#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:P27918 uniprotkb:P10909 intact:EBI-9038570|uniprotkb:O15134|uniprotkb:O15135|uniprotkb:O15136|uniprotkb:O75826|ensembl:ENSP00000247153|ensembl:ENSP00000380189 intact:EBI-1104674|uniprotkb:B3KSE6|uniprotkb:P11380|uniprotkb:P11381|uniprotkb:Q5HYC1|uniprotkb:Q7Z5B9|uniprotkb:B2R9Q1|uniprotkb:Q2TU75|ensembl:ENSP00000315130|ensembl:ENSP00000385419|ensembl:ENSP00000429620 psi-mi:prop_human(display_long)|uniprotkb:CFP(gene name)|psi-mi:CFP(display_short)|uniprotkb:PFC(gene name synonym)|uniprotkb:Complement factor P(gene name synonym) psi-mi:clus_human(display_long)|uniprotkb:CLU(gene name)|psi-mi:CLU(display_short)|uniprotkb:APOJ(gene name synonym)|uniprotkb:CLI(gene name synonym)|uniprotkb:KUB1(gene name synonym)|uniprotkb:Complement-associated protein SP-40,40(gene name synonym)|uniprotkb:Complement cytolysis inhibitor(gene name synonym)|uniprotkb:NA1/NA2(gene name synonym)|uniprotkb:Apolipoprotein J(gene name synonym)|uniprotkb:Testosterone-repressed prostate message 2(gene name synonym)|uniprotkb:Ku70-binding protein 1(gene name synonym)|uniprotkb:Aging-associated gene 4 protein(gene name synonym)|uniprotkb:AAG4(orf name)|uniprotkb:Sulfated glycoprotein 2(gene name synonym) psi-mi:"MI:0006"(anti bait coimmunoprecipitation) Pauly et al. (2013) imex:IM-27335|pubmed:24797388 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0914"(association) psi-mi:"MI:0469"(IntAct) intact:EBI-21995211|imex:IM-27335-1 - psi-mi:"MI:1060"(spoke expansion) 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_001138724.1|refseq:NP_002612.1|ensembl:ENSG00000126759(gene)|ensembl:ENST00000247153(transcript)|ensembl:ENST00000396992(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0005788"(endoplasmic reticulum lumen)|go:"GO:0006955"(immune response)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0035580"(specific granule lumen)|go:"GO:0042742"(defense response to bacterium)|go:"GO:1904724"(tertiary granule lumen)|interpro:IPR000884(Thrombospondin, type I)|interpro:IPR036383|rcsb pdb:1W0R|rcsb pdb:1W0S|rcsb pdb:6RUR|rcsb pdb:6RUS|rcsb pdb:6RUV|rcsb pdb:6RV6|rcsb pdb:6S08|rcsb pdb:6S0A|rcsb pdb:6S0B|rcsb pdb:6SEJ|reactome:R-HSA-173736|reactome:R-HSA-174577|reactome:R-HSA-5083635|reactome:R-HSA-5173214|reactome:R-HSA-6798695|reactome:R-HSA-977606 go:"GO:0006629"(lipid metabolic process)|go:"GO:0006956"(complement activation)|go:"GO:0006958"(complement activation, classical pathway)|go:"GO:0009615"(response to virus)|go:"GO:0009986"(cell surface)|go:"GO:0010628"(positive regulation of gene expression)|go:"GO:0017038"(protein import)|go:"GO:0031093"(platelet alpha granule lumen)|go:"GO:0031333"(negative regulation of protein-containing complex assembly)|go:"GO:0031334"(positive regulation of protein-containing complex assembly)|go:"GO:0031625"(ubiquitin protein ligase binding)|go:"GO:0032286"(central nervous system myelin maintenance)|go:"GO:0032436"(positive regulation of proteasomal ubiquitin-dependent protein catabolic process)|go:"GO:0032760"(positive regulation of tumor necrosis factor production)|go:"GO:0032991"(protein-containing complex)|go:"GO:0005829"(cytosol)|ensembl:ENSG00000120885(gene)|ensembl:ENST00000316403(transcript)|ensembl:ENST00000405140(transcript)|ensembl:ENST00000523500(transcript)|go:"GO:0000902"(cell morphogenesis)|go:"GO:0001540"(amyloid-beta binding)|go:"GO:0001774"(microglial cell activation)|go:"GO:0001836"(release of cytochrome c from mitochondria)|go:"GO:0002434"(immune complex clearance)|go:"GO:0005102"(signaling receptor binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0005634"(nucleus)|go:"GO:0005737"(cytoplasm)|go:"GO:0005739"(mitochondrion)|go:"GO:0005743"(mitochondrial inner membrane)|go:"GO:0005794"(Golgi apparatus)|go:"GO:0034366"(spherical high-density lipoprotein particle)|go:"GO:0042127"(regulation of cell population proliferation)|go:"GO:0042583"(chromaffin granule)|go:"GO:0042981"(regulation of apoptotic process)|go:"GO:0043065"(positive regulation of apoptotic process)|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0043691"(reverse cholesterol transport)|go:"GO:0044877"(protein-containing complex binding)|go:"GO:0045087"(innate immune response)|go:"GO:0045202"(synapse)|go:"GO:0045429"(positive regulation of nitric oxide biosynthetic process)|go:"GO:0046982"(protein heterodimerization activity)|go:"GO:0048156"(tau protein binding)|go:"GO:0048260"(positive regulation of receptor-mediated endocytosis)|go:"GO:0048471"(perinuclear region of cytoplasm)|go:"GO:0050750"(low-density lipoprotein particle receptor binding)|go:"GO:0050821"(protein stabilization)|go:"GO:0051082"(unfolded protein binding)|go:"GO:0051087"(chaperone binding)|go:"GO:0051092"(positive regulation of NF-kappaB transcription factor activity)|go:"GO:0051131"(chaperone-mediated protein complex assembly)|go:"GO:0051787"(misfolded protein binding)|go:"GO:0051788"(response to misfolded protein)|go:"GO:0061077"(chaperone-mediated protein folding)|go:"GO:0061518"(microglial cell proliferation)|go:"GO:0061740"(protein targeting to lysosome involved in chaperone-mediated autophagy)|go:"GO:0062023"(collagen-containing extracellular matrix)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:0090201"(negative regulation of release of cytochrome c from mitochondria)|go:"GO:0097193"(intrinsic apoptotic signaling pathway)|go:"GO:0097418"(neurofibrillary tangle)|go:"GO:0097440"(apical dendrite)|go:"GO:0099020"(perinuclear endoplasmic reticulum lumen)|go:"GO:0140597"(protein carrier chaperone)|go:"GO:1900221"(regulation of amyloid-beta clearance)|go:"GO:1901214"(regulation of neuron death)|go:"GO:1901216"(positive regulation of neuron death)|go:"GO:1902004"(positive regulation of amyloid-beta formation)|go:"GO:1902230"(negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage)|go:"GO:1902430"(negative regulation of amyloid-beta formation)|go:"GO:1902847"(regulation of neuronal signal transduction)|go:"GO:1902949"(positive regulation of tau-protein kinase activity)|go:"GO:1902998"(positive regulation of neurofibrillary tangle assembly)|go:"GO:1903573"(negative regulation of response to endoplasmic reticulum stress)|go:"GO:1905892"(negative regulation of cellular response to thapsigargin)|go:"GO:1905895"(negative regulation of cellular response to tunicamycin)|go:"GO:1905907"(negative regulation of amyloid fibril formation)|go:"GO:1905908"(positive regulation of amyloid fibril formation)|go:"GO:2000060"(positive regulation of ubiquitin-dependent protein catabolic process)|go:"GO:2001244"(positive regulation of intrinsic apoptotic signaling pathway)|interpro:IPR000753(Clusterin-like)|interpro:IPR016014(Clusterin, N-terminal)|interpro:IPR016015(Clusterin, C-terminal)|interpro:IPR016016(Clusterin)|interpro:IPR033986|mint:P10909|reactome:R-HSA-114608|reactome:R-HSA-166665|reactome:R-HSA-6803157|go:"GO:0060548"(negative regulation of cell death)|reactome:R-HSA-977606|refseq:NP_001822.3|dip:DIP-37546N - comment:Several Co3 fragments were stated to have been detected, including C3 beta chain, C3c alpha chain fragments and C3dg. Murine and human IgG immunoglobulins were also detected. - figure legend:3A|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:9606(human-serum)|taxid:9606(Homo sapiens) - 2019/08/16 2019/09/04 rogid:XBExMxbnkfjvnV9zHMRZgxZWKaw9606 rogid:qlCJp4zYTklC3YZNQvbLmZBiz4U9606 rigid:HohjWC63x6ZM1Ej9Us6/VMPFQ2A false - - - - psi-mi:"MI:0102"(sequence tag identification) psi-mi:"MI:0102"(sequence tag identification) uniprotkb:P27918 uniprotkb:P01024 intact:EBI-9038570|uniprotkb:O15134|uniprotkb:O15135|uniprotkb:O15136|uniprotkb:O75826|ensembl:ENSP00000247153|ensembl:ENSP00000380189 intact:EBI-905851|uniprotkb:A7E236|ensembl:ENSP00000245907 psi-mi:prop_human(display_long)|uniprotkb:CFP(gene name)|psi-mi:CFP(display_short)|uniprotkb:PFC(gene name synonym)|uniprotkb:Complement factor P(gene name synonym) 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:0006"(anti bait coimmunoprecipitation) Pauly et al. (2013) imex:IM-27335|pubmed:24797388 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0914"(association) psi-mi:"MI:0469"(IntAct) intact:EBI-21995211|imex:IM-27335-1 - psi-mi:"MI:1060"(spoke expansion) 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_001138724.1|refseq:NP_002612.1|ensembl:ENSG00000126759(gene)|ensembl:ENST00000247153(transcript)|ensembl:ENST00000396992(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0005788"(endoplasmic reticulum lumen)|go:"GO:0006955"(immune response)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0035580"(specific granule lumen)|go:"GO:0042742"(defense response to bacterium)|go:"GO:1904724"(tertiary granule lumen)|interpro:IPR000884(Thrombospondin, type I)|interpro:IPR036383|rcsb pdb:1W0R|rcsb pdb:1W0S|rcsb pdb:6RUR|rcsb pdb:6RUS|rcsb pdb:6RUV|rcsb pdb:6RV6|rcsb pdb:6S08|rcsb pdb:6S0A|rcsb pdb:6S0B|rcsb pdb:6SEJ|reactome:R-HSA-173736|reactome:R-HSA-174577|reactome:R-HSA-5083635|reactome:R-HSA-5173214|reactome:R-HSA-6798695|reactome:R-HSA-977606 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 - comment:Several Co3 fragments were stated to have been detected, including C3 beta chain, C3c alpha chain fragments and C3dg. Murine and human IgG immunoglobulins were also detected. - figure legend:3A|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:9606(human-serum)|taxid:9606(Homo sapiens) - 2019/08/16 2019/09/04 rogid:XBExMxbnkfjvnV9zHMRZgxZWKaw9606 rogid:6Axa89cCPpUXFsLnd7sCurZzLYI9606 rigid:HohjWC63x6ZM1Ej9Us6/VMPFQ2A false - - - - psi-mi:"MI:0102"(sequence tag identification) psi-mi:"MI:0102"(sequence tag identification) uniprotkb:P27918 matrixdb:MULT_84_human intact:EBI-9038570|uniprotkb:O15134|uniprotkb:O15135|uniprotkb:O15136|uniprotkb:O75826|ensembl:ENSP00000247153|ensembl:ENSP00000380189 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 psi-mi:prop_human(display_long)|uniprotkb:CFP(gene name)|psi-mi:CFP(display_short)|uniprotkb:PFC(gene name synonym)|uniprotkb:Complement factor P(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) Pauly et al. (2013) imex:IM-27335|pubmed:24797388 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-21995248|imex:IM-27335-3 - - 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_001138724.1|refseq:NP_002612.1|ensembl:ENSG00000126759(gene)|ensembl:ENST00000247153(transcript)|ensembl:ENST00000396992(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0005788"(endoplasmic reticulum lumen)|go:"GO:0006955"(immune response)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0035580"(specific granule lumen)|go:"GO:0042742"(defense response to bacterium)|go:"GO:1904724"(tertiary granule lumen)|interpro:IPR000884(Thrombospondin, type I)|interpro:IPR036383|rcsb pdb:1W0R|rcsb pdb:1W0S|rcsb pdb:6RUR|rcsb pdb:6RUS|rcsb pdb:6RUV|rcsb pdb:6RV6|rcsb pdb:6S08|rcsb pdb:6S0A|rcsb pdb:6S0B|rcsb pdb:6SEJ|reactome:R-HSA-173736|reactome:R-HSA-174577|reactome:R-HSA-5083635|reactome:R-HSA-5173214|reactome:R-HSA-6798695|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 3A|comment:"Binding was inhibited by monoclonal antibodies (mAb1340 and mAb A233) to Properdin."|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/06 rogid:XBExMxbnkfjvnV9zHMRZgxZWKaw9606 - - false - - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P00751 matrixdb:MULT_84_human intact:EBI-1223668|uniprotkb:Q53F89|uniprotkb:O15006|uniprotkb:Q29944|uniprotkb:Q5ST50|uniprotkb:Q96HX6|uniprotkb:Q9BTF5|uniprotkb:Q9BX92|uniprotkb:B0QZQ6|uniprotkb:Q5JP67|ensembl:ENSP00000382862|ensembl:ENSP00000388352|ensembl:ENSP00000389604|ensembl:ENSP00000391902|ensembl:ENSP00000411474|ensembl:ENSP00000411515|ensembl:ENSP00000413351|ensembl:ENSP00000414341|ensembl:ENSP00000414889|ensembl:ENSP00000416561|ensembl:ENSP00000401719 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 psi-mi:cfab_human(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:Properdin factor B(gene name synonym)|uniprotkb:Glycine-rich beta glycoprotein(gene name synonym)|uniprotkb:PBF2(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) Pauly et al. (2013) imex:IM-27335|pubmed:24797388 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-21995258|imex:IM-27335-5 - - 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_001701.2|dip:DIP-38319N|ensembl:ENSG00000239754(gene)|ensembl:ENSG00000241253(gene)|ensembl:ENSG00000241534(gene)|ensembl:ENSG00000242335(gene)|ensembl:ENSG00000243570(gene)|ensembl:ENSG00000243649(gene)|ensembl:ENST00000399981(transcript)|ensembl:ENST00000417261(transcript)|ensembl:ENST00000419411(transcript)|ensembl:ENST00000419920(transcript)|ensembl:ENST00000424727(transcript)|ensembl:ENST00000425368(transcript)|ensembl:ENST00000426239(transcript)|ensembl:ENST00000427888(transcript)|ensembl:ENST00000433503(transcript)|ensembl:ENST00000436692(transcript)|ensembl:ENST00000455591(transcript)|go:"GO:0001848"(complement binding)|go:"GO:0004252"(serine-type endopeptidase activity)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0005886"(plasma membrane)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR001254(Peptidase S1 and S6, chymotrypsin/Hap)|interpro:IPR001314(Peptidase S1A, chymotrypsin)|interpro:IPR002035(von Willebrand factor, type A)|interpro:IPR009003(Peptidase, trypsin-like serine and cysteine)|interpro:IPR011360(Complement B/C2)|interpro:IPR018114|interpro:IPR028341|interpro:IPR033116|interpro:IPR035976|interpro:IPR036465|mint:P00751|rcsb pdb:1DLE|rcsb pdb:1Q0P|rcsb pdb:1RRK|rcsb pdb:1RS0|rcsb pdb:1RTK|rcsb pdb:2OK5|rcsb pdb:2WIN|rcsb pdb:2XWB|rcsb pdb:2XWJ|rcsb pdb:3HRZ|rcsb pdb:3HS0|rcsb pdb:6QSW|rcsb pdb:6QSX|rcsb pdb:6RAV|rcsb pdb:6RUR|rcsb pdb:6RUV|rcsb pdb:6T8U|rcsb pdb:6T8V|rcsb pdb:6T8W|rcsb pdb:7JTN|rcsb pdb:7JTQ|reactome:R-HSA-173736|reactome:R-HSA-174577|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 3B|comment:Binding of Factor B to C3b was inhibited by monoclonal antibodies to Properdin.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/16 2019/10/06 rogid:A6O1R+3K/DVzxKoEh2sLjEmDY/s9606 - - false - - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody)