#ID(s) interactor A ID(s) interactor B Alt. ID(s) interactor A Alt. ID(s) interactor B Alias(es) interactor A Alias(es) interactor B Interaction detection method(s) Publication 1st author(s) Publication Identifier(s) Taxid interactor A Taxid interactor B Interaction type(s) Source database(s) Interaction identifier(s) Confidence value(s) Expansion method(s) Biological role(s) interactor A Biological role(s) interactor B Experimental role(s) interactor A Experimental role(s) interactor B Type(s) interactor A Type(s) interactor B Xref(s) interactor A Xref(s) interactor B Interaction Xref(s) Annotation(s) interactor A Annotation(s) interactor B Interaction annotation(s) Host organism(s) Interaction parameter(s) Creation date Update date Checksum(s) interactor A Checksum(s) interactor B Interaction Checksum(s) Negative Feature(s) interactor A Feature(s) interactor B Stoichiometry(s) interactor A Stoichiometry(s) interactor B Identification method participant A Identification method participant B uniprotkb:Q03591 matrixdb:MULT_84_human intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:c3b_human(display_short)|psi-mi:MULT_84_human(display_long)|intact:Complement C3b complex(complex recommended name)|intact:C3b dimer(complex systematic name) psi-mi:"MI:0411"(enzyme linked immunosorbent assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-21994221|imex:IM-27334-1 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0498"(prey) psi-mi:"MI:0496"(bait) psi-mi:"MI:0326"(protein) psi-mi:"MI:1302"(stable complex) ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 pubmed:27782329(see-also)|pubmed:6225800(see-also)|evidence ontology:"ECO:0000353"|efo:"Orphanet:280133"(see-also)|efo:"Orphanet:2134"(see-also)|efo:"Orphanet:93575"(see-also)|efo:"EFO:0001365"(see-also)|pubmed:27013439(see-also)|pubmed:19196712(see-also)|pubmed:17051160(see-also)|go:"GO:0005615"(extracellular space)|go:"GO:0001848"(complement binding)|go:"GO:1903028"(positive regulation of opsonization)|go:"GO:0006956"(complement activation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0044533"(positive regulation of apoptotic process in another organism)|go:"GO:0050778"(positive regulation of immune response)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0008228"(opsonization)|pubmed:6559201(see-also)|pubmed:15454921(see-also)|pubmed:21205667(see-also)|pubmed:17051150(see-also)|complex portal:CPX-973(complex-primary)|pubmed:26489954(see-also) - - curated-complex:"A protein complex of the alternative pathway of complement activation of the innate immune system. Complement C3 precurser is activated by cleavage into C3a and C3b by C3 convertases, either C4bC2a in the classical and lectin pathways or C3(H2O)Bb, C3bBb, C3bBbC3b, C3bBbP or C3bBbC3bP in the alternative pathway. C3b acts as an opsonin and interacts with glycoproteins and carbohydrates on pathogenic or apoptotic target cell surfaces through its reactive thioester moiety. Opsonization of target cells leads to enhanced phagocytosis, lysis of target cells via membrane attack complex (CPX-6159) assembly, clearance of antibody-antigen complexes and up-regulation of the adaptive response. Activation of C3b leads to an amplification cascade that generates more C3 convertase, deposits more C3b at the local site and switches C3 convertases to C5 convertases. To protect host cells from inadvertent complement activation the activation of C3b is tightly regulated by either disrupting the C3 convertases or aiding in the proteolytic degradation of C3b. Bacteria and viruses possess C3b proteases to evade the complement response. Lack of protection, due to familial mutations in the complement genes or the presence of autoantibodies against regulators has been linked to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G) in kidneys and age-related macular degeneration (AMD) in eyes. Conditions of chronic and acute inflammations, as in rheumatoid arthritis, strokes, and heart attacks, become aggravated by complement activation against the disturbed tissue."|complex-properties:"The alternative pathway is continuously activated at a low level. C3 precursor is first processed by the removal of 4 Arg residues and spontaneous hydrolysis due to the breakdown of the internal thioester bond forms C3(H2O) (disulfide bonded P01024-PRO_0000005909 & P01024-PRO_0000005908). C3(H2O) subsequently binds factor B that is cleaved by Factor D (P00746) into 2 fragments: CFBa and CFBb. CFBb, a serine protease, then combines with complement factor C3(H2O) or C3b to generate the C3 or C5 convertases. Proteolytic cleavage of C3 to C3b is accompanied by large conformational changes that result in the exposure of cryptic binding sites required for convertase assembly and regulation. This includes a significant movement of the thioester-bond-containing domain through which C3b attaches to target surfaces."|complex-assembly:Heterodimer|disease:"Complement component 3 (C3) deficiency [Orphanet:280133]: a rare, autosomal recessive defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis."|disease:"Atypical hemolytic-uremic syndrome with C3 anomaly [Orphanet:2134 & Orphanet:93575]: an autosomal dominant, atypical form of hemolytic-uremic syndrome (aHUS, a thrombotic microangiopathy) characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction."|disease:"Age-related macular degeneration [EFO:0001365]: age-related macular degeneration usually in older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. Manifests as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Occurs in dry and wet forms. Most common cause of irreversible vision loss in the developed world." figure legend:1B|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2020/02/19 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 - - false - - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P08603 matrixdb:MULT_84_human intact:EBI-1223708|uniprotkb:A5PL14|uniprotkb:Q2TAZ5|uniprotkb:P78435|uniprotkb:Q14570|uniprotkb:Q38G77|uniprotkb:Q5TFM3|uniprotkb:Q8N708|uniprotkb:Q9NU86|ensembl:ENSP00000356399 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 psi-mi:cfah_human(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym) psi-mi:c3b_human(display_short)|psi-mi:MULT_84_human(display_long)|intact:Complement C3b complex(complex recommended name)|intact:C3b dimer(complex systematic name) psi-mi:"MI:0411"(enzyme linked immunosorbent assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-21994230|imex:IM-27334-3 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0498"(prey) psi-mi:"MI:0496"(bait) psi-mi:"MI:0326"(protein) psi-mi:"MI:1302"(stable complex) refseq:NP_000177.2|dip:DIP-38303N|ensembl:ENSG00000000971(gene)|ensembl:ENST00000367429(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0008201"(heparin binding)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0042802"(identical protein binding)|go:"GO:0043395"(heparan sulfate proteoglycan binding)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:1903659"(regulation of complement-dependent cytotoxicity)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:P08603|rcsb pdb:1FHC|rcsb pdb:1HAQ|rcsb pdb:1HCC|rcsb pdb:1HFH|rcsb pdb:1HFI|rcsb pdb:1KOV|rcsb pdb:2QFH|rcsb pdb:2RLP|rcsb pdb:2RLQ|rcsb pdb:2UWN|rcsb pdb:2V8E|rcsb pdb:2W80|rcsb pdb:2BZM|rcsb pdb:2G7I|rcsb pdb:2W81|rcsb pdb:2WII|rcsb pdb:2XQW|rcsb pdb:3GAU|rcsb pdb:3GAV|rcsb pdb:3GAW|rcsb pdb:3KXV|rcsb pdb:3KZJ|rcsb pdb:3OXU|rcsb pdb:3R62|rcsb pdb:3RJ3|rcsb pdb:3SW0|rcsb pdb:4AYD|rcsb pdb:4AYE|rcsb pdb:4AYI|rcsb pdb:4AYM|rcsb pdb:4B2R|rcsb pdb:4B2S|rcsb pdb:2IC4|rcsb pdb:2JGW|rcsb pdb:2JGX|rcsb pdb:4J38|rcsb pdb:4K12|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:2KMS|rcsb pdb:2QFG|rcsb pdb:5WTB|rcsb pdb:6ATG|reactome:R-HSA-977606 pubmed:27782329(see-also)|pubmed:6225800(see-also)|evidence ontology:"ECO:0000353"|efo:"Orphanet:280133"(see-also)|efo:"Orphanet:2134"(see-also)|efo:"Orphanet:93575"(see-also)|efo:"EFO:0001365"(see-also)|pubmed:27013439(see-also)|pubmed:19196712(see-also)|pubmed:17051160(see-also)|go:"GO:0005615"(extracellular space)|go:"GO:0001848"(complement binding)|go:"GO:1903028"(positive regulation of opsonization)|go:"GO:0006956"(complement activation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0044533"(positive regulation of apoptotic process in another organism)|go:"GO:0050778"(positive regulation of immune response)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0008228"(opsonization)|pubmed:6559201(see-also)|pubmed:15454921(see-also)|pubmed:21205667(see-also)|pubmed:17051150(see-also)|complex portal:CPX-973(complex-primary)|pubmed:26489954(see-also) - - curated-complex:"A protein complex of the alternative pathway of complement activation of the innate immune system. Complement C3 precurser is activated by cleavage into C3a and C3b by C3 convertases, either C4bC2a in the classical and lectin pathways or C3(H2O)Bb, C3bBb, C3bBbC3b, C3bBbP or C3bBbC3bP in the alternative pathway. C3b acts as an opsonin and interacts with glycoproteins and carbohydrates on pathogenic or apoptotic target cell surfaces through its reactive thioester moiety. Opsonization of target cells leads to enhanced phagocytosis, lysis of target cells via membrane attack complex (CPX-6159) assembly, clearance of antibody-antigen complexes and up-regulation of the adaptive response. Activation of C3b leads to an amplification cascade that generates more C3 convertase, deposits more C3b at the local site and switches C3 convertases to C5 convertases. To protect host cells from inadvertent complement activation the activation of C3b is tightly regulated by either disrupting the C3 convertases or aiding in the proteolytic degradation of C3b. Bacteria and viruses possess C3b proteases to evade the complement response. Lack of protection, due to familial mutations in the complement genes or the presence of autoantibodies against regulators has been linked to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G) in kidneys and age-related macular degeneration (AMD) in eyes. Conditions of chronic and acute inflammations, as in rheumatoid arthritis, strokes, and heart attacks, become aggravated by complement activation against the disturbed tissue."|complex-properties:"The alternative pathway is continuously activated at a low level. C3 precursor is first processed by the removal of 4 Arg residues and spontaneous hydrolysis due to the breakdown of the internal thioester bond forms C3(H2O) (disulfide bonded P01024-PRO_0000005909 & P01024-PRO_0000005908). C3(H2O) subsequently binds factor B that is cleaved by Factor D (P00746) into 2 fragments: CFBa and CFBb. CFBb, a serine protease, then combines with complement factor C3(H2O) or C3b to generate the C3 or C5 convertases. Proteolytic cleavage of C3 to C3b is accompanied by large conformational changes that result in the exposure of cryptic binding sites required for convertase assembly and regulation. This includes a significant movement of the thioester-bond-containing domain through which C3b attaches to target surfaces."|complex-assembly:Heterodimer|disease:"Complement component 3 (C3) deficiency [Orphanet:280133]: a rare, autosomal recessive defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis."|disease:"Atypical hemolytic-uremic syndrome with C3 anomaly [Orphanet:2134 & Orphanet:93575]: an autosomal dominant, atypical form of hemolytic-uremic syndrome (aHUS, a thrombotic microangiopathy) characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction."|disease:"Age-related macular degeneration [EFO:0001365]: age-related macular degeneration usually in older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. Manifests as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Occurs in dry and wet forms. Most common cause of irreversible vision loss in the developed world." figure legend:1Bi|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2020/02/19 rogid:1mjo+AJLIQnEsMFqsGsmUFbfUxk9606 - - false - - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P01031 uniprotkb:Q03591 intact:EBI-8558308|intact:UNK-5392818|uniprotkb:Q27I61|intact:UNK-5368655|uniprotkb:Q14CJ0|intact:UNK-5396112|ensembl:ENSP00000223642 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 psi-mi:co5_human(display_long)|uniprotkb:C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4(gene name synonym)|uniprotkb:CPAMD4(gene name synonym)|uniprotkb:C5(gene name)|psi-mi:C5(display_short) psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:"MI:0411"(enzyme linked immunosorbent assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-21995000|imex:IM-27334-27 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0498"(prey) psi-mi:"MI:0496"(bait) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) refseq:NP_001304092.1|refseq:NP_001726.2|ensembl:ENSG00000106804(gene)|ensembl:ENST00000223642(transcript)|go:"GO:0000187"(obsolete activation of MAPK activity)|go:"GO:0001701"(in utero embryonic development)|go:"GO:0004866"(endopeptidase inhibitor activity)|go:"GO:0005102"(signaling receptor binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005579"(membrane attack complex)|go:"GO:0005615"(extracellular space)|go:"GO:0006935"(chemotaxis)|go:"GO:0006954"(inflammatory response)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0006958"(complement activation, classical pathway)|go:"GO:0007166"(cell surface receptor signaling pathway)|go:"GO:0007186"(G protein-coupled receptor signaling pathway)|go:"GO:0008009"(chemokine activity)|go:"GO:0010575"(positive regulation of vascular endothelial growth factor production)|go:"GO:0010760"(negative regulation of macrophage chemotaxis)|go:"GO:0019835"(cytolysis)|go:"GO:0032722"(positive regulation of chemokine production)|go:"GO:0045766"(positive regulation of angiogenesis)|go:"GO:0070062"(extracellular exosome)|interpro:IPR000020(Anaphylatoxin/fibulin)|interpro:IPR001134(Netrin, C-terminal)|interpro:IPR001599(Alpha-2-macroglobulin)|interpro:IPR001840(Complement C3a/C4a/C5a anaphylatoxin)|interpro:IPR002890(Alpha-2-macroglobulin, N-terminal)|interpro:IPR008930(Terpenoid cylases/protein prenyltransferase alpha-alpha toroid)|interpro:IPR008993(TIMP-like, OB-fold)|interpro:IPR009048(Alpha-macroglobulin, receptor-binding)|interpro:IPR011625(Alpha-2-macroglobulin, N-terminal 2)|interpro:IPR011626(A-macroglobulin complement component)|interpro:IPR013783(Immunoglobulin-like fold)|interpro:IPR018081|interpro:IPR018933|interpro:IPR036595|interpro:IPR037562|interpro:IPR040839|interpro:IPR041425|interpro:IPR041555|rcsb pdb:1CFA|rcsb pdb:1KJS|rcsb pdb:1XWE|rcsb pdb:3CU7|rcsb pdb:3HQA|rcsb pdb:3HQB|rcsb pdb:3KLS|rcsb pdb:3KM9|rcsb pdb:3PRX|rcsb pdb:3PVM|rcsb pdb:4A5W|rcsb pdb:4E0S|rcsb pdb:4P39|rcsb pdb:4UU9|rcsb pdb:5B4P|rcsb pdb:5B71|rcsb pdb:5HCC|rcsb pdb:5HCD|rcsb pdb:5HCE|rcsb pdb:5I5K|rcsb pdb:6H03|rcsb pdb:6H04|rcsb pdb:6RPT|rcsb pdb:7AD6|rcsb pdb:7AD7|reactome:R-HSA-166665|reactome:R-HSA-174577|reactome:R-HSA-375276|reactome:R-HSA-418594|reactome:R-HSA-977606 ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 - function:Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled|comment:mint|function:"Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis)"|function:"Defects in C5 are the cause of complement C5 deficiency [MIM:609536]. Patients with dysfunction of C5 display a propensity for severe recurrent infections"|function:"Genetic variation in C5 can be associated with susceptibility to liver fibrosis [MIM:120900]. Liver fibrosis is a common consequence of all chronic liver diseases, irrespective of etiology. Common C5 variants can influence the progression and severity of fibrogenesis" - figure legend:4A/D|comment:C5 and C5b6 bound to CFHR1, when immobilized via the C-terminus.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/09/03 rogid:EpfpW2TQ68YvIqNRfr6uIyA6MUU9606 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 rigid:8FCV55OW72ObuL5D+1URfdy21xM false - - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) wwpdb:4a5w uniprotkb:Q03591 intact:EBI-12513275|wwpdb:4e0s|reactome:R-HSA-173711 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 psi-mi:co5-co6_human(display_short)|psi-mi:4a5w(display_long)|intact:C5bC6 complex(complex synonym)|intact:C5b-6 complex(complex synonym)|intact:C5b6 complement complex(complex recommended name)|intact:"C5:C6"(complex systematic name)|intact:C5b-C6 complex(complex synonym) psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:"MI:0411"(enzyme linked immunosorbent assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-21995006|imex:IM-27334-9 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0498"(prey) psi-mi:"MI:0496"(bait) psi-mi:"MI:1302"(stable complex) psi-mi:"MI:0326"(protein) complex portal:CPX-677(complex-primary)|go:"GO:0006956"(complement activation)|pubmed:22832194(see-also)|evidence ontology:"ECO:0000353" ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 - curated-complex:"Involved in the complement system. The complement system is a part of the innate immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism. The complex is formed after C5 cleavage by C5 convertase into C5a and C5b. C5b has a transient binding site for C6. Without C6 binding, C5b will irreversibly decay to a state incapable of binding C6. The complex initiates pore formation via the sequential recruitment of homologous proteins: C7, C8, and 12-18 copies of C9, each of which comprises a central MAC-perforin domain flanked by auxiliary domains. Activation of the complement system results in formation of membrane attack complexes (MACs), pores that disrupt lipid bilayers and lyse bacteria and other pathogens."|complex-assembly:Heterotrimer|complex-properties:Bimolecular complex of Mr = 300,000. C5b grabs the top of C6 like a pair of pincers. The C-terminal region of C6 forms the major interface with C5b. The C5b-C6 interface buries 3100 A2 of solvent accessible surface area. - figure legend:4A|comment:C5 and C5b6 bound to CFHR1, when immobilized via the C-terminus.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2020/02/19 - rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 - false - - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P08603 uniprotkb:Q03591 intact:EBI-1223708|uniprotkb:A5PL14|uniprotkb:Q2TAZ5|uniprotkb:P78435|uniprotkb:Q14570|uniprotkb:Q38G77|uniprotkb:Q5TFM3|uniprotkb:Q8N708|uniprotkb:Q9NU86|ensembl:ENSP00000356399 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 psi-mi:cfah_human(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym) psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:"MI:0663"(confocal microscopy) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0403"(colocalization) psi-mi:"MI:0469"(IntAct) intact:EBI-21994590|imex:IM-27334-21 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) refseq:NP_000177.2|dip:DIP-38303N|ensembl:ENSG00000000971(gene)|ensembl:ENST00000367429(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0008201"(heparin binding)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0042802"(identical protein binding)|go:"GO:0043395"(heparan sulfate proteoglycan binding)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:1903659"(regulation of complement-dependent cytotoxicity)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:P08603|rcsb pdb:1FHC|rcsb pdb:1HAQ|rcsb pdb:1HCC|rcsb pdb:1HFH|rcsb pdb:1HFI|rcsb pdb:1KOV|rcsb pdb:2QFH|rcsb pdb:2RLP|rcsb pdb:2RLQ|rcsb pdb:2UWN|rcsb pdb:2V8E|rcsb pdb:2W80|rcsb pdb:2BZM|rcsb pdb:2G7I|rcsb pdb:2W81|rcsb pdb:2WII|rcsb pdb:2XQW|rcsb pdb:3GAU|rcsb pdb:3GAV|rcsb pdb:3GAW|rcsb pdb:3KXV|rcsb pdb:3KZJ|rcsb pdb:3OXU|rcsb pdb:3R62|rcsb pdb:3RJ3|rcsb pdb:3SW0|rcsb pdb:4AYD|rcsb pdb:4AYE|rcsb pdb:4AYI|rcsb pdb:4AYM|rcsb pdb:4B2R|rcsb pdb:4B2S|rcsb pdb:2IC4|rcsb pdb:2JGW|rcsb pdb:2JGX|rcsb pdb:4J38|rcsb pdb:4K12|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:2KMS|rcsb pdb:2QFG|rcsb pdb:5WTB|rcsb pdb:6ATG|reactome:R-HSA-977606 ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 go:"GO:0009986"(cell surface) - - figure legend:1E|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/09/03 rogid:1mjo+AJLIQnEsMFqsGsmUFbfUxk9606 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 rigid:N749OwXJMKffTa5a0pcSvH53k0A false - - - - psi-mi:"MI:1200"(immunocytochemistry) psi-mi:"MI:1200"(immunocytochemistry) uniprotkb:P08603 uniprotkb:P05156 intact:EBI-1223708|uniprotkb:A5PL14|uniprotkb:Q2TAZ5|uniprotkb:P78435|uniprotkb:Q14570|uniprotkb:Q38G77|uniprotkb:Q5TFM3|uniprotkb:Q8N708|uniprotkb:Q9NU86|ensembl:ENSP00000356399 intact:EBI-9352022|uniprotkb:O60442|ensembl:ENSP00000378130 psi-mi:cfah_human(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym) psi-mi:cfai_human(display_long)|uniprotkb:CFI(gene name)|psi-mi:CFI(display_short)|uniprotkb:IF(gene name synonym)|uniprotkb:C3B/C4B inactivator(gene name synonym) psi-mi:"MI:0435"(protease assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-21994633|imex:IM-27334-23 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0682"(cofactor) psi-mi:"MI:0501"(enzyme) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) refseq:NP_000177.2|dip:DIP-38303N|ensembl:ENSG00000000971(gene)|ensembl:ENST00000367429(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0008201"(heparin binding)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0042802"(identical protein binding)|go:"GO:0043395"(heparan sulfate proteoglycan binding)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:1903659"(regulation of complement-dependent cytotoxicity)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:P08603|rcsb pdb:1FHC|rcsb pdb:1HAQ|rcsb pdb:1HCC|rcsb pdb:1HFH|rcsb pdb:1HFI|rcsb pdb:1KOV|rcsb pdb:2QFH|rcsb pdb:2RLP|rcsb pdb:2RLQ|rcsb pdb:2UWN|rcsb pdb:2V8E|rcsb pdb:2W80|rcsb pdb:2BZM|rcsb pdb:2G7I|rcsb pdb:2W81|rcsb pdb:2WII|rcsb pdb:2XQW|rcsb pdb:3GAU|rcsb pdb:3GAV|rcsb pdb:3GAW|rcsb pdb:3KXV|rcsb pdb:3KZJ|rcsb pdb:3OXU|rcsb pdb:3R62|rcsb pdb:3RJ3|rcsb pdb:3SW0|rcsb pdb:4AYD|rcsb pdb:4AYE|rcsb pdb:4AYI|rcsb pdb:4AYM|rcsb pdb:4B2R|rcsb pdb:4B2S|rcsb pdb:2IC4|rcsb pdb:2JGW|rcsb pdb:2JGX|rcsb pdb:4J38|rcsb pdb:4K12|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:2KMS|rcsb pdb:2QFG|rcsb pdb:5WTB|rcsb pdb:6ATG|reactome:R-HSA-977606 refseq:NP_001317964.1|refseq:NP_000195.2|ensembl:ENSG00000205403(gene)|ensembl:ENST00000394634(transcript)|go:"GO:0004252"(serine-type endopeptidase activity)|go:"GO:0005044"(scavenger receptor activity)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006958"(complement activation, classical pathway)|go:"GO:0016020"(membrane)|go:"GO:0045087"(innate immune response)|go:"GO:0046872"(metal ion binding)|go:"GO:0070062"(extracellular exosome)|interpro:IPR001190(Speract/scavenger receptor)|interpro:IPR001254(Peptidase S1 and S6, chymotrypsin/Hap)|interpro:IPR001314(Peptidase S1A, chymotrypsin)|interpro:IPR002172(Low density lipoprotein-receptor, class A, cysteine-rich)|interpro:IPR002350(Proteinase inhibitor I1, Kazal)|interpro:IPR003884(Factor I membrane attack complex)|interpro:IPR009003(Peptidase, trypsin-like serine and cysteine)|interpro:IPR017448(Speract/scavenger receptor related)|interpro:IPR018114|interpro:IPR023415|interpro:IPR033116|interpro:IPR036055|interpro:IPR036058|interpro:IPR036772|interpro:IPR043504|mint:P05156|rcsb pdb:2XRC|rcsb pdb:5O32|reactome:R-HSA-977606 go:"GO:0004252"(serine-type endopeptidase activity) - - figure legend:1F-2|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/05 rogid:1mjo+AJLIQnEsMFqsGsmUFbfUxk9606 rogid:2zm8YwMWNSX3vv6fLIJ3WZ6hrLc9606 rigid:C2DKt6ABOFr+x+h2wwp0Gxk0oSI false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) uniprotkb:P08603 uniprotkb:Q03591 intact:EBI-1223708|uniprotkb:A5PL14|uniprotkb:Q2TAZ5|uniprotkb:P78435|uniprotkb:Q14570|uniprotkb:Q38G77|uniprotkb:Q5TFM3|uniprotkb:Q8N708|uniprotkb:Q9NU86|ensembl:ENSP00000356399 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 psi-mi:cfah_human(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym) psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:"MI:0435"(protease assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-21994633|imex:IM-27334-23 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0682"(cofactor) psi-mi:"MI:0941"(competitor) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) refseq:NP_000177.2|dip:DIP-38303N|ensembl:ENSG00000000971(gene)|ensembl:ENST00000367429(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0008201"(heparin binding)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0042802"(identical protein binding)|go:"GO:0043395"(heparan sulfate proteoglycan binding)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:1903659"(regulation of complement-dependent cytotoxicity)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:P08603|rcsb pdb:1FHC|rcsb pdb:1HAQ|rcsb pdb:1HCC|rcsb pdb:1HFH|rcsb pdb:1HFI|rcsb pdb:1KOV|rcsb pdb:2QFH|rcsb pdb:2RLP|rcsb pdb:2RLQ|rcsb pdb:2UWN|rcsb pdb:2V8E|rcsb pdb:2W80|rcsb pdb:2BZM|rcsb pdb:2G7I|rcsb pdb:2W81|rcsb pdb:2WII|rcsb pdb:2XQW|rcsb pdb:3GAU|rcsb pdb:3GAV|rcsb pdb:3GAW|rcsb pdb:3KXV|rcsb pdb:3KZJ|rcsb pdb:3OXU|rcsb pdb:3R62|rcsb pdb:3RJ3|rcsb pdb:3SW0|rcsb pdb:4AYD|rcsb pdb:4AYE|rcsb pdb:4AYI|rcsb pdb:4AYM|rcsb pdb:4B2R|rcsb pdb:4B2S|rcsb pdb:2IC4|rcsb pdb:2JGW|rcsb pdb:2JGX|rcsb pdb:4J38|rcsb pdb:4K12|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:2KMS|rcsb pdb:2QFG|rcsb pdb:5WTB|rcsb pdb:6ATG|reactome:R-HSA-977606 ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 go:"GO:0004252"(serine-type endopeptidase activity) - - figure legend:1F-2|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/05 rogid:1mjo+AJLIQnEsMFqsGsmUFbfUxk9606 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 rigid:C2DKt6ABOFr+x+h2wwp0Gxk0oSI false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) uniprotkb:P08603 uniprotkb:P01024-PRO_0000005911 intact:EBI-1223708|uniprotkb:A5PL14|uniprotkb:Q2TAZ5|uniprotkb:P78435|uniprotkb:Q14570|uniprotkb:Q38G77|uniprotkb:Q5TFM3|uniprotkb:Q8N708|uniprotkb:Q9NU86|ensembl:ENSP00000356399 intact:EBI-12735725 psi-mi:cfah_human(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym) psi-mi:p01024-pro_0000005911(display_long)|uniprotkb:C3(gene name)|psi-mi:C3(display_short)|uniprotkb:CPAMD1(gene name synonym)|uniprotkb:C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1(gene name synonym) psi-mi:"MI:0435"(protease assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-21994633|imex:IM-27334-23 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0682"(cofactor) psi-mi:"MI:0502"(enzyme target) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) refseq:NP_000177.2|dip:DIP-38303N|ensembl:ENSG00000000971(gene)|ensembl:ENST00000367429(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0008201"(heparin binding)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0042802"(identical protein binding)|go:"GO:0043395"(heparan sulfate proteoglycan binding)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:1903659"(regulation of complement-dependent cytotoxicity)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:P08603|rcsb pdb:1FHC|rcsb pdb:1HAQ|rcsb pdb:1HCC|rcsb pdb:1HFH|rcsb pdb:1HFI|rcsb pdb:1KOV|rcsb pdb:2QFH|rcsb pdb:2RLP|rcsb pdb:2RLQ|rcsb pdb:2UWN|rcsb pdb:2V8E|rcsb pdb:2W80|rcsb pdb:2BZM|rcsb pdb:2G7I|rcsb pdb:2W81|rcsb pdb:2WII|rcsb pdb:2XQW|rcsb pdb:3GAU|rcsb pdb:3GAV|rcsb pdb:3GAW|rcsb pdb:3KXV|rcsb pdb:3KZJ|rcsb pdb:3OXU|rcsb pdb:3R62|rcsb pdb:3RJ3|rcsb pdb:3SW0|rcsb pdb:4AYD|rcsb pdb:4AYE|rcsb pdb:4AYI|rcsb pdb:4AYM|rcsb pdb:4B2R|rcsb pdb:4B2S|rcsb pdb:2IC4|rcsb pdb:2JGW|rcsb pdb:2JGX|rcsb pdb:4J38|rcsb pdb:4K12|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:2KMS|rcsb pdb:2QFG|rcsb pdb:5WTB|rcsb pdb:6ATG|reactome:R-HSA-977606 intact:EBI-905851(chain-parent) go:"GO:0004252"(serine-type endopeptidase activity) - chain-seq-start:749|chain-seq-end:1663 figure legend:1F-2|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/05 rogid:1mjo+AJLIQnEsMFqsGsmUFbfUxk9606 rogid:PGQNhqtLcK90Rf1IY85ARmU6Jbs9606 rigid:C2DKt6ABOFr+x+h2wwp0Gxk0oSI false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) uniprotkb:P08603 uniprotkb:P05156 intact:EBI-1223708|uniprotkb:A5PL14|uniprotkb:Q2TAZ5|uniprotkb:P78435|uniprotkb:Q14570|uniprotkb:Q38G77|uniprotkb:Q5TFM3|uniprotkb:Q8N708|uniprotkb:Q9NU86|ensembl:ENSP00000356399 intact:EBI-9352022|uniprotkb:O60442|ensembl:ENSP00000378130 psi-mi:cfah_human(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym) psi-mi:cfai_human(display_long)|uniprotkb:CFI(gene name)|psi-mi:CFI(display_short)|uniprotkb:IF(gene name synonym)|uniprotkb:C3B/C4B inactivator(gene name synonym) psi-mi:"MI:0435"(protease assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-21994645|imex:IM-27334-5 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0682"(cofactor) psi-mi:"MI:0501"(enzyme) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) refseq:NP_000177.2|dip:DIP-38303N|ensembl:ENSG00000000971(gene)|ensembl:ENST00000367429(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0008201"(heparin binding)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0042802"(identical protein binding)|go:"GO:0043395"(heparan sulfate proteoglycan binding)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:1903659"(regulation of complement-dependent cytotoxicity)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:P08603|rcsb pdb:1FHC|rcsb pdb:1HAQ|rcsb pdb:1HCC|rcsb pdb:1HFH|rcsb pdb:1HFI|rcsb pdb:1KOV|rcsb pdb:2QFH|rcsb pdb:2RLP|rcsb pdb:2RLQ|rcsb pdb:2UWN|rcsb pdb:2V8E|rcsb pdb:2W80|rcsb pdb:2BZM|rcsb pdb:2G7I|rcsb pdb:2W81|rcsb pdb:2WII|rcsb pdb:2XQW|rcsb pdb:3GAU|rcsb pdb:3GAV|rcsb pdb:3GAW|rcsb pdb:3KXV|rcsb pdb:3KZJ|rcsb pdb:3OXU|rcsb pdb:3R62|rcsb pdb:3RJ3|rcsb pdb:3SW0|rcsb pdb:4AYD|rcsb pdb:4AYE|rcsb pdb:4AYI|rcsb pdb:4AYM|rcsb pdb:4B2R|rcsb pdb:4B2S|rcsb pdb:2IC4|rcsb pdb:2JGW|rcsb pdb:2JGX|rcsb pdb:4J38|rcsb pdb:4K12|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:2KMS|rcsb pdb:2QFG|rcsb pdb:5WTB|rcsb pdb:6ATG|reactome:R-HSA-977606 refseq:NP_001317964.1|refseq:NP_000195.2|ensembl:ENSG00000205403(gene)|ensembl:ENST00000394634(transcript)|go:"GO:0004252"(serine-type endopeptidase activity)|go:"GO:0005044"(scavenger receptor activity)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006958"(complement activation, classical pathway)|go:"GO:0016020"(membrane)|go:"GO:0045087"(innate immune response)|go:"GO:0046872"(metal ion binding)|go:"GO:0070062"(extracellular exosome)|interpro:IPR001190(Speract/scavenger receptor)|interpro:IPR001254(Peptidase S1 and S6, chymotrypsin/Hap)|interpro:IPR001314(Peptidase S1A, chymotrypsin)|interpro:IPR002172(Low density lipoprotein-receptor, class A, cysteine-rich)|interpro:IPR002350(Proteinase inhibitor I1, Kazal)|interpro:IPR003884(Factor I membrane attack complex)|interpro:IPR009003(Peptidase, trypsin-like serine and cysteine)|interpro:IPR017448(Speract/scavenger receptor related)|interpro:IPR018114|interpro:IPR023415|interpro:IPR033116|interpro:IPR036055|interpro:IPR036058|interpro:IPR036772|interpro:IPR043504|mint:P05156|rcsb pdb:2XRC|rcsb pdb:5O32|reactome:R-HSA-977606 go:"GO:0004252"(serine-type endopeptidase activity) - - figure legend:1F-1|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/05 rogid:1mjo+AJLIQnEsMFqsGsmUFbfUxk9606 rogid:2zm8YwMWNSX3vv6fLIJ3WZ6hrLc9606 rigid:BQuL/Df+EOUBuGm31kzXfQDZ12E false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) uniprotkb:P08603 uniprotkb:P01024-PRO_0000005911 intact:EBI-1223708|uniprotkb:A5PL14|uniprotkb:Q2TAZ5|uniprotkb:P78435|uniprotkb:Q14570|uniprotkb:Q38G77|uniprotkb:Q5TFM3|uniprotkb:Q8N708|uniprotkb:Q9NU86|ensembl:ENSP00000356399 intact:EBI-12735725 psi-mi:cfah_human(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym) psi-mi:p01024-pro_0000005911(display_long)|uniprotkb:C3(gene name)|psi-mi:C3(display_short)|uniprotkb:CPAMD1(gene name synonym)|uniprotkb:C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1(gene name synonym) psi-mi:"MI:0435"(protease assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-21994645|imex:IM-27334-5 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0682"(cofactor) psi-mi:"MI:0502"(enzyme target) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) refseq:NP_000177.2|dip:DIP-38303N|ensembl:ENSG00000000971(gene)|ensembl:ENST00000367429(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0008201"(heparin binding)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0042802"(identical protein binding)|go:"GO:0043395"(heparan sulfate proteoglycan binding)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:1903659"(regulation of complement-dependent cytotoxicity)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:P08603|rcsb pdb:1FHC|rcsb pdb:1HAQ|rcsb pdb:1HCC|rcsb pdb:1HFH|rcsb pdb:1HFI|rcsb pdb:1KOV|rcsb pdb:2QFH|rcsb pdb:2RLP|rcsb pdb:2RLQ|rcsb pdb:2UWN|rcsb pdb:2V8E|rcsb pdb:2W80|rcsb pdb:2BZM|rcsb pdb:2G7I|rcsb pdb:2W81|rcsb pdb:2WII|rcsb pdb:2XQW|rcsb pdb:3GAU|rcsb pdb:3GAV|rcsb pdb:3GAW|rcsb pdb:3KXV|rcsb pdb:3KZJ|rcsb pdb:3OXU|rcsb pdb:3R62|rcsb pdb:3RJ3|rcsb pdb:3SW0|rcsb pdb:4AYD|rcsb pdb:4AYE|rcsb pdb:4AYI|rcsb pdb:4AYM|rcsb pdb:4B2R|rcsb pdb:4B2S|rcsb pdb:2IC4|rcsb pdb:2JGW|rcsb pdb:2JGX|rcsb pdb:4J38|rcsb pdb:4K12|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:2KMS|rcsb pdb:2QFG|rcsb pdb:5WTB|rcsb pdb:6ATG|reactome:R-HSA-977606 intact:EBI-905851(chain-parent) go:"GO:0004252"(serine-type endopeptidase activity) - chain-seq-start:749|chain-seq-end:1663 figure legend:1F-1|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/05 rogid:1mjo+AJLIQnEsMFqsGsmUFbfUxk9606 rogid:PGQNhqtLcK90Rf1IY85ARmU6Jbs9606 rigid:BQuL/Df+EOUBuGm31kzXfQDZ12E false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) matrixdb:MULT_84_human uniprotkb:P08603 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 intact:EBI-1223708|uniprotkb:A5PL14|uniprotkb:Q2TAZ5|uniprotkb:P78435|uniprotkb:Q14570|uniprotkb:Q38G77|uniprotkb:Q5TFM3|uniprotkb:Q8N708|uniprotkb:Q9NU86|ensembl:ENSP00000356399 psi-mi:c3b_human(display_short)|psi-mi:MULT_84_human(display_long)|intact:Complement C3b complex(complex recommended name)|intact:C3b dimer(complex systematic name) psi-mi:cfah_human(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym) psi-mi:"MI:0435"(protease assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-21994963|imex:IM-27334-25 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0684"(ancillary) psi-mi:"MI:0586"(inhibitor) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:1302"(stable complex) psi-mi:"MI:0326"(protein) pubmed:27782329(see-also)|pubmed:6225800(see-also)|evidence ontology:"ECO:0000353"|efo:"Orphanet:280133"(see-also)|efo:"Orphanet:2134"(see-also)|efo:"Orphanet:93575"(see-also)|efo:"EFO:0001365"(see-also)|pubmed:27013439(see-also)|pubmed:19196712(see-also)|pubmed:17051160(see-also)|go:"GO:0005615"(extracellular space)|go:"GO:0001848"(complement binding)|go:"GO:1903028"(positive regulation of opsonization)|go:"GO:0006956"(complement activation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0044533"(positive regulation of apoptotic process in another organism)|go:"GO:0050778"(positive regulation of immune response)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0008228"(opsonization)|pubmed:6559201(see-also)|pubmed:15454921(see-also)|pubmed:21205667(see-also)|pubmed:17051150(see-also)|complex portal:CPX-973(complex-primary)|pubmed:26489954(see-also) refseq:NP_000177.2|dip:DIP-38303N|ensembl:ENSG00000000971(gene)|ensembl:ENST00000367429(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0008201"(heparin binding)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0042802"(identical protein binding)|go:"GO:0043395"(heparan sulfate proteoglycan binding)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:1903659"(regulation of complement-dependent cytotoxicity)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:P08603|rcsb pdb:1FHC|rcsb pdb:1HAQ|rcsb pdb:1HCC|rcsb pdb:1HFH|rcsb pdb:1HFI|rcsb pdb:1KOV|rcsb pdb:2QFH|rcsb pdb:2RLP|rcsb pdb:2RLQ|rcsb pdb:2UWN|rcsb pdb:2V8E|rcsb pdb:2W80|rcsb pdb:2BZM|rcsb pdb:2G7I|rcsb pdb:2W81|rcsb pdb:2WII|rcsb pdb:2XQW|rcsb pdb:3GAU|rcsb pdb:3GAV|rcsb pdb:3GAW|rcsb pdb:3KXV|rcsb pdb:3KZJ|rcsb pdb:3OXU|rcsb pdb:3R62|rcsb pdb:3RJ3|rcsb pdb:3SW0|rcsb pdb:4AYD|rcsb pdb:4AYE|rcsb pdb:4AYI|rcsb pdb:4AYM|rcsb pdb:4B2R|rcsb pdb:4B2S|rcsb pdb:2IC4|rcsb pdb:2JGW|rcsb pdb:2JGX|rcsb pdb:4J38|rcsb pdb:4K12|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:2KMS|rcsb pdb:2QFG|rcsb pdb:5WTB|rcsb pdb:6ATG|reactome:R-HSA-977606 go:"GO:0004252"(serine-type endopeptidase activity) curated-complex:"A protein complex of the alternative pathway of complement activation of the innate immune system. Complement C3 precurser is activated by cleavage into C3a and C3b by C3 convertases, either C4bC2a in the classical and lectin pathways or C3(H2O)Bb, C3bBb, C3bBbC3b, C3bBbP or C3bBbC3bP in the alternative pathway. C3b acts as an opsonin and interacts with glycoproteins and carbohydrates on pathogenic or apoptotic target cell surfaces through its reactive thioester moiety. Opsonization of target cells leads to enhanced phagocytosis, lysis of target cells via membrane attack complex (CPX-6159) assembly, clearance of antibody-antigen complexes and up-regulation of the adaptive response. Activation of C3b leads to an amplification cascade that generates more C3 convertase, deposits more C3b at the local site and switches C3 convertases to C5 convertases. To protect host cells from inadvertent complement activation the activation of C3b is tightly regulated by either disrupting the C3 convertases or aiding in the proteolytic degradation of C3b. Bacteria and viruses possess C3b proteases to evade the complement response. Lack of protection, due to familial mutations in the complement genes or the presence of autoantibodies against regulators has been linked to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G) in kidneys and age-related macular degeneration (AMD) in eyes. Conditions of chronic and acute inflammations, as in rheumatoid arthritis, strokes, and heart attacks, become aggravated by complement activation against the disturbed tissue."|complex-properties:"The alternative pathway is continuously activated at a low level. C3 precursor is first processed by the removal of 4 Arg residues and spontaneous hydrolysis due to the breakdown of the internal thioester bond forms C3(H2O) (disulfide bonded P01024-PRO_0000005909 & P01024-PRO_0000005908). C3(H2O) subsequently binds factor B that is cleaved by Factor D (P00746) into 2 fragments: CFBa and CFBb. CFBb, a serine protease, then combines with complement factor C3(H2O) or C3b to generate the C3 or C5 convertases. Proteolytic cleavage of C3 to C3b is accompanied by large conformational changes that result in the exposure of cryptic binding sites required for convertase assembly and regulation. This includes a significant movement of the thioester-bond-containing domain through which C3b attaches to target surfaces."|complex-assembly:Heterodimer|disease:"Complement component 3 (C3) deficiency [Orphanet:280133]: a rare, autosomal recessive defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis."|disease:"Atypical hemolytic-uremic syndrome with C3 anomaly [Orphanet:2134 & Orphanet:93575]: an autosomal dominant, atypical form of hemolytic-uremic syndrome (aHUS, a thrombotic microangiopathy) characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction."|disease:"Age-related macular degeneration [EFO:0001365]: age-related macular degeneration usually in older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. Manifests as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Occurs in dry and wet forms. Most common cause of irreversible vision loss in the developed world." - figure legend:2B|comment:CFHR1 does not affect the C3 convertase. In contrast, CFH strongly inhibited C3a generation.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/05 - rogid:1mjo+AJLIQnEsMFqsGsmUFbfUxk9606 - false - - - - psi-mi:"MI:0411"(enzyme linked immunosorbent assay) psi-mi:"MI:0411"(enzyme linked immunosorbent assay) matrixdb:MULT_84_human uniprotkb:P01024 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 intact:EBI-905851|uniprotkb:A7E236|ensembl:ENSP00000245907 psi-mi:c3b_human(display_short)|psi-mi:MULT_84_human(display_long)|intact:Complement C3b complex(complex recommended name)|intact:C3b dimer(complex systematic name) psi-mi:co3_human(display_long)|uniprotkb:C3(gene name)|psi-mi:C3(display_short)|uniprotkb:CPAMD1(gene name synonym)|uniprotkb:C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1(gene name synonym) psi-mi:"MI:0435"(protease assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-21994963|imex:IM-27334-25 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0684"(ancillary) psi-mi:"MI:0502"(enzyme target) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:1302"(stable complex) psi-mi:"MI:0326"(protein) pubmed:27782329(see-also)|pubmed:6225800(see-also)|evidence ontology:"ECO:0000353"|efo:"Orphanet:280133"(see-also)|efo:"Orphanet:2134"(see-also)|efo:"Orphanet:93575"(see-also)|efo:"EFO:0001365"(see-also)|pubmed:27013439(see-also)|pubmed:19196712(see-also)|pubmed:17051160(see-also)|go:"GO:0005615"(extracellular space)|go:"GO:0001848"(complement binding)|go:"GO:1903028"(positive regulation of opsonization)|go:"GO:0006956"(complement activation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0044533"(positive regulation of apoptotic process in another organism)|go:"GO:0050778"(positive regulation of immune response)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0008228"(opsonization)|pubmed:6559201(see-also)|pubmed:15454921(see-also)|pubmed:21205667(see-also)|pubmed:17051150(see-also)|complex portal:CPX-973(complex-primary)|pubmed:26489954(see-also) refseq:NP_000055.2|dip:DIP-35180N|ensembl:ENSG00000125730(gene)|ensembl:ENST00000245907(transcript)|go:"GO:0001798"(positive regulation of type IIa hypersensitivity)|go:"GO:0001934"(positive regulation of protein phosphorylation)|go:"GO:0001970"(positive regulation of activation of membrane attack complex)|go:"GO:0004866"(endopeptidase inhibitor activity)|go:"GO:0005102"(signaling receptor binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0005788"(endoplasmic reticulum lumen)|go:"GO:0005886"(plasma membrane)|go:"GO:0006631"(fatty acid metabolic process)|go:"GO:0006954"(inflammatory response)|go:"GO:0006955"(immune response)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0006958"(complement activation, classical pathway)|go:"GO:0007165"(signal transduction)|go:"GO:0007186"(G protein-coupled receptor signaling pathway)|go:"GO:0009617"(response to bacterium)|go:"GO:0009986"(cell surface)|go:"GO:0010575"(positive regulation of vascular endothelial growth factor production)|go:"GO:0010828"(positive regulation of glucose transmembrane transport)|go:"GO:0010866"(regulation of triglyceride biosynthetic process)|go:"GO:0010884"(positive regulation of lipid storage)|go:"GO:0016322"(neuron remodeling)|go:"GO:0031715"(C5L2 anaphylatoxin chemotactic receptor binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0034774"(secretory granule lumen)|go:"GO:0035578"(azurophil granule lumen)|go:"GO:0035846"(oviduct epithelium development)|go:"GO:0045745"(positive regulation of G protein-coupled receptor signaling pathway)|go:"GO:0045766"(positive regulation of angiogenesis)|go:"GO:0048260"(positive regulation of receptor-mediated endocytosis)|go:"GO:0060100"(positive regulation of phagocytosis, engulfment)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:0097242"(amyloid-beta clearance)|go:"GO:0097278"(complement-dependent cytotoxicity)|go:"GO:0150062"(complement-mediated synapse pruning)|go:"GO:0150064"(vertebrate eye-specific patterning)|go:"GO:1905114"(cell surface receptor signaling pathway involved in cell-cell signaling)|go:"GO:2000427"(positive regulation of apoptotic cell clearance)|interpro:IPR000020(Anaphylatoxin/fibulin)|interpro:IPR001134(Netrin, C-terminal)|interpro:IPR001599(Alpha-2-macroglobulin)|interpro:IPR001840(Complement C3a/C4a/C5a anaphylatoxin)|interpro:IPR002890(Alpha-2-macroglobulin, N-terminal)|interpro:IPR008930(Terpenoid cylases/protein prenyltransferase alpha-alpha toroid)|interpro:IPR008993(TIMP-like, OB-fold)|interpro:IPR009048(Alpha-macroglobulin, receptor-binding)|interpro:IPR011625(Alpha-2-macroglobulin, N-terminal 2)|interpro:IPR011626(A-macroglobulin complement component)|interpro:IPR013783(Immunoglobulin-like fold)|interpro:IPR018081|interpro:IPR018933|interpro:IPR019742|interpro:IPR035711|interpro:IPR035815|interpro:IPR036595|interpro:IPR040839|interpro:IPR041425|interpro:IPR041555|mint:P01024|rcsb pdb:1C3D|rcsb pdb:1GHQ|rcsb pdb:1W2S|rcsb pdb:2A73|rcsb pdb:2A74|rcsb pdb:2GOX|rcsb pdb:2I07|rcsb pdb:2ICE|rcsb pdb:2ICF|rcsb pdb:2NOJ|rcsb pdb:2QKI|rcsb pdb:2WII|rcsb pdb:2WIN|rcsb pdb:2WY7|rcsb pdb:2WY8|rcsb pdb:2XQW|rcsb pdb:2XWB|rcsb pdb:2XWJ|rcsb pdb:3D5R|rcsb pdb:3D5S|rcsb pdb:3G6J|rcsb pdb:3L3O|rcsb pdb:3L5N|rcsb pdb:3NMS|rcsb pdb:3OED|rcsb pdb:3OHX|rcsb pdb:3OXU|rcsb pdb:3RJ3|rcsb pdb:3T4A|rcsb pdb:4HW5|rcsb pdb:4HWJ|rcsb pdb:4I6O|rcsb pdb:4M76|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5FO7|rcsb pdb:5FO8|rcsb pdb:5FO9|rcsb pdb:5FOA|rcsb pdb:5FOB|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:6EHG|rcsb pdb:6RMT|rcsb pdb:6RMU|rcsb pdb:6RUR|rcsb pdb:6RUV|rcsb pdb:6S0B|rcsb pdb:6YO6|reactome:R-HSA-173736|reactome:R-HSA-174577|reactome:R-HSA-198933|reactome:R-HSA-375276|reactome:R-HSA-381426|reactome:R-HSA-418594|reactome:R-HSA-6798695|reactome:R-HSA-8957275|reactome:R-HSA-9660826|reactome:R-HSA-977606 go:"GO:0004252"(serine-type endopeptidase activity) curated-complex:"A protein complex of the alternative pathway of complement activation of the innate immune system. Complement C3 precurser is activated by cleavage into C3a and C3b by C3 convertases, either C4bC2a in the classical and lectin pathways or C3(H2O)Bb, C3bBb, C3bBbC3b, C3bBbP or C3bBbC3bP in the alternative pathway. C3b acts as an opsonin and interacts with glycoproteins and carbohydrates on pathogenic or apoptotic target cell surfaces through its reactive thioester moiety. Opsonization of target cells leads to enhanced phagocytosis, lysis of target cells via membrane attack complex (CPX-6159) assembly, clearance of antibody-antigen complexes and up-regulation of the adaptive response. Activation of C3b leads to an amplification cascade that generates more C3 convertase, deposits more C3b at the local site and switches C3 convertases to C5 convertases. To protect host cells from inadvertent complement activation the activation of C3b is tightly regulated by either disrupting the C3 convertases or aiding in the proteolytic degradation of C3b. Bacteria and viruses possess C3b proteases to evade the complement response. Lack of protection, due to familial mutations in the complement genes or the presence of autoantibodies against regulators has been linked to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G) in kidneys and age-related macular degeneration (AMD) in eyes. Conditions of chronic and acute inflammations, as in rheumatoid arthritis, strokes, and heart attacks, become aggravated by complement activation against the disturbed tissue."|complex-properties:"The alternative pathway is continuously activated at a low level. C3 precursor is first processed by the removal of 4 Arg residues and spontaneous hydrolysis due to the breakdown of the internal thioester bond forms C3(H2O) (disulfide bonded P01024-PRO_0000005909 & P01024-PRO_0000005908). C3(H2O) subsequently binds factor B that is cleaved by Factor D (P00746) into 2 fragments: CFBa and CFBb. CFBb, a serine protease, then combines with complement factor C3(H2O) or C3b to generate the C3 or C5 convertases. Proteolytic cleavage of C3 to C3b is accompanied by large conformational changes that result in the exposure of cryptic binding sites required for convertase assembly and regulation. This includes a significant movement of the thioester-bond-containing domain through which C3b attaches to target surfaces."|complex-assembly:Heterodimer|disease:"Complement component 3 (C3) deficiency [Orphanet:280133]: a rare, autosomal recessive defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis."|disease:"Atypical hemolytic-uremic syndrome with C3 anomaly [Orphanet:2134 & Orphanet:93575]: an autosomal dominant, atypical form of hemolytic-uremic syndrome (aHUS, a thrombotic microangiopathy) characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction."|disease:"Age-related macular degeneration [EFO:0001365]: age-related macular degeneration usually in older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. Manifests as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Occurs in dry and wet forms. Most common cause of irreversible vision loss in the developed world." - figure legend:2B|comment:CFHR1 does not affect the C3 convertase. In contrast, CFH strongly inhibited C3a generation.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/05 - rogid:6Axa89cCPpUXFsLnd7sCurZzLYI9606 - false - - - - psi-mi:"MI:0411"(enzyme linked immunosorbent assay) psi-mi:"MI:0411"(enzyme linked immunosorbent assay) matrixdb:MULT_84_human uniprotkb:P00751-PRO_0000027547 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 intact:EBI-21988629 psi-mi:c3b_human(display_short)|psi-mi:MULT_84_human(display_long)|intact:Complement C3b complex(complex recommended name)|intact:C3b dimer(complex systematic name) psi-mi:p00751-pro_0000027547(display_long)|uniprotkb:CFB(gene name)|psi-mi:CFB(display_short)|uniprotkb:BF(gene name synonym)|uniprotkb:BFD(gene name synonym)|uniprotkb:C3/C5 convertase(gene name synonym)|uniprotkb:Glycine-rich beta glycoprotein(gene name synonym)|uniprotkb:PBF2(gene name synonym)|uniprotkb:Properdin factor B(gene name synonym) psi-mi:"MI:0435"(protease assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-21994963|imex:IM-27334-25 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0684"(ancillary) psi-mi:"MI:0501"(enzyme) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:1302"(stable complex) psi-mi:"MI:0326"(protein) pubmed:27782329(see-also)|pubmed:6225800(see-also)|evidence ontology:"ECO:0000353"|efo:"Orphanet:280133"(see-also)|efo:"Orphanet:2134"(see-also)|efo:"Orphanet:93575"(see-also)|efo:"EFO:0001365"(see-also)|pubmed:27013439(see-also)|pubmed:19196712(see-also)|pubmed:17051160(see-also)|go:"GO:0005615"(extracellular space)|go:"GO:0001848"(complement binding)|go:"GO:1903028"(positive regulation of opsonization)|go:"GO:0006956"(complement activation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0044533"(positive regulation of apoptotic process in another organism)|go:"GO:0050778"(positive regulation of immune response)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0008228"(opsonization)|pubmed:6559201(see-also)|pubmed:15454921(see-also)|pubmed:21205667(see-also)|pubmed:17051150(see-also)|complex portal:CPX-973(complex-primary)|pubmed:26489954(see-also) intact:EBI-1223668(chain-parent) go:"GO:0004252"(serine-type endopeptidase activity) curated-complex:"A protein complex of the alternative pathway of complement activation of the innate immune system. Complement C3 precurser is activated by cleavage into C3a and C3b by C3 convertases, either C4bC2a in the classical and lectin pathways or C3(H2O)Bb, C3bBb, C3bBbC3b, C3bBbP or C3bBbC3bP in the alternative pathway. C3b acts as an opsonin and interacts with glycoproteins and carbohydrates on pathogenic or apoptotic target cell surfaces through its reactive thioester moiety. Opsonization of target cells leads to enhanced phagocytosis, lysis of target cells via membrane attack complex (CPX-6159) assembly, clearance of antibody-antigen complexes and up-regulation of the adaptive response. Activation of C3b leads to an amplification cascade that generates more C3 convertase, deposits more C3b at the local site and switches C3 convertases to C5 convertases. To protect host cells from inadvertent complement activation the activation of C3b is tightly regulated by either disrupting the C3 convertases or aiding in the proteolytic degradation of C3b. Bacteria and viruses possess C3b proteases to evade the complement response. Lack of protection, due to familial mutations in the complement genes or the presence of autoantibodies against regulators has been linked to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G) in kidneys and age-related macular degeneration (AMD) in eyes. Conditions of chronic and acute inflammations, as in rheumatoid arthritis, strokes, and heart attacks, become aggravated by complement activation against the disturbed tissue."|complex-properties:"The alternative pathway is continuously activated at a low level. C3 precursor is first processed by the removal of 4 Arg residues and spontaneous hydrolysis due to the breakdown of the internal thioester bond forms C3(H2O) (disulfide bonded P01024-PRO_0000005909 & P01024-PRO_0000005908). C3(H2O) subsequently binds factor B that is cleaved by Factor D (P00746) into 2 fragments: CFBa and CFBb. CFBb, a serine protease, then combines with complement factor C3(H2O) or C3b to generate the C3 or C5 convertases. Proteolytic cleavage of C3 to C3b is accompanied by large conformational changes that result in the exposure of cryptic binding sites required for convertase assembly and regulation. This includes a significant movement of the thioester-bond-containing domain through which C3b attaches to target surfaces."|complex-assembly:Heterodimer|disease:"Complement component 3 (C3) deficiency [Orphanet:280133]: a rare, autosomal recessive defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis."|disease:"Atypical hemolytic-uremic syndrome with C3 anomaly [Orphanet:2134 & Orphanet:93575]: an autosomal dominant, atypical form of hemolytic-uremic syndrome (aHUS, a thrombotic microangiopathy) characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction."|disease:"Age-related macular degeneration [EFO:0001365]: age-related macular degeneration usually in older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. Manifests as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Occurs in dry and wet forms. Most common cause of irreversible vision loss in the developed world." chain-seq-start:260|chain-seq-end:764 figure legend:2B|comment:CFHR1 does not affect the C3 convertase. In contrast, CFH strongly inhibited C3a generation.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/05 - rogid:INYV2BPbjbUsThnuF2mPvKEn/iA9606 - false - - - - psi-mi:"MI:0411"(enzyme linked immunosorbent assay) psi-mi:"MI:0411"(enzyme linked immunosorbent assay) matrixdb:MULT_84_human uniprotkb:P01024 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 intact:EBI-905851|uniprotkb:A7E236|ensembl:ENSP00000245907 psi-mi:c3b_human(display_short)|psi-mi:MULT_84_human(display_long)|intact:Complement C3b complex(complex recommended name)|intact:C3b dimer(complex systematic name) psi-mi:co3_human(display_long)|uniprotkb:C3(gene name)|psi-mi:C3(display_short)|uniprotkb:CPAMD1(gene name synonym)|uniprotkb:C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1(gene name synonym) psi-mi:"MI:0435"(protease assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-21994983|imex:IM-27334-7 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0684"(ancillary) psi-mi:"MI:0502"(enzyme target) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:1302"(stable complex) psi-mi:"MI:0326"(protein) pubmed:27782329(see-also)|pubmed:6225800(see-also)|evidence ontology:"ECO:0000353"|efo:"Orphanet:280133"(see-also)|efo:"Orphanet:2134"(see-also)|efo:"Orphanet:93575"(see-also)|efo:"EFO:0001365"(see-also)|pubmed:27013439(see-also)|pubmed:19196712(see-also)|pubmed:17051160(see-also)|go:"GO:0005615"(extracellular space)|go:"GO:0001848"(complement binding)|go:"GO:1903028"(positive regulation of opsonization)|go:"GO:0006956"(complement activation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0044533"(positive regulation of apoptotic process in another organism)|go:"GO:0050778"(positive regulation of immune response)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0008228"(opsonization)|pubmed:6559201(see-also)|pubmed:15454921(see-also)|pubmed:21205667(see-also)|pubmed:17051150(see-also)|complex portal:CPX-973(complex-primary)|pubmed:26489954(see-also) refseq:NP_000055.2|dip:DIP-35180N|ensembl:ENSG00000125730(gene)|ensembl:ENST00000245907(transcript)|go:"GO:0001798"(positive regulation of type IIa hypersensitivity)|go:"GO:0001934"(positive regulation of protein phosphorylation)|go:"GO:0001970"(positive regulation of activation of membrane attack complex)|go:"GO:0004866"(endopeptidase inhibitor activity)|go:"GO:0005102"(signaling receptor binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0005788"(endoplasmic reticulum lumen)|go:"GO:0005886"(plasma membrane)|go:"GO:0006631"(fatty acid metabolic process)|go:"GO:0006954"(inflammatory response)|go:"GO:0006955"(immune response)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0006958"(complement activation, classical pathway)|go:"GO:0007165"(signal transduction)|go:"GO:0007186"(G protein-coupled receptor signaling pathway)|go:"GO:0009617"(response to bacterium)|go:"GO:0009986"(cell surface)|go:"GO:0010575"(positive regulation of vascular endothelial growth factor production)|go:"GO:0010828"(positive regulation of glucose transmembrane transport)|go:"GO:0010866"(regulation of triglyceride biosynthetic process)|go:"GO:0010884"(positive regulation of lipid storage)|go:"GO:0016322"(neuron remodeling)|go:"GO:0031715"(C5L2 anaphylatoxin chemotactic receptor binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0034774"(secretory granule lumen)|go:"GO:0035578"(azurophil granule lumen)|go:"GO:0035846"(oviduct epithelium development)|go:"GO:0045745"(positive regulation of G protein-coupled receptor signaling pathway)|go:"GO:0045766"(positive regulation of angiogenesis)|go:"GO:0048260"(positive regulation of receptor-mediated endocytosis)|go:"GO:0060100"(positive regulation of phagocytosis, engulfment)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:0097242"(amyloid-beta clearance)|go:"GO:0097278"(complement-dependent cytotoxicity)|go:"GO:0150062"(complement-mediated synapse pruning)|go:"GO:0150064"(vertebrate eye-specific patterning)|go:"GO:1905114"(cell surface receptor signaling pathway involved in cell-cell signaling)|go:"GO:2000427"(positive regulation of apoptotic cell clearance)|interpro:IPR000020(Anaphylatoxin/fibulin)|interpro:IPR001134(Netrin, C-terminal)|interpro:IPR001599(Alpha-2-macroglobulin)|interpro:IPR001840(Complement C3a/C4a/C5a anaphylatoxin)|interpro:IPR002890(Alpha-2-macroglobulin, N-terminal)|interpro:IPR008930(Terpenoid cylases/protein prenyltransferase alpha-alpha toroid)|interpro:IPR008993(TIMP-like, OB-fold)|interpro:IPR009048(Alpha-macroglobulin, receptor-binding)|interpro:IPR011625(Alpha-2-macroglobulin, N-terminal 2)|interpro:IPR011626(A-macroglobulin complement component)|interpro:IPR013783(Immunoglobulin-like fold)|interpro:IPR018081|interpro:IPR018933|interpro:IPR019742|interpro:IPR035711|interpro:IPR035815|interpro:IPR036595|interpro:IPR040839|interpro:IPR041425|interpro:IPR041555|mint:P01024|rcsb pdb:1C3D|rcsb pdb:1GHQ|rcsb pdb:1W2S|rcsb pdb:2A73|rcsb pdb:2A74|rcsb pdb:2GOX|rcsb pdb:2I07|rcsb pdb:2ICE|rcsb pdb:2ICF|rcsb pdb:2NOJ|rcsb pdb:2QKI|rcsb pdb:2WII|rcsb pdb:2WIN|rcsb pdb:2WY7|rcsb pdb:2WY8|rcsb pdb:2XQW|rcsb pdb:2XWB|rcsb pdb:2XWJ|rcsb pdb:3D5R|rcsb pdb:3D5S|rcsb pdb:3G6J|rcsb pdb:3L3O|rcsb pdb:3L5N|rcsb pdb:3NMS|rcsb pdb:3OED|rcsb pdb:3OHX|rcsb pdb:3OXU|rcsb pdb:3RJ3|rcsb pdb:3T4A|rcsb pdb:4HW5|rcsb pdb:4HWJ|rcsb pdb:4I6O|rcsb pdb:4M76|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5FO7|rcsb pdb:5FO8|rcsb pdb:5FO9|rcsb pdb:5FOA|rcsb pdb:5FOB|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:6EHG|rcsb pdb:6RMT|rcsb pdb:6RMU|rcsb pdb:6RUR|rcsb pdb:6RUV|rcsb pdb:6S0B|rcsb pdb:6YO6|reactome:R-HSA-173736|reactome:R-HSA-174577|reactome:R-HSA-198933|reactome:R-HSA-375276|reactome:R-HSA-381426|reactome:R-HSA-418594|reactome:R-HSA-6798695|reactome:R-HSA-8957275|reactome:R-HSA-9660826|reactome:R-HSA-977606 go:"GO:0004252"(serine-type endopeptidase activity) curated-complex:"A protein complex of the alternative pathway of complement activation of the innate immune system. Complement C3 precurser is activated by cleavage into C3a and C3b by C3 convertases, either C4bC2a in the classical and lectin pathways or C3(H2O)Bb, C3bBb, C3bBbC3b, C3bBbP or C3bBbC3bP in the alternative pathway. C3b acts as an opsonin and interacts with glycoproteins and carbohydrates on pathogenic or apoptotic target cell surfaces through its reactive thioester moiety. Opsonization of target cells leads to enhanced phagocytosis, lysis of target cells via membrane attack complex (CPX-6159) assembly, clearance of antibody-antigen complexes and up-regulation of the adaptive response. Activation of C3b leads to an amplification cascade that generates more C3 convertase, deposits more C3b at the local site and switches C3 convertases to C5 convertases. To protect host cells from inadvertent complement activation the activation of C3b is tightly regulated by either disrupting the C3 convertases or aiding in the proteolytic degradation of C3b. Bacteria and viruses possess C3b proteases to evade the complement response. Lack of protection, due to familial mutations in the complement genes or the presence of autoantibodies against regulators has been linked to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G) in kidneys and age-related macular degeneration (AMD) in eyes. Conditions of chronic and acute inflammations, as in rheumatoid arthritis, strokes, and heart attacks, become aggravated by complement activation against the disturbed tissue."|complex-properties:"The alternative pathway is continuously activated at a low level. C3 precursor is first processed by the removal of 4 Arg residues and spontaneous hydrolysis due to the breakdown of the internal thioester bond forms C3(H2O) (disulfide bonded P01024-PRO_0000005909 & P01024-PRO_0000005908). C3(H2O) subsequently binds factor B that is cleaved by Factor D (P00746) into 2 fragments: CFBa and CFBb. CFBb, a serine protease, then combines with complement factor C3(H2O) or C3b to generate the C3 or C5 convertases. Proteolytic cleavage of C3 to C3b is accompanied by large conformational changes that result in the exposure of cryptic binding sites required for convertase assembly and regulation. This includes a significant movement of the thioester-bond-containing domain through which C3b attaches to target surfaces."|complex-assembly:Heterodimer|disease:"Complement component 3 (C3) deficiency [Orphanet:280133]: a rare, autosomal recessive defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis."|disease:"Atypical hemolytic-uremic syndrome with C3 anomaly [Orphanet:2134 & Orphanet:93575]: an autosomal dominant, atypical form of hemolytic-uremic syndrome (aHUS, a thrombotic microangiopathy) characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction."|disease:"Age-related macular degeneration [EFO:0001365]: age-related macular degeneration usually in older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. Manifests as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Occurs in dry and wet forms. Most common cause of irreversible vision loss in the developed world." - figure legend:2B|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/05 - rogid:6Axa89cCPpUXFsLnd7sCurZzLYI9606 - false - - - - psi-mi:"MI:0411"(enzyme linked immunosorbent assay) psi-mi:"MI:0411"(enzyme linked immunosorbent assay) matrixdb:MULT_84_human uniprotkb:P00751-PRO_0000027547 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 intact:EBI-21988629 psi-mi:c3b_human(display_short)|psi-mi:MULT_84_human(display_long)|intact:Complement C3b complex(complex recommended name)|intact:C3b dimer(complex systematic name) psi-mi:p00751-pro_0000027547(display_long)|uniprotkb:CFB(gene name)|psi-mi:CFB(display_short)|uniprotkb:BF(gene name synonym)|uniprotkb:BFD(gene name synonym)|uniprotkb:C3/C5 convertase(gene name synonym)|uniprotkb:Glycine-rich beta glycoprotein(gene name synonym)|uniprotkb:PBF2(gene name synonym)|uniprotkb:Properdin factor B(gene name synonym) psi-mi:"MI:0435"(protease assay) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-21994983|imex:IM-27334-7 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0684"(ancillary) psi-mi:"MI:0501"(enzyme) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:1302"(stable complex) psi-mi:"MI:0326"(protein) pubmed:27782329(see-also)|pubmed:6225800(see-also)|evidence ontology:"ECO:0000353"|efo:"Orphanet:280133"(see-also)|efo:"Orphanet:2134"(see-also)|efo:"Orphanet:93575"(see-also)|efo:"EFO:0001365"(see-also)|pubmed:27013439(see-also)|pubmed:19196712(see-also)|pubmed:17051160(see-also)|go:"GO:0005615"(extracellular space)|go:"GO:0001848"(complement binding)|go:"GO:1903028"(positive regulation of opsonization)|go:"GO:0006956"(complement activation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0044533"(positive regulation of apoptotic process in another organism)|go:"GO:0050778"(positive regulation of immune response)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0008228"(opsonization)|pubmed:6559201(see-also)|pubmed:15454921(see-also)|pubmed:21205667(see-also)|pubmed:17051150(see-also)|complex portal:CPX-973(complex-primary)|pubmed:26489954(see-also) intact:EBI-1223668(chain-parent) go:"GO:0004252"(serine-type endopeptidase activity) curated-complex:"A protein complex of the alternative pathway of complement activation of the innate immune system. Complement C3 precurser is activated by cleavage into C3a and C3b by C3 convertases, either C4bC2a in the classical and lectin pathways or C3(H2O)Bb, C3bBb, C3bBbC3b, C3bBbP or C3bBbC3bP in the alternative pathway. C3b acts as an opsonin and interacts with glycoproteins and carbohydrates on pathogenic or apoptotic target cell surfaces through its reactive thioester moiety. Opsonization of target cells leads to enhanced phagocytosis, lysis of target cells via membrane attack complex (CPX-6159) assembly, clearance of antibody-antigen complexes and up-regulation of the adaptive response. Activation of C3b leads to an amplification cascade that generates more C3 convertase, deposits more C3b at the local site and switches C3 convertases to C5 convertases. To protect host cells from inadvertent complement activation the activation of C3b is tightly regulated by either disrupting the C3 convertases or aiding in the proteolytic degradation of C3b. Bacteria and viruses possess C3b proteases to evade the complement response. Lack of protection, due to familial mutations in the complement genes or the presence of autoantibodies against regulators has been linked to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G) in kidneys and age-related macular degeneration (AMD) in eyes. Conditions of chronic and acute inflammations, as in rheumatoid arthritis, strokes, and heart attacks, become aggravated by complement activation against the disturbed tissue."|complex-properties:"The alternative pathway is continuously activated at a low level. C3 precursor is first processed by the removal of 4 Arg residues and spontaneous hydrolysis due to the breakdown of the internal thioester bond forms C3(H2O) (disulfide bonded P01024-PRO_0000005909 & P01024-PRO_0000005908). C3(H2O) subsequently binds factor B that is cleaved by Factor D (P00746) into 2 fragments: CFBa and CFBb. CFBb, a serine protease, then combines with complement factor C3(H2O) or C3b to generate the C3 or C5 convertases. Proteolytic cleavage of C3 to C3b is accompanied by large conformational changes that result in the exposure of cryptic binding sites required for convertase assembly and regulation. This includes a significant movement of the thioester-bond-containing domain through which C3b attaches to target surfaces."|complex-assembly:Heterodimer|disease:"Complement component 3 (C3) deficiency [Orphanet:280133]: a rare, autosomal recessive defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis."|disease:"Atypical hemolytic-uremic syndrome with C3 anomaly [Orphanet:2134 & Orphanet:93575]: an autosomal dominant, atypical form of hemolytic-uremic syndrome (aHUS, a thrombotic microangiopathy) characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction."|disease:"Age-related macular degeneration [EFO:0001365]: age-related macular degeneration usually in older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. Manifests as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Occurs in dry and wet forms. Most common cause of irreversible vision loss in the developed world." chain-seq-start:260|chain-seq-end:764 figure legend:2B|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/05 - rogid:INYV2BPbjbUsThnuF2mPvKEn/iA9606 - false - - - - psi-mi:"MI:0411"(enzyme linked immunosorbent assay) psi-mi:"MI:0411"(enzyme linked immunosorbent assay) uniprotkb:P01031 uniprotkb:Q03591 intact:EBI-8558308|intact:UNK-5392818|uniprotkb:Q27I61|intact:UNK-5368655|uniprotkb:Q14CJ0|intact:UNK-5396112|ensembl:ENSP00000223642 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 psi-mi:co5_human(display_long)|uniprotkb:C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4(gene name synonym)|uniprotkb:CPAMD4(gene name synonym)|uniprotkb:C5(gene name)|psi-mi:C5(display_short) psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:"MI:0006"(anti bait coimmunoprecipitation) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0915"(physical association) psi-mi:"MI:0469"(IntAct) intact:EBI-21995029|imex:IM-27334-11 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0496"(bait) psi-mi:"MI:0498"(prey) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) refseq:NP_001304092.1|refseq:NP_001726.2|ensembl:ENSG00000106804(gene)|ensembl:ENST00000223642(transcript)|go:"GO:0000187"(obsolete activation of MAPK activity)|go:"GO:0001701"(in utero embryonic development)|go:"GO:0004866"(endopeptidase inhibitor activity)|go:"GO:0005102"(signaling receptor binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005579"(membrane attack complex)|go:"GO:0005615"(extracellular space)|go:"GO:0006935"(chemotaxis)|go:"GO:0006954"(inflammatory response)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0006958"(complement activation, classical pathway)|go:"GO:0007166"(cell surface receptor signaling pathway)|go:"GO:0007186"(G protein-coupled receptor signaling pathway)|go:"GO:0008009"(chemokine activity)|go:"GO:0010575"(positive regulation of vascular endothelial growth factor production)|go:"GO:0010760"(negative regulation of macrophage chemotaxis)|go:"GO:0019835"(cytolysis)|go:"GO:0032722"(positive regulation of chemokine production)|go:"GO:0045766"(positive regulation of angiogenesis)|go:"GO:0070062"(extracellular exosome)|interpro:IPR000020(Anaphylatoxin/fibulin)|interpro:IPR001134(Netrin, C-terminal)|interpro:IPR001599(Alpha-2-macroglobulin)|interpro:IPR001840(Complement C3a/C4a/C5a anaphylatoxin)|interpro:IPR002890(Alpha-2-macroglobulin, N-terminal)|interpro:IPR008930(Terpenoid cylases/protein prenyltransferase alpha-alpha toroid)|interpro:IPR008993(TIMP-like, OB-fold)|interpro:IPR009048(Alpha-macroglobulin, receptor-binding)|interpro:IPR011625(Alpha-2-macroglobulin, N-terminal 2)|interpro:IPR011626(A-macroglobulin complement component)|interpro:IPR013783(Immunoglobulin-like fold)|interpro:IPR018081|interpro:IPR018933|interpro:IPR036595|interpro:IPR037562|interpro:IPR040839|interpro:IPR041425|interpro:IPR041555|rcsb pdb:1CFA|rcsb pdb:1KJS|rcsb pdb:1XWE|rcsb pdb:3CU7|rcsb pdb:3HQA|rcsb pdb:3HQB|rcsb pdb:3KLS|rcsb pdb:3KM9|rcsb pdb:3PRX|rcsb pdb:3PVM|rcsb pdb:4A5W|rcsb pdb:4E0S|rcsb pdb:4P39|rcsb pdb:4UU9|rcsb pdb:5B4P|rcsb pdb:5B71|rcsb pdb:5HCC|rcsb pdb:5HCD|rcsb pdb:5HCE|rcsb pdb:5I5K|rcsb pdb:6H03|rcsb pdb:6H04|rcsb pdb:6RPT|rcsb pdb:7AD6|rcsb pdb:7AD7|reactome:R-HSA-166665|reactome:R-HSA-174577|reactome:R-HSA-375276|reactome:R-HSA-418594|reactome:R-HSA-977606 ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 - function:Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled|comment:mint|function:"Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis)"|function:"Defects in C5 are the cause of complement C5 deficiency [MIM:609536]. Patients with dysfunction of C5 display a propensity for severe recurrent infections"|function:"Genetic variation in C5 can be associated with susceptibility to liver fibrosis [MIM:120900]. Liver fibrosis is a common consequence of all chronic liver diseases, irrespective of etiology. Common C5 variants can influence the progression and severity of fibrogenesis" - figure legend:4B|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:9606(human-plasma)|taxid:9606(homo sapiens blood plasma) - 2019/08/16 2019/09/03 rogid:EpfpW2TQ68YvIqNRfr6uIyA6MUU9606 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 rigid:8FCV55OW72ObuL5D+1URfdy21xM false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) uniprotkb:P01031 uniprotkb:Q03591 intact:EBI-8558308|intact:UNK-5392818|uniprotkb:Q27I61|intact:UNK-5368655|uniprotkb:Q14CJ0|intact:UNK-5396112|ensembl:ENSP00000223642 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 psi-mi:co5_human(display_long)|uniprotkb:C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4(gene name synonym)|uniprotkb:CPAMD4(gene name synonym)|uniprotkb:C5(gene name)|psi-mi:C5(display_short) psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:"MI:0107"(surface plasmon resonance) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-21995040|imex:IM-27334-13 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0498"(prey) psi-mi:"MI:0496"(bait) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) refseq:NP_001304092.1|refseq:NP_001726.2|ensembl:ENSG00000106804(gene)|ensembl:ENST00000223642(transcript)|go:"GO:0000187"(obsolete activation of MAPK activity)|go:"GO:0001701"(in utero embryonic development)|go:"GO:0004866"(endopeptidase inhibitor activity)|go:"GO:0005102"(signaling receptor binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005579"(membrane attack complex)|go:"GO:0005615"(extracellular space)|go:"GO:0006935"(chemotaxis)|go:"GO:0006954"(inflammatory response)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0006958"(complement activation, classical pathway)|go:"GO:0007166"(cell surface receptor signaling pathway)|go:"GO:0007186"(G protein-coupled receptor signaling pathway)|go:"GO:0008009"(chemokine activity)|go:"GO:0010575"(positive regulation of vascular endothelial growth factor production)|go:"GO:0010760"(negative regulation of macrophage chemotaxis)|go:"GO:0019835"(cytolysis)|go:"GO:0032722"(positive regulation of chemokine production)|go:"GO:0045766"(positive regulation of angiogenesis)|go:"GO:0070062"(extracellular exosome)|interpro:IPR000020(Anaphylatoxin/fibulin)|interpro:IPR001134(Netrin, C-terminal)|interpro:IPR001599(Alpha-2-macroglobulin)|interpro:IPR001840(Complement C3a/C4a/C5a anaphylatoxin)|interpro:IPR002890(Alpha-2-macroglobulin, N-terminal)|interpro:IPR008930(Terpenoid cylases/protein prenyltransferase alpha-alpha toroid)|interpro:IPR008993(TIMP-like, OB-fold)|interpro:IPR009048(Alpha-macroglobulin, receptor-binding)|interpro:IPR011625(Alpha-2-macroglobulin, N-terminal 2)|interpro:IPR011626(A-macroglobulin complement component)|interpro:IPR013783(Immunoglobulin-like fold)|interpro:IPR018081|interpro:IPR018933|interpro:IPR036595|interpro:IPR037562|interpro:IPR040839|interpro:IPR041425|interpro:IPR041555|rcsb pdb:1CFA|rcsb pdb:1KJS|rcsb pdb:1XWE|rcsb pdb:3CU7|rcsb pdb:3HQA|rcsb pdb:3HQB|rcsb pdb:3KLS|rcsb pdb:3KM9|rcsb pdb:3PRX|rcsb pdb:3PVM|rcsb pdb:4A5W|rcsb pdb:4E0S|rcsb pdb:4P39|rcsb pdb:4UU9|rcsb pdb:5B4P|rcsb pdb:5B71|rcsb pdb:5HCC|rcsb pdb:5HCD|rcsb pdb:5HCE|rcsb pdb:5I5K|rcsb pdb:6H03|rcsb pdb:6H04|rcsb pdb:6RPT|rcsb pdb:7AD6|rcsb pdb:7AD7|reactome:R-HSA-166665|reactome:R-HSA-174577|reactome:R-HSA-375276|reactome:R-HSA-418594|reactome:R-HSA-977606 ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 - function:Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled|comment:mint|function:"Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. C5a also stimulates the locomotion of polymorphonuclear leukocytes (chemokinesis) and direct their migration toward sites of inflammation (chemotaxis)"|function:"Defects in C5 are the cause of complement C5 deficiency [MIM:609536]. Patients with dysfunction of C5 display a propensity for severe recurrent infections"|function:"Genetic variation in C5 can be associated with susceptibility to liver fibrosis [MIM:120900]. Liver fibrosis is a common consequence of all chronic liver diseases, irrespective of etiology. Common C5 variants can influence the progression and severity of fibrogenesis" - figure legend:4C|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/09/03 rogid:EpfpW2TQ68YvIqNRfr6uIyA6MUU9606 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 rigid:8FCV55OW72ObuL5D+1URfdy21xM false - - - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:Q03591 matrixdb:MULT_84_human intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:c3b_human(display_short)|psi-mi:MULT_84_human(display_long)|intact:Complement C3b complex(complex recommended name)|intact:C3b dimer(complex systematic name) psi-mi:"MI:0107"(surface plasmon resonance) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-21995108|imex:IM-27334-17 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0498"(prey) psi-mi:"MI:0496"(bait) psi-mi:"MI:0326"(protein) psi-mi:"MI:1302"(stable complex) ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 pubmed:27782329(see-also)|pubmed:6225800(see-also)|evidence ontology:"ECO:0000353"|efo:"Orphanet:280133"(see-also)|efo:"Orphanet:2134"(see-also)|efo:"Orphanet:93575"(see-also)|efo:"EFO:0001365"(see-also)|pubmed:27013439(see-also)|pubmed:19196712(see-also)|pubmed:17051160(see-also)|go:"GO:0005615"(extracellular space)|go:"GO:0001848"(complement binding)|go:"GO:1903028"(positive regulation of opsonization)|go:"GO:0006956"(complement activation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0044533"(positive regulation of apoptotic process in another organism)|go:"GO:0050778"(positive regulation of immune response)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0008228"(opsonization)|pubmed:6559201(see-also)|pubmed:15454921(see-also)|pubmed:21205667(see-also)|pubmed:17051150(see-also)|complex portal:CPX-973(complex-primary)|pubmed:26489954(see-also) - - curated-complex:"A protein complex of the alternative pathway of complement activation of the innate immune system. Complement C3 precurser is activated by cleavage into C3a and C3b by C3 convertases, either C4bC2a in the classical and lectin pathways or C3(H2O)Bb, C3bBb, C3bBbC3b, C3bBbP or C3bBbC3bP in the alternative pathway. C3b acts as an opsonin and interacts with glycoproteins and carbohydrates on pathogenic or apoptotic target cell surfaces through its reactive thioester moiety. Opsonization of target cells leads to enhanced phagocytosis, lysis of target cells via membrane attack complex (CPX-6159) assembly, clearance of antibody-antigen complexes and up-regulation of the adaptive response. Activation of C3b leads to an amplification cascade that generates more C3 convertase, deposits more C3b at the local site and switches C3 convertases to C5 convertases. To protect host cells from inadvertent complement activation the activation of C3b is tightly regulated by either disrupting the C3 convertases or aiding in the proteolytic degradation of C3b. Bacteria and viruses possess C3b proteases to evade the complement response. Lack of protection, due to familial mutations in the complement genes or the presence of autoantibodies against regulators has been linked to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G) in kidneys and age-related macular degeneration (AMD) in eyes. Conditions of chronic and acute inflammations, as in rheumatoid arthritis, strokes, and heart attacks, become aggravated by complement activation against the disturbed tissue."