112898PathwayCoagulation Blood coagulation can be initiated by either an extrinsic or an intrinsic pathway, resulting in a cascade of serine protease activation that ultimately leads to the formation of thrombin, which converts soluble fibrinogen to an insoluble fibrin clot. The extrinsic, or tissue factor, pathway is initiated upon vascular injury, when the membrane-bound protein tissue factor (TF) comes into contact with factor VII or VIIa in plasma. The TF-VIIa complex is the strongest known activator of the coagulation cascade, and converts factors IX and X to IXa and Xa, respectively. Factors VII, IX, and X are vitamin-K-dependent proteins produced in the liver. In the intrinsic, or contact, pathway, injury exposes collagen to the bloodstream where is binds to factor XII and activates it to XIIa. Factor XIIa converts prekallikrein to kallikrein and factor XI to XIa. Both the extrinsic and intrinsic pathways result in the activation of factor IX to IXa, which forms the 'tenase' complex with factor VIIIa, calcium and phospholipids. This complex converts factor X to Xa and is important in haemostasis. Factor Xa complexes with factor Va (which functions as a non-enzymatic cofactor), calcium and a phospholipid membrane surface to form what is called the prothrombinase complex, which converts prothrombin to thrombin. Thrombin converts soluble fibrinogen to insoluble fibrin polymer, which is stabilized by cross-linking by coagulation factor XIIIa.ProteinPW120591CenterPathwayVisualizationContext12086732504250#000099PathwayVisualization112761112898Coagulation Blood coagulation can be initiated by either an extrinsic or an intrinsic pathway, resulting in a cascade of serine protease activation that ultimately leads to the formation of thrombin, which converts soluble fibrinogen to an insoluble fibrin clot. The extrinsic, or tissue factor, pathway is initiated upon vascular injury, when the membrane-bound protein tissue factor (TF) comes into contact with factor VII or VIIa in plasma. The TF-VIIa complex is the strongest known activator of the coagulation cascade, and converts factors IX and X to IXa and Xa, respectively. Factors VII, IX, and X are vitamin-K-dependent proteins produced in the liver. In the intrinsic, or contact, pathway, injury exposes collagen to the bloodstream where is binds to factor XII and activates it to XIIa. Factor XIIa converts prekallikrein to kallikrein and factor XI to XIa. Both the extrinsic and intrinsic pathways result in the activation of factor IX to IXa, which forms the 'tenase' complex with factor VIIIa, calcium and phospholipids. This complex converts factor X to Xa and is important in haemostasis. Factor Xa complexes with factor Va (which functions as a non-enzymatic cofactor), calcium and a phospholipid membrane surface to form what is called the prothrombinase complex, which converts prothrombin to thrombin. Thrombin converts soluble fibrinogen to insoluble fibrin polymer, which is stabilized by cross-linking by coagulation factor XIIIa.Protein12109283XII activated to XIIa by CollagenActivatingSubPathway10857911562ProteinComplex11410858011563ProteinComplex11410858111564ProteinComplex114109284XII activated to XIIa by Plasma kallikreinActivatingSubPathway10858211562ProteinComplex11410858311565ProteinComplex11410858411564ProteinComplex114109285Plasma prekallikrein activated to Plasma kallikrein by XIIaActivatingSubPathway10858511566ProteinComplex11410858611564ProteinComplex11410858711565ProteinComplex109286Coagulation factor XIII A and B activate to Coagulation factor XIIIaActivatingSubPathway10858811567ProteinComplex10858911568ProteinComplex10859011569ProteinComplex109287Activate Coagulatin factor VII to VIIa by binding to Tissue FactorActivatingSubPathway10859111570ProteinComplex10859211571ProteinComplex10859311572ProteinComplex2Platelet CL:00002331CellCL:00000004Cardiomyocyte CL:00007463NeuronCL:00005408Beta cellCL:00006395HepatocyteCL:00001821Homo sapiens9606EukaryoteHuman12Mus musculus10090EukaryoteMouse3Escherichia coli562Prokaryote6Caenorhabditis elegans6239EukaryoteRoundworm18Saccharomyces cerevisiae4932EukaryoteYeast4Arabidopsis thaliana3702EukaryoteThale cress5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat10Drosophila melanogaster7227EukaryoteFruit fly5CytoplasmGO:000573710Cell MembraneGO:00058861CytosolGO:000582911Extracellular SpaceGO:000561519sarcoplasmic reticulumGO:00165292MitochondrionGO:00057397Endoplasmic Reticulum MembraneGO:000578924Mitochondrial Intermembrane SpaceGO:000575825Golgi apparatusGO:000579414Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:000574313Endoplasmic ReticulumGO:00057836LysosomeGO:000576416Lysosomal LumenGO:004320236MembraneGO:00160202Endothelium BTO:00003935cardiocyteBTO:00015391LiverBTO:000075972918PancreasBTO:00009888Blood VesselBTO:0001102741116212PW_BS0000168511PW_BS00000814101PW_BS0000142111PW_BS00000215111PW_BS000015215114PW_BS0000213551914PW_BS0000353211PW_BS00000346114PW_BS000046471914PW_BS00004749711PW_BS000049422411PW_BS000042432511PW_BS0000435811411PW_BS000058171211PW_BS000017181311PW_BS0000189611PW_BS000009711113PW_BS00007172513PW_BS00007229111PW_BS0000296618518PW_BS000066101711PW_BS0000102811611PW_BS0000281115121PW_BS000111101531PW_BS000101205561PW_BS0000242111018PW_BS0000241601181PW_BS0001601901118PW_BS0000242137181PW_BS0000241985181PW_BS00002421013181PW_BS0000241644PW_BS0001642851041PW_BS000024151141PW_BS0001513081011PW_BS00002411PW_BS0000013317121PW_BS0000281151012PW_BS0001151321121PW_BS00013235625121PW_BS00002834524121PW_BS00002813013121PW_BS0001301141112PW_BS0001147413PW_BS000074228361PW_BS0000245181PW_BS000051122551PW_BS000122405105PW_BS000115124151PW_BS0001244182451PW_BS0001154192551PW_BS000115383751PW_BS0001001251351PW_BS000125409115PW_BS0001151355171PW_BS0001353761017PW_BS0000531181171PW_BS00011845424171PW_BS00011545525171PW_BS0001153987171PW_BS00011313613171PW_BS0001361371117PW_BS0001372975101PW_BS0000244781010PW_BS00011548924101PW_BS0001152991101PW_BS00002449025101PW_BS0001154957101PW_BS000115209106PW_BS0000245062461PW_BS000115388161PW_BS0001125072561PW_BS000115390761PW_BS0001121122121PW_BS000112407251PW_BS0001151192171PW_BS000119261115PW_BS000026311511PW_BS0000313361121PW_BS000028429151PW_BS0001154641171PW_BS00011540411121PW_BS00011533217121PW_BS000028326812PW_BS000028353CalciumHMDB0000464Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Physiologically, it exists as an ion in the body. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.14127-61-8C0007627129108CA%2b2266DB01373[Ca++]CaInChI=1S/Ca/q+2BHPQYMZQTOCNFJ-UHFFFAOYSA-Ncalcium(2+) ion40.07839.9625911550calcium(2+) ion22FDB003513Ca;Calcium element;Ca(2+);Ca2+;Calcium ion;Calcium, doubly charged positive ionPW_C000353Ca2+2761630385531460129411599321997351046311634611644714784914914215524321165821381727961829379315971316072394229418666478210482228534011157801017179205723221172581607281190117742131183719811842210121981641221528515288151153503086933617738933177600115781541327826635678526345787241307890811480413748058922881826511202201221204654051210491241213004181213774191218503831219231251223704091228951351230993761236131181238704541239364551244033981244761361249241371255712971257114781259814891260092991260504901265334951272032091274345061274603881275025071281053909CortexoloneHMDB0000015Cortexolone is the precursor of cortisol. Accumulation of cortexolone can happen in a defect known as congenital adrenal hyperplasia, which is due to 11-beta-hydroxylase deficiency, resulting in androgen excess, virilization, and hypertension (PMID: 2022736). Cortexolone is a 17-hydroxycorticosteroid with glucocorticoid and anti-inflammatory activities (PubChem).152-58-9C054884407072832411-DEOXY-CORTISOL389582[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12CC21H30O4InChI=1S/C21H30O4/c1-19-8-5-14(23)11-13(19)3-4-15-16(19)6-9-20(2)17(15)7-10-21(20,25)18(24)12-22/h11,15-17,22,25H,3-10,12H2,1-2H3/t15-,16+,17+,19+,20+,21+/m1/s1WHBHBVVOGNECLV-OBQKJFGGSA-N(1S,2R,10R,11S,14R,15S)-14-hydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one346.4605346.214409448-4.142(1S,2R,10R,11S,14R,15S)-14-hydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one00FDB02187211-deoxy-17-hydroxy-corticosterone;11-deoxy-17-hydroxycorticosterone;11-deoxy-cortisol;11-deoxycortisol;11-deoxyhydrocortisone;11-desoxy-17-hydroxycorticosterone;11-desoxycortisol;11-desoxyhydrocortisone;11-dioxy-cortisol;11-dioxycortisol;17,21-dihydroxy-4-pregnene-3,20-dione;17,21-dihydroxypregn-4-ene-3,20-dione;17,21-dihydroxyprogesterone;17-hydroxy-11-deoxycorticosterone;17alpha-hydroxycortexone;20-dione 17,21-dihydroxypregn-4-ene-3;4-pregnene-17alpha,21-diol-3,20-dione;Cortodoxone;Reichstein s;Reichstein's compound s;Reichstein's substance sPW_C000009Cortexo11231623113231915789811121218234071243761191746Vitamin K1 2,3-epoxideHMDB0002972Vitamin K1 2,3-epoxide is a vitamin K derivative. Vitamin K is needed for the posttranslational modification of certain proteins, mostly required for blood coagulation. Within the cell, vitamin K undergoes electron reduction to a reduced form of vitamin K (called vitamin K hydroquinone) by the enzyme vitamin K epoxide reductase (or VKOR). Another enzyme then oxidizes vitamin K hydroquinone to allow carboxylation of glutamate into gamma-carboxyglutamate (Gla). This enzyme is called the gamma-glutamyl carboxylase or the vitamin K-dependent carboxylase. The carboxylation reaction will only proceed if the carboxylase enzyme is able to oxidize vitamin K hydroquinone into vitamin K epoxide at the same time; the carboxylation and epoxidation reactions are said to be coupled reactions. Vitamin K epoxide is then re-converted into vitamin K by the vitamin K epoxide reductase. These two enzymes comprise the so-called vitamin K cycle. One of the reasons why vitamin K is rarely deficient in a human diet is because vitamin K is continually recycled in our cells. Vitamin K 2,3-epoxide is the substrate for vitamin K 2,3-epoxide reductase (VKOR) complex. Significantly increased level of serum vitamin K epoxide has been found in patients with familial multiple coagulation factor deficiency (PMID: 12384421). Accumulation of vitamin K1-2,3-epoxide in plasma is also a sensitive marker of coumarin-like activity of drugs (PMID: 2401753).
25486-55-9C05849915772837123-EPOXY-23-DIHYDRO-2-METHYL-14-NAPHTHOQ82688CC(C)CCCC(C)CCCC(C)CCC\C(C)=C\CC12OC1(C)C(=O)C1=C(C=CC=C1)C2=OC31H46O3InChI=1S/C31H46O3/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-31-29(33)27-19-8-7-18-26(27)28(32)30(31,6)34-31/h7-8,18-20,22-24H,9-17,21H2,1-6H3/b25-20+KUTXFBIHPWIDJQ-LKUDQCMESA-N(1aS,7aR)-1a-methyl-7a-[(2E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl]-1aH,2H,7H,7aH-naphtho[2,3-b]oxirene-2,7-dione466.706466.344695341-7.320(1aS,7aR)-1a-methyl-7a-[(2E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl]naphtho[2,3-b]oxirene-2,7-dione00FDB023087(2,3-epoxyphytyl)menaquinone;1,4-naphthoquinone, 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-2,3-epoxyphylloquinone;2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone;2,3-epoxyphylloquinone;Naphth[2,3-b]oxirene-2,7-dione, 1a,7a-dihydro-1a-methyl-7a-(3,7,11,15-tetramethyl-2-hexadecenyl)-phylloquinone oxide;Phylloquinone 2,3-epoxide;Phylloquinone-2,3-epoxide;Vitamin k 2,3-epoxide;Vitamin k epoxide;Vitamin k1 oxide;1a,7a-dihydro-1a-methyl-7a-(3,7,11,15-tetramethyl-2-hexadecenyl)-naphth[2,3-b]oxirene-2,7-dione;Phylloquinone epoxide;Phylloquinone oxide;Phylloquinone, epoxide;Vitamin k1 2,3-epoxide;Vitamin k1, epoxidePW_C001746VitKo49526147231166129456018792243361212814291238524642089Reduced Vitamin K (phylloquinone)HMDB0004198Vitamin K is a family of fat-soluble compounds with a common chemical structure based on 2-methyl-1,4-naphthoquinone.
