#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:P36980-PRO_0000005897 uniprotkb:P36980-PRO_0000005897 intact:EBI-21988278 intact:EBI-21988278 psi-mi:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:"MI:0071"(molecular sieving) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988276|imex:IM-27276-21 - - 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) intact:EBI-21976709(chain-parent) intact:EBI-21976709(chain-parent) - chain-seq-start:19|chain-seq-end:270 chain-seq-start:19|chain-seq-end:270 figure legend:1 B/C|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/06 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 rigid:I8W3QZqnTRM9d9hk0UjcGXvIyU0 false myc tag:c-c|his tag:c-c myc tag:c-c|his tag:c-c 2 0 psi-mi:"MI:0817"(molecular weight estimation by silver staining)|psi-mi:"MI:0113"(western blot) psi-mi:"MI:0817"(molecular weight estimation by silver staining)|psi-mi:"MI:0113"(western blot) uniprotkb:P36980 uniprotkb:P36980 intact:EBI-21976709|uniprotkb:Q14310|uniprotkb:Q5T9T1|ensembl:ENSP00000356385 intact:EBI-21976709|uniprotkb:Q14310|uniprotkb:Q5T9T1|ensembl:ENSP00000356385 psi-mi:fhr2_human(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:DDESK59(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:HFL3(gene name synonym) psi-mi:fhr2_human(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:DDESK59(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:HFL3(gene name synonym) psi-mi:"MI:0071"(molecular sieving) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988291|imex:IM-27276-23 - - 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_001299601.1|refseq:NP_005657.1|ensembl:ENST00000367415(transcript)|go:"GO:0005576"(extracellular region)|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)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|rcsb pdb:3ZD1|rcsb pdb:5EA0|reactome:R-HSA-977606|ensembl:ENSG00000080910(gene) refseq:NP_001299601.1|refseq:NP_005657.1|ensembl:ENST00000367415(transcript)|go:"GO:0005576"(extracellular region)|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)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|rcsb pdb:3ZD1|rcsb pdb:5EA0|reactome:R-HSA-977606|ensembl:ENSG00000080910(gene) - - - figure legend:1 B/D|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/06 rogid:dYw4bCXCH0UiK22QrAf1ApfZE/s9606 rogid:dYw4bCXCH0UiK22QrAf1ApfZE/s9606 rigid:NwB2keU6AKkDLQXN7xn7G/1qTZY false myc tag:c-c|his tag:c-c|sufficient binding region:19-144 myc tag:c-c|his tag:c-c|sufficient binding region:19-144 2 0 psi-mi:"MI:0817"(molecular weight estimation by silver staining)|psi-mi:"MI:0113"(western blot) psi-mi:"MI:0817"(molecular weight estimation by silver staining)|psi-mi:"MI:0113"(western blot) uniprotkb:P36980-PRO_0000005897 matrixdb:MULT_84_human intact:EBI-21988278 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 psi-mi:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988343|imex:IM-27276-1 - - 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) intact:EBI-21976709(chain-parent) 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) - chain-seq-start:19|chain-seq-end:270 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-1, Figure 3B/C|comment:C3b/CFHR2 interaction.|comment:The presence of factor H may affect CFHR2 binding to C3b and to C3d.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/07 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 - - false myc tag:c-c|his tag:c-c - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) matrixdb:MULT_84_human uniprotkb:P36980-PRO_0000005897 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 intact:EBI-21988278 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:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:"MI:0411"(enzyme linked immunosorbent assay) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988364|imex:IM-27276-27 - - 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: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-21976709(chain-parent) - 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:19|chain-seq-end:270 figure legend:2B-2, 3B/C|comment:C3b/Factor H interaction.|comment:The presence of CFHR2 does not compete off factor H from either C3b nor from C3d.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/21 - rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 - false - - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P36980-PRO_0000005897 uniprotkb:P01024-PRO_0000005913 intact:EBI-21988278 intact:EBI-21988425 psi-mi:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:p01024-pro_0000005913(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:0411"(enzyme linked immunosorbent assay) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988416|imex:IM-27276-29 - - 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) intact:EBI-21976709(chain-parent) intact:EBI-905851(chain-parent) - chain-seq-start:19|chain-seq-end:270 chain-seq-start:955|chain-seq-end:1303 figure legend:2B-3|comment:C3dg/CFHR2 interaction.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/08/20 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 rogid:SVadmf2wemhTxgqZ2zqxo8bQHhU9606 rigid:gfVglr/yvS8bW/BYtsgCkfwTECo false myc tag:c-c|his tag:c-c his tag:n-n|xpress tag:n-n - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P36980-PRO_0000005897 uniprotkb:P01024-PRO_0000005913 intact:EBI-21988278 intact:EBI-21988425 psi-mi:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:p01024-pro_0000005913(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:0411"(enzyme linked immunosorbent assay) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988435|imex:IM-27276-31 - - 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:0326"(protein) intact:EBI-21976709(chain-parent) intact:EBI-905851(chain-parent) - chain-seq-start:19|chain-seq-end:270 chain-seq-start:955|chain-seq-end:1303 figure legend:2B-4|comment:C3dg/Factor H interaction.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/21 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 rogid:SVadmf2wemhTxgqZ2zqxo8bQHhU9606 rigid:gfVglr/yvS8bW/BYtsgCkfwTECo false - his tag:n-n|xpress tag:n-n - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P36980-PRO_0000005897 uniprotkb:P01024-PRO_0000005915 intact:EBI-21988278 intact:EBI-6863106 psi-mi:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:p01024-pro_0000005915(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:0411"(enzyme linked immunosorbent assay) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988448|imex:IM-27276-3 - - 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:0326"(protein) intact:EBI-21976709(chain-parent) intact:EBI-905851(chain-parent) - chain-seq-start:19|chain-seq-end:270 chain-seq-start:1002|chain-seq-end:1303 figure legend:2B-5, 3B/C|comment:C3d/CFHR2 interaction.|comment:The presence of factor H may affect CFHR2 binding to C3b and to C3d.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/08/20 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 rogid:zfMONKzhTZE0rk2UquV4V+6BTZI9606 rigid:QfUWCo2084aX+/s5EjeVVl4JLzY false his tag:c-c|myc tag:c-c - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P36980-PRO_0000005897 uniprotkb:P01024-PRO_0000005915 intact:EBI-21988278 intact:EBI-6863106 psi-mi:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:p01024-pro_0000005915(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:0411"(enzyme linked immunosorbent assay) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988457|imex:IM-27276-5 - - 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:0326"(protein) intact:EBI-21976709(chain-parent) intact:EBI-905851(chain-parent) - chain-seq-start:19|chain-seq-end:270 chain-seq-start:1002|chain-seq-end:1303 figure legend:2B-6, 3B/C|comment:C3d/Factor H interaction.|comment:The presence of CFHR2 does not compete off factor H from either C3b nor from C3d.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/21 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 rogid:zfMONKzhTZE0rk2UquV4V+6BTZI9606 rigid:QfUWCo2084aX+/s5EjeVVl4JLzY false - - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P36980 matrixdb:MULT_84_human intact:EBI-21976709|uniprotkb:Q14310|uniprotkb:Q5T9T1|ensembl:ENSP00000356385 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 psi-mi:fhr2_human(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:DDESK59(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:HFL3(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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988528|imex:IM-27276-7 - - 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:1302"(stable complex) refseq:NP_001299601.1|refseq:NP_005657.1|ensembl:ENST00000367415(transcript)|go:"GO:0005576"(extracellular region)|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)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|rcsb pdb:3ZD1|rcsb pdb:5EA0|reactome:R-HSA-977606|ensembl:ENSG00000080910(gene) 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:2C-1|comment:C3b/CFHR2 interaction.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/07 rogid:dYw4bCXCH0UiK22QrAf1ApfZE/s9606 - - false myc tag:c-c|his tag:c-c|sufficient binding region:145-270 - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P36980 uniprotkb:P01024-PRO_0000005915 intact:EBI-21976709|uniprotkb:Q14310|uniprotkb:Q5T9T1|ensembl:ENSP00000356385 intact:EBI-6863106 psi-mi:fhr2_human(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:DDESK59(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:HFL3(gene name synonym) psi-mi:p01024-pro_0000005915(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:0411"(enzyme linked immunosorbent assay) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988540|imex:IM-27276-9 - - 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_001299601.1|refseq:NP_005657.1|ensembl:ENST00000367415(transcript)|go:"GO:0005576"(extracellular region)|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)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|rcsb pdb:3ZD1|rcsb pdb:5EA0|reactome:R-HSA-977606|ensembl:ENSG00000080910(gene) intact:EBI-905851(chain-parent) - - chain-seq-start:1002|chain-seq-end:1303 figure legend:2C-2|comment:C3d/CFHR2 interaction.