#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
matrixdb:MULT_84_human	uniprotkb:P08603-PRO_0000005894	intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832	intact:EBI-22114230	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:p08603-pro_0000005894(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym)	psi-mi:"MI:0107"(surface plasmon resonance)	Schramm et al. (2015)	pubmed:25608561|imex:IM-27732	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-25431893|imex:IM-27732-1	-	-	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: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-1223708(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:1231	figure legend:Fig. 2a-c, Table S3|comment:The impact of C3 mutations on the interaction was inferred from dissociation rate presented in table S3|dataset:Rare diseases - Interactions investigated in the context of Rare genetic disease|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	kd:8.2x10^-9(molar)	2020/02/20	2020/02/24	-	rogid:XBVVm1S9GOtP5be24RqAkVBULzQ9606	-	false	mutation decreasing interaction strength:43-43|mutation with no effect:303-303|mutation disrupting interaction strength:315-315|mutation decreasing interaction strength:346-346|mutation decreasing interaction strength:346-346|mutation decreasing interaction strength:366-366|mutation decreasing interaction strength:367-367|mutation decreasing interaction strength:368-368|mutation decreasing interaction strength:409-409|mutation decreasing interaction strength:413-413|mutation with no effect:456-456|mutation with no effect:581-581|mutation with no effect:635-635|mutation with no effect:801-801|mutation disrupting interaction strength:163-163|mutation decreasing interaction strength:570-570|mutation with no effect:139-139|mutation decreasing interaction strength:140-140|mutation decreasing interaction strength:140-140|mutation disrupting interaction strength:163-163|mutation decreasing interaction strength:294-294|mutation decreasing interaction strength:294-294|mutation decreasing interaction strength:570-570|mutation with no effect:286-286|mutation decreasing interaction strength:347-347|mutation decreasing interaction strength:346-346|mutation with no effect:716-716|mutation with no effect:910-910	-	-	-	psi-mi:"MI:0396"(predetermined participant)	psi-mi:"MI:0396"(predetermined participant)
matrixdb:MULT_84_human	uniprotkb:P15529	intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832	intact:EBI-2623451|uniprotkb:A0T1T0|uniprotkb:A0T1T1|uniprotkb:Q9UCJ4|uniprotkb:Q5VWS7|uniprotkb:Q5VWT1|uniprotkb:Q7Z3R5|uniprotkb:Q9NNW2|uniprotkb:Q6N0A1|uniprotkb:Q5VWS6|uniprotkb:Q5VWS8|uniprotkb:A0T1T2|uniprotkb:Q9NNW3|uniprotkb:Q5HY94|uniprotkb:Q5VWS9|uniprotkb:Q53GV9|uniprotkb:Q15429|uniprotkb:Q9NNW4|uniprotkb:Q5VWT0|uniprotkb:Q5VWT2|ensembl:ENSP00000350893	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:mcp_human(display_long)|uniprotkb:MCP(gene name synonym)|uniprotkb:MIC10(gene name synonym)|uniprotkb:TLX(gene name synonym)|uniprotkb:Trophoblast leukocyte common antigen(gene name synonym)|uniprotkb:CD46(gene name)|psi-mi:CD46(display_short)	psi-mi:"MI:0107"(surface plasmon resonance)	Schramm et al. (2015)	pubmed:25608561|imex:IM-27732	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-25434809|imex:IM-27732-3	-	-	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: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:XP_011507865.1|refseq:XP_011507866.1|refseq:NP_002380.3|refseq:NP_722548.1|refseq:NP_758860.1|refseq:NP_758861.1|refseq:NP_758862.1|refseq:NP_758863.1|refseq:NP_758869.1|refseq:NP_758871.1|refseq:XP_016856797.1|refseq:XP_016856798.1|refseq:XP_016856799.1|ensembl:ENSG00000117335(gene)|ensembl:ENST00000358170(transcript)|go:"GO:0001618"(virus receptor activity)|go:"GO:0002079"(inner