Phylloquinone is often called vitamin K1, phytomenadione or phytonadione. Sometimes a distinction is made with phylloquinone considered natural and phytonadione considered synthetic. A stereoisomer of phylloquinone is called vitamin k1 (note the difference in capitalization). (Wikipedia). Phylloquinone is present in food of plant origin, such as green, leafy vegetables and certain plant oils, and is the predominant form in the diet. Bacterial and other forms of vitamin K, referred to as the menaquinones, differ in structure from phylloquinone in their 3-substituted lipophilic side chain. Menaquinone-4 (MK-4), which is alkylated from menadione, is present in animal feeds or is the product of tissue-specific conversion directly from dietary phylloquinone. Vitamin K is a cofactor specific to the formation of gamma-carboxyglutamyl (Gla) residues in certain proteins, including prothrombin necessary for normal hemostatic function. The naturally occurring forms of vitamin K are quinones (i.e. phylloquinone and menaquinones) so vitamin K is reduced to the vitamin K hydroquinone prior to catalyzing the gamma-carboxylation reaction. The active site for the carboxylation reaction is on the napthoquinone ring, which is identical for all forms of vitamin K, including phylloquinone and MK-4. (PMID 16857056).84-80-0C058505284607180674447652DB01022CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC\C(C)=C\CC1=C(C)C(=O)C2=C(C=CC=C2)C1=OC31H46O2InChI=1S/C31H46O2/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-27-26(6)30(32)28-18-7-8-19-29(28)31(27)33/h7-8,18-20,22-24H,9-17,21H2,1-6H3/b25-20+/t23-,24-/m1/s1MBWXNTAXLNYFJB-NKFFZRIASA-N2-methyl-3-[(2E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl]naphthalene-1,4-diol450.6957450.349780716-6.982vitamin K hydroquinone00FDB023333Vitamin k hydroquinone (phylloquinone);2-methyl-3-(3,7,11,15-tetramethyl-2-hexadecenyl)-1,4-naphthalenedione;2-methyl-3-[(2e)-3,7,11,15-tetramethyl-2-hexadecenyl]naphthoquinone;2-methyl-3-phytyl-1,4-naphthochinon;2-methyl-3-phytyl-1,4-naphthoquinone;3-phytylmenadione;Alpha-phylloquinone;Fitomenadiona;Phyllochinon;Phyllochinonum;Phytomenadione;Phytomenadionum;Phytonadione;Phytonadionum;Phytylmenadione;Trans-phylloquinone;Vitamin k1PW_C002089ReVitK496261471311610297922133612127642912384746444Precursors of Prothrombin and coagulation factors VII, IX, ad XProteinComplexPW_EC000044P00734UniProtPOPACFV45Prothrombin and coagulation factors VII, IX and XProteinComplexPW_EC000045P00734UniProtPACFVIA20356Coagulation factor XIQ9DAT3
Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
F11123.4.21.2720341Coagulation factor XIIQ6PER0
Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa (By similarity).
F12123.4.21.3813394411420358Coagulation factor IXQ3UES1
Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.
F9123.4.21.2213393511420361Coagulation factor VIIIA2AN88
Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
F81213393311413991ProthrombinP19221
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing (By similarity).
F2123.4.21.579383130793841327938511413239140420366Coagulation factor VQ3UV80
Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin.
F51220367Coagulation factor XQ99L32
Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
F10123.4.21.613393411420370Fibrinogen alpha chainQ99K47
Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots (PubMed:7649481). In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization (PubMed:11389004). Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood (PubMed:7649481). However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo (PubMed:10930441). Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway (PubMed:19332769). Maternal fibrinogen is essential for successful pregnancy (PubMed:7649481). Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage (PubMed:12629066). May also facilitate the immune response via both innate and T-cell mediated pathways (PubMed:23487423).
Fga1213393611420375Fibrinogen beta chainQ91ZP1
Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways.
Fgb1213393711420380Fibrinogen gamma chainQ91ZP0
Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix (By similarity). Fibrin has a major function in hemostasis as one of the primary components of blood clots (By similarity). In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization (By similarity). Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo (By similarity). Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway (PubMed:19332769). Maternal fibrinogen is essential for successful pregnancy (By similarity). Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage (By similarity). May also facilitate the immune response via both innate and T-cell mediated pathways (By similarity).
Fgg1213393811420381Coagulation factor XIII A chainQ8BIP2
Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. Also cross-link alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin.
F13a1122.3.2.1313393911420385Coagulation factor XIII B chainB1AY02
The B chain of factor XIII is not catalytically active, but is thought to stabilize the A subunits and regulate the rate of transglutaminase formation by thrombin.
F13b1213394011420390PlasminogenQ91WJ5
Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells (By similarity).
Plg123.4.21.713394111420396Tissue-type plasminogen activatorQ91VP2
Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events.
Plat123.4.21.6813394211420398Coagulation factor VIIQ61109
Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium (By similarity).
F7123.4.21.2120403Tissue factorP20352
Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade.
F31216195Vitamin K epoxide reductase complex subunit 1Q9CRC0
Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.
Vkorc1121.17.4.413238913013257933613258033216202Vitamin K-dependent gamma-carboxylaseQ8CCB3
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide.
Ggcx124.1.1.9013239013013394333220347Collagen alpha-1(I) chainQ810J9
Type I collagen is a member of group I collagen (fibrillar forming collagen).
Col1a11213394511420352Plasma kallikreinQ8R0P5
The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin.
Klkb1123.4.21.341339461147736UnknownUnknown123.1.1.1, 3.1.1.565529130793341117933513379336112795321137994832979951134799673318180913213170711513171212813223852313224632813227433613232311413236433213236611613257232613257753513258153813258234813258353913258454113286336213348735413488240413895Vitamin K epoxide reductase complex subunit 1-like protein 1Q6TEK5
Involved in vitamin K metabolism. Can reduce inactive vitamin K 2,3-epoxide to active vitamin K (in vitro), and may contribute to vitamin K-mediated protection against oxidative stress. Plays a role in vitamin K-dependent gamma-carboxylation of Glu residues in target proteins.
Vkorc1l1121.17.4.47922613013896Vitamin K-dependent gamma-carboxylaseQ9QYC7
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide.
Ggcx124.1.1.90792301301361504911573Coagulation factor XI12PW_P011573207322035611574Coagulation factor XIa12PW_P0115742073320356996353111564Coagulation factor XIIa12PW_P01156420721203419929111575Coagulation factor IX12PW_P011575207342035811576Coagulation factor IXa12PW_P0115762073520358997353111577Coagulation factor VIII12PW_P011577207362036111578Coagulation factor VIIIa12PW_P011578207372036110901Thrombin12PW_P010901194451399111579Coagulation factor V12PW_P011579207382036611580Coagulation factor Va12PW_P011580207392036611581Coagulation factor X12PW_P0115812074020367998353111582Coagulation factor Xa12PW_P011582207412036711583Tenase complex12PW_P01158320742203612074320358999353110899Prothrombin12PW_P010899194431399111585Fibrinogen12PW_P01158520746203702074720375207482038011586Fibrin (loose)12PW_P01158620749203702075020375207512038011587Fibrin (mesh)12PW_P01158720752203702075320375207542038011569Coagulation factor XIIIa12PW_P01156920726203812072720385994353111588Fibrin degradation products12PW_P01158820755203702075620375207572038011589Plasmin12PW_P011589207582039010903Plasminogen12PW_P01090319447773611590Tissue-type plasminogen activator12PW_P011590207592039611572Tissue factor:Coagulation factor VIIa12PW_P0115722073020398207312040399535317350Vitamin K epoxide reductase complex subunit 112PW_P00735015212138957353Vitamin K-dependent gamma-carboxylase12PW_P007353152151389611562Coagulation factor XII12PW_P011562207192034111563Collagen alpha-1(I) chain12PW_P011563207202034711565Plasma kallikrein12PW_P011565207222035211567Coagulation factor XIII A chain12PW_P0115672072420381993353111568Coagulation factor XIII B chain12PW_P011568207252038511570Coagulation factor VII12PW_P011570207282039811571Tissue factor12PW_P011571207292040311566Plasma prekallikrein12PW_P0115662072320352111584Prothrombinase complex12PW_P0115842074420366207452036710003531178817falsePW_R178817Right674914115731ProteinComplexfalse674915115741ProteinComplexfalse168891115643.4.21.38178818falsePW_R178818Right674916115751ProteinComplexfalse674917115761ProteinComplexfalse168892115743.4.21.27178819falsePW_R178819Right674918115771ProteinComplexfalse674919115781ProteinComplexfalse168893109013.4.21.5178820falsePW_R178820Right674920115791ProteinComplexfalse674921115801ProteinComplexfalse168894109013.4.21.5178821falsePW_R178821Right674922115811ProteinComplexfalse674923115821ProteinComplexfalse168895115833.4.21.22168896115723.4.21.21178822falsePW_R178822Right674924108991ProteinComplexfalse674925109011ProteinComplexfalse168897115843.4.21.6178823falsePW_R178823Right674926115851ProteinComplexfalse674927115861ProteinComplexfalse168898109013.4.21.5178824falsePW_R178824Right674928115861ProteinComplexfalse674929115871ProteinComplexfalse168899115692.3.2.13178825falsePW_R178825Right674930115871ProteinComplexfalse674931115881ProteinComplexfalse168900115893.4.21.7178826falsePW_R178826Right674932109031ProteinComplexfalse674933115891ProteinComplexfalse168901115903.4.21.68178827falsePW_R178827Right67493417461Compoundfalse67493520891Compoundfalse16890273501.1.4.1178828falsePW_R178828Right67493620891Compoundfalse67493717461Compoundfalse16890373534.1.1.90178829falsePW_R178829Right674938441ElementCollectionfalse674939451ElementCollectionfalse16890473534.1.1.9010070PW_T01007010362451ElementCollection336326Right26723943539false1885119510regular10025267239599false1605108510regular1002526723963539false2145134010regular1002526723973539true635104010regular1002526723983531149false2570118510regular1002526723993539false2940143510regular1002526724003531149false2500147510regular1002526724013531149true755132010regular1002526724023531149false2845166010regular1002526724033531149true1550149510regular1002526724043531149false3080218010regular1002526724053539true144089010regular1002526724063539true165590010regular10025267240717463false30086010regular100110267240820893false88585010regular100120267240920893true0010regular100120267241017463true0010regular100110267241199false160079010regular10025267241291149true159579010regular1002526724133539false2635206010regular1002526724143539false3130114510regular10025267241591149false147061010regular10025143394437114false735125512regular10090143404537114false375125512regular10090143414537336true385134512regular10090143424537326true635134512regular10090935691203562false133511358subunitregular15070935692203562false186011458proteinregular15070935693203412true5508408subunitregular15070935694203582false160512758subunitregular15070935695203582false215512858proteinregular15070935696203562true63510458subunitregular15070935697203611142false22909608proteinregular15070935698203611142false222013258proteinregular15070935699139911142false248011358subunitregular15070935700203662false320013858subunitregular15070935701203662false256514608proteinregular15070935702139912false291513858subunitregular15070935703203671142false188514358subunitregular15070935704203671142false248514208proteinregular15070935705203611142true76012508subunitregular15070935706203581142true75513208subunitregular15070935707139911142false219016108subunitregular15070935708139911142false282016108proteinregular15070935709203701142false253517108subunitregular15070935710203751142false253517608subunitregular15070935711203801142false253518058subunitregular150709357122037011416false307017508proteinregular17090935713203751142true177514958subunitregular15070935714203801142true177515208subunitregular15070935715139911142true155014958subunitregular1507093571620370114136false287526458proteinregular175155935717203751142true201018108subunitregular15070935718203801142true187018158subunitregular15070935719203811142false299021308proteinregular15070935720203851142true25758subunitregular15070935721203702true183520208subunitregular15070935722203752true183520508subunitregular15070935723203802true183520858subunitregular15070935724203702false358026258proteinregular15070935725203752true224521508subunitregular15070935726203802true216020858subunitregular15070935727203902false323026258proteinregular15070935728203901142false323022908subunitregular15070935729203901142true202519458subunitregular15070935730203961142false323024658subunitregular15070935731203672false346012458subunitregular15070935732203672true173511758subunitregular15070935733203982true15209658proteinregular15070935734204032true2601158subunitregular15070935735161953322false5757308subunitregular15070935736162023322false53510808subunitregular15070935737203411142false15758008subunitregular15070935738203471142false21605058subunitregular15070935739203412false158010358proteinregular15070935740203411142true6905658subunitregular15070935741203521142false13608008subunitregular15070935742203411142true10306658proteinregular15070935743203812false261020708subunitregular15070935744203852false261021858subunitregular15070935745203816true330908proteinregular16080935746203852true320808subunitregular15070935747203982false32209108subunitregular15070935748204032false23655058subunitregular15070935749203982false310510958proteinregular15070935750204032true105358subunitregular15070935751203521142false12706208proteinregular15070935752203411142false14456208proteinregular1507079876011573112761931854935691798761115741127619318559356923488026723943643765Cofactor798762115641127619318569356933488126723953643767Cofactor79876311575112761931857935694798764115761127619318589356953488226723963643769Cofactor798765115741127619318599356963488326723973643771Cofactor7987661157711276111493186093569779876711578112761114931861935698798768109011127611149318629356993488426723983643774Cofactor7987691157911276193186393570079877011580112761931864935701798771109011127619318659357023488526723993643777Cofactor798772115811127611149318669357033488626724003643778Cofactor79877311582112761114931867935704798774115831127611149318689357059318699357063488726724013643781Cofactor79877510899112761114931870935707798776109011127611149318719357083488826724023643783Cofactor7987771158511276111493187293570993187393571093187493571179877811586112761114931875935712931876935713931877935714798779109011127611149318789357153488926724033643787Cofactor79878011587112761114931879935716931880935717931881935718798781115691127611149318829357199318839357203489026724043643790Cofactor798782115871127619318849357219318859357229318869357237987831158811276193188793572493188893572593188993572679878411589112761931890935727798785109031127611149318919357287987861158911276111493189293572979878711590112761114931893935730798788115811127619318949357313489126724053643795Cofactor79878911582112761931895935732798790115721127619318969357339318979357343489226724063643798Cofactor798791735011276193189893573579879273531127619318999357367987931156211276111493190093573779879411563112761114931901935738798795115641127619319029357393489326724113643809Cofactor7987961156211276111493190393574079879711565112761114931904935741798798115641127611149319059357423489426724123643813Cofactor798799115671127619319069357433489526724133643815Cofactor79880011568112761931907935744798801115691127619319089357459319099357467988021157011276193191093574779880311571112761931911935748798804115721127619319129357499319139357503489626724143643821Cofactor79880511566112761114931914935751798806115641127611149319159357523489726724153643824Cofactor3643764M1410 1135 C1446 1080 1550 1070 1580 1070 5false183643765M600 150 L600 200 L650 150 z10true183643766M1935 1145 C1903 1083 1760 1070 1730 1070 5false18trueM 717.5299975319052 868.3366083298732 L 730 860 L 716.5452841708815 853.3689652423119false3643767M375 175 L375 225 L425 175 z10true183643768M1680 1275 C1710 1212 1830 1180 1860 1180 5false183643769M600 150 L600 200 L650 150 z10true183643770M2230 1285 C2192 1214 2040 1180 2010 1180 5false18trueM 987.2576570145123 1033.0859179155007 L 1000 1041 L 1000.4826246400679 1026.0077662285835false3643771M375 175 L375 225 L425 175 z10true183643772M2440 995 C2506 1001 2563 1107 2555 1135 5false183643773M2370 1360 C2400 1360 2545 1343 2555 1205 5false18trueM 1142.9903810567666 1112.5 L 1130 1120 L 1142.9903810567666 1127.5false3643774M150 150 L150 200 L200 150 z10true183643775M3200 1420 C3170 1420 3095 1420 3065 1420 5false183643776M2715 1495 C2745 1495 2885 1420 2915 1420 5false18trueM 1442.9903810567666 1287.5 L 1430 1295 L 1442.9903810567666 1302.5false3643777M150 150 L150 200 L200 150 z10true183643778M150 150 L150 200 L200 150 z10true183643779M1960 1435 C2006 1353 2125 1320 2155 1320 5false183643780M2560 1420 C2509 1336 2335 1320 2305 1320 5false18trueM 1187.0096189432334 1257.5 L 1200 1250 L 1187.0096189432334 1242.5false3643781M375 205 L375 255 L425 205 z10true183643782M2265 1610 C2273 1506 2420 1454 2485 1455 5false183643783M150 150 L150 200 L200 150 z10true183643784M2895 1610 C2882 1495 2698 1455 2635 1455 5false18trueM 1595.8550173541616 1468.11011806588 L 1605 1480 L 1610.7244484800265 1466.135271744476false3643785M2610 1710 C2656 1652 2790 1645 2820 1645 5false183643786M3155 1750 C3143 1689 3000 1645 2970 1645 5false18trueM 1762.0096189432334 1562.5 L 1775 1555 L 1762.0096189432334 1547.5false3643787M375 190 L375 240 L425 190 z10true183643788M3155 1840 C3155 1870 3065 2100 3065 2130 5false183643789M2965 2652 C2965 2622 3065 2230 3065 2200 5false18trueM 1947.5 1819.0096189432334 L 1955 1832 L 1962.5 1819.0096189432334falsefalsefalse3643790M150 150 L150 200 L200 150 z10true183643791M3050 2725 C3080 2725 3200 2660 3230 2660 5false183643792M3580 2660 C3550 2660 3410 2660 3380 2660 5false18trueM 2147.0096189432334 2127.5 L 2160 2120 L 2147.0096189432334 2112.5false3643793M3305 2360 C3305 2388 3305 2420 3305 2465 5false183643794M3305 2625 C3305 2599 3306 2561 3305 2535 5false18trueM 2106.5 2027.9903810567666 L 2099 2015 L 2091.5 2027.9903810567666false3643795M150 150 L150 200 L200 150 z10true183643796M3105 1130 C2801 1126 2571 1356 2560 1420 5false18trueM 1503.9903810567666 1144.5 L 1491 1152 L 1503.9903810567666 1159.5false3643797M3535 1245 C3537 1200 3319 1131 3255 1130 5false18falsefalse3643798M150 150 L150 200 L200 150 z10true183643799M350 860 C353 816 399 771 575 765 5false183643800M935 850 C923 797 843 762 725 765 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false3643801M610 1080 C723 1085 923 1048 935 970 5false183643802M350 970 C352 1019 465 1079 610 1080 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false3643803M785 1255 C785 1194 678 1149 610 1150 5false183643804M425 1255 C424 1202 541 1150 610 1150 5false18trueM 417.2562767252032 1242.1534148567266 L 425 1255 L 432.253607448556 1241.8704463525125false3643805M425 1395 C418 1744 835 1657 1010 1659 C1278 1659 1684 1685 1680 1345 83false18trueM 1687.5 1357.9903810567666 L 1680 1345 L 1672.5 1357.9903810567666false3643806M1009 1659 C1364 1651 1961 1697 1960 1505 83false18trueM 1225.0644009829866 1558.611518094107 L 1240 1560 L 1233.7346610946918 1546.371150877582false3643807M1725 835 C1757 846 1751 999 1709 1045 149false18trueM 297.0096189432334 257.5 L 310 250 L 297.0096189432334 