IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Nature communications 2019 imex curation Irmscher S., Brix SR., Zipfel SLH., Halder LD., Mutlutürk S., Wulf S., Girdauskas E., Reichenspurner H., Stahl RAK., Jungnickel B., Wiech T., Zipfel PF., Skerka C. [Email sent requesting species of C3b and FHR2 dimerisation mutant details - on 21/8/19). dear checker; apologies if I have missed interactions; the figures for the most part do not state any method details;so very hard to see what to curate. I have checked the occurance of every protein in the "Proteins" section to see if there are any interactions missed, but they do NOT list all the proteins they use here - e.g C3b, (presumably from Complement Tech). + other proteins. The authors have confirmed that C3b is of Human origin, and have confirmed that the mutation in the FHR2 dimerisation mutant, as used in Figure 7 J/K, is correct. christine.skerka@hki-jena.de 04-05-20: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-kidney Human kidney kidney kidney [Renal] pla proximity ligation assay pELISA pELISA PLA antibody detection identification by antibody antibody detection Irmscher S., Brix SR., Zipfel SLH., Halder LD., Mutlutürk S., Wulf S., Girdauskas E., Reichenspurner H., Stahl RAK., Jungnickel B., Wiech T., Zipfel PF., Skerka C. [Email sent requesting species of C3b and FHR2 dimerisation mutant details - on 21/8/19). dear checker; apologies if I have missed interactions; the figures for the most part do not state any method details;so very hard to see what to curate. I have checked the occurance of every protein in the "Proteins" section to see if there are any interactions missed, but they do NOT list all the proteins they use here - e.g C3b, (presumably from Complement Tech). + other proteins. Cells obtained from Kidney biopsies taken from AAV (antibody-associated vasculitis) patients. The authors have confirmed that C3b is of Human origin, and have confirmed that the mutation in the FHR2 dimerisation mutant, as used in Figure 7 J/K, is correct. christine.skerka@hki-jena.de Accepted 2020-MAR-04 AT 08:54 GMT AT 08:54 GMT by LIVIAP Nature communications 2019 Only protein-protein interactions imex curation imex curation Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Nature communications 2019 imex curation Irmscher S., Brix SR., Zipfel SLH., Halder LD., Mutlutürk S., Wulf S., Girdauskas E., Reichenspurner H., Stahl RAK., Jungnickel B., Wiech T., Zipfel PF., Skerka C. [Email sent requesting species of C3b and FHR2 dimerisation mutant details - on 21/8/19). dear checker; apologies if I have missed interactions; the figures for the most part do not state any method details;so very hard to see what to curate. I have checked the occurance of every protein in the "Proteins" section to see if there are any interactions missed, but they do NOT list all the proteins they use here - e.g C3b, (presumably from Complement Tech). + other proteins. The authors have confirmed that C3b is of Human origin, and have confirmed that the mutation in the FHR2 dimerisation mutant, as used in Figure 7 J/K, is correct. christine.skerka@hki-jena.de 04-05-20: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro elisa enzyme linked immunosorbent assay ELISA ELISA elisa antibody detection identification by antibody antibody detection Irmscher S., Brix SR., Zipfel SLH., Halder LD., Mutlutürk S., Wulf S., Girdauskas E., Reichenspurner H., Stahl RAK., Jungnickel B., Wiech T., Zipfel PF., Skerka C. 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. [see also ref. 38 pmid: 27814381] [Email sent requesting species of C3b and FHR2 dimerisation mutant details - on 21/8/19). dear checker; apologies if I have missed interactions; the figures for the most part do not state any method details;so very hard to see what to curate. I have checked the occurance of every protein in the "Proteins" section to see if there are any interactions missed, but they do NOT list all the proteins they use here - e.g C3b, (presumably from Complement Tech). + other proteins. The authors have confirmed that C3b is of Human origin, and have confirmed that the mutation in the FHR2 dimerisation mutant, as used in Figure 7 J/K, is correct. christine.skerka@hki-jena.de Accepted 2020-MAR-04 AT 08:54 GMT AT 08:54 GMT by LIVIAP Nature communications 2019 Only protein-protein interactions imex curation imex curation Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Nature communications 2019 imex curation Irmscher S., Brix SR., Zipfel SLH., Halder LD., Mutlutürk S., Wulf S., Girdauskas E., Reichenspurner H., Stahl RAK., Jungnickel B., Wiech T., Zipfel PF., Skerka C. [Email sent requesting species of C3b and FHR2 dimerisation mutant details - on 21/8/19). dear checker; apologies if I have missed interactions; the figures for the most part do not state any method details;so very hard to see what to curate. I have checked the occurance of every protein in the "Proteins" section to see if there are any interactions missed, but they do NOT list all the proteins they use here - e.g C3b, (presumably from Complement Tech). + other proteins. The authors have confirmed that C3b is of Human origin, and have confirmed that the mutation in the FHR2 dimerisation mutant, as used in Figure 7 J/K, is correct. christine.skerka@hki-jena.de 04-05-20: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro spr surface plasmon resonance Optical biosensor BIAcore(r) BIAcore(r) Optical biosensor spr predetermined predetermined participant predetermined Irmscher S., Brix SR., Zipfel SLH., Halder LD., Mutlutürk S., Wulf S., Girdauskas E., Reichenspurner H., Stahl RAK., Jungnickel B., Wiech T., Zipfel PF., Skerka C. [Email sent requesting species of C3b and FHR2 dimerisation mutant details - on 21/8/19). dear checker; apologies if I have missed interactions; the figures for the most part do not state any method details;so very hard to see what to curate. I have checked the occurance of every protein in the "Proteins" section to see if there are any interactions missed, but they do NOT list all the proteins they use here - e.g C3b, (presumably from Complement Tech). + other proteins. The authors have confirmed that C3b is of Human origin, and have confirmed that the mutation in the FHR2 dimerisation mutant, as used in Figure 7 J/K, is correct. christine.skerka@hki-jena.de Accepted 2020-MAR-04 AT 08:54 GMT AT 08:54 GMT by LIVIAP Nature communications 2019 Only protein-protein interactions imex curation imex curation Mock publication and experiment for abstract interactions that are not interaction evidences. Mock publication and experiment for abstract interactions that are not interaction evidences. unspecified method Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Nature communications 2019 imex curation Irmscher S., Brix SR., Zipfel SLH., Halder LD., Mutlutürk S., Wulf S., Girdauskas E., Reichenspurner H., Stahl RAK., Jungnickel B., Wiech T., Zipfel PF., Skerka C. [Email sent requesting species of C3b and FHR2 dimerisation mutant details - on 21/8/19). dear checker; apologies if I have missed interactions; the figures for the most part do not state any method details;so very hard to see what to curate. I have checked the occurance of every protein in the "Proteins" section to see if there are any interactions missed, but they do NOT list all the proteins they use here - e.g C3b, (presumably from Complement Tech). + other proteins. The authors have confirmed that C3b is of Human origin, and have confirmed that the mutation in the FHR2 dimerisation mutant, as used in Figure 7 J/K, is correct. christine.skerka@hki-jena.de 04-05-20: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro pla proximity ligation assay pELISA pELISA PLA antibody detection identification by antibody antibody detection Irmscher S., Brix SR., Zipfel SLH., Halder LD., Mutlutürk S., Wulf S., Girdauskas E., Reichenspurner H., Stahl RAK., Jungnickel B., Wiech T., Zipfel PF., Skerka C. [Email sent requesting species of C3b and FHR2 dimerisation mutant details - on 21/8/19). dear checker; apologies if I have missed interactions; the figures for the most part do not state any method details;so very hard to see what to curate. I have checked the occurance of every protein in the "Proteins" section to see if there are any interactions missed, but they do NOT list all the proteins they use here - e.g C3b, (presumably from Complement Tech). + other proteins. An ex vivo whole blood model system with necrotic cells; non-necrotic and necrotic cells from the same donor were mixed, and normal serum added before staining. The authors have confirmed that C3b is of Human origin, and have confirmed that the mutation in the FHR2 dimerisation mutant, as used in Figure 7 J/K, is correct. christine.skerka@hki-jena.de Accepted 2020-MAR-04 AT 08:54 GMT AT 08:54 GMT by LIVIAP Nature communications 2019 Only protein-protein interactions imex curation imex curation Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Nature communications 2019 imex curation Irmscher S., Brix SR., Zipfel SLH., Halder LD., Mutlutürk S., Wulf S., Girdauskas E., Reichenspurner H., Stahl RAK., Jungnickel B., Wiech T., Zipfel PF., Skerka C. [Email sent requesting species of C3b and FHR2 dimerisation mutant details - on 21/8/19). dear checker; apologies if I have missed interactions; the figures for the most part do not state any method details;so very hard to see what to curate. I have checked the occurance of every protein in the "Proteins" section to see if there are any interactions missed, but they do NOT list all the proteins they use here - e.g C3b, (presumably from Complement Tech). + other proteins. The authors have confirmed that C3b is of Human origin, and have confirmed that the mutation in the FHR2 dimerisation mutant, as used in Figure 7 J/K, is correct. christine.skerka@hki-jena.de 04-05-20: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-aorta Homo sapiens aorta pla proximity ligation assay pELISA pELISA PLA antibody detection identification by antibody antibody detection Irmscher S., Brix SR., Zipfel SLH., Halder LD., Mutlutürk S., Wulf S., Girdauskas E., Reichenspurner H., Stahl RAK., Jungnickel B., Wiech T., Zipfel PF., Skerka C. [Email sent requesting species of C3b and FHR2 dimerisation mutant details - on 21/8/19). dear checker; apologies if I have missed interactions; the figures for the most part do not state any method details;so very hard to see what to curate. I have checked the occurance of every protein in the "Proteins" section to see if there are any interactions missed, but they do NOT list all the proteins they use here - e.g C3b, (presumably from Complement Tech). + other proteins. Atherosclerotic plaques were obtained by surgical excision from patients with high-grade aortic sclerosis. The authors have confirmed that C3b is of Human origin, and have confirmed that the mutation in the FHR2 dimerisation mutant, as used in Figure 7 J/K, is correct. christine.skerka@hki-jena.de Accepted 2020-MAR-04 AT 08:54 GMT AT 08:54 GMT by LIVIAP Nature communications 2019 Only protein-protein interactions imex curation imex curation agre2_human Adhesion G protein-coupled receptor E2 ADGRE2 EGF-like module receptor 2 EGF-like module-containing mucin-like hormone receptor-like 2 EMR2 protein protein human Homo sapiens Human MGGRVFLVFLAFCVWLTLPGAETQDSRGCARWCPQDSSCVNATACRCNPGFSSFSEIITTPMETCDDINECATLSKVSCGKFSDCWNTEGSYDCVCSPGYEPVSGAKTFKNESENTCQDVDECQQNPRLCKSYGTCVNTLGSYTCQCLPGFKLKPEDPKLCTDVNECTSGQNPCHSSTHCLNNVGSYQCRCRPGWQPIPGSPNGPNNTVCEDVDECSSGQHQCDSSTVCFNTVGSYSCRCRPGWKPRHGIPNNQKDTVCEDMTFSTWTPPPGVHSQTLSRFFDKVQDLGRDYKPGLANNTIQSILQALDELLEAPGDLETLPRLQQHCVASHLLDGLEDVLRGLSKNLSNGLLNFSYPAGTELSLEVQKQVDRSVTLRQNQAVMQLDWNQAQKSGDPGPSVVGLVSIPGMGKLLAEAPLVLEPEKQMLLHETHQGLLQDGSPILLSDVISAFLSNNDTQNLSSPVTFTFSHRSVIPRQKVLCVFWEHGQNGCGHWATTGCSTIGTRDTSTICRCTHLSSFAVLMAHYDVQEEDPVLTVITYMGLSVSLLCLLLAALTFLLCKAIQNTSTSLHLQLSLCLFLAHLLFLVAIDQTGHKVLCSIIAGTLHYLYLATLTWMLLEALYLFLTARNLTVVNYSSINRFMKKLMFPVGYGVPAVTVAISAASRPHLYGTPSRCWLQPEKGFIWGFLGPVCAIFSVNLVLFLVTLWILKNRLSSLNSEVSTLRNTRMLAFKATAQLFILGCTWCLGILQVGPAARVMAYLFTIINSLQGVFIFLVYCLLSQQVREQYGKWSKGIRKLKTESEMHTLSSSAKADTSKPSTVN 4D38C30A07B46FF4 fhr2_human Complement factor H-related protein 2 CFHR2 CFHL2 DDESK59 FHR2 H factor-like 3 H factor-like protein 2 HFL3 protein protein human Homo sapiens Human MWLLVSVILISRISSVGGEAMFCDFPKINHGILYDEEKYKPFSQVPTGEVFYYSCEYNFVSPSKSFWTRITCAEEGWSPTPKCLRLCFFPFVENGHSESSGQTHLEGDTVQIICNTGYRLQNNENNISCVERGWSTPPKCRSTISAEKCGPPPPIDNGDITSFLLSVYAPGSSVEYQCQNLYQLEGNNQITCRNGQWSEPPKCLDPCVISQEIMEKYNIKLKWTNQQKLYSRTGDIVEFVCKSGYHPTKSHSFRAMCQNGKLVYPSCEEK E1B2E9F139B217A8 fhr1_human Complement factor H-related protein 1 CFHR1 CFHL CFHL1 CFHL1P CFHR1P FHR1 HFL1 HFL2 H factor-like protein 1 H36 protein protein human Homo sapiens Human MWLLVSVILISRISSVGGEATFCDFPKINHGILYDEEKYKPFSQVPTGEVFYYSCEYNFVSPSKSFWTRITCTEEGWSPTPKCLRLCFFPFVENGHSESSGQTHLEGDTVQIICNTGYRLQNNENNISCVERGWSTPPKCRSTDTSCVNPPTVQNAHILSRQMSKYPSGERVRYECRSPYEMFGDEEVMCLNGNWTEPPQCKDSTGKCGPPPPIDNGDITSFPLSVYAPASSVEYQCQNLYQLEGNKRITCRNGQWSEPPKCLHPCVISREIMENYNIALRWTAKQKLYLRTGESAEFVCKRGYRLSSRSHTLRTTCWDGKLEYPTCAKR C0A1B38B8B34B6EF p01024-pro_0000005908 Complement C3 beta chain C3 CPAMD1 C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1 protein protein human Homo sapiens Human SPMYSIITPNILRLESEETMVLEAHDAQGDVPVTVTVHDFPGKKLVLSSEKTVLTPATNHMGNVTFTIPANREFKSEKGRNKFVTVQATFGTQVVEKVVLVSLQSGYLFIQTDKTIYTPGSTVLYRIFTVNHKLLPVGRTVMVNIENPEGIPVKQDSLSSQNQLGVLPLSWDIPELVNMGQWKIRAYYENSPQQVFSTEFEVKEYVLPSFEVIVEPTEKFYYIYNEKGLEVTITARFLYGKKVEGTAFVIFGIQDGEQRISLPESLKRIPIEDGSGEVVLSRKVLLDGVQNPRAEDLVGKSLYVSATVILHSGSDMVQAERSGIPIVTSPYQIHFTKTPKYFKPGMPFDLMVFVTNPDGSPAYRVPVAVQGEDTVQSLTQGDGVAKLSINTHPSQKPLSITVRTKKQELSEAEQATRTMQALPYSTVGNSNNYLHLSVLRTELRPGETLNVNFLLRMDRAHEAKIRYYTYLIMNKGRLLKAGRQVREPGQDLVVLPLSITTDFIPSFRLVAYYTLIGASGQREVVADSVWVDVKDSCVGSLVVKSGQSEDRQPVPGQQMTLKIEGDHGARVVLVAVDKGVFVLNKKNKLTQSKIWDVVEKADIGCTPGSGKDYAGVFSDAGLTFTSSSGQQTAQRAELQCPQPAA 23 667 C4754001F1A97259 p01024-pro_0000005911 Complement C3b alpha' chain C3 CPAMD1 C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1 protein protein human Homo sapiens Human SNLDEDIIAEENIVSRSEFPESWLWNVEDLKEPPKNGISTKLMNIFLKDSITTWEILAVSMSDKKGICVADPFEVTVMQDFFIDLRLPYSVVRNEQVEIRAVLYNYRQNQELKVRVELLHNPAFCSLATTKRRHQQTVTIPPKSSLSVPYVIVPLKTGLQEVEVKAAVYHHFISDGVRKSLKVVPEGIRMNKTVAVRTLDPERLGREGVQKEDIPPADLSDQVPDTESETRILLQGTPVAQMTEDAVDAERLKHLIVTPSGCGEQNMIGMTPTVIAVHYLDETEQWEKFGLEKRQGALELIKKGYTQQLAFRQPSSAFAAFVKRAPSTWLTAYVVKVFSLAVNLIAIDSQVLCGAVKWLILEKQKPDGVFQEDAPVIHQEMIGGLRNNNEKDMALTAFVLISLQEAKDICEEQVNSLPGSITKAGDFLEANYMNLQRSYTVAIAGYALAQMGRLKGPLLNKFLTTAKDKNRWEDPGKQLYNVEATSYALLALLQLKDFDFVPPVVRWLNEQRYYGGGYGSTQATFMVFQALAQYQKDAPDHQELNLDVSLQLPSRSSKITHRIHWESASLLRSEETKENEGFTVTAEGKGQGTLSVVTMYHAKAKDQLTCNKFDLKVTIKPAPETEKRPQDAKNTMILEICTRYRGDQDATMSILDISMMTGFAPDTDDLKQLANGVDRYISKYELDKAFSDRNTLIIYLDKVSHSEDDCLAFKVHQYFNVELIQPGAVKVYAYYNLEESCTRFYHPEKEDGKLNKLCRDELCRCAEENCFIQKSDDKVTLEERLDKACEPGVDYVYKTRLVKVQLSNDFDEYIMAIEQTIKSGSDEVQVGQQRTFISPIKCREALKLEEKKHYLMWGLSSDFWGEKPNLSYIIGKDTWVEHWPEEDECQDEENQKQCQDLGAFTESMVVFGCPN 749 1663 1E32EA0CEA20EA81 cfhr1-adgre2-1 2 7 unspecified role unspecified role prey prey purified purified C-terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region sufficient to bind sufficient binding region sufficient to bind range range certain certain sequence position certain crigr-cho chinese hamster ovary cell line cho chinese hamster ovary cell line Also called LR73 cells. 9 unspecified role unspecified role bait bait purified purified picpa Pichia pastoris (Yeast) Yeast Pichia pastoris direct interaction direct interaction 4G cfhr1-adgre2-2 3 7 unspecified role unspecified role bait bait purified purified C-terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region sufficient to bind sufficient binding region sufficient to bind range range certain certain sequence position certain crigr-cho chinese hamster ovary cell line cho chinese hamster ovary cell line Also called LR73 cells. 9 unspecified role unspecified role prey prey purified purified picpa Pichia pastoris (Yeast) Yeast Pichia pastoris direct interaction direct interaction 4H adgre2-cfhr1-1 5 7 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level human-monocyte Human mononuclear cells monocyte Monocyte, mononuclear cell 9 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level human-serum Homo sapiens serum Serum physical association physical association 5J, Supplementary Fig. 3H FHR1/EMR2 complexes were identified on monocytes that were in contact with necrotic cells or cell debris. adgre2-cfhr1-2 1 7 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level 9 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level proximity proximity close-contact colocalization neighbourhood interaction 7C, Supplementary Fig 4C FHR1/EMR2 complexes were identified in patients with antibody-associated vasculitis (AAV) and atherosclerosis (AS). adgre2-cfhr1-3 6 7 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level 9 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level proximity proximity close-contact colocalization neighbourhood interaction Supplementary Fig 4B FHR1/EMR2 complexes were identified in patients with antibody-associated vasculitis (AAV) and atherosclerosis (AS). cfhr1-adgre2-3 2 33 unspecified role unspecified role bait bait purified purified human-serum Homo sapiens serum Serum 9 unspecified role unspecified role prey prey purified purified picpa Pichia pastoris (Yeast) Yeast Pichia pastoris direct interaction direct interaction Supplementary figure 3F cfhr1-adgre2-4 2 9 unspecified role unspecified role prey prey purified purified picpa Pichia pastoris (Yeast) Yeast Pichia pastoris 9 unspecified role unspecified role bait bait purified purified SCR/Sushi_domains 1+2 sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain picpa Pichia pastoris (Yeast) Yeast Pichia pastoris direct interaction direct interaction 7 J cfhr1-cfhr1-1 2 9 unspecified role unspecified role prey prey purified purified picpa Pichia pastoris (Yeast) Yeast Pichia pastoris 9 unspecified role unspecified role bait bait purified purified SCR/Sushi_domains 1+2 sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain picpa Pichia pastoris (Yeast) Yeast Pichia pastoris 8 competitor competitor competitor unspecified role unspecified role purified purified P36980:p.[Tyr52Ser;Ser54Tyr;Tyr57Glu] mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain S Y certain certain sequence position certain certain certain sequence position certain Y S certain certain sequence position certain certain certain sequence position certain Y E Wed Sep 18 13:46:59 BST 2019 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Tyr52Ser;Ser54Tyr;Tyr57Glu]' Tue Jun 30 19:55:06 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Tyr52Ser;Ser54Tyr;Tyr57Glu]' picpa Pichia pastoris (Yeast) Yeast Pichia