acrosomal membrane)|go:"GO:0002250"(adaptive immune response)|go:"GO:0002456"(T cell mediated immunity)|go:"GO:0005886"(plasma membrane)|go:"GO:0005887"(integral component of plasma membrane)|go:"GO:0005925"(focal adhesion)|go:"GO:0006958"(complement activation, classical pathway)|go:"GO:0008593"(regulation of Notch signaling pathway)|go:"GO:0007338"(single fertilization)|go:"GO:0009986"(cell surface)|go:"GO:0010628"(positive regulation of gene expression)|go:"GO:0010629"(negative regulation of gene expression)|go:"GO:0032733"(positive regulation of interleukin-10 production)|go:"GO:0035581"(sequestering of extracellular ligand from receptor)|go:"GO:0038023"(signaling receptor activity)|go:"GO:0042102"(positive regulation of T cell proliferation)|go:"GO:0043382"(positive regulation of memory T cell differentiation)|go:"GO:0045087"(innate immune response)|go:"GO:0045296"(cadherin binding)|go:"GO:0045591"(positive regulation of regulatory T cell differentiation)|go:"GO:0045959"(negative regulation of complement activation, classical pathway)|go:"GO:0070062"(extracellular exosome)|go:"GO:0071636"(positive regulation of transforming growth factor beta production)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR017341(Membrane cofactor protein, CD46)|interpro:IPR035976|rcsb pdb:1CKL|rcsb pdb:1HR4|rcsb pdb:2O39|rcsb pdb:3INB|rcsb pdb:3L89|rcsb pdb:3O8E|rcsb pdb:5FO8|reactome:R-HSA-977606|dip:DIP-41232N	-	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:Fig. 3a-c, Table S3|comment:The impact of C3 mutations on the interaction was inferred from dissociation rate presented in table S3|dataset:Rare diseases - Interactions investigated in the context of Rare genetic disease|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	kd:77.0x10^-9(molar)	2020/02/20	2020/02/24	-	rogid:nhB+pnkhLRsOA01ekJ50pkUu3og9606	-	false	mutation decreasing interaction strength:570-570|mutation decreasing interaction strength:346-346|mutation decreasing interaction strength:347-347|mutation decreasing interaction strength:43-43|mutation with no effect:303-303|mutation decreasing interaction strength:315-315|mutation decreasing interaction strength:346-346|mutation decreasing interaction strength:346-346|mutation decreasing interaction strength:366-366|mutation decreasing interaction strength:367-367|mutation decreasing interaction strength:368-368|mutation decreasing interaction strength:409-409|mutation decreasing interaction strength:413-413|mutation with no effect:456-456|mutation with no effect:581-581|mutation with no effect:635-635|mutation with no effect:801-801|mutation with no effect:163-163|mutation decreasing interaction strength:570-570|mutation decreasing interaction strength:139-139|mutation decreasing interaction strength:140-140|mutation decreasing interaction strength:140-140|mutation with no effect:163-163|mutation with no effect:286-286|mutation decreasing interaction strength:294-294|mutation decreasing interaction strength:294-294	-	-	-	psi-mi:"MI:0396"(predetermined participant)	psi-mi:"MI:0396"(predetermined participant)
uniprotkb:P08603	matrixdb:MULT_84_human	intact:EBI-1223708|uniprotkb:A5PL14|uniprotkb:Q2TAZ5|uniprotkb:P78435|uniprotkb:Q14570|uniprotkb:Q38G77|uniprotkb:Q5TFM3|uniprotkb:Q8N708|uniprotkb:Q9NU86|ensembl:ENSP00000356399	intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832	psi-mi:cfah_human(display_long)|uniprotkb:CFH(gene name)|psi-mi:CFH(display_short)|uniprotkb:HF(gene name synonym)|uniprotkb:HF1(gene name synonym)|uniprotkb:HF2(gene name synonym)|uniprotkb:H factor 1(gene name synonym)	psi-mi:c3b_human(display_short)|psi-mi:MULT_84_human(display_long)|intact:Complement C3b complex(complex recommended name)|intact:C3b dimer(complex systematic name)	psi-mi:"MI:0107"(surface plasmon resonance)	Schramm et al. (2015)	pubmed:25608561|imex:IM-27732	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-25434950|imex:IM-27732-5	-	-	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_000177.2|dip:DIP-38303N|ensembl:ENSG00000000971(gene)|ensembl:ENST00000367429(transcript)|go:"GO:0005576"(extracellular region)|go:"GO:0005615"(extracellular space)|go:"GO:0006956"(complement activation)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0008201"(heparin binding)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0042802"(identical protein binding)|go:"GO:0043395"(heparan sulfate proteoglycan binding)|go:"GO:0070062"(extracellular exosome)|go:"GO:0072562"(blood microparticle)|go:"GO:1903659"(regulation of complement-dependent cytotoxicity)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|mint:P08603|rcsb pdb:1FHC|rcsb pdb:1HAQ|rcsb pdb:1HCC|rcsb pdb:1HFH|rcsb pdb:1HFI|rcsb pdb:1KOV|rcsb pdb:2QFH|rcsb pdb:2RLP|rcsb pdb:2RLQ|rcsb pdb:2UWN|rcsb pdb:2V8E|rcsb pdb:2W80|rcsb pdb:2BZM|rcsb pdb:2G7I|rcsb pdb:2W81|rcsb pdb:2WII|rcsb pdb:2XQW|rcsb pdb:3GAU|rcsb pdb:3GAV|rcsb pdb:3GAW|rcsb pdb:3KXV|rcsb pdb:3KZJ|rcsb pdb:3OXU|rcsb pdb:3R62|rcsb pdb:3RJ3|rcsb pdb:3SW0|rcsb pdb:4AYD|rcsb pdb:4AYE|rcsb pdb:4AYI|rcsb pdb:4AYM|rcsb pdb:4B2R|rcsb pdb:4B2S|rcsb pdb:2IC4|rcsb pdb:2JGW|rcsb pdb:2JGX|rcsb pdb:4J38|rcsb pdb:4K12|rcsb pdb:4ONT|rcsb pdb:4ZH1|rcsb pdb:5NBQ|rcsb pdb:5O32|rcsb pdb:5O35|rcsb pdb:2KMS|rcsb pdb:2QFG|rcsb pdb:5WTB|rcsb pdb:6ATG|reactome:R-HSA-977606	pubmed:27782329(see-also)|pubmed:6225800(see-also)|evidence ontology:"ECO:0000353"|efo:"Orphanet:280133"(see-also)|efo:"Orphanet:2134"(see-also)|efo:"Orphanet:93575"(see-also)|efo:"EFO:0001365"(see-also)|pubmed:27013439(see-also)|pubmed:19196712(see-also)|pubmed:17051160(see-also)|go:"GO:0005615"(extracellular space)|go:"GO:0001848"(complement binding)|go:"GO:1903028"(positive regulation of opsonization)|go:"GO:0006956"(complement activation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0044533"(positive regulation of apoptotic process in another organism)|go:"GO:0050778"(positive regulation of immune response)|go:"GO:0030449"(regulation of complement activation)|go:"GO:0008228"(opsonization)|pubmed:6559201(see-also)|pubmed:15454921(see-also)|pubmed:21205667(see-also)|pubmed:17051150(see-also)|complex portal:CPX-973(complex-primary)|pubmed:26489954(see-also)	-	-	curated-complex:"A protein complex of the alternative pathway of complement activation of the innate immune system. Complement C3 precurser is activated by cleavage into C3a and C3b by C3 convertases, either C4bC2a in the classical and lectin pathways or C3(H2O)Bb, C3bBb, C3bBbC3b, C3bBbP or C3bBbC3bP in the alternative pathway.     C3b acts as an opsonin and interacts with glycoproteins and carbohydrates on pathogenic or apoptotic target cell surfaces through its reactive thioester moiety. Opsonization of target cells leads to enhanced phagocytosis, lysis of target cells via membrane attack complex (CPX-6159) assembly, clearance of antibody-antigen complexes and up-regulation of the adaptive response.     Activation of C3b leads to an amplification cascade that generates more C3 convertase, deposits more C3b at the local site and switches C3 convertases to C5 convertases.     To protect host cells from inadvertent complement activation the activation of C3b is tightly regulated by either disrupting the C3 convertases or aiding in the proteolytic degradation of C3b. Bacteria and viruses possess C3b proteases to evade the complement response.     Lack of protection, due to familial mutations in the complement genes or the presence of autoantibodies against regulators has been linked to atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathies (C3G) in kidneys and age-related macular degeneration (AMD) in eyes. Conditions of chronic and acute inflammations, as in rheumatoid arthritis, strokes, and heart attacks, become aggravated by complement activation against the disturbed tissue."|complex-properties:"The alternative pathway is continuously activated at a low level. C3 precursor is first processed by the removal of 4 Arg residues and spontaneous hydrolysis due to the breakdown of the internal thioester bond forms C3(H2O) (disulfide bonded P01024-PRO_0000005909 & P01024-PRO_0000005908).     C3(H2O) subsequently binds factor B that is cleaved by Factor D (P00746) into 2 fragments: CFBa and CFBb. CFBb, a serine protease, then combines with complement factor C3(H2O) or C3b to generate the C3 or C5 convertases.     Proteolytic cleavage of C3 to C3b is accompanied by large conformational changes that result in the exposure of cryptic binding sites required for convertase assembly and regulation. This includes a significant movement of the thioester-bond-containing domain through which C3b attaches to target surfaces."|complex-assembly:Heterodimer|disease:"Complement component 3 (C3) deficiency [Orphanet:280133]: a rare, autosomal recessive defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis."|disease:"Atypical hemolytic-uremic syndrome with C3 anomaly [Orphanet:2134 & Orphanet:93575]: an autosomal dominant, atypical form of hemolytic-uremic syndrome (aHUS, a thrombotic microangiopathy) characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction."|disease:"Age-related macular degeneration [EFO:0001365]: age-related macular degeneration usually in older adults which results in a loss of vision in the center of the visual field (the macula lutea) because of damage to the retina. Manifests as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Occurs in dry and wet forms. Most common cause of irreversible vision loss in the developed world."	figure legend:Fig. 2e|dataset:Rare diseases - Interactions investigated in the context of Rare genetic disease|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	-	2020/02/20	2020/02/24	rogid:1mjo+AJLIQnEsMFqsGsmUFbfUxk9606	-	-	false	sufficient binding region:1107..1107-1230..1230	mutation decreasing interaction strength:43-43|mutation with no effect:303-303|mutation decreasing interaction strength:315-315|mutation decreasing interaction strength:346-346|mutation decreasing interaction strength:346-346|mutation decreasing interaction strength:366-366|mutation decreasing interaction strength:367-367|mutation decreasing interaction strength:368-368|mutation decreasing interaction strength:409-409|mutation decreasing interaction strength:413-413|mutation with no effect:456-456|mutation with no effect:581-581|mutation with no effect:635-635|mutation with no effect:801-801|mutation decreasing interaction strength:163-163|mutation with no effect:570-570|mutation with no effect:139-139|mutation with no effect:140-140|mutation with no effect:140-140|mutation decreasing interaction strength:163-163|mutation decreasing interaction strength:286-286|mutation decreasing interaction strength:294-294|mutation decreasing interaction strength:294-294	-	-	psi-mi:"MI:0396"(predetermined participant)	psi-mi:"MI:0396"(predetermined participant)
uniprotkb:P17927	matrixdb:MULT_84_human	intact:EBI-2807625|ensembl:ENSP00000356018|ensembl:ENSP00000356020|ensembl:ENSP00000383744|uniprotkb:Q5SR43|uniprotkb:Q9UQV2|uniprotkb:Q5SR45|uniprotkb:Q16745|uniprotkb:Q16744	intact:EBI-12735745|wwpdb:5fo7|wwpdb:3g6j|wwpdb:2i07|reactome:R-HSA-166832	psi-mi:cr1_human(display_long)|uniprotkb:CR1(gene name)|psi-mi:CR1(display_short)|uniprotkb:C3BR(gene name synonym)|uniprotkb:C3b/C4b receptor(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)	Schramm et al. (2015)	pubmed:25608561|imex:IM-27732	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-25435060|imex:IM-27732-7	-	-	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)	ensembl:ENSG00000203710(gene)|go:"GO:0001855"(complement component C4b binding)|go:"GO:0001861"(complement component C4b receptor activity)|go:"GO:0001970"(positive regulation of activation of membrane attack complex)|go:"GO:0001971"(negative regulation of activation of membrane attack complex)|go:"GO:0002430"(complement receptor mediated signaling pathway)|go:"GO:0002435"(immune complex clearance by erythrocytes)|go:"GO:0002638"(negative regulation of immunoglobulin production)|go:"GO:0004877"(complement component C3b receptor activity)|go:"GO:0005615"(extracellular space)|go:"GO:0005856"(cytoskeleton)|ensembl:ENST00000367051(transcript)|go:"GO:0005886"(plasma membrane)|go:"GO:0005887"(integral component of plasma membrane)|ensembl:ENST00000367053(transcript)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0006958"(complement activation, classical pathway)|ensembl:ENST00000400960(transcript)|go:"GO:0007009"(plasma membrane organization)|go:"GO:0008284"(positive regulation of cell population proliferation)|go:"GO:0009986"(cell surface)|go:"GO:0030667"(secretory granule membrane)|go:"GO:0001618"(virus receptor activity)|go:"GO:0032689"(negative regulation of interferon-gamma production)|go:"GO:0001851"(complement component C3b binding)|go:"GO:0032703"(negative regulation of interleukin-2 production)|go:"GO:0042130"(negative regulation of T cell proliferation)|go:"GO:0044853"(plasma membrane raft)|go:"GO:0045591"(positive regulation of regulatory T cell differentiation)|go:"GO:0045916"(negative regulation of complement activation)|go:"GO:0045918"(negative regulation of cytolysis)|go:"GO:0045957"(negative regulation of complement activation, alternative pathway)|go:"GO:0045959"(negative regulation of complement activation, classical pathway)|go:"GO:0070062"(extracellular exosome)|go:"GO:0101003"(ficolin-1-rich granule membrane)|go:"GO:1900004"(negative regulation of serine-type endopeptidase activity)|go:"GO:1900005"(positive regulation of serine-type endopeptidase activity)|go:"GO:1900099"(negative regulation of plasma cell differentiation)|go:"GO:1904669"(ATP export)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|rcsb pdb:1GKG|rcsb pdb:1GKN|rcsb pdb:1GOP|rcsb pdb:1PPQ|rcsb pdb:2MCY|rcsb pdb:2MCZ|rcsb pdb:2Q7Z|reactome:R-HSA-6798695|reactome:R-HSA-8877330|reactome:R-HSA-977606|rcsb pdb:5FO9|refseq:NP_000564.2|refseq:NP_000642.3	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:Fig. 4a-c, Table S3|comment:The impact of C3 mutations on the interaction was inferred from dissociation rate presented in table S3|dataset:Rare diseases - Interactions investigated in the context of Rare genetic disease|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	kd:4.2x10^-9(molar)	2020/02/20	2020/02/24	rogid:gwNvQZmPMP1PCX8z/svSxkVBZt49606	-	-	false	-	mutation with no effect:43-43|mutation with no effect:303-303|mutation decreasing interaction strength:315-315|mutation with no effect:346-346|mutation with no effect:346-346|mutation decreasing interaction strength:366-366|mutation with no effect:367-367|mutation with no effect:368-368|mutation with no effect:409-409|mutation with no effect:413-413|mutation with no effect:456-456|mutation with no effect:581-581|mutation with no effect:635-635|mutation with no effect:801-801|mutation with no effect:163-163|mutation with no effect:570-570|mutation decreasing interaction strength:139-139|mutation with no effect:140-140|mutation with no effect:140-140|mutation with no effect:163-163|mutation with no effect:286-286|mutation with no effect:294-294|mutation with no effect:294-294|mutation with no effect:716-716|mutation with no effect:910-910|mutation with no effect:139-139|mutation with no effect:570-570|mutation with no effect:346-346|mutation with no effect:347-347	-	-	psi-mi:"MI:0396"(predetermined participant)	psi-mi:"MI:0396"(predetermined participant)
uniprotkb:P17927	uniprotkb:P01024-PRO_0000005915	intact:EBI-2807625|ensembl:ENSP00000356018|ensembl:ENSP00000356020|ensembl:ENSP00000383744|uniprotkb:Q5SR43|uniprotkb:Q9UQV2|uniprotkb:Q5SR45|uniprotkb:Q16745|uniprotkb:Q16744	intact:EBI-6863106	psi-mi:cr1_human(display_long)|uniprotkb:CR1(gene name)|psi-mi:CR1(display_short)|uniprotkb:C3BR(gene name synonym)|uniprotkb:C3b/C4b receptor(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:0107"(surface plasmon resonance)	Schramm et al. (2015)	pubmed:25608561|imex:IM-27732	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-25508540|imex:IM-27732-8	-	-	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)	ensembl:ENSG00000203710(gene)|go:"GO:0001855"(complement component C4b binding)|go:"GO:0001861"(complement component C4b receptor activity)|go:"GO:0001970"(positive regulation of activation of membrane attack complex)|go:"GO:0001971"(negative regulation of activation of membrane attack complex)|go:"GO:0002430"(complement receptor mediated signaling pathway)|go:"GO:0002435"(immune complex clearance by erythrocytes)|go:"GO:0002638"(negative regulation of immunoglobulin production)|go:"GO:0004877"(complement component C3b receptor activity)|go:"GO:0005615"(extracellular space)|go:"GO:0005856"(cytoskeleton)|ensembl:ENST00000367051(transcript)|go:"GO:0005886"(plasma membrane)|go:"GO:0005887"(integral component of plasma membrane)|ensembl:ENST00000367053(transcript)|go:"GO:0006957"(complement activation, alternative pathway)|go:"GO:0006958"(complement activation, classical pathway)|ensembl:ENST00000400960(transcript)|go:"GO:0007009"(plasma membrane organization)|go:"GO:0008284"(positive regulation of cell population proliferation)|go:"GO:0009986"(cell surface)|go:"GO:0030667"(secretory granule membrane)|go:"GO:0001618"(virus receptor activity)|go:"GO:0032689"(negative regulation of interferon-gamma production)|go:"GO:0001851"(complement component C3b binding)|go:"GO:0032703"(negative regulation of interleukin-2 production)|go:"GO:0042130"(negative regulation of T cell proliferation)|go:"GO:0044853"(plasma membrane raft)|go:"GO:0045591"(positive regulation of regulatory T cell differentiation)|go:"GO:0045916"(negative regulation of complement activation)|go:"GO:0045918"(negative regulation of cytolysis)|go:"GO:0045957"(negative regulation of complement activation, alternative pathway)|go:"GO:0045959"(negative regulation of complement activation, classical pathway)|go:"GO:0070062"(extracellular exosome)|go:"GO:0101003"(ficolin-1-rich granule membrane)|go:"GO:1900004"(negative regulation of serine-type endopeptidase activity)|go:"GO:1900005"(positive regulation of serine-type endopeptidase activity)|go:"GO:1900099"(negative regulation of plasma cell differentiation)|go:"GO:1904669"(ATP export)|interpro:IPR000436(Sushi/SCR/CCP)|interpro:IPR035976|rcsb pdb:1GKG|rcsb pdb:1GKN|rcsb pdb:1GOP|rcsb pdb:1PPQ|rcsb pdb:2MCY|rcsb pdb:2MCZ|rcsb pdb:2Q7Z|reactome:R-HSA-6798695|reactome:R-HSA-8877330|reactome:R-HSA-977606|rcsb pdb:5FO9|refseq:NP_000564.2|refseq:NP_000642.3	intact:EBI-905851(chain-parent)	-	-	chain-seq-start:1002|chain-seq-end:1303	figure legend:Fig. 4e|comment:"Interaction was detected at only low ionic strength buffer (25 mM NaCl)"|dataset:Rare diseases - Interactions investigated in the context of Rare genetic disease|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	kd:23.0x10^-6(molar)	2020/02/20	2020/04/11	rogid:gwNvQZmPMP1PCX8z/svSxkVBZt49606	rogid:zfMONKzhTZE0rk2UquV4V+6BTZI9606	rigid:vHA+wB2+Z+xzffpDHmAMssyKraQ	false	-	-	-	-	psi-mi:"MI:0396"(predetermined participant)	psi-mi:"MI:0396"(predetermined participant)