242.5false3643808M2160 540 C1996 568 1764 883 1739 975 149false18falsefalse3643809M600 85 L600 135 L650 85 z10true183643810M1580 1070 C1550 1070 1755 835 1725 835 5true183643811M1575 835 C1556 857 1555 991 1603 1049 149false18trueM 392.41909384706423 811.9433327199906 L 400 799 L 385.00029197838586 798.9064090478472false3643812M1510 835 C1586 886 1539 898 1572 980 149false18falsefalsefalsefalse3643813M600 85 L600 135 L650 85 z10true183643814M1030 700 C1000 700 870 600 840 600 5true183643815M150 150 L150 200 L200 150 z10true183643816M2990 2165 C2901 2161 2816 2170 2760 2105 149false18trueM 2110.9468550441647 1623.261556296296 L 2096 1622 L 2102.380887721186 1635.5751343230784false3643817M2990 2165 C2908 2160 2813 2157 2760 2220 149false183643818M2080 1657 C2103 1673 2143 1700 2167 1717 149true183643819M3180 1095 C3191 893 2421 702 2440 575 149false183643820M3180 1095 C3175 964 3286 1029 3295 980 149false18trueM 1954.9468550441647 896.261556296296 L 1940 895 L 1946.380887721186 908.5751343230784false3643821M150 150 L150 200 L200 150 z10true183643822M11 12 C34 28 74 55 98 72 149true183643823M1520 690 C1520 717 1436 774 1435 800 149false18trueM 1428.004802091561 786.730968150548 L 1435 800 L 1442.9937197110307 787.3074649820661false3643824M150 150 L150 200 L200 150 z10true183643825M1345 690 C1345 716 1435 774 1435 800 149false18trueM 1427.5 787.0096189432334 L 1435 800 L 1442.5 787.0096189432334false3643826M11 12 C34 28 74 55 98 72 5true183643827M1219 1658 C1256 1661 2261 1878 2265 1680 83false18trueM 1743.0644009829866 1770.611518094107 L 1758 1772 L 1751.7346610946918 1758.371150877582false3643828M1581 1653 C1734 1683 1839 1799 1957 1862 C2147 1955 3386 2009 3676 1889 C3838 1844 3843 1125 3728 1007 C3621 923 3548 955 3370 945 83false18trueM 3386.24113183082 862.9521331000902 L 3373 870 L 3385.7241976932232 877.943223090394false795508112761178817179207987603643764Left179217987613643766Right751734168891798762795509112761178818114179227987633643768Left179237987643643770Right751735168892798765795510112761178819114179247987663643772Left179257987673643773Right751736168893798768795511112761178820114179267987693643775Left179277987703643776Right751737168894798771795512112761178821114179287987723643779Left179297987733643780Right751738168895798774795513112761178822114179307987753643782Left179317987763643784Right795514112761178823114179327987773643785Left179337987783643786Right751739168898798779795515112761178824114179347987783643788Left179357987803643789Right751740168899798781795516112761178825114179367987823643791Left179377987833643792Right751741168900798784795517112761178826114179387987853643793Left179397987863643794Right751742168901798787795518112761178821179407987883643796Left179417987893643797Right751743168896798790795519112761178827321750926724073643799Left321751026724083643800Right751744168902798791795520112761178828321751126724093643801Left321751226724103643802Right75174516890379879279552111276117882911413491143393643803Left13492143403643804Right7517461689047987927740610070112761303143413643805Left304143423643806Right10892610928311276114true2401516regular21817987933643807Left21827987943643808Left21837987953643810Right10892710928411276114true2258016regular21847987963643811Left21857987973643812Left21867987983643814Right10892810928611276114true0016regular21877987993643816Left21887988003643817Left21897988013643818Right10892910928711276114true0016regular21907988023643819Left21917988033643820Left21927988043643822Right10893010928511276114true0016regular21937988053643823Left21947988063643825Left21957987973643826Right67639364382767640364382818555374216051.01.002115802501855547523702701.91.9021217713918555575259026951.91.90212177139185556722901702.52.50292001451855577519652651.91.90212177139185558664406951.31.3023280360369077M95 760 C95 710 145 660 195 660 C449 660 780 660 1034 660 C1084 660 1134 710 1134 760 C1134 938 1134 1168 1134 1346 C1134 1396 1084 1446 1034 1446 C780 1446 449 1446 195 1446 C145 1446 95 1396 95 1346 C95 1168 95 938 95 760 1true61039.0786.044898315Platelet Factor 321301345201.01.01601544898415Tenase complex21501400201.01.01601544898515Platelet factor 324701480201.01.01601544898615Prothrombinase complex24851550201.01.01601544898715ENDOTHELIAL CELL1995310201.01.01601544898815SUBENDOTHELIUM2240260201.01.01601544898915VASCULAR INJURY2255450201.01.01601544899015ENDOTHELIAL CELL25952740201.01.01601544899115SUBENDOTHELIUM28702900201.01.01601544899215COAGULATION28802760201.01.016015180092237511712392663930302544269127591800934004252258912101517441188928