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/08/20 rogid:dYw4bCXCH0UiK22QrAf1ApfZE/s9606 rogid:zfMONKzhTZE0rk2UquV4V+6BTZI9606 rigid:jVqiWurQlhXVzIjxEKfd6PulLMI false myc tag:c-c|his tag:c-c|sufficient binding region:145-270 - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P36980-PRO_0000005897 matrixdb:MULT_84_human intact:EBI-21988278 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 psi-mi:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988554|imex:IM-27276-11 - - 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:1302"(stable complex) intact:EBI-21976709(chain-parent) 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) - chain-seq-start:19|chain-seq-end:270 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:2C-3|comment:C3b/Factor H interaction.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/21 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 - - false - - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P36980-PRO_0000005897 uniprotkb:P01024-PRO_0000005915 intact:EBI-21988278 intact:EBI-6863106 psi-mi:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:p01024-pro_0000005915(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:0411"(enzyme linked immunosorbent assay) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988568|imex:IM-27276-13 - - 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) intact:EBI-21976709(chain-parent) intact:EBI-905851(chain-parent) - chain-seq-start:19|chain-seq-end:270 chain-seq-start:1002|chain-seq-end:1303 figure legend:2C-4|comment:C3d/Factor H interaction.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/21 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 rogid:zfMONKzhTZE0rk2UquV4V+6BTZI9606 rigid:QfUWCo2084aX+/s5EjeVVl4JLzY false - - - - psi-mi:"MI:0421"(identification by antibody) psi-mi:"MI:0421"(identification by antibody) uniprotkb:P36980-PRO_0000005897 matrixdb:MULT_84_human intact:EBI-21988278 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 psi-mi:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988585|imex:IM-27276-15 - - 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) intact:EBI-21976709(chain-parent) 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) - chain-seq-start:19|chain-seq-end:270 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:3A-1|comment:C3b/CFHR2 interaction.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) kd:4.2x10^-6(molar) 2019/08/05 2019/10/07 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 - - false myc tag:c-c|his tag:c-c biotin tag:?-? - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) matrixdb:MULT_84_human uniprotkb:P36980-PRO_0000005897 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 intact:EBI-21988278 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:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:"MI:0107"(surface plasmon resonance) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988594|imex:IM-27276-33 - - 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: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-21976709(chain-parent) - 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:19|chain-seq-end:270 figure legend:3A-2|comment:C3b/Factor H interaction.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) kd:0.57x10^-6(molar) 2019/08/05 2019/10/21 - rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 - false biotin tag:?-? - - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) 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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988626|imex:IM-27276-17 - 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:5|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/06 - rogid:6Axa89cCPpUXFsLnd7sCurZzLYI9606 - false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) 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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988626|imex:IM-27276-17 - 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:5|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/06 - rogid:INYV2BPbjbUsThnuF2mPvKEn/iA9606 - false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) 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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988652|imex:IM-27276-35 - 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:5-2, 6A|comment:C3a bands were detected by Western blot in figure 5. However it was shown that Factor H can dissociate factor B from the in vitro assembled convertase C3bBb when western blotting for Factor B was used.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/21 - rogid:6Axa89cCPpUXFsLnd7sCurZzLYI9606 - false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) 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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988652|imex:IM-27276-35 - 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:5-2, 6A|comment:C3a bands were detected by Western blot in figure 5. However it was shown that Factor H can dissociate factor B from the in vitro assembled convertase C3bBb when western blotting for Factor B was used.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/21 - rogid:INYV2BPbjbUsThnuF2mPvKEn/iA9606 - false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) matrixdb:MULT_84_human uniprotkb:P36980-PRO_0000005897 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 intact:EBI-21988278 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:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:"MI:0435"(protease assay) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988652|imex:IM-27276-35 - 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) intact:EBI-21976709(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:19|chain-seq-end:270 figure legend:5-2, 6A|comment:C3a bands were detected by Western blot in figure 5. However it was shown that Factor H can dissociate factor B from the in vitro assembled convertase C3bBb when western blotting for Factor B was used.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/21 - rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 - false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) 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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988662|imex:IM-27276-37 - 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:5-3, 6A|comment:C3a bands were detected by Western blot in figure 5. However it was shown that CFHR2 can not dissociate factor B from the in vitro assembled convertase C3bBb when western blotting for Factor B was used.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/06 - rogid:6Axa89cCPpUXFsLnd7sCurZzLYI9606 - false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) 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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988662|imex:IM-27276-37 - 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:5-3, 6A|comment:C3a bands were detected by Western blot in figure 5. However it was shown that CFHR2 can not dissociate factor B from the in vitro assembled convertase C3bBb when western blotting for Factor B was used.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/06 - rogid:INYV2BPbjbUsThnuF2mPvKEn/iA9606 - false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) matrixdb:MULT_84_human uniprotkb:P36980-PRO_0000005897 intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832 intact:EBI-21988278 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:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:"MI:0435"(protease assay) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988662|imex:IM-27276-37 - 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) intact:EBI-21976709(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:19|chain-seq-end:270 figure legend:5-3, 6A|comment:C3a bands were detected by Western blot in figure 5. However it was shown that CFHR2 can not dissociate factor B from the in vitro assembled convertase C3bBb when western blotting for Factor B was used.|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/06 - rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 - false - myc tag:c-c|his tag:c-c - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) uniprotkb:P05156 uniprotkb:P01024-PRO_0000005911 intact:EBI-9352022|uniprotkb:O60442|ensembl:ENSP00000378130 intact:EBI-12735725 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: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) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988711|imex:IM-27276-19 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0501"(enzyme) 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_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 intact:EBI-905851(chain-parent) go:"GO:0004252"(serine-type endopeptidase activity) - chain-seq-start:749|chain-seq-end:1663 figure legend:6C|comment:"C3b is a complex composed of the modified C3-alpha chain (a') (M.W. 105,000) and the intact C3-beta chain (M.W. 75,000). Factor I cleaves the a' chain of the C3b complex."|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/21 rogid:2zm8YwMWNSX3vv6fLIJ3WZ6hrLc9606 rogid:PGQNhqtLcK90Rf1IY85ARmU6Jbs9606 rigid:BvZvbRw7U5aVcpw4hJOf5QPmphI false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot) uniprotkb:P05156 uniprotkb:P36980-PRO_0000005897 intact:EBI-9352022|uniprotkb:O60442|ensembl:ENSP00000378130 intact:EBI-21988278 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:p36980-pro_0000005897(display_long)|uniprotkb:CFHR2(gene name)|psi-mi:CFHR2(display_short)|uniprotkb:CFHL2(gene name synonym)|uniprotkb:FHR2(gene name synonym)|uniprotkb:HFL3(gene name synonym)|uniprotkb:H factor-like 3(gene name synonym)|uniprotkb:H factor-like protein 2(gene name synonym)|uniprotkb:DDESK59(gene name synonym) psi-mi:"MI:0435"(protease assay) Eberhardt et al. (2012) pubmed:24260121|imex:IM-27276 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-21988711|imex:IM-27276-19 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0501"(enzyme) psi-mi:"MI:0682"(cofactor) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) 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 intact:EBI-21976709(chain-parent) go:"GO:0004252"(serine-type endopeptidase activity) - chain-seq-start:19|chain-seq-end:270 figure legend:6C|comment:"C3b is a complex composed of the modified C3-alpha chain (a') (M.W. 105,000) and the intact C3-beta chain (M.W. 75,000). Factor I cleaves the a' chain of the C3b complex."|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2019/08/05 2019/10/21 rogid:2zm8YwMWNSX3vv6fLIJ3WZ6hrLc9606 rogid:dJVPsDOOwKnDca0muKon+2jVjHo9606 rigid:BvZvbRw7U5aVcpw4hJOf5QPmphI false - - - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot)