte adhesion and infiltration into tissues, while also limiting damage to underlying tissue. APC supports endothelial barrier function and reduces
1673:
to give erythro-L-beta-hydroxy-aspartate (bHA). The modification is required for functional activity as was demonstrated by mutating Asp71 to Glu. (3) N-linked
6094:
2187:. This mutation is also called a R506Q. The mutation leading to the loss of this cleavage site actually stops APC from effectively inactivating both Factor V
1756:
The protein C pathways are the specific chemical reactions that control the level of expression of APC and its activity in the body. Protein C is
3580:
Riewald M, Petrovan RJ, Donner A, Mueller BM, Ruf W (June 2002). "Activation of endothelial cell protease activated receptor 1 by the protein C pathway".
3260:"The structure and evolution of a 461 amino acid human protein C precursor and its messenger RNA, based upon the DNA sequence of cloned human liver cDNAs"
1677:
at three possible glycosylation sites. Plasma human
Protein C has been reported to be 23% carbohydrate by weight. (4) Disulfide formation. (5) Multiple
1535:
Human protein C is a vitamin K-dependent glycoprotein structurally similar to other vitamin K-dependent proteins affecting blood clotting, such as
849:
170:
5954:
830:
3040:
Kisiel W, Canfield WM, Ericsson LH, Davie EW (December 1977). "Anticoagulant properties of bovine plasma protein C following activation by thrombin".
4327:
MartĂ-Carvajal AJ, SolĂ I, Lathyris D, Cardona AF (March 2012). MartĂ-Carvajal AJ (ed.). "Human recombinant activated protein C for severe sepsis".
4468:"Eosinophil cationic granule proteins impair thrombomodulin function. A potential mechanism for thromboembolism in hypereosinophilic heart disease"
2195:. Thus, the person's blood clots too readily, and he is perpetually at an increased risk for thrombosis. Individuals heterozygous for the Factor V
5694:
1685:, a 24 amino acid propeptide and then cleavages at amino acids 155-156 and 157-158 to yield the two-chain structure of the circulating zymogen.
5210:
2456:
2438:
1421:
which produced a map of the gene responsible for producing protein C in the liver. In 1987 a seminal experiment was performed (Taylor
2269:(DrotAA) for the clinical treatment of adults suffering from severe sepsis and with a high risk of death. Drotrecogin alfa-activated is a
5602:
2326:
1476:
may be ameliorated by infusion of APC, and mortality rates of septic patients may be significantly decreased. Near the end of that year,
1117:
4525:
1996:, and it is unknown to what degree Factor V and protein S are cofactors in its proteolysis. It is known that APC works on Factor VIII
1124:
3932:"Peptide bond cleavages and loss of functional activity during inactivation of factor Va and factor VaR506Q by activated protein C"
1829:
4621:: Crystal structure of the Endothelial protein C receptor with phospholipid in the groove in complex with Gla domain of protein C.
5714:
4653:
2723:
Eichacker PQ, Natanson C, Danner RL (October 2006). "Surviving sepsis--practice guidelines, marketing campaigns, and Eli Lilly".
2151:
1322:, has been surrounded by controversy. Eli Lilly ran an aggressive marketing campaign to promote its use for people with severe
3814:"Disruption of the endothelial cell protein C receptor gene in mice causes placental thrombosis and early embryonic lethality"
6472:
4577:
2519:
2494:
2421:
6462:
5471:
1965:
by making three cleavages (Arg, Arg, Arg). The cleavages at both Arg and Arg diminish the molecule's attraction to Factor X
69:
5687:
5030:
4122:"Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases"
2400:
5203:
3728:
Yan SC, Grinnell BW, Wold F (July 1989). "Post-translational modifications of proteins: some problems left to solve".
334:
6159:
5672:
5597:
5519:
5514:
5070:
3895:
España F, Berrettini M, Griffin JH (August 1989). "Purification and characterization of plasma protein C inhibitor".
1283:, another protein heavily involved in coagulation, and protein C's activation is greatly promoted by the presence of
5648:
1782:
respectively. When still bound to EPCR, activated protein C performs its cytoprotective effects, acting on the
4920:
1946:, increasing the rate at which thrombin is produced by four orders of magnitude (10,000x). Inactivation of Factor V
1508:
311:
2346: GLA-domainless protein C is produced by selective proteolysis between residues 82 and 83 to remove the
1551:. Protein C synthesis occurs in the liver and begins with a single-chain precursor molecule: a 32 amino acid
5476:
5312:
2425:
2404:
1821:
1797:
1713:
state. On the endothelium, APC performs a major role in regulating blood clotting, inflammation, and cell death (
1654:
5302:
3075:
Vehar GA, Davie EW (February 1980). "Preparation and properties of bovine factor VIII (antihemophilic factor)".
2102:
and inflammation, all problems of sepsis. APC protects endothelial barrier function by inducing PAR-1 dependent
1275:. Its structure is that of a two-chain polypeptide consisting of a light chain and a heavy chain connected by a
5680:
5252:
2179:
1790:
1698:
1495:
1300:
1288:
894:
6315:
5552:
5196:
4358:
Griffin JH, Fernández JA, Mosnier LO, Liu D, Cheng T, Guo H, et al. (2006). "The promise of protein C".
4024:"Effects of exogenous recombinant APC in mouse models of ischemia reperfusion injury and of atherosclerosis"
875:
5914:
5504:
5357:
4631:
4022:
Wildhagen KC, Schrijver R, Beckers L, ten Cate H, Reutelingsperger CP, Lutgens E, et al. (July 2014).
2927:
Kisiel W, Ericsson LH, Davie EW (November 1976). "Proteolytic activation of protein C from bovine plasma".
2294:
2262:
2247:
which are released during infection: cleavage of these histones eliminates their pro inflammatory effects.
1481:
1477:
233:
208:
150:
6467:
5167:
4646:
3487:
Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. (March 2001).
2375:
1809:
1367:
6430:
5157:
4597:
2306:
1817:
1800:
by reducing the amount either of available thrombomodulin or of EPCR. This may be done by inflammatory
1527:. The nucleotide sequence that codes for human protein C is approximately 11,000 bases long.
347:
246:
1992:
is present to stabilise it. Some have questioned the significance of APC's inactivation of Factor VIII
6416:
6403:
6390:
6377:
6364:
6351:
6338:
6300:
5829:
5814:
5592:
5120:
5080:
4570:
4401:
2888:"A new vitamin K-dependent protein. Purification from bovine plasma and preliminary characterization"
1327:
340:
239:
4228:"Plasmodium falciparum histones induce endothelial proinflammatory response and barrier dysfunction"
3763:
Weiler-Guettler H, Christie PD, Beeler DL, Healy AM, Hancock WW, Rayburn H, et al. (May 1998).
3309:"Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon"
2354:(residues 47–88). The N-terminus was removed in order to make crystallization of the protein easier.
137:
6310:
6264:
6207:
5711:
5060:
5035:
2548:
Nicolaes GA, Dahlbäck B (February 2003). "Congenital and acquired activated protein C resistance".
1920:
1096:
1092:
1088:
1067:
1063:
1059:
1055:
1051:
1047:
1043:
1033:
1029:
1025:
1021:
997:
989:
985:
158:
3930:
Nicolaes GA, Tans G, Thomassen MC, Hemker HC, Pabinger I, Varadi K, et al. (September 1995).
6212:
6104:
6069:
6064:
3001:"Protein C anticoagulant activity in relation to anti-inflammatory and anti-apoptotic activities"
2760:"Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients"
2107:
1430:
1402:
1385:. Seegers was, at the time, searching for vitamin K-dependent coagulation factors undetected by
1100:
1017:
993:
964:
5418:
5414:
5095:
4639:
2155:
2061:
2034:
5382:
3765:"A targeted point mutation in thrombomodulin generates viable mice with a prethrombotic state"
3112:"Regulation of activated protein C by a new protein. A possible function for bovine protein S"
6233:
6152:
6059:
5909:
5533:
5277:
5246:
5236:
4396:
4275:
Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, et al. (September 2005).
2274:
2240:
2143:
1319:
1295:(white blood cells) that APC affects. Because of the crucial role that protein C plays as an
1204:
2215:
does. These mutations include various other versions of Factor V, spontaneous generation of
1386:
6305:
6049:
4563:
4522:
4133:
4035:
3589:
3424:
3369:
2613:
2127:
2103:
2022:
2000:
by cleaving at two sites, Arg and Arg, either of which is sufficient to disable Factor VIII
1605:
1480:, a recombinant human activated protein C, became the first drug approved by the U.S.
1410:
1257:
222:
5574:
178:
141:, APC, PC, PROC1, THPH3, THPH4, protein C, inactivator of coagulation factors Va and VIIIa
8:
6487:
6269:
5949:
5939:
5756:
5751:
5584:
5561:
5542:
5524:
5219:
5100:
5025:
4912:
4889:
4853:
4825:
4427:"Proteolytic formation and properties of gamma-carboxyglutamic acid-domainless protein C"
2367:
1845:
1443:
1238:
4137:
4039:
3593:
3428:
3373:
2617:
1191:, that is, an inactive enzyme. The activated form plays an important role in regulating
6482:
6477:
6202:
5227:
5050:
4306:
4252:
4227:
4208:
4154:
4121:
4058:
4023:
3999:
3972:
3705:
3678:
3656:
3613:
3557:
3532:
3448:
3240:
2836:
2811:
2784:
2759:
2573:
2111:
2095:
2042:
1864:
Protein C is a major component in anticoagulation in the human body. It acts as a
1837:
1783:
1729:
1382:
182:
26:
5702:
4492:
4467:
4443:
4426:
3789:
3764:
3333:
3308:
3284:
3259:
3177:
3152:
3128:
3111:
2904:
2887:
2636:
2601:
764:
759:
754:
749:
744:
739:
734:
729:
724:
719:
714:
709:
693:
688:
683:
678:
673:
668:
652:
647:
642:
637:
632:
627:
6492:
5931:
5612:
5569:
5125:
4954:
4544:
4535:
4497:
4448:
4375:
4340:
4298:
4257:
4226:
Gillrie MR, Lee K, Gowda DC, Davis SP, Monestier M, Cui L, et al. (March 2012).
4200:
4195:
4178:
4159:
4102:
4063:
4004:
3973:"Inhibition of thrombin formation by active site mutated (S360A) activated protein C"
3953:
3912:
3908:
3877:
3835:
3794:
3745:
3741:
3710:
3648:
3605:
3562:
3510:
3440:
3397:
3392:
3357:
3338:
3289:
3232:
3227:
3210:
3182:
3133:
3092:
3057:
3022:
2944:
2909:
2868:
2841:
2789:
2740:
2705:
2641:
2577:
2565:
2515:
2490:
2302:
2223:
2147:
2135:
1928:
1833:
1828:. This cytokine is conjectured to improve activation of protein C by forming an
1825:
1702:
1640:
1567:
1498:(PAR-1) and this process accounts for the protein's modulation of the immune system.
1490:
1414:
130:
62:
4277:"Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death"
3812:
Gu JM, Crawley JT, Ferrell G, Zhang F, Li W, Esmon NL, et al. (November 2002).
3617:
3307:
Taylor FB, Chang A, Esmon CT, D'Angelo A, Vigano-D'Angelo S, Blick KE (March 1987).
2211:. Other genetic mutations cause APC resistance, but none to the extent that Factor V
6248:
6243:
6217:
6145:
5723:
5625:
5620:
5040:
4857:
4810:
4487:
4479:
4438:
4367:
4336:
4332:
4310:
4288:
4247:
4239:
4212:
4190:
4149:
4141:
4094:
4053:
4043:
3994:
3984:
3943:
3904:
3869:
3825:
3784:
3776:
3737:
3700:
3690:
3660:
3640:
3597:
3552:
3548:
3544:
3500:
3452:
3432:
3387:
3377:
3328:
3320:
3279:
3271:
3258:
Beckmann RJ, Schmidt RJ, Santerre RF, Plutzky J, Crabtree GR, Long GL (July 1985).
3244:
3222:
3172:
3164:
3123:
3084:
3049:
3012:
2936:
2899:
2831:
2827:
2823:
2779:
2775:
2771:
2732:
2695:
2631:
2621:
2557:
2266:
2256:
2207:
Around 5% of APC resistance are not associated with the above mutation and Factor V
2201:
2053:
1786:
1435:
1315:
1292:
427:
358:
302:
257:
30:
3873:
3533:"Drotrecogin alfa (activated): the first FDA-approved treatment for severe sepsis"
162:
6295:
6279:
6192:
5964:
5959:
5731:
5707:
5292:
5271:
5257:
4997:
4969:
4885:
4529:
4243:
4048:
2700:
2683:
2366: In hypereosinophilia, excess eosinophil-specific granule proteins (such as
2310:
2290:
2270:
2184:
2080:
2030:
1865:
1670:
1625:
1609:
1454:
1331:
1311:
1234:
1192:
402:
186:
3971:
Nicolaes GA, Bock PE, Segers K, Wildhagen KC, Dahlbäck B, Rosing J (July 2010).
3505:
3489:"Efficacy and safety of recombinant human activated protein C for severe sepsis"
3488:
2461:
National Center for
Biotechnology Information, U.S. National Library of Medicine
2443:
National Center for
Biotechnology Information, U.S. National Library of Medicine
6444:
6333:
6274:
5630:
5147:
4666:
4371:
4145:
3695:
3362:
Proceedings of the
National Academy of Sciences of the United States of America
2606:
Proceedings of the
National Academy of Sciences of the United States of America
2371:
2131:
1904:
1694:
1682:
1636:
1597:
1589:
1579:
1555:
1469:
1379:
1303:, suffer from a significantly increased risk of forming dangerous blood clots (
1284:
1276:
503:
1903:, which is a crucial element in blood clotting; together they are part of the
1464:). Two years later, Gla-domainless APC was imaged at a resolution of 2.8
6456:
6238:
6197:
6109:
5982:
5971:
5703:
5443:
5367:
5322:
5152:
5140:
4820:
3948:
3931:
3677:
D'Ursi P, Marino F, Caprera A, Milanesi L, Faioni EM, Rovida E (March 2007).
3275:
1955:
1737:
1674:
1666:
1662:
1658:
1465:
1450:
1356:
1344:
1296:
614:
4661:
3989:
3601:
2758:
MartĂ-Carvajal AJ, SolĂ I, Gluud C, Lathyris D, Cardona AF (December 2012).
2626:
2273:
form of human activated protein C (rhAPC). It is marketed as Xigris by
563:
441:
6187:
6005:
5899:
5741:
5640:
5486:
5451:
5065:
4977:
4844:
4674:
4670:
4379:
4344:
4302:
4261:
4204:
4163:
4106:
4067:
4008:
3881:
3839:
3830:
3813:
3714:
3652:
3609:
3566:
3514:
3382:
3236:
3026:
2872:
2845:
2793:
2744:
2709:
2569:
2305:). Clinical use of APC has also been proposed for improving the outcome of
2216:
2160:
2057:
1924:
1757:
1725:
1632:
1426:
1393:. In 1980, Vehar and Davie discovered that APC also inactivates Factor VIII
1363:
1272:
1268:
1196:
585:
420:
199:
4501:
4452:
4098:
3957:
3916:
3798:
3749:
3444:
3401:
3342:
3293:
3186:
3137:
3096:
2913:
2645:
2178:
At least 177 disease-causing mutations in this gene have been discovered.
1709:
specimens, the mouse dies from excessive blood-clotting while still in an
1164:
1159:
6411:
6346:
6182:
6124:
6119:
5768:
5494:
5429:
5400:
5347:
5177:
5172:
5162:
5135:
5105:
5090:
4959:
4815:
4805:
4682:
4293:
4276:
3644:
3151:
Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C (November 1981).
3061:
2948:
2561:
2298:
2099:
2049:
1939:
1876:
1768:
1741:
1678:
1585:
1574:-linked carbohydrates on each chain. The protein has one light chain (21
1246:
1227:
1216:
939:
920:
3088:
3053:
2940:
2736:
1631:
The Gla domain is particularly useful for binding to negatively charged
45:
6086:
6028:
5809:
5804:
5784:
5410:
5372:
5332:
5327:
5317:
5005:
4113:
2351:
2347:
2139:
2065:
1973:, inhibiting the latter from diminishing APC's inactivation of Factor V
1813:
1647:
efficiently. Another is necessary for interacting with thrombomodulin.
1621:
1601:
1592:
structure of preproprotein C (top) and the mature heterodimer (bottom).
1575:
1559:
1552:
1540:
1520:
1304:
319:
216:
166:
5188:
4483:
3324:
3168:
1425:) whereby it was demonstrated that activated protein C prevented
107:
103:
99:
95:
91:
6385:
6359:
6114:
6100:
5919:
5799:
5789:
5509:
5466:
5461:
5342:
5337:
5115:
5085:
5075:
4987:
4466:
Slungaard A, Vercellotti GM, Tran T, Gleich GJ, Key NS (April 1993).
3436:
2812:"Recombinant human activated protein C for severe sepsis in neonates"
2512:
Concise dictionary of pharmacological agents: properties and synonyms
2487:
Concise dictionary of pharmacological agents: properties and synonyms
2088:
2084:
2073:
2072:. Studies on both rats and humans have demonstrated that APC reduces
1916:
1745:
1733:
1714:
1563:
1544:
1398:
1264:
1200:
794:
386:
373:
285:
272:
174:
22:
3780:
6439:
6000:
5995:
5944:
5794:
5779:
5746:
5405:
5395:
5390:
4934:
4929:
4924:
4902:
4897:
4875:
4870:
4830:
2231:
2227:
2168:
1900:
1872:
1856:
1801:
1761:
1596:
Inactive protein C comprises 419 amino acids in multiple
1548:
1536:
1280:
1220:
1148:
3762:
1844:) for their reaction. In addition, Protein C is inhibited by
6054:
6044:
5990:
5904:
5736:
5657:
5499:
4982:
4865:
4662:
4549:
4539:
4326:
4021:
3017:
3000:
2244:
1868:
1721:
1617:
1613:
1566:
of Lys and Arg is removed; this causes the transformation into a
1453:. In 1994, the relatively common genetic mutation that produces
1375:
1188:
906:
861:
779:
775:
1860:
Blood coagulation and the protein C anticoagulation pathway
1494:
published an article that first showed protein C activates
154:
6398:
6168:
6081:
6023:
5424:
5281:
5055:
4774:
4734:
4518:
3676:
3630:
2757:
2226:
is an acquired protein C deficiency due to treatment with
2164:
2069:
1888:
1710:
1485:
1473:
1323:
1242:
1132:
816:
594:
4555:
4465:
3679:"ProCMD: a database and 3D web resource for protein C mutants"
3414:
3257:
6372:
6090:
6076:
6015:
5889:
5884:
5879:
5874:
5869:
5864:
5472:
Protein Z-related protease inhibitor (ZPI) (inhibits FX, FXI)
5266:
5261:
4949:
4944:
4789:
4784:
4779:
4769:
4764:
4759:
4739:
4724:
4719:
4704:
4691:
2026:
1706:
1612:(97–132 and 136–176); an activation peptide (200–211); and a
4534:
Overview of all the structural information available in the
3579:
3306:
2350:
portion of the protein that includes essentially all of the
2301:, in addition to preventing cell death from lack of oxygen (
5859:
5854:
5849:
5844:
5839:
5834:
5824:
5819:
5286:
5130:
5045:
4939:
4754:
4749:
4744:
4729:
4714:
4709:
4699:
3970:
3929:
3486:
3150:
3039:
2285:
2025:
activity. Important proteins that APC up-regulates include
1805:
1524:
1253:
735:
positive regulation of establishment of endothelial barrier
6137:
4357:
3153:"Deficiency of protein C in congenital thrombotic disease"
2083:. Antiapoptosis is achieved with diminished activation of
2602:"The nucleotide sequence of the gene for human protein C"
2038:
1899:, are highly procoagulant cofactors in the generation of
1693:
The activation of protein C is strongly promoted by
1360:
745:
endoplasmic reticulum to Golgi vesicle-mediated transport
4083:
3355:
1643:
augments protein C's ability to inactivate Factor V
1472:
of 2001, it was recognised that many of the symptoms of
1314:
form of human Activated Protein C (rhAPC) known as
1299:, those with deficiencies in protein C, or some kind of
410:
3894:
3208:
2722:
2091:, improved Bax/Bcl-2 ratio and down-regulation of p53.
1984:
is not as well understood. The half-life of Factor VIII
1748:
of activated protein C is around 15 minutes.
1681:
of the polypeptide backbone to remove an 18 amino acid
1442:
In 1993, a heritable resistance to APC was detected by
5477:
Tissue factor pathway inhibitor (TFPI) (inhibits FIII)
4274:
2681:
1279:. The protein C zymogen is activated when it binds to
6428:
4521:
online database for peptidases and their inhibitors:
3811:
3356:
Dahlbäck B, Carlsson M, Svensson PJ (February 1993).
575:
4225:
3860:
Esmon CT (September 2003). "The protein C pathway".
2599:
2297:(tPA), to protect the brain from tPA's very harmful
2926:
2858:
2146:for the deficiency, there may be a presentation of
1207:of blood vessel walls in humans and other animals.
5543:Thrombin-activatable fibrinolysis inhibitor (TAFI)
2682:Mosnier LO, Zlokovic BV, Griffin JH (April 2007).
2417:
2415:
2413:
2396:
2394:
2392:
1701:(EPCR), the latter of which is found primarily on
1347:role in the human body was first noted by Seegers
5603:Activated protein C–protein C inhibitor (APC–PCI)
4424:
4179:"The discovery of activated protein C resistance"
4119:
3209:Goldenberg NA, Manco-Johnson MJ (November 2008).
1374:because it was the third protein ("peak C") that
357:
256:
6454:
4391:
4389:
2547:
1628:typical of serine proteases (His, Asp and Ser).
1624:of the heavy chain. The active site contains a
5452:Antithrombin (inhibits FII, FIX, FX, FXI, FXII)
3756:
3727:
2410:
2389:
1891:. These proteins that APC inactivates, Factor V
1351:in 1960, who gave protein C its original name,
4079:
4077:
2998:
2600:Foster DC, Yoshitake S, Davie EW (July 1985).
2422:GRCm38: Ensembl release 89: ENSMUSG00000024386
2056:. APC affects endothelial cells by inhibiting
1578:) and one heavy chain (41 kDa) connected by a
1405:by Walker. In 1982, a family study by Griffin
6153:
5688:
5204:
4647:
4571:
4386:
3204:
3202:
3200:
3198:
3196:
2037:. APC effects significant down-regulation of
1887:), and one of the amino acids in the bond is
1871:: APC proteolyses peptide bonds in activated
1836:(GAG) domain of thrombomodulin, reducing the
1653:. Human Protein C has at least five types of
4351:
2994:
2992:
2990:
2988:
2986:
2984:
2982:
2980:
2978:
2809:
2751:
2716:
2076:-induced pulmonary injury and inflammation.
750:negative regulation of inflammatory response
4425:Esmon NL, DeBault LE, Esmon CT (May 1983).
4329:The Cochrane Database of Systematic Reviews
4219:
4074:
2976:
2974:
2972:
2970:
2968:
2966:
2964:
2962:
2960:
2958:
2816:The Cochrane Database of Systematic Reviews
2764:The Cochrane Database of Systematic Reviews
2401:GRCh38: Ensembl release 89: ENSG00000115718
2134:, causes a significantly increased risk of
1988:is only around two minutes unless Factor IX
1907:. Cofactors in the inactivation of Factor V
1530:
1366:in 1976, and Stenflo determined it to be a
760:regulation of circulating fibrinogen levels
6160:
6146:
5695:
5681:
5211:
5197:
4654:
4640:
4578:
4564:
4015:
3193:
3074:
2677:
2675:
2543:
2541:
2539:
2537:
2535:
2533:
2531:
2509:
2484:
1851:
1728:at concentrations between 65 and 135
1610:epidermal growth factor (EGF)-like domains
5520:Plasminogen activator inhibitor-2 (PAI-2)
5515:Plasminogen activator inhibitor-1 (PAI-1)
4491:
4459:
4442:
4292:
4251:
4194:
4153:
4120:Ĺ imÄŤĂková D, Heneberg P (December 2019).
4057:
4047:
3998:
3988:
3964:
3947:
3923:
3829:
3788:
3704:
3694:
3624:
3556:
3504:
3391:
3381:
3349:
3332:
3283:
3226:
3176:
3127:
3016:
2999:Mosnier LO, Griffin JH (September 2006).
2903:
2835:
2783:
2699:
2673:
2671:
2669:
2667:
2665:
2663:
2661:
2659:
2657:
2655:
2635:
2625:
2011:
1249:. In humans, protein C is encoded by the
1215:) performs these operations primarily by
534:fetal liver hematopoietic progenitor cell
4176:
4170:
3855:
3853:
3851:
3849:
3672:
3670:
3526:
3524:
3251:
2955:
2805:
2803:
2595:
2593:
2591:
2589:
2587:
2480:
2478:
2476:
2474:
2472:
2470:
2284:APC has been studied as way of treating
1855:
1832:from protein C's Gla domain to the
1584:
1326:and septic shock and sponsored the 2004
730:negative regulation of apoptotic process
720:negative regulation of blood coagulation
5218:
4960:Structural maintenance of chromosomes 3
4548:(Vitamin K-dependent protein C) at the
4268:
3573:
3459:
3408:
3144:
3033:
2885:
2879:
2852:
2528:
2327:Activated protein C–protein C inhibitor
1355:. Protein C was first isolated by
765:post-translational protein modification
16:Mammalian protein found in Homo sapiens
6455:
5708:serine proteases/serine endopeptidases
5313:High-molecular-weight kininogen (HMWK)
4418:
4322:
4320:
3888:
3300:
3109:
3103:
2920:
2684:"The cytoprotective protein C pathway"
2652:
2152:disseminated intravascular coagulation
1796:The activity of protein C may be
1724:form is present in normal adult human
6141:
5676:
5192:
4635:
4559:
4472:The Journal of Clinical Investigation
4360:Blood Cells, Molecules & Diseases
4183:Journal of Thrombosis and Haemostasis
3859:
3846:
3769:The Journal of Clinical Investigation
3667:
3530:
3521:
3465:PROWESS: recombinant Human Activated
3313:The Journal of Clinical Investigation
3157:The Journal of Clinical Investigation
3068:
2861:Thrombosis et Diathesis Haemorrhagica
2800:
2584:
2503:
2467:
2048:APC has anti-inflammatory effects on
1820:heart disease. Protein C may be
1263:The zymogenic form of protein C is a
362:
323:
318:
261:
220:
215:
1635:for anticoagulation and to EPCR for
1310:Research into the clinical use of a
1289:endothelial protein C receptors
5598:Thrombin–antithrombin complex (TAT)
4431:The Journal of Biological Chemistry
4317:
4281:The New England Journal of Medicine
3977:The Journal of Biological Chemistry
3936:The Journal of Biological Chemistry
3818:The Journal of Biological Chemistry
3493:The New England Journal of Medicine
3116:The Journal of Biological Chemistry
2892:The Journal of Biological Chemistry
2725:The New England Journal of Medicine
2250:
2180:Activated protein C resistance
2130:, in its mild form associated with
1699:endothelial protein C receptor
13:
5505:Tissue plasminogen activator (tPA)
5462:Protein S (cofactor for protein C)
3805:
2810:Kylat RI, Ohlsson A (April 2012).
2121:
1816:, which may explain thrombosis in
1562:. Protein C is formed when a
715:negative regulation of coagulation
648:serine-type endopeptidase activity
14:
6504:
5071:Cholesterylester transfer protein
4921:Chondroitin sulfate proteoglycans
4511:
4232:The American Journal of Pathology
6438:
4611:
4596:
4196:10.1046/j.1538-7836.2003.00016.x
3228:10.1111/j.1365-2516.2008.01838.x
2307:pancreatic islet transplantation
1655:post-translational modifications
1651:Post-translational modifications
1509:HUGO Gene Nomenclature Committee
584:
346:
339:
333:
310:
245:
238:
232:
207:
44:
5593:Prothrombin fragment 1+2 (F1+2)
5253:Platelet membrane glycoproteins
4585:
3721:
1980:The inactivation of Factor VIII
1519:". It is located on the second
5457:Protein C (inhibits FV, FVIII)
4337:10.1002/14651858.CD004388.pub5
3730:Trends in Biochemical Sciences
3549:10.1080/08998280.2002.11927844
2828:10.1002/14651858.CD005385.pub3
2776:10.1002/14651858.CD004388.pub6
2449:
2431:
1523:(2q13-q14) and comprises nine
1468:. Beginning with the PROWESS
1433:with lethal concentrations of
643:serine-type peptidase activity
595:More reference expression data
564:More reference expression data
484:olfactory zone of nasal mucosa
1:
5920:Urinary plasminogen activator
4444:10.1016/S0021-9258(20)81925-5
3874:10.1378/chest.124.3_suppl.26S
3129:10.1016/S0021-9258(19)70660-7
2905:10.1016/S0021-9258(17)33886-3
2550:Seminars in Vascular Medicine
2383:
2106:activation and up-regulating
2058:inflammatory mediator release
2004:and convert it to Factor VIII
1791:protease-activated receptor-1
1688:
1496:protease-activated receptor-1
1449:and associated with familial
331:
230:
6473:Peripheral membrane proteins
5915:Tissue plasminogen activator
4244:10.1016/j.ajpath.2011.11.037
4049:10.1371/journal.pone.0101446
3909:10.1016/0049-3848(89)90069-8
3742:10.1016/0968-0004(89)90060-1
2701:10.1182/blood-2006-09-003004
2358:
2338:
2295:tissue plasminogen activator
2263:Food and Drug Administration
2238:Activated protein C cleaves
1774:, turning them into Factor V
1604:(residues 43–88); a helical
1478:Drotrecogin alfa (activated)
1330:Guidelines. However, a 2012
1185:blood coagulation factor XIV
7:
6463:Genes on human chromosome 2
6167:
5333:Factor XII (Hageman factor)
5247:von Willebrand factor (vWF)
5168:Tumor necrosis factor alpha
4606:: Human activated protein C
4177:Dahlbäck B (January 2003).
3506:10.1056/NEJM200103083441001
2376:eosinophil cationic protein
2320:
2062:vascular adhesion molecules
1751:
1669:of Asp71 in one of the two
1501:
1368:vitamin K-dependent protein
674:endoplasmic reticulum lumen
10:
6509:
5653:-antiplasmin complex (PAP)
5368:Factor III (tissue factor)
5158:Thyroxine-binding proteins
4372:10.1016/j.bcmd.2005.12.023
4146:10.1038/s41598-019-54976-4
3696:10.1186/1471-2105-8-S1-S11
3633:Thrombosis and Haemostasis
2886:Stenflo J (January 1976).
2510:Hall JA, Morton I (1999).
2485:Hall JA, Morton I (1999).
2267:Drotrecogin alfa-activated
2254:
1383:ion-exchange chromotograph
1338:
1316:Drotrecogin alfa-activated
464:mucosa of transverse colon
20:
6324:
6316:Michaelis–Menten kinetics
6288:
6257:
6226:
6175:
6037:
6014:
6006:Proteinase 3/Myeloblastin
5980:
5930:
5767:
5722:
5639:
5611:
5583:
5560:
5551:
5485:
5442:
5381:
5356:
5301:
5235:
5226:
5121:Serum amyloid P component
5081:Colony-stimulating factor
5018:
4996:
4968:
4911:
4884:
4852:
4843:
4798:
4690:
4681:
4591:
4402:European Medicines Agency
2457:"Mouse PubMed Reference:"
2439:"Human PubMed Reference:"
2138:in adults. If a fetus is
2128:protein C deficiency
1411:protein C deficiency
1328:Surviving Sepsis Campaign
1233:. APC is classified as a
1163:
1158:
1154:
1147:
1131:
1118:Chr 2: 127.42 – 127.43 Mb
1112:
1085:
1081:
1040:
1016:
1009:
982:
978:
961:
957:
950:
937:
933:
918:
914:
905:
892:
888:
873:
869:
860:
847:
843:
828:
824:
815:
800:
793:
789:
773:
613:
609:
592:
583:
574:
561:
510:
501:
448:
439:
409:
401:
397:
380:
367:
330:
309:
300:
296:
279:
266:
229:
206:
197:
193:
148:
145:
135:
128:
123:
88:
83:
66:
61:
56:
52:
43:
38:
6208:Diffusion-limited enzyme
5575:β-Thromboglobulin (β-TG)
5061:B-cell activating factor
5036:Alpha 1-antichymotrypsin
3949:10.1074/jbc.270.36.21158
2332:
1961:APC inactivates Factor V
1921:high-density lipoprotein
1846:protein C inhibitor
1531:Structure and processing
1209:Activated protein C
1125:Chr 18: 32.26 – 32.27 Mb
21:Not to be confused with
5570:Platelet factor 4 (PF4)
5467:Protein Z (inhibits FX)
5401:Prothrombin (factor II)
3990:10.1074/jbc.M110.131029
3602:10.1126/science.1071699
3531:Hosac AM (April 2002).
3110:Walker FJ (June 1980).
3005:Frontiers in Bioscience
2627:10.1073/pnas.82.14.4673
2108:sphingosine-1-phosphate
1852:Anticoagulative effects
1810:tumor necrosis factor-α
6060:Proprotein convertases
5626:Fibrinopeptide B (FpB)
5621:Fibrinopeptide A (FpA)
5293:Glycoprotein VI (GPVI)
5258:Glycoprotein Ib (GPIb)
5096:Membrane glycoproteins
4093:(6 Suppl): 160S–198S.
3831:10.1074/jbc.M207538200
3383:10.1073/pnas.90.3.1004
3276:10.1093/nar/13.14.5233
3264:Nucleic Acids Research
3211:"Protein C deficiency"
2261:In November 2001, the
2156:venous thromboembolism
2012:Cytoprotective effects
1905:prothrombinase complex
1861:
1593:
1370:. He named it protein
1219:inactivating proteins
472:metanephric glomerulus
6301:Eadie–Hofstee diagram
6234:Allosteric regulation
5910:Plasminogen activator
5444:Anticoagulant factors
5411:Fibrinogen (factor I)
5406:Thrombin (factor IIa)
5278:Glycoprotein IIb/IIIa
5272:Glycoprotein IX (GP9)
5239:(platelet activation)
4099:10.1378/chest.08-0670
2275:Eli Lilly and Company
2241:Plasmodium falciparum
2144:compound heterozygous
2132:simple heterozygosity
1859:
1679:proteolytic cleavages
1608:segment (89–96); two
1588:
1582:between Cys and Cys.
1429:and death in baboons
1320:Eli Lilly and Company
684:endoplasmic reticulum
325:Chromosome 18 (mouse)
6311:Lineweaver–Burk plot
6050:Prolyl endopeptidase
5631:Fibrin monomers (FM)
5487:Fibrinolytic factors
5305:(contact activation)
4294:10.1056/NEJMoa050935
3868:(3 Suppl): 26S–32S.
3645:10.1160/TH11-08-0522
2562:10.1055/s-2003-38331
2104:sphingosine kinase-1
2060:and down-regulating
2023:transcription factor
1830:electrostatic bridge
1484:for treating severe
1401:was recognised as a
1353:autoprothrombin II-a
1318:, branded Xigris by
1256:, which is found on
1237:since it contains a
1203:and maintaining the
679:extracellular region
223:Chromosome 2 (human)
84:List of PDB id codes
57:Available structures
5585:Thrombin generation
5562:Platelet activation
5553:Coagulation markers
5228:Coagulation factors
5220:Coagulation cascade
5101:Myelin protein zero
5026:Activin and inhibin
4826:Phytohaemagglutinin
4406:. 17 September 2018
4138:2019NatSR...918577S
4040:2014PLoSO...9j1446W
3983:(30): 22890–22900.
3942:(36): 21158–21166.
3897:Thrombosis Research
3824:(45): 43335–43343.
3594:2002Sci...296.1880R
3588:(5574): 1880–1882.
3429:1994Natur.369...64B
3374:1993PNAS...90.1004D
3089:10.1021/bi00544a001
3054:10.1021/bi00645a029
2941:10.1021/bi00667a022
2737:10.1056/NEJMp068197
2618:1985PNAS...82.4673F
2514:. Kluwer Academic.
2489:. Kluwer Academic.
2368:major basic protein
1460:was noted (Bertina
1409:. first associated
1271:that circulates in
1181:autoprothrombin IIA
694:extracellular space
628:calcium ion binding
550:seminiferous tubule
452:right lobe of liver
6468:Coagulation system
6270:Enzyme superfamily
6203:Enzyme promiscuity
5425:Fibrin (factor Ia)
5237:Primary hemostasis
5051:Asialoglycoprotein
4528:2007-09-16 at the
4126:Scientific Reports
3683:BMC Bioinformatics
2112:sphingosine kinase
1929:glycosphingolipids
1862:
1838:Michaelis constant
1720:Protein C in
1661:on the first nine
1594:
1397:, and soon after,
895:ENSMUSG00000024386
703:Biological process
662:Cellular component
653:hydrolase activity
633:peptidase activity
621:Molecular function
514:left lobe of liver
27:C-reactive protein
6426:
6425:
6135:
6134:
5932:Complement system
5724:Digestive enzymes
5670:
5669:
5666:
5665:
5613:Fibrin generation
5438:
5437:
5358:Extrinsic pathway
5303:Intrinsic pathway
5186:
5185:
5126:Sialoglycoprotein
5014:
5013:
4955:Platelet factor 4
4839:
4838:
4629:
4628:
4484:10.1172/JCI116382
4287:(13): 1332–1341.
3325:10.1172/JCI112902
3270:(14): 5233–5247.
3169:10.1172/JCI110385
3122:(12): 5521–5524.
3048:(26): 5824–5831.
2935:(22): 4893–4900.
2731:(16): 1640–1642.
2612:(14): 4673–4677.
2521:978-0-7514-0499-9
2496:978-0-7514-0499-9
2224:Warfarin necrosis
2154:and simultaneous
2148:purpura fulminans
2136:venous thrombosis
1834:glycosaminoglycan
1826:platelet factor 4
1818:hypereosinophilic
1703:endothelial cells
1639:. One particular
1415:venous thrombosis
1413:with symptoms of
1301:resistance to APC
1174:
1173:
1170:
1169:
1143:
1142:
1108:
1107:
1075:
1074:
1005:
1004:
972:
971:
946:
945:
927:
926:
901:
900:
882:
881:
856:
855:
837:
836:
785:
784:
755:liver development
725:blood coagulation
605:
604:
601:
600:
570:
569:
557:
556:
495:
494:
393:
392:
292:
291:
119:
118:
115:
114:
67:Ortholog search:
6500:
6443:
6442:
6434:
6306:Hanes–Woolf plot
6249:Enzyme activator
6244:Enzyme inhibitor
6218:Enzyme catalysis
6162:
6155:
6148:
6139:
6138:
5697:
5690:
5683:
5674:
5673:
5558:
5557:
5233:
5232:
5213:
5206:
5199:
5190:
5189:
5041:Apolipoprotein H
4850:
4849:
4811:Intrinsic factor
4688:
4687:
4656:
4649:
4642:
4633:
4632:
4615:
4600:
4580:
4573:
4566:
4557:
4556:
4506:
4505:
4495:
4478:(4): 1721–1730.
4463:
4457:
4456:
4446:
4437:(9): 5548–5553.
4422:
4416:
4415:
4413:
4411:
4393:
4384:
4383:
4355:
4349:
4348:
4324:
4315:
4314:
4296:
4272:
4266:
4265:
4255:
4238:(3): 1028–1039.
4223:
4217:
4216:
4198:
4174:
4168:
4167:
4157:
4117:
4111:
4110:
4081:
4072:
4071:
4061:
4051:
4019:
4013:
4012:
4002:
3992:
3968:
3962:
3961:
3951:
3927:
3921:
3920:
3892:
3886:
3885:
3857:
3844:
3843:
3833:
3809:
3803:
3802:
3792:
3775:(9): 1983–1991.
3760:
3754:
3753:
3725:
3719:
3718:
3708:
3698:
3689:(Suppl 1): S11.
3674:
3665:
3664:
3639:(6): 1034–1045.
3628:
3622:
3621:
3577:
3571:
3570:
3560:
3528:
3519:
3518:
3508:
3463:
3457:
3456:
3437:10.1038/369064a0
3412:
3406:
3405:
3395:
3385:
3368:(3): 1004–1008.
3353:
3347:
3346:
3336:
3304:
3298:
3297:
3287:
3255:
3249:
3248:
3230:
3221:(6): 1214–1221.
3206:
3191:
3190:
3180:
3163:(5): 1370–1373.
3148:
3142:
3141:
3131:
3107:
3101:
3100:
3072:
3066:
3065:
3037:
3031:
3030:
3020:
2996:
2953:
2952:
2924:
2918:
2917:
2907:
2883:
2877:
2876:
2856:
2850:
2849:
2839:
2807:
2798:
2797:
2787:
2770:(12): CD004388.
2755:
2749:
2748:
2720:
2714:
2713:
2703:
2694:(8): 3161–3172.
2679:
2650:
2649:
2639:
2629:
2597:
2582:
2581:
2545:
2526:
2525:
2507:
2501:
2500:
2482:
2465:
2464:
2453:
2447:
2446:
2435:
2429:
2419:
2408:
2398:
2361:
2341:
2257:drotrecogin alfa
2251:Role in medicine
2163:, deposition of
1671:EGF-like domains
1511:is "PROC" from "
1179:, also known as
1156:
1155:
1127:
1120:
1103:
1079:
1078:
1070:
1014:
1013:
1010:RefSeq (protein)
1000:
976:
975:
967:
955:
954:
931:
930:
912:
911:
886:
885:
867:
866:
841:
840:
822:
821:
791:
790:
611:
610:
597:
588:
581:
580:
566:
506:
504:Top expressed in
499:
498:
444:
442:Top expressed in
437:
436:
416:
415:
399:
398:
389:
376:
365:
350:
343:
337:
326:
314:
298:
297:
288:
275:
264:
249:
242:
236:
225:
211:
195:
194:
189:
187:PROC - orthologs
140:
133:
110:
81:
80:
75:
54:
53:
48:
36:
35:
31:protein kinase C
6508:
6507:
6503:
6502:
6501:
6499:
6498:
6497:
6453:
6452:
6449:
6437:
6429:
6427:
6422:
6334:Oxidoreductases
6320:
6296:Enzyme kinetics
6284:
6280:List of enzymes
6253:
6222:
6193:Catalytic triad
6171:
6166:
6136:
6131:
6033:
6010:
5976:
5926:
5763:
5732:Enteropeptidase
5718:
5701:
5671:
5662:
5652:
5635:
5607:
5579:
5547:
5537:
5528:
5481:
5434:
5377:
5360:(tissue factor)
5359:
5352:
5304:
5297:
5238:
5222:
5217:
5187:
5182:
5010:
4992:
4964:
4907:
4880:
4835:
4794:
4677:
4660:
4630:
4625:
4622:
4616:
4607:
4601:
4587:
4584:
4530:Wayback Machine
4514:
4509:
4464:
4460:
4423:
4419:
4409:
4407:
4397:"Ceprotin EPAR"
4395:
4394:
4387:
4356:
4352:
4331:(3): CD004388.
4325:
4318:
4273:
4269:
4224:
4220:
4175:
4171:
4118:
4114:
4082:
4075:
4020:
4016:
3969:
3965:
3928:
3924:
3893:
3889:
3858:
3847:
3810:
3806:
3781:10.1172/JCI2006
3761:
3757:
3726:
3722:
3675:
3668:
3629:
3625:
3578:
3574:
3529:
3522:
3499:(10): 699–709.
3464:
3460:
3423:(6475): 64–67.
3413:
3409:
3354:
3350:
3305:
3301:
3256:
3252:
3207:
3194:
3149:
3145:
3108:
3104:
3073:
3069:
3038:
3034:
2997:
2956:
2925:
2921:
2884:
2880:
2857:
2853:
2822:(4): CD005385.
2808:
2801:
2756:
2752:
2721:
2717:
2680:
2653:
2598:
2585:
2546:
2529:
2522:
2508:
2504:
2497:
2483:
2468:
2455:
2454:
2450:
2437:
2436:
2432:
2420:
2411:
2399:
2390:
2386:
2379:
2355:
2335:
2323:
2311:type I diabetes
2291:ischemic stroke
2259:
2253:
2214:
2210:
2198:
2194:
2191:and Factor VIII
2190:
2185:Factor V Leiden
2124:
2122:Role in disease
2081:neuroprotective
2014:
2007:
2003:
1999:
1995:
1991:
1987:
1983:
1976:
1972:
1968:
1964:
1953:
1949:
1945:
1937:
1914:
1911:and Factor VIII
1910:
1898:
1895:and Factor VIII
1894:
1886:
1883:and Factor VIII
1882:
1866:serine protease
1854:
1843:
1781:
1778:and Factor VIII
1777:
1772:
1765:
1754:
1691:
1646:
1626:catalytic triad
1533:
1504:
1458:
1396:
1392:
1387:clotting assays
1341:
1332:Cochrane review
1235:serine protease
1231:
1224:
1217:proteolytically
1193:anticoagulation
1165:View/Edit Mouse
1160:View/Edit Human
1123:
1116:
1113:Location (UCSC)
1099:
1095:
1091:
1087:
1066:
1062:
1058:
1054:
1050:
1046:
1042:
1036:
1032:
1028:
1024:
1020:
996:
992:
988:
984:
963:
876:ENSG00000115718
769:
698:
669:Golgi apparatus
657:
638:protein binding
593:
562:
553:
548:
544:
540:
536:
532:
528:
526:proximal tubule
524:
520:
516:
502:
491:
486:
482:
478:
476:body of stomach
474:
470:
466:
462:
458:
454:
440:
384:
371:
363:
353:
352:
351:
344:
324:
301:Gene location (
283:
270:
262:
252:
251:
250:
243:
221:
198:Gene location (
149:
136:
129:
90:
68:
34:
17:
12:
11:
5:
6506:
6496:
6495:
6490:
6485:
6480:
6475:
6470:
6465:
6448:
6447:
6424:
6423:
6421:
6420:
6407:
6394:
6381:
6368:
6355:
6342:
6328:
6326:
6322:
6321:
6319:
6318:
6313:
6308:
6303:
6298:
6292:
6290:
6286:
6285:
6283:
6282:
6277:
6272:
6267:
6261:
6259:
6258:Classification
6255:
6254:
6252:
6251:
6246:
6241:
6236:
6230:
6228:
6224:
6223:
6221:
6220:
6215:
6210:
6205:
6200:
6195:
6190:
6185:
6179:
6177:
6173:
6172:
6165:
6164:
6157:
6150:
6142:
6133:
6132:
6130:
6129:
6128:
6127:
6122:
6112:
6107:
6098:
6084:
6079:
6074:
6073:
6072:
6067:
6057:
6052:
6047:
6041:
6039:
6035:
6034:
6032:
6031:
6026:
6020:
6018:
6012:
6011:
6009:
6008:
6003:
5998:
5993:
5987:
5985:
5978:
5977:
5975:
5974:
5969:
5968:
5967:
5962:
5952:
5947:
5942:
5936:
5934:
5928:
5927:
5925:
5924:
5923:
5922:
5917:
5907:
5895:
5894:
5893:
5892:
5887:
5882:
5877:
5872:
5867:
5862:
5857:
5852:
5847:
5842:
5837:
5832:
5827:
5822:
5817:
5807:
5802:
5797:
5792:
5787:
5782:
5773:
5771:
5765:
5764:
5762:
5761:
5760:
5759:
5754:
5744:
5739:
5734:
5728:
5726:
5720:
5719:
5704:Endopeptidases
5700:
5699:
5692:
5685:
5677:
5668:
5667:
5664:
5663:
5661:
5660:
5655:
5650:
5645:
5643:
5637:
5636:
5634:
5633:
5628:
5623:
5617:
5615:
5609:
5608:
5606:
5605:
5600:
5595:
5589:
5587:
5581:
5580:
5578:
5577:
5572:
5566:
5564:
5555:
5549:
5548:
5546:
5545:
5540:
5538:-Macroglobulin
5535:
5531:
5526:
5522:
5517:
5512:
5507:
5502:
5497:
5491:
5489:
5483:
5482:
5480:
5479:
5474:
5469:
5464:
5459:
5454:
5448:
5446:
5440:
5439:
5436:
5435:
5433:
5432:
5427:
5422:
5408:
5403:
5398:
5393:
5387:
5385:
5383:Common pathway
5379:
5378:
5376:
5375:
5370:
5364:
5362:
5354:
5353:
5351:
5350:
5345:
5340:
5335:
5330:
5325:
5320:
5315:
5309:
5307:
5299:
5298:
5296:
5295:
5290:
5284:
5275:
5269:
5264:
5249:
5243:
5241:
5230:
5224:
5223:
5216:
5215:
5208:
5201:
5193:
5184:
5183:
5181:
5180:
5175:
5170:
5165:
5160:
5155:
5150:
5148:Thrombopoietin
5145:
5144:
5143:
5138:
5133:
5123:
5118:
5113:
5108:
5103:
5098:
5093:
5088:
5083:
5078:
5073:
5068:
5063:
5058:
5053:
5048:
5043:
5038:
5033:
5028:
5022:
5020:
5016:
5015:
5012:
5011:
5009:
5008:
5002:
5000:
4994:
4993:
4991:
4990:
4985:
4980:
4974:
4972:
4966:
4965:
4963:
4962:
4957:
4952:
4947:
4942:
4937:
4932:
4927:
4917:
4915:
4909:
4908:
4906:
4905:
4900:
4894:
4892:
4882:
4881:
4879:
4878:
4873:
4868:
4862:
4860:
4847:
4841:
4840:
4837:
4836:
4834:
4833:
4828:
4823:
4818:
4813:
4808:
4802:
4800:
4796:
4795:
4793:
4792:
4787:
4782:
4777:
4772:
4767:
4762:
4757:
4752:
4747:
4742:
4737:
4732:
4727:
4722:
4717:
4712:
4707:
4702:
4696:
4694:
4685:
4679:
4678:
4667:glycoconjugate
4659:
4658:
4651:
4644:
4636:
4627:
4626:
4624:
4623:
4617:
4610:
4608:
4602:
4595:
4592:
4589:
4588:
4583:
4582:
4575:
4568:
4560:
4554:
4553:
4532:
4513:
4512:External links
4510:
4508:
4507:
4458:
4417:
4385:
4366:(2): 211–216.
4350:
4316:
4267:
4218:
4169:
4112:
4073:
4034:(7): e101446.
4014:
3963:
3922:
3903:(3): 369–384.
3887:
3845:
3804:
3755:
3736:(7): 264–268.
3720:
3666:
3623:
3572:
3543:(2): 224–227.
3520:
3458:
3407:
3348:
3319:(3): 918–925.
3299:
3250:
3192:
3143:
3102:
3083:(3): 401–410.
3067:
3032:
2954:
2919:
2898:(2): 355–363.
2878:
2851:
2799:
2750:
2715:
2651:
2583:
2527:
2520:
2502:
2495:
2466:
2448:
2430:
2409:
2387:
2385:
2382:
2381:
2380:
2372:erythropoietin
2356:
2334:
2331:
2330:
2329:
2322:
2319:
2252:
2249:
2217:autoantibodies
2212:
2208:
2196:
2192:
2188:
2171:of the liver.
2123:
2120:
2013:
2010:
2005:
2001:
1997:
1993:
1989:
1985:
1981:
1974:
1970:
1966:
1962:
1951:
1947:
1943:
1935:
1912:
1908:
1896:
1892:
1884:
1880:
1853:
1850:
1841:
1806:interleukin-1β
1798:down-regulated
1779:
1775:
1770:
1763:
1753:
1750:
1695:thrombomodulin
1690:
1687:
1683:signal peptide
1644:
1637:cytoprotection
1580:disulfide bond
1556:signal peptide
1532:
1529:
1503:
1500:
1470:clinical trial
1456:
1394:
1390:
1380:DEAE-Sepharose
1340:
1337:
1285:thrombomodulin
1277:disulfide bond
1229:
1222:
1177:Protein C
1172:
1171:
1168:
1167:
1162:
1152:
1151:
1145:
1144:
1141:
1140:
1138:
1136:
1129:
1128:
1121:
1114:
1110:
1109:
1106:
1105:
1083:
1082:
1076:
1073:
1072:
1038:
1037:
1011:
1007:
1006:
1003:
1002:
980:
979:
973:
970:
969:
959:
958:
952:
948:
947:
944:
943:
935:
934:
928:
925:
924:
916:
915:
909:
903:
902:
899:
898:
890:
889:
883:
880:
879:
871:
870:
864:
858:
857:
854:
853:
845:
844:
838:
835:
834:
826:
825:
819:
813:
812:
807:
802:
798:
797:
787:
786:
783:
782:
771:
770:
768:
767:
762:
757:
752:
747:
742:
737:
732:
727:
722:
717:
712:
706:
704:
700:
699:
697:
696:
691:
686:
681:
676:
671:
665:
663:
659:
658:
656:
655:
650:
645:
640:
635:
630:
624:
622:
618:
617:
607:
606:
603:
602:
599:
598:
590:
589:
578:
572:
571:
568:
567:
559:
558:
555:
554:
552:
551:
547:
543:
539:
538:primary oocyte
535:
531:
527:
523:
519:
515:
511:
508:
507:
496:
493:
492:
490:
489:
485:
481:
477:
473:
469:
465:
461:
457:
453:
449:
446:
445:
433:
432:
424:
413:
407:
406:
403:RNA expression
395:
394:
391:
390:
382:
378:
377:
369:
366:
361:
355:
354:
345:
338:
332:
328:
327:
322:
316:
315:
307:
306:
294:
293:
290:
289:
281:
277:
276:
268:
265:
260:
254:
253:
244:
237:
231:
227:
226:
219:
213:
212:
204:
203:
191:
190:
147:
143:
142:
134:
126:
125:
121:
120:
117:
116:
113:
112:
86:
85:
77:
76:
65:
59:
58:
50:
49:
41:
40:
15:
9:
6:
4:
3:
2:
6505:
6494:
6491:
6489:
6486:
6484:
6481:
6479:
6476:
6474:
6471:
6469:
6466:
6464:
6461:
6460:
6458:
6451:
6446:
6441:
6436:
6435:
6432:
6418:
6414:
6413:
6408:
6405:
6401:
6400:
6395:
6392:
6388:
6387:
6382:
6379:
6375:
6374:
6369:
6366:
6362:
6361:
6356:
6353:
6349:
6348:
6343:
6340:
6336:
6335:
6330:
6329:
6327:
6323:
6317:
6314:
6312:
6309:
6307:
6304:
6302:
6299:
6297:
6294:
6293:
6291:
6287:
6281:
6278:
6276:
6275:Enzyme family
6273:
6271:
6268:
6266:
6263:
6262:
6260:
6256:
6250:
6247:
6245:
6242:
6240:
6239:Cooperativity
6237:
6235:
6232:
6231:
6229:
6225:
6219:
6216:
6214:
6211:
6209:
6206:
6204:
6201:
6199:
6198:Oxyanion hole
6196:
6194:
6191:
6189:
6186:
6184:
6181:
6180:
6178:
6174:
6170:
6163:
6158:
6156:
6151:
6149:
6144:
6143:
6140:
6126:
6123:
6121:
6118:
6117:
6116:
6113:
6111:
6110:Streptokinase
6108:
6106:
6102:
6099:
6096:
6092:
6088:
6085:
6083:
6080:
6078:
6075:
6071:
6068:
6066:
6063:
6062:
6061:
6058:
6056:
6053:
6051:
6048:
6046:
6043:
6042:
6040:
6036:
6030:
6027:
6025:
6022:
6021:
6019:
6017:
6013:
6007:
6004:
6002:
5999:
5997:
5994:
5992:
5989:
5988:
5986:
5984:
5983:immune system
5979:
5973:
5972:C3-convertase
5970:
5966:
5963:
5961:
5958:
5957:
5956:
5953:
5951:
5948:
5946:
5943:
5941:
5938:
5937:
5935:
5933:
5929:
5921:
5918:
5916:
5913:
5912:
5911:
5908:
5906:
5903:
5901:
5897:
5896:
5891:
5888:
5886:
5883:
5881:
5878:
5876:
5873:
5871:
5868:
5866:
5863:
5861:
5858:
5856:
5853:
5851:
5848:
5846:
5843:
5841:
5838:
5836:
5833:
5831:
5828:
5826:
5823:
5821:
5818:
5816:
5813:
5812:
5811:
5808:
5806:
5803:
5801:
5798:
5796:
5793:
5791:
5788:
5786:
5783:
5781:
5778:
5775:
5774:
5772:
5770:
5766:
5758:
5755:
5753:
5750:
5749:
5748:
5745:
5743:
5740:
5738:
5735:
5733:
5730:
5729:
5727:
5725:
5721:
5716:
5713:
5709:
5705:
5698:
5693:
5691:
5686:
5684:
5679:
5678:
5675:
5659:
5656:
5654:
5647:
5646:
5644:
5642:
5638:
5632:
5629:
5627:
5624:
5622:
5619:
5618:
5616:
5614:
5610:
5604:
5601:
5599:
5596:
5594:
5591:
5590:
5588:
5586:
5582:
5576:
5573:
5571:
5568:
5567:
5565:
5563:
5559:
5556:
5554:
5550:
5544:
5541:
5539:
5532:
5530:
5523:
5521:
5518:
5516:
5513:
5511:
5508:
5506:
5503:
5501:
5498:
5496:
5493:
5492:
5490:
5488:
5484:
5478:
5475:
5473:
5470:
5468:
5465:
5463:
5460:
5458:
5455:
5453:
5450:
5449:
5447:
5445:
5441:
5431:
5428:
5426:
5423:
5420:
5416:
5412:
5409:
5407:
5404:
5402:
5399:
5397:
5394:
5392:
5389:
5388:
5386:
5384:
5380:
5374:
5371:
5369:
5366:
5365:
5363:
5361:
5355:
5349:
5346:
5344:
5341:
5339:
5336:
5334:
5331:
5329:
5326:
5324:
5323:Prekallikrein
5321:
5319:
5316:
5314:
5311:
5310:
5308:
5306:
5300:
5294:
5291:
5288:
5285:
5283:
5279:
5276:
5273:
5270:
5268:
5265:
5263:
5259:
5256:
5254:
5250:
5248:
5245:
5244:
5242:
5240:
5234:
5231:
5229:
5225:
5221:
5214:
5209:
5207:
5202:
5200:
5195:
5194:
5191:
5179:
5176:
5174:
5171:
5169:
5166:
5164:
5161:
5159:
5156:
5154:
5153:Thyroglobulin
5151:
5149:
5146:
5142:
5141:Glycophorin C
5139:
5137:
5134:
5132:
5129:
5128:
5127:
5124:
5122:
5119:
5117:
5114:
5112:
5109:
5107:
5104:
5102:
5099:
5097:
5094:
5092:
5089:
5087:
5084:
5082:
5079:
5077:
5074:
5072:
5069:
5067:
5064:
5062:
5059:
5057:
5054:
5052:
5049:
5047:
5044:
5042:
5039:
5037:
5034:
5032:
5029:
5027:
5024:
5023:
5021:
5017:
5007:
5004:
5003:
5001:
4999:
4995:
4989:
4986:
4984:
4981:
4979:
4976:
4975:
4973:
4971:
4967:
4961:
4958:
4956:
4953:
4951:
4948:
4946:
4943:
4941:
4938:
4936:
4933:
4931:
4928:
4926:
4922:
4919:
4918:
4916:
4914:
4910:
4904:
4901:
4899:
4896:
4895:
4893:
4891:
4887:
4883:
4877:
4874:
4872:
4869:
4867:
4864:
4863:
4861:
4859:
4855:
4851:
4848:
4846:
4845:Proteoglycans
4842:
4832:
4829:
4827:
4824:
4822:
4821:Peptidoglycan
4819:
4817:
4814:
4812:
4809:
4807:
4804:
4803:
4801:
4797:
4791:
4788:
4786:
4783:
4781:
4778:
4776:
4773:
4771:
4768:
4766:
4763:
4761:
4758:
4756:
4753:
4751:
4748:
4746:
4743:
4741:
4738:
4736:
4733:
4731:
4728:
4726:
4723:
4721:
4718:
4716:
4713:
4711:
4708:
4706:
4703:
4701:
4698:
4697:
4695:
4693:
4689:
4686:
4684:
4680:
4676:
4675:glycopeptides
4672:
4671:glycoproteins
4668:
4664:
4657:
4652:
4650:
4645:
4643:
4638:
4637:
4634:
4620:
4614:
4609:
4605:
4599:
4594:
4593:
4590:
4581:
4576:
4574:
4569:
4567:
4562:
4561:
4558:
4551:
4547:
4546:
4541:
4537:
4533:
4531:
4527:
4524:
4520:
4516:
4515:
4503:
4499:
4494:
4489:
4485:
4481:
4477:
4473:
4469:
4462:
4454:
4450:
4445:
4440:
4436:
4432:
4428:
4421:
4405:
4403:
4398:
4392:
4390:
4381:
4377:
4373:
4369:
4365:
4361:
4354:
4346:
4342:
4338:
4334:
4330:
4323:
4321:
4312:
4308:
4304:
4300:
4295:
4290:
4286:
4282:
4278:
4271:
4263:
4259:
4254:
4249:
4245:
4241:
4237:
4233:
4229:
4222:
4214:
4210:
4206:
4202:
4197:
4192:
4188:
4184:
4180:
4173:
4165:
4161:
4156:
4151:
4147:
4143:
4139:
4135:
4131:
4127:
4123:
4116:
4108:
4104:
4100:
4096:
4092:
4088:
4080:
4078:
4069:
4065:
4060:
4055:
4050:
4045:
4041:
4037:
4033:
4029:
4025:
4018:
4010:
4006:
4001:
3996:
3991:
3986:
3982:
3978:
3974:
3967:
3959:
3955:
3950:
3945:
3941:
3937:
3933:
3926:
3918:
3914:
3910:
3906:
3902:
3898:
3891:
3883:
3879:
3875:
3871:
3867:
3863:
3856:
3854:
3852:
3850:
3841:
3837:
3832:
3827:
3823:
3819:
3815:
3808:
3800:
3796:
3791:
3786:
3782:
3778:
3774:
3770:
3766:
3759:
3751:
3747:
3743:
3739:
3735:
3731:
3724:
3716:
3712:
3707:
3702:
3697:
3692:
3688:
3684:
3680:
3673:
3671:
3662:
3658:
3654:
3650:
3646:
3642:
3638:
3634:
3627:
3619:
3615:
3611:
3607:
3603:
3599:
3595:
3591:
3587:
3583:
3576:
3568:
3564:
3559:
3554:
3550:
3546:
3542:
3538:
3534:
3527:
3525:
3516:
3512:
3507:
3502:
3498:
3494:
3490:
3484:
3480:
3477:valuation in
3476:
3472:
3468:
3462:
3454:
3450:
3446:
3442:
3438:
3434:
3430:
3426:
3422:
3418:
3411:
3403:
3399:
3394:
3389:
3384:
3379:
3375:
3371:
3367:
3363:
3359:
3352:
3344:
3340:
3335:
3330:
3326:
3322:
3318:
3314:
3310:
3303:
3295:
3291:
3286:
3281:
3277:
3273:
3269:
3265:
3261:
3254:
3246:
3242:
3238:
3234:
3229:
3224:
3220:
3216:
3212:
3205:
3203:
3201:
3199:
3197:
3188:
3184:
3179:
3174:
3170:
3166:
3162:
3158:
3154:
3147:
3139:
3135:
3130:
3125:
3121:
3117:
3113:
3106:
3098:
3094:
3090:
3086:
3082:
3078:
3071:
3063:
3059:
3055:
3051:
3047:
3043:
3036:
3028:
3024:
3019:
3014:
3011:: 2381–2399.
3010:
3006:
3002:
2995:
2993:
2991:
2989:
2987:
2985:
2983:
2981:
2979:
2977:
2975:
2973:
2971:
2969:
2967:
2965:
2963:
2961:
2959:
2950:
2946:
2942:
2938:
2934:
2930:
2923:
2915:
2911:
2906:
2901:
2897:
2893:
2889:
2882:
2874:
2870:
2866:
2862:
2855:
2847:
2843:
2838:
2833:
2829:
2825:
2821:
2817:
2813:
2806:
2804:
2795:
2791:
2786:
2781:
2777:
2773:
2769:
2765:
2761:
2754:
2746:
2742:
2738:
2734:
2730:
2726:
2719:
2711:
2707:
2702:
2697:
2693:
2689:
2685:
2678:
2676:
2674:
2672:
2670:
2668:
2666:
2664:
2662:
2660:
2658:
2656:
2647:
2643:
2638:
2633:
2628:
2623:
2619:
2615:
2611:
2607:
2603:
2596:
2594:
2592:
2590:
2588:
2579:
2575:
2571:
2567:
2563:
2559:
2555:
2551:
2544:
2542:
2540:
2538:
2536:
2534:
2532:
2523:
2517:
2513:
2506:
2498:
2492:
2488:
2481:
2479:
2477:
2475:
2473:
2471:
2462:
2458:
2452:
2444:
2440:
2434:
2427:
2423:
2418:
2416:
2414:
2406:
2402:
2397:
2395:
2393:
2388:
2377:
2373:
2369:
2365:
2360:
2357:
2353:
2349:
2345:
2340:
2337:
2336:
2328:
2325:
2324:
2318:
2314:
2312:
2308:
2304:
2300:
2296:
2292:
2287:
2282:
2278:
2276:
2272:
2268:
2264:
2258:
2248:
2246:
2243:
2242:
2236:
2233:
2229:
2225:
2221:
2218:
2205:
2203:
2186:
2181:
2176:
2172:
2170:
2166:
2162:
2157:
2153:
2149:
2145:
2141:
2137:
2133:
2129:
2119:
2118:and in vivo.
2115:
2113:
2109:
2105:
2101:
2097:
2092:
2090:
2086:
2082:
2077:
2075:
2071:
2067:
2063:
2059:
2055:
2051:
2046:
2044:
2040:
2036:
2032:
2028:
2024:
2018:
2009:
1978:
1959:
1957:
1956:haemophilia A
1941:
1932:
1930:
1926:
1925:phospholipids
1922:
1918:
1906:
1902:
1890:
1878:
1874:
1870:
1867:
1858:
1849:
1847:
1839:
1835:
1831:
1827:
1823:
1819:
1815:
1811:
1808:(IL-1β ) and
1807:
1803:
1799:
1794:
1792:
1788:
1785:
1773:
1766:
1759:
1749:
1747:
1743:
1739:
1735:
1731:
1727:
1723:
1718:
1716:
1712:
1708:
1704:
1700:
1696:
1686:
1684:
1680:
1676:
1675:glycosylation
1672:
1668:
1667:Hydroxylation
1664:
1663:glutamic acid
1660:
1659:carboxylation
1656:
1652:
1648:
1642:
1638:
1634:
1633:phospholipids
1629:
1627:
1623:
1619:
1615:
1611:
1607:
1603:
1599:
1591:
1587:
1583:
1581:
1577:
1573:
1569:
1565:
1561:
1557:
1554:
1550:
1546:
1542:
1538:
1528:
1526:
1522:
1518:
1514:
1510:
1499:
1497:
1493:
1492:
1487:
1483:
1479:
1475:
1471:
1467:
1463:
1459:
1452:
1451:thrombophilia
1448:
1445:
1440:
1439:
1437:
1432:
1428:
1424:
1420:
1416:
1412:
1408:
1404:
1400:
1388:
1384:
1381:
1377:
1373:
1369:
1365:
1362:
1358:
1357:Johan Stenflo
1354:
1350:
1346:
1345:anticoagulant
1336:
1333:
1329:
1325:
1321:
1317:
1313:
1308:
1306:
1302:
1298:
1297:anticoagulant
1294:
1290:
1286:
1282:
1278:
1274:
1270:
1266:
1261:
1259:
1255:
1252:
1248:
1244:
1240:
1236:
1232:
1225:
1218:
1214:
1210:
1206:
1202:
1198:
1194:
1190:
1186:
1182:
1178:
1166:
1161:
1157:
1153:
1150:
1146:
1139:
1137:
1134:
1130:
1126:
1122:
1119:
1115:
1111:
1104:
1102:
1098:
1094:
1090:
1084:
1080:
1077:
1071:
1069:
1065:
1061:
1057:
1053:
1049:
1045:
1039:
1035:
1031:
1027:
1023:
1019:
1015:
1012:
1008:
1001:
999:
995:
991:
987:
981:
977:
974:
968:
966:
960:
956:
953:
951:RefSeq (mRNA)
949:
942:
941:
936:
932:
929:
923:
922:
917:
913:
910:
908:
904:
897:
896:
891:
887:
884:
878:
877:
872:
868:
865:
863:
859:
852:
851:
846:
842:
839:
833:
832:
827:
823:
820:
818:
814:
811:
808:
806:
803:
799:
796:
792:
788:
781:
777:
772:
766:
763:
761:
758:
756:
753:
751:
748:
746:
743:
741:
738:
736:
733:
731:
728:
726:
723:
721:
718:
716:
713:
711:
708:
707:
705:
702:
701:
695:
692:
690:
687:
685:
682:
680:
677:
675:
672:
670:
667:
666:
664:
661:
660:
654:
651:
649:
646:
644:
641:
639:
636:
634:
631:
629:
626:
625:
623:
620:
619:
616:
615:Gene ontology
612:
608:
596:
591:
587:
582:
579:
577:
573:
565:
560:
549:
545:
541:
537:
533:
529:
525:
521:
517:
513:
512:
509:
505:
500:
497:
487:
483:
479:
475:
471:
467:
463:
459:
456:kidney tubule
455:
451:
450:
447:
443:
438:
435:
434:
431:
429:
425:
423:
422:
418:
417:
414:
412:
408:
404:
400:
396:
388:
383:
379:
375:
370:
364:18|18 B1
360:
356:
349:
342:
336:
329:
321:
317:
313:
308:
304:
299:
295:
287:
282:
278:
274:
269:
259:
255:
248:
241:
235:
228:
224:
218:
214:
210:
205:
201:
196:
192:
188:
184:
180:
176:
172:
168:
164:
160:
156:
152:
144:
139:
132:
127:
122:
111:
109:
105:
101:
97:
93:
87:
82:
79:
78:
74:
71:
64:
60:
55:
51:
47:
42:
37:
32:
28:
24:
19:
6450:
6412:Translocases
6409:
6396:
6383:
6370:
6357:
6347:Transferases
6344:
6331:
6188:Binding site
5900:fibrinolysis
5898:
5776:
5742:Chymotrypsin
5658:D-Dimer (DD)
5641:Fibrinolysis
5529:-Antiplasmin
5456:
5251:
5110:
5066:4-1BB ligand
4978:Fibromodulin
4683:Mucoproteins
4618:
4603:
4543:
4475:
4471:
4461:
4434:
4430:
4420:
4408:. Retrieved
4400:
4363:
4359:
4353:
4328:
4284:
4280:
4270:
4235:
4231:
4221:
4186:
4182:
4172:
4132:(1): 18577.
4129:
4125:
4115:
4090:
4086:
4031:
4027:
4017:
3980:
3976:
3966:
3939:
3935:
3925:
3900:
3896:
3890:
3865:
3861:
3821:
3817:
3807:
3772:
3768:
3758:
3733:
3729:
3723:
3686:
3682:
3636:
3632:
3626:
3585:
3581:
3575:
3540:
3536:
3496:
3492:
3482:
3478:
3474:
3470:
3466:
3461:
3420:
3416:
3410:
3365:
3361:
3351:
3316:
3312:
3302:
3267:
3263:
3253:
3218:
3214:
3160:
3156:
3146:
3119:
3115:
3105:
3080:
3077:Biochemistry
3076:
3070:
3045:
3042:Biochemistry
3041:
3035:
3018:10.2741/1977
3008:
3004:
2932:
2929:Biochemistry
2928:
2922:
2895:
2891:
2881:
2864:
2860:
2854:
2819:
2815:
2767:
2763:
2753:
2728:
2724:
2718:
2691:
2687:
2609:
2605:
2556:(1): 33–46.
2553:
2549:
2511:
2505:
2486:
2460:
2451:
2442:
2433:
2363:
2359:
2343:
2339:
2315:
2309:in treating
2299:side effects
2283:
2279:
2260:
2239:
2237:
2222:
2206:
2177:
2173:
2161:coagulopathy
2125:
2116:
2093:
2078:
2047:
2019:
2015:
1979:
1960:
1942:and Factor X
1933:
1919:, Factor V,
1863:
1822:up-regulated
1795:
1755:
1726:blood plasma
1719:
1692:
1657:: (1) gamma-
1650:
1649:
1630:
1595:
1571:
1558:preceding a
1534:
1516:
1512:
1505:
1489:
1461:
1446:
1441:
1434:
1427:coagulopathy
1422:
1418:
1406:
1371:
1352:
1348:
1343:Protein C's
1342:
1309:
1273:blood plasma
1269:glycoprotein
1262:
1258:chromosome 2
1250:
1212:
1208:
1205:permeability
1197:inflammation
1184:
1180:
1176:
1175:
1097:NP_001300867
1093:NP_001036233
1089:NP_001036232
1086:
1068:NP_001362542
1064:NP_001362540
1060:NP_001362539
1056:NP_001362538
1052:NP_001362537
1048:NP_001362536
1044:NP_001362535
1041:
1034:NP_001362534
1030:NP_001362533
1026:NP_001362532
1022:NP_001362531
998:NM_001313938
990:NM_001042768
986:NM_001042767
983:
962:
938:
919:
893:
874:
848:
829:
809:
804:
522:human kidney
518:right kidney
460:human kidney
426:
419:
284:127,429,246
271:127,418,427
146:External IDs
89:
18:
6183:Active site
5805:Factor XIIa
5785:Factor VIIa
5769:Coagulation
5495:Plasminogen
5430:Factor XIII
5348:Factor VIII
5178:Vitronectin
5173:Uteroglobin
5163:Transcortin
5136:Glycophorin
5106:Osteonectin
5091:Lactoferrin
4816:Orosomucoid
4806:Haptoglobin
4586:PDB gallery
4410:29 November
3537:Proceedings
3215:Haemophilia
2867:: 218–249.
2271:recombinant
2100:hypotension
2050:endothelial
1940:prothrombin
1877:Factor VIII
1769:Factor VIII
1758:pleiotropic
1742:adolescence
1738:term infant
1568:heterodimer
1537:prothrombin
1488:. In 2002,
1312:recombinant
1267:-dependent
1247:active site
1228:Factor VIII
740:proteolysis
689:Golgi lumen
546:Paneth cell
530:gallbladder
480:granulocyte
385:32,272,623
372:32,256,179
124:Identifiers
6488:Hematology
6457:Categories
6386:Isomerases
6360:Hydrolases
6227:Regulation
6087:Subtilisin
6029:Batroxobin
5810:Kallikrein
5800:Factor XIa
5790:Factor IXa
5757:Pancreatic
5752:Neutrophil
5373:Factor VII
5328:Kallikrein
5318:Bradykinin
5006:Syndecan 1
4189:(1): 3–9.
2428:, May 2017
2407:, May 2017
2384:References
2352:GLA domain
2348:N-terminal
2255:See also:
2202:Caucasians
2140:homozygous
2126:A genetic
2066:chemotaxis
2054:leukocytes
2052:cells and
1923:, anionic
1814:eosinophil
1804:, such as
1689:Physiology
1622:N-terminus
1602:Gla domain
1560:propeptide
1553:N-terminus
1541:Factor VII
1521:chromosome
1305:thrombosis
1293:leukocytes
1201:cell death
710:hemostasis
468:glomerulus
430:(ortholog)
167:HomoloGene
6483:Angiology
6478:EC 3.4.21
6265:EC number
6115:Cathepsin
6101:Sedolisin
6077:Prostasin
5795:Factor Xa
5649:Plasmin-α
5510:Urokinase
5343:Factor IX
5338:Factor XI
5116:Protein S
5111:Protein C
5086:Hemopexin
5076:Clusterin
4988:Keratocan
3473:orldwide
2578:260369702
2265:approved
2150:, severe
2089:caspase 8
2085:caspase 3
2074:endotoxin
1938:binds to
1917:protein S
1879:(Factor V
1802:cytokines
1787:substrate
1746:half-life
1715:apoptosis
1711:embryonic
1564:dipeptide
1545:Factor IX
1466:Ångströms
1399:Protein S
1265:vitamin K
1101:NP_032960
1018:NP_000303
994:NM_008934
965:NM_000312
795:Orthologs
175:GeneCards
23:C-peptide
6493:Zymogens
6289:Kinetics
6213:Cofactor
6176:Activity
6016:Venombin
6001:Tryptase
5996:Granzyme
5950:Factor I
5945:Factor D
5940:Factor B
5780:Thrombin
5777:factors:
5747:Elastase
5396:Factor V
5391:Factor X
4935:Brevican
4930:Neurocan
4925:Aggrecan
4903:Perlecan
4898:Testican
4876:Versican
4871:Biglycan
4831:Ovomucin
4526:Archived
4380:16464623
4345:22419295
4303:16192478
4262:22260922
4205:12871530
4164:31819097
4107:18574265
4068:25032959
4028:PLOS ONE
4009:20484050
3882:12970121
3840:12218060
3715:17430555
3653:22072231
3618:43006410
3610:12052963
3567:16333441
3515:11236773
3237:19141162
3027:16720321
2873:13765990
2846:22513930
2794:23235609
2745:17050887
2710:17110453
2570:15199491
2424:–
2403:–
2321:See also
2245:histones
2232:gangrene
2228:warfarin
2169:necrosis
2096:swelling
1934:Factor V
1915:include
1901:thrombin
1873:Factor V
1784:effector
1762:Factor V
1752:Pathways
1606:aromatic
1549:Factor X
1502:Genetics
1455:Factor V
1444:Dahlbäck
1403:cofactor
1281:thrombin
1221:Factor V
1149:Wikidata
774:Sources:
542:yolk sac
6445:Biology
6399:Ligases
6169:Enzymes
6055:Pronase
6045:Acrosin
5991:Chymase
5905:Plasmin
5737:Trypsin
5500:Plasmin
4983:Lumican
4866:Decorin
4663:Protein
4550:PDBe-KB
4540:UniProt
4523:S01.218
4502:8386194
4453:6304092
4311:6918625
4253:3448071
4213:2147784
4155:6901466
4134:Bibcode
4059:4102480
4036:Bibcode
4000:2906281
3958:7673148
3917:2551064
3799:9576763
3750:2672445
3706:1885840
3661:3060393
3590:Bibcode
3582:Science
3558:1276518
3485:epsis;
3469:tein C
3453:4314040
3445:8164741
3425:Bibcode
3402:8430067
3370:Bibcode
3343:3102560
3294:2991859
3245:2979452
3187:6895379
3138:6892911
3097:7356933
2914:1245477
2837:6984667
2785:6464614
2646:2991887
2614:Bibcode
2426:Ensembl
2405:Ensembl
2303:hypoxia
1869:zymogen
1789:PAR-1,
1722:zymogen
1641:exosite
1618:zymogen
1614:trypsin
1598:domains
1491:Science
1436:E. coli
1431:infused
1378:from a
1339:History
1245:in its
1239:residue
1189:zymogen
1187:, is a
907:UniProt
862:Ensembl
801:Species
780:QuickGO
405:pattern
131:Aliases
6431:Portal
6373:Lyases
6082:Reelin
6024:Ancrod
5981:Other
5715:3.4.21
5287:GPIIIa
5056:Avidin
4735:MUC5AC
4545:P04070
4519:MEROPS
4500:
4493:288152
4490:
4451:
4378:
4343:
4309:
4301:
4260:
4250:
4211:
4203:
4162:
4152:
4105:
4066:
4056:
4007:
3997:
3956:
3915:
3880:
3838:
3797:
3790:508785
3787:
3748:
3713:
3703:
3659:
3651:
3616:
3608:
3565:
3555:
3513:
3481:evere
3451:
3443:
3417:Nature
3400:
3390:
3341:
3334:424237
3331:
3292:
3285:321861
3282:
3243:
3235:
3185:
3178:370934
3175:
3136:
3095:
3062:588557
3060:
3025:
2949:990250
2947:
2912:
2871:
2844:
2834:
2792:
2782:
2743:
2708:
2644:
2637:390448
2634:
2576:
2568:
2518:
2493:
2362:
2342:
2213:Leiden
2209:Leiden
2197:Leiden
2165:fibrin
2070:sepsis
1889:serine
1744:. The
1707:murine
1600:: one
1590:Domain
1486:sepsis
1474:sepsis
1462:et al.
1457:Leiden
1447:et al.
1423:et al.
1419:et al.
1376:eluted
1364:plasma
1361:bovine
1349:et al.
1324:sepsis
1243:serine
1199:, and
1135:search
1133:PubMed
940:P33587
921:P04070
817:Entrez
576:BioGPS
488:fundus
263:2q14.3
155:612283
6325:Types
6091:Furin
6038:Other
5965:MASP2
5960:MASP1
5890:KLK15
5885:KLK14
5880:KLK13
5875:KLK12
5870:KLK11
5865:KLK10
5282:GPIIb
5267:GP1BB
5262:GP1BA
5019:Other
4950:CSPG5
4945:CSPG4
4799:Other
4790:MUC20
4785:MUC19
4780:MUC17
4775:MUC16
4770:MUC15
4765:MUC13
4760:MUC12
4740:MUC5B
4725:MUC3B
4720:MUC3A
4705:CD164
4692:Mucin
4404:(EMA)
4307:S2CID
4209:S2CID
4087:Chest
3862:Chest
3657:S2CID
3614:S2CID
3449:S2CID
3393:45799
3241:S2CID
2688:Blood
2574:S2CID
2333:Notes
2110:with
2027:Bcl-2
1570:with
1525:exons
1515:tein
1407:et al
1359:from
850:19123
810:Mouse
805:Human
776:Amigo
428:Mouse
421:Human
368:Start
303:Mouse
267:Start
200:Human
171:37288
163:97771
29:, or
6417:list
6410:EC7
6404:list
6397:EC6
6391:list
6384:EC5
6378:list
6371:EC4
6365:list
6358:EC3
6352:list
6345:EC2
6339:list
6332:EC1
6105:TPP1
5955:MASP
5860:KLK9
5855:KLK8
5850:KLK7
5845:KLK6
5840:KLK5
5835:KLK4
5830:KLK3
5825:KLK2
5820:KLK1
5131:CD43
5046:CD70
5031:ADAM
4940:CD44
4755:MUC8
4750:MUC7
4745:MUC6
4730:MUC4
4715:MUC2
4710:MUC1
4700:CD43
4673:and
4619:1lqv
4604:1aut
4538:for
4517:The
4498:PMID
4449:PMID
4412:2020
4376:PMID
4341:PMID
4299:PMID
4258:PMID
4201:PMID
4160:PMID
4103:PMID
4064:PMID
4005:PMID
3954:PMID
3913:PMID
3878:PMID
3836:PMID
3795:PMID
3746:PMID
3711:PMID
3649:PMID
3606:PMID
3563:PMID
3511:PMID
3441:PMID
3398:PMID
3339:PMID
3290:PMID
3233:PMID
3183:PMID
3134:PMID
3093:PMID
3058:PMID
3023:PMID
2945:PMID
2910:PMID
2869:PMID
2842:PMID
2820:2012
2790:PMID
2768:2018
2741:PMID
2706:PMID
2642:PMID
2566:PMID
2516:ISBN
2491:ISBN
2374:and
2286:lung
2167:and
2087:and
2041:and
2033:and
2031:eNOS
1927:and
1875:and
1767:and
1697:and
1547:and
1287:and
1254:gene
1251:PROC
1226:and
1183:and
831:5624
411:Bgee
359:Band
320:Chr.
258:Band
217:Chr.
179:PROC
151:OMIM
138:PROC
108:4DT7
104:3JTC
100:3F6U
96:1LQV
92:1AUT
73:RCSB
70:PDBe
39:PROC
6095:S1P
5815:PSA
5419:FGG
5415:FGA
4536:PDB
4488:PMC
4480:doi
4439:doi
4435:258
4368:doi
4333:doi
4289:doi
4285:353
4248:PMC
4240:doi
4236:180
4191:doi
4150:PMC
4142:doi
4095:doi
4091:133
4054:PMC
4044:doi
3995:PMC
3985:doi
3981:285
3944:doi
3940:270
3905:doi
3870:doi
3866:124
3826:doi
3822:277
3785:PMC
3777:doi
3773:101
3738:doi
3701:PMC
3691:doi
3641:doi
3637:106
3598:doi
3586:296
3553:PMC
3545:doi
3501:doi
3497:344
3467:PRO
3433:doi
3421:369
3388:PMC
3378:doi
3329:PMC
3321:doi
3280:PMC
3272:doi
3223:doi
3173:PMC
3165:doi
3124:doi
3120:255
3085:doi
3050:doi
3013:doi
2937:doi
2900:doi
2896:251
2832:PMC
2824:doi
2780:PMC
2772:doi
2733:doi
2729:355
2696:doi
2692:109
2632:PMC
2622:doi
2558:doi
2142:or
2043:Bax
2039:p53
2035:IAP
1824:by
1576:kDa
1513:pro
1482:FDA
1307:).
1241:of
1213:APC
381:End
280:End
183:OMA
159:MGI
63:PDB
6459::
5712:EC
5706::
5417:,
4998:HS
4970:KS
4923::
4913:CS
4890:CS
4886:HS
4858:DS
4854:CS
4669::
4665:,
4542::
4496:.
4486:.
4476:91
4474:.
4470:.
4447:.
4433:.
4429:.
4399:.
4388:^
4374:.
4364:36
4362:.
4339:.
4319:^
4305:.
4297:.
4283:.
4279:.
4256:.
4246:.
4234:.
4230:.
4207:.
4199:.
4185:.
4181:.
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4148:.
4140:.
4128:.
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4101:.
4089:.
4076:^
4062:.
4052:.
4042:.
4030:.
4026:.
4003:.
3993:.
3979:.
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3952:.
3938:.
3934:.
3911:.
3901:55
3899:.
3876:.
3864:.
3848:^
3834:.
3820:.
3816:.
3793:.
3783:.
3771:.
3767:.
3744:.
3734:14
3732:.
3709:.
3699:.
3685:.
3681:.
3669:^
3655:.
3647:.
3635:.
3612:.
3604:.
3596:.
3584:.
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3541:15
3539:.
3535:.
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3509:.
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3431:.
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3366:90
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3337:.
3327:.
3317:79
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3278:.
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3161:68
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3081:19
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2863:.
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2802:^
2788:.
2778:.
2766:.
2762:.
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2727:.
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2640:.
2630:.
2620:.
2610:82
2608:.
2604:.
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2572:.
2564:.
2552:.
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2469:^
2459:.
2441:.
2412:^
2391:^
2370:,
2364:β:
2344:α:
2313:.
2277:,
2204:.
2114:.
2098:,
2045:.
2029:,
2008:.
1977:.
1958:.
1931:.
1848:.
1840:(K
1734:dL
1730:IU
1543:,
1539:,
1260:.
1195:,
778:/
387:bp
374:bp
286:bp
273:bp
181:;
177::
173:;
169::
165:;
161::
157:;
153::
106:,
102:,
98:,
94:,
25:,
6433::
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6415:(
6406:)
6402:(
6393:)
6389:(
6380:)
6376:(
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6350:(
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6337:(
6161:e
6154:t
6147:v
6125:G
6120:A
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6097:4
6093:/
6089:/
6070:2
6065:1
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5717:)
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5696:e
5689:t
5682:v
5651:2
5536:2
5534:α
5527:2
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5280:(
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