ENTRY       hsa04610                    Pathway
NAME        Complement and coagulation cascades - Homo sapiens (human)
DESCRIPTION The complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation: the classical pathway, the lectin pathway, and the alternative pathway. All of these pathways generate a crucial enzymatic activity that, in turn, generates the effector molecules of complement. The main consequences of complement activation are the opsonization of pathogens, the recruitment of inflammatory and immunocompetent cells, and the direct killing of pathogens. Blood coagulation is another series of proenzyme-to-serine protease conversions, culminating the formation of thrombin, the enzyme responsible for the conversion of soluble fibrinogen to the insoluble fibrin clot. Protease-activated receptors, such as those activated by thrombin, are members of G protein-coupled receptors and function as a mediator of innate immunity. The kallikrein-kinin system is an endogenous metabolic cascade, triggering of which results in the release of vasoactive kinins (bradykinin-related peptides). Kinin peptides are implicated in many physiological and pathological processes including the regulation of blood pressure and sodium homeostasis, inflammatory processes, and the cardioprotective effects of preconditioning.
CLASS       Organismal Systems; Immune system
PATHWAY_MAP hsa04610  Complement and coagulation cascades
NETWORK     nt06164  Kaposi sarcoma-associated herpesvirus (KSHV)
            nt06168  Herpes simplex virus 1 (HSV-1)
            nt06171  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
            nt06513  Complement cascade
            nt06514  Coagulation cascade
  ELEMENT   N01487  Classical pathway of complement cascade, C4/C2 to C3 convertase formation
            N01489  Classical/Lectin pathway of complement cascade, C5 convertase formation
            N01490  Common pathway of complement cascade, MAC formation
            N01491  Lectin pathway of complement cascade, C4/C2 to C3 convertase formation
            N01493  Alternative pathway of complement cascade, C3 convertase formation
            N01494  Alternative pathway of complement cascade, C3/5 convertase formation
            N01495  Classical/Lectin pathway of complement cascade, C4b breakdown
            N01496  Alternative pathway of complement cascade, C3b breakdown
            N01503  Extrinsic pathway of coagulation cascade, F7 activation
            N01504  Regulation of complement cascade, CFHR
            N01505  Regulation of complement cascade, MAC inhibition
            N01506  Intrinsic pathway of coagulation cascade, F12 activation
            N01507  Intrinsic pathway of coagulation cascade, F11 activation
            N01508  Intrinsic pathway of coagulation cascade, F9 activation
            N01509  Intrinsic pathway of coagulation cascade, F8 activation
            N01510  Common pathway of coagulation cascade, F10 activation
            N01511  Common pathway of coagulation cascade, F5 activation
            N01512  Common pathway of coagulation cascade, prothrombin activation
            N01513  Common pathway of coagulation cascade, fibrinogen to fibrin
            N01514  Common pathway of coagulation cascade, F13 activation
            N01515  Regulation of coagulation cascade, protein C system
            N01516  Kallikrein-kinin system, prekallikrein activation
            N01517  Kallikrein-kinin system, HMWK to bradykinin
            N01518  Fibrinolytic system
            N01519  Regulation of coagulation cascade, AT3
            N01520  Regulation of fibrinolytic system, C1INH
            N01521  Regulation of coagulation cascade, HCF2
            N01522  Regulation of fibrinolytic system, AAP
            N01523  Regulation of fibrinolytic system, AAT
            N01524  Regulation of fibrinolytic system, PAI
DRUG        D00160  Aminocaproic acid (USP/INN)
            D00181  Argatroban (USP)
            D00291  Desmopressin (INN)
            D01136  Tranexamic acid (JP18/USP/INN)
            D01672  Gabexate mesilate (JP18)
            D01844  Fondaparinux sodium (JAN/USP/INN)
            D01981  Ximelagatran (JAN/USAN/INN)
            D02112  Heparin sodium (JP18/USP/INN)
            D02235  Desmopressin acetate (USP)
            D02956  Anticoagulant heparin (USP)
            D02980  Adomiparin sodium (USAN)
            D03136  Bivalirudin (USAN/INN)
            D03213  Apixaban (JAN/USAN/INN)
            D03330  Kallidinogenase (JP18/INN)
            D03337  Reviparin sodium (JAN)
            D03353  Dalteparin sodium (JAN/USP/INN)
            D03644  Danaparoid sodium (JAN/USAN)
            D03673  Deligoparin sodium (USAN/INN)
            D03674  Enoxaparin sodium (JAN/USP/INN)
            D03677  Deltibant (USAN/INN)
            D03692  Desirudin (USAN/INN)
            D03722  Efegatran sulfate (USAN)
            D03728  Napsagatran (USAN)
            D03766  Diaplasinin (USAN)
            D03931  Ecallantide (USAN/INN)
            D03940  Eculizumab (USAN/INN)
            D04029  Razaxaban hydrochloride (USAN)
            D04183  Fidexaban (USAN/INN)
            D04427  Heparin calcium (JP18)
            D04492  Icatibant acetate (JAN/USAN)
            D04977  Parnaparin sodium (JP18)
            D06142  Tifacogin (USAN/INN)
            D06398  Tinzaparin sodium (USAN)
            D06410  Thrombomodulin alfa (USAN/INN)
            D06880  Lepirudin (INN)
            D07082  Dabigatran etexilate mesylate (USAN)
            D07086  Rivaroxaban (JAN/USAN/INN)
            D07143  Melagatran (INN)
            D07144  Dabigatran etexilate (USAN/INN)
            D07510  Adomiparin (USAN)
            D07568  Aminomethylbenzoic acid
            D08004  Gabexate (INN)
            D08547  Sulodexide (INN)
            D08656  Aleplasinin (USAN/INN)
            D08873  Betrixaban (USAN)
            D08913  Eribaxaban (USAN)
            D09546  Edoxaban tosilate hydrate (JAN)
            D09707  Dabigatran (USAN/INN)
            D09710  Edoxaban (USAN/INN)
            D09765  Vorapaxar (USAN/INN)
            D09766  Vorapaxar sulfate (JAN/USAN)
            D09817  Darexaban maleate (JAN)
            D09866  Atopaxar (USAN)
            D09867  Atopaxar hydrobromide (USAN)
            D09923  Letaxaban (USAN/INN)
            D10150  Pegnivacogin sodium (USAN)
            D10418  Delparantag pentahydrochloride (USAN)
            D10471  Idraparinux sodium (USAN)
            D10484  Pegnivacogin (USAN)
            D10758  Turoctocog alfa pegol (genetical recombination) (JAN)
            D10821  Emicizumab (USAN/INN)
            D10845  Conestat alfa (INN)
            D11029  Andexanet alfa (USAN/INN)
            D11054  Ravulizumab (USAN)
            D11093  Avacopan (JAN/USAN/INN)
            D11094  Lanadelumab (USAN)
            D11160  Caplacizumab (USAN/INN)
            D11261  Marstacimab (USAN)
            D11280  Bivalirudin trifluoroacetate (USAN)
            D11331  Olendalizumab (USAN)
            D11473  Nomacopan (USAN)
            D11477  Pozelimab (USAN)
            D11530  Sutimlimab (USAN/INN)
            D11531  Narsoplimab (USAN)
            D11568  Edoxaban tosylate (USAN)
            D11613  Pegcetacoplan (JAN/USAN/INN)
            D11641  Danicopan (JAN/USAN/INN)
            D11673  Berotralstat (USAN)
            D11674  Berotralstat hydrochloride (JAN/USAN)
            D11696  Crovalimab (USAN/INN)
            D11748  Avacincaptad pegol sodium (USAN)
            D11802  Milvexian (USAN)
            D11810  Fitusiran sodium (JAN)
            D11813  Tisotumab (USAN)
            D11814  Tisotumab vedotin (USAN/INN)
            D11838  Vilobelimab (USAN)
            D11847  Concizumab (USAN)
            D11965  alpha 1-Antitrypsin
            D12149  Plasminogen
            D12208  Gefurulimab (USAN)
            D12251  Iptacopan (USAN/INN)
            D12252  Iptacopan hydrochloride (USAN)
            D12356  Zilucoplan sodium (JAN)
            D12357  Zilucoplan (USAN/INN)
            D12396  Sebetralstat (USAN)
            D12421  Freeze-dried activated human blood coagulation factor VII concentrate containing factor X
            D12434  Valoctocogene roxaparvovec (USAN/INN)
            D12481  Vemircopan (USAN/INN)
            D12500  Etranacogene dezaparvovec (USAN/INN)
            D12541  Gruticibart (USAN)
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        2155  F7; coagulation factor VII [KO:K01320] [EC:3.4.21.21]
            2152  F3; coagulation factor III, tissue factor [KO:K03901]
            2161  F12; coagulation factor XII [KO:K01328] [EC:3.4.21.38]
            2160  F11; coagulation factor XI [KO:K01323] [EC:3.4.21.27]
            2158  F9; coagulation factor IX [KO:K01321] [EC:3.4.21.22]
            7450  VWF; von Willebrand factor [KO:K03900]
            2157  F8; coagulation factor VIII [KO:K03899]
            2159  F10; coagulation factor X [KO:K01314] [EC:3.4.21.6]
            2153  F5; coagulation factor V [KO:K03902]
            2147  F2; coagulation factor II, thrombin [KO:K01313] [EC:3.4.21.5]
            2243  FGA; fibrinogen alpha chain [KO:K03903]
            2244  FGB; fibrinogen beta chain [KO:K03904]
            2266  FGG; fibrinogen gamma chain [KO:K03905]
            2162  F13A1; coagulation factor XIII A chain [KO:K03917] [EC:2.3.2.13]
            2165  F13B; coagulation factor XIII B chain [KO:K03906]
            2149  F2R; coagulation factor II thrombin receptor [KO:K03914]
            2151  F2RL2; coagulation factor II thrombin receptor like 2 [KO:K04235]
            9002  F2RL3; F2R like thrombin or trypsin receptor 3 [KO:K04236]
            1361  CPB2; carboxypeptidase B2 [KO:K01300] [EC:3.4.17.20]
            7056  THBD; thrombomodulin [KO:K03907]
            10544  PROCR; protein C receptor [KO:K06557]
            5624  PROC; protein C, inactivator of coagulation factors Va and VIIIa [KO:K01344] [EC:3.4.21.69]
            5627  PROS1; protein S [KO:K03908]
            5054  SERPINE1; serpin family E member 1 [KO:K03982]
            5055  SERPINB2; serpin family B member 2 [KO:K19821]
            5104  SERPINA5; serpin family A member 5 [KO:K03913]
            5270  SERPINE2; serpin family E member 2 [KO:K16643]
            5327  PLAT; plasminogen activator, tissue type [KO:K01343] [EC:3.4.21.68]
            5328  PLAU; plasminogen activator, urokinase [KO:K01348] [EC:3.4.21.73]
            5329  PLAUR; plasminogen activator, urokinase receptor [KO:K03985]
            5340  PLG; plasminogen [KO:K01315] [EC:3.4.21.7]
            3818  KLKB1; kallikrein B1 [KO:K01324] [EC:3.4.21.34]
            3827  KNG1; kininogen 1 [KO:K03898]
            623  BDKRB1; bradykinin receptor B1 [KO:K03915]
            624  BDKRB2; bradykinin receptor B2 [KO:K03916]
            7035  TFPI; tissue factor pathway inhibitor [KO:K03909]
            5265  SERPINA1; serpin family A member 1 [KO:K03984]
            462  SERPINC1; serpin family C member 1 [KO:K03911]
            3053  SERPIND1; serpin family D member 1 [KO:K03912]
            710  SERPING1; serpin family G member 1 [KO:K04001]
            5345  SERPINF2; serpin family F member 2 [KO:K03983]
            2  A2M; alpha-2-macroglobulin [KO:K03910]
            712  C1QA; complement C1q A chain [KO:K03986]
            713  C1QB; complement C1q B chain [KO:K03987]
            714  C1QC; complement C1q C chain [KO:K03988]
            715  C1R; complement C1r [KO:K01330] [EC:3.4.21.41]
            716  C1S; complement C1s [KO:K01331] [EC:3.4.21.42]
            4153  MBL2; mannose binding lectin 2 [KO:K03991]
            5648  MASP1; MBL associated serine protease 1 [KO:K03992] [EC:3.4.21.-]
            10747  MASP2; MBL associated serine protease 2 [KO:K03993] [EC:3.4.21.104]
            720  C4A; complement C4A (Rodgers blood group) [KO:K03989]
            721  C4B; complement C4B (Chido blood group) [KO:K03989]
            717  C2; complement C2 [KO:K01332] [EC:3.4.21.43]
            718  C3; complement C3 [KO:K03990]
            629  CFB; complement factor B [KO:K01335] [EC:3.4.21.47]
            1675  CFD; complement factor D [KO:K01334] [EC:3.4.21.46]
            727  C5; complement C5 [KO:K03994]
            729  C6; complement C6 [KO:K03995]
            730  C7; complement C7 [KO:K03996]
            731  C8A; complement C8 alpha chain [KO:K03997]
            732  C8B; complement C8 beta chain [KO:K03998]
            733  C8G; complement C8 gamma chain [KO:K03999]
            735  C9; complement C9 [KO:K04000]
            719  C3AR1; complement C3a receptor 1 [KO:K04009]
            11326  VSIG4; V-set and immunoglobulin domain containing 4 [KO:K19822]
            1378  CR1; complement C3b/C4b receptor 1 (Knops blood group) [KO:K04011]
            1379  CR1L; complement C3b/C4b receptor 1 like [KO:K04011]
            1380  CR2; complement C3d receptor 2 [KO:K04012]
            3684  ITGAM; integrin subunit alpha M [KO:K06461]
            3689  ITGB2; integrin subunit beta 2 [KO:K06464]
            3687  ITGAX; integrin subunit alpha X [KO:K06462]
            728  C5AR1; complement C5a receptor 1 [KO:K04010]
            722  C4BPA; complement component 4 binding protein alpha [KO:K04002]
            725  C4BPB; complement component 4 binding protein beta [KO:K04003]
            3426  CFI; complement factor I [KO:K01333] [EC:3.4.21.45]
            3075  CFH; complement factor H [KO:K04004]
            4179  CD46; CD46 molecule [KO:K04007]
            1604  CD55; CD55 molecule (Cromer blood group) [KO:K04006]
            10878  CFHR3; complement factor H related 3 [KO:K23815]
            3078  CFHR1; complement factor H related 1 [KO:K23815]
            3080  CFHR2; complement factor H related 2 [KO:K23815]
            10877  CFHR4; complement factor H related 4 [KO:K23816]
            81494  CFHR5; complement factor H related 5 [KO:K23817]
            966  CD59; CD59 molecule (CD59 blood group) [KO:K04008]
            1191  CLU; clusterin [KO:K17252]
            7448  VTN; vitronectin [KO:K06251]
COMPOUND    C00290  Fibrin
            C00306  Bradykinin
            C00471  Plasmin
            C00752  Thrombin
            C01065  Coagulation factor Xa
            C01715  Plasma kallikrein
            C02002  C3a anaphylatoxin
            C03259  Coagulation factor IXa
            C03262  Coagulation factor XIa
            C03378  Coagulation factor VIIa
            C03379  Coagulation factor XIIa
            C03780  Coagulation factor Va
            C04001  Coagulation factor VIIIa
            C16510  C5a anaphylatoxin
            C22531  Complement component 2a
            C22532  Complement component 2b
            C22533  Complement component 3b
            C22534  Complement component 3f
            C22535  Complement iC3b
            C22536  Complement component 3dg
            C22537  Complement component 3c
            C22538  Complement component 3d
            C22539  Complement C3(H2O)
            C22540  Complement factor Bb
            C22541  Complement component 4a
            C22542  Complement component 4b
            C22543  Complement component 4c
            C22544  Complement component 4d
            C22545  Complement component 5b
            C22546  Coagulation factor XIIIa
            C22547  APC
REFERENCE   PMID:26489954
  AUTHORS   Bajic G, Degn SE, Thiel S, Andersen GR
  TITLE     Complement activation, regulation, and molecular basis for complement-related diseases.
  JOURNAL   EMBO J 34:2735-57 (2015)
            DOI:10.15252/embj.201591881
REFERENCE   PMID:25568220
  AUTHORS   Mathern DR, Heeger PS
  TITLE     Molecules Great and Small: The Complement System.
  JOURNAL   Clin J Am Soc Nephrol 10:1636-50 (2015)
            DOI:10.2215/CJN.06230614
REFERENCE   PMID:26082779
  AUTHORS   Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT
  TITLE     Complement System Part I - Molecular Mechanisms of Activation and Regulation.
  JOURNAL   Front Immunol 6:262 (2015)
            DOI:10.3389/fimmu.2015.00262
REFERENCE   PMID:21811895
  AUTHORS   Oikonomopoulou K, Ricklin D, Ward PA, Lambris JD
  TITLE     Interactions between coagulation and complement--their role in inflammation.
  JOURNAL   Semin Immunopathol 34:151-65 (2012)
            DOI:10.1007/s00281-011-0280-x
REFERENCE   PMID:25705421
  AUTHORS   Kurosawa S, Stearns-Kurosawa DJ
  TITLE     Complement, thrombotic microangiopathy and disseminated intravascular coagulation.
  JOURNAL   J Intensive Care 2:65 (2014)
            DOI:10.1186/s40560-014-0061-4
REFERENCE   PMID:23110467
  AUTHORS   Hillmeister P, Persson PB
  TITLE     The Kallikrein-Kinin system.
  JOURNAL   Acta Physiol (Oxf) 206:215-9 (2012)
            DOI:10.1111/apha.12007
REFERENCE   PMID:17635716
  AUTHORS   Rau JC, Beaulieu LM, Huntington JA, Church FC
  TITLE     Serpins in thrombosis, hemostasis and fibrinolysis.
  JOURNAL   J Thromb Haemost 5 Suppl 1:102-15 (2007)
            DOI:10.1111/j.1538-7836.2007.02516.x
REFERENCE   PMID:26324800
  AUTHORS   Crooks MG, Hart SP
  TITLE     Coagulation and anticoagulation in idiopathic pulmonary fibrosis.
  JOURNAL   Eur Respir Rev 24:392-9 (2015)
            DOI:10.1183/16000617.00008414
REFERENCE   PMID:23911436
  AUTHORS   Christiaans SC, Wagener BM, Esmon CT, Pittet JF
  TITLE     Protein C and acute inflammation: a clinical and biological perspective.
  JOURNAL   Am J Physiol Lung Cell Mol Physiol 305:L455-66 (2013)
            DOI:10.1152/ajplung.00093.2013
REFERENCE   PMID:24924409
  AUTHORS   Alberelli MA, De Candia E
  TITLE     Functional role of protease activated receptors in vascular biology.
  JOURNAL   Vascul Pharmacol 62:72-81 (2014)
            DOI:10.1016/j.vph.2014.06.001
REFERENCE   PMID:20027185
  AUTHORS   Smith HW, Marshall CJ
  TITLE     Regulation of cell signalling by uPAR.
  JOURNAL   Nat Rev Mol Cell Biol 11:23-36 (2010)
            DOI:10.1038/nrm2821
REFERENCE   PMID:23564577
  AUTHORS   Ricklin D, Lambris JD
  TITLE     Complement in immune and inflammatory disorders: pathophysiological mechanisms.
  JOURNAL   J Immunol 190:3831-8 (2013)
            DOI:10.4049/jimmunol.1203487
REFERENCE   PMID:23564578
  AUTHORS   Ricklin D, Lambris JD
  TITLE     Complement in immune and inflammatory disorders: therapeutic interventions.
  JOURNAL   J Immunol 190:3839-47 (2013)
            DOI:10.4049/jimmunol.1203200
REFERENCE   PMID:25309880
  AUTHORS   Loof TG, Deicke C, Medina E
  TITLE     The role of coagulation/fibrinolysis during Streptococcus pyogenes infection.
  JOURNAL   Front Cell Infect Microbiol 4:128 (2014)
            DOI:10.3389/fcimb.2014.00128
REFERENCE   PMID:25979655
  AUTHORS   Jozsi M, Tortajada A, Uzonyi B, Goicoechea de Jorge E, Rodriguez de Cordoba S
  TITLE     Factor H-related proteins determine complement-activating surfaces.
  JOURNAL   Trends Immunol 36:374-84 (2015)
            DOI:10.1016/j.it.2015.04.008
REL_PATHWAY hsa04611  Platelet activation
            hsa04662  B cell receptor signaling pathway
            hsa04750  Inflammatory mediator regulation of TRP channels
KO_PATHWAY  ko04610
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