|complex-properties:"The alternative pathway is continuously activated at a low level. C3 precursor is first processed by the removal of 4 Arg residues and spontaneous hydrolysis due to the breakdown of the internal thioester bond forms C3(H2O) (disulfide bonded P01024-PRO_0000005909 & P01024-PRO_0000005908). C3(H2O) subsequently binds factor B that is cleaved by Factor D (P00746) into 2 fragments: CFBa and CFBb. CFBb, a serine protease, then combines with complement factor C3(H2O) or C3b to generate the C3 or C5 convertases. Proteolytic cleavage of C3 to C3b is accompanied by large conformational changes that result in the exposure of cryptic binding sites required for convertase assembly and regulation. This includes a significant movement of the thioester-bond-containing domain through which C3b attaches to target surfaces."|complex-assembly:Heterodimer|disease:"Complement component 3 (C3) deficiency [Orphanet:280133]: a rare, autosomal recessive defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis."|disease:"Atypical hemolytic-uremic syndrome with C3 anomaly [Orphanet:2134 & Orphanet:93575]: an autosomal dominant, atypical form of hemolytic-uremic syndrome (aHUS, a thrombotic microangiopathy) characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction."|disease:"Age-related macular degeneration [EFO:0001365]: age-related macular degeneration usually in older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. Manifests as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Occurs in dry and wet forms. Most common cause of irreversible vision loss in the developed world." figure legend:Supplementary figure 2A/C|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) kd:6.4x10^-6(molar) 2019/08/16 2020/02/19 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 - - false sufficient binding region:145..145-329..329 - - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) chebi:"CHEBI:28304" uniprotkb:Q03591 intact:EBI-1379423 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 psi-mi:heparin(display_short)|psi-mi:"CHEBI:28304"(display_long) psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:"MI:0107"(surface plasmon resonance) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:-2(chemical synthesis)|taxid:-2("Chemical synthesis (Chemical synthesis)") taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-21995122|imex:IM-27334-19 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0496"(bait) psi-mi:"MI:0498"(prey) psi-mi:"MI:0328"(small molecule) psi-mi:"MI:0326"(protein) - ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 - - - figure legend:Supplementary figure 2B|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/09/03 - rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 - false - sufficient binding region:145..145-329..329 - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:P08603 matrixdb:MULT_84_human intact:EBI-1223708|uniprotkb:A5PL14|uniprotkb:Q2TAZ5|uniprotkb:P78435|uniprotkb:Q14570|uniprotkb:Q38G77|uniprotkb:Q5TFM3|uniprotkb:Q8N708|uniprotkb:Q9NU86|ensembl:ENSP00000356399 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 psi-mi:cfah_human(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym) psi-mi:c3b_human(display_short)|psi-mi:MULT_84_human(display_long)|intact:Complement C3b complex(complex recommended name)|intact:C3b dimer(complex systematic name) psi-mi:"MI:0107"(surface plasmon resonance) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-21995129|imex:IM-27334-31 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0498"(prey) psi-mi:"MI:0496"(bait) psi-mi:"MI:0326"(protein) psi-mi:"MI:1302"(stable complex) refseq:NP_000177.2|dip:DIP-38303N|ensembl:ENSG00000000971(gene)|ensembl:ENST00000367429(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0008201"(heparin binding)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0042802"(identical protein binding)|go:"GO:0043395"(heparan sulfate proteoglycan binding)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:1903659"(regulation of complement-dependent cytotoxicity)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:P08603|rcsb pdb:1FHC|rcsb pdb:1HAQ|rcsb pdb:1HCC|rcsb pdb:1HFH|rcsb pdb:1HFI|rcsb pdb:1KOV|rcsb pdb:2QFH|rcsb pdb:2RLP|rcsb pdb:2RLQ|rcsb pdb:2UWN|rcsb pdb:2V8E|rcsb pdb:2W80|rcsb pdb:2BZM|rcsb pdb:2G7I|rcsb pdb:2W81|rcsb pdb:2WII|rcsb pdb:2XQW|rcsb pdb:3GAU|rcsb pdb:3GAV|rcsb pdb:3GAW|rcsb pdb:3KXV|rcsb pdb:3KZJ|rcsb pdb:3OXU|rcsb pdb:3R62|rcsb pdb:3RJ3|rcsb pdb:3SW0|rcsb pdb:4AYD|rcsb pdb:4AYE|rcsb pdb:4AYI|rcsb pdb:4AYM|rcsb pdb:4B2R|rcsb pdb:4B2S|rcsb pdb:2IC4|rcsb pdb:2JGW|rcsb pdb:2JGX|rcsb pdb:4J38|rcsb pdb:4K12|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:2KMS|rcsb pdb:2QFG|rcsb pdb:5WTB|rcsb pdb:6ATG|reactome:R-HSA-977606 pubmed:27782329(see-also)|pubmed:6225800(see-also)|evidence ontology:"ECO:0000353"|efo:"Orphanet:280133"(see-also)|efo:"Orphanet:2134"(see-also)|efo:"Orphanet:93575"(see-also)|efo:"EFO:0001365"(see-also)|pubmed:27013439(see-also)|pubmed:19196712(see-also)|pubmed:17051160(see-also)|go:"GO:0005615"(extracellular space)|go:"GO:0001848"(complement binding)|go:"GO:1903028"(positive regulation of opsonization)|go:"GO:0006956"(complement activation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0044533"(positive regulation of apoptotic process in another organism)|go:"GO:0050778"(positive regulation of immune response)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0008228"(opsonization)|pubmed:6559201(see-also)|pubmed:15454921(see-also)|pubmed:21205667(see-also)|pubmed:17051150(see-also)|complex portal:CPX-973(complex-primary)|pubmed:26489954(see-also) - - curated-complex:"A protein complex of the alternative pathway of complement activation of the innate immune system. Complement C3 precurser is activated by cleavage into C3a and C3b by C3 convertases, either C4bC2a in the classical and lectin pathways or C3(H2O)Bb, C3bBb, C3bBbC3b, C3bBbP or C3bBbC3bP in the alternative pathway. C3b acts as an opsonin and interacts with glycoproteins and carbohydrates on pathogenic or apoptotic target cell surfaces through its reactive thioester moiety. Opsonization of target cells leads to enhanced phagocytosis, lysis of target cells via membrane attack complex (CPX-6159) assembly, clearance of antibody-antigen complexes and up-regulation of the adaptive response. Activation of C3b leads to an amplification cascade that generates more C3 convertase, deposits more C3b at the local site and switches C3 convertases to C5 convertases. To protect host cells from inadvertent complement activation the activation of C3b is tightly regulated by either disrupting the C3 convertases or aiding in the proteolytic degradation of C3b. Bacteria and viruses possess C3b proteases to evade the complement response. Lack of protection, due to familial mutations in the complement genes or the presence of autoantibodies against regulators has been linked to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G) in kidneys and age-related macular degeneration (AMD) in eyes. Conditions of chronic and acute inflammations, as in rheumatoid arthritis, strokes, and heart attacks, become aggravated by complement activation against the disturbed tissue."|complex-properties:"The alternative pathway is continuously activated at a low level. C3 precursor is first processed by the removal of 4 Arg residues and spontaneous hydrolysis due to the breakdown of the internal thioester bond forms C3(H2O) (disulfide bonded P01024-PRO_0000005909 & P01024-PRO_0000005908). C3(H2O) subsequently binds factor B that is cleaved by Factor D (P00746) into 2 fragments: CFBa and CFBb. CFBb, a serine protease, then combines with complement factor C3(H2O) or C3b to generate the C3 or C5 convertases. Proteolytic cleavage of C3 to C3b is accompanied by large conformational changes that result in the exposure of cryptic binding sites required for convertase assembly and regulation. This includes a significant movement of the thioester-bond-containing domain through which C3b attaches to target surfaces."|complex-assembly:Heterodimer|disease:"Complement component 3 (C3) deficiency [Orphanet:280133]: a rare, autosomal recessive defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis."|disease:"Atypical hemolytic-uremic syndrome with C3 anomaly [Orphanet:2134 & Orphanet:93575]: an autosomal dominant, atypical form of hemolytic-uremic syndrome (aHUS, a thrombotic microangiopathy) characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction."|disease:"Age-related macular degeneration [EFO:0001365]: age-related macular degeneration usually in older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. Manifests as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Occurs in dry and wet forms. Most common cause of irreversible vision loss in the developed world." figure legend:Supplementary figure 2D|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) kd:2.6x10^-6(molar) 2019/08/16 2020/02/19 rogid:1mjo+AJLIQnEsMFqsGsmUFbfUxk9606 - - false sufficient binding region:1046..1046-1230..1230 - - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:Q03591 uniprotkb:Q03591 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:"MI:0982"(electrophoretic mobility-based method) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-21995093|imex:IM-27334-29 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 - - - figure legend:Supplementary figure 1A/B|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:4922(picpa)|taxid:4922("Pichia pastoris (Yeast)") - 2019/08/16 2019/11/04 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 rigid:bEve3SUg9q4GC0vX6Ea0hXCPDus false sufficient binding region:145..145-329..329 sufficient binding region:145..145-329..329 2 0 psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) uniprotkb:Q03591 uniprotkb:Q03591 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 intact:EBI-3935840|uniprotkb:Q9UJ17|uniprotkb:Q3B774|uniprotkb:A8K465|ensembl:ENSP00000314299 psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:fhr1_human(display_long)|uniprotkb:CFHR1(gene name)|psi-mi:CFHR1(display_short)|uniprotkb:CFHL(gene name synonym)|uniprotkb:CFHL1(gene name synonym)|uniprotkb:CFHL1P(gene name synonym)|uniprotkb:CFHR1P(gene name synonym)|uniprotkb:FHR1(gene name synonym)|uniprotkb:HFL1(gene name synonym)|uniprotkb:HFL2(gene name synonym)|uniprotkb:H factor-like protein 1(gene name synonym)|uniprotkb:H36(gene name synonym) psi-mi:"MI:0982"(electrophoretic mobility-based method) Heinen et al. (2009) imex:IM-27334|pubmed:19528535 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-21995102|imex:IM-27334-15 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 ensembl:ENSG00000244414(gene)|ensembl:ENST00000320493(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0032091"(negative regulation of protein binding)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042802"(identical protein binding)|go:"GO:0051838"(cytolysis by host of symbiont cells)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:Q03591|rcsb pdb:3ZD2|rcsb pdb:4MUC|reactome:R-HSA-977606|refseq:NP_002104.2 - - - figure legend:Supplementary figure 1B|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:9606(human-plasma)|taxid:9606(homo sapiens blood plasma) - 2019/08/16 2019/11/04 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 rogid:dXRmpm1kRulEmJS9dtU4ICqi24c9606 rigid:bEve3SUg9q4GC0vX6Ea0hXCPDus false - - 2 0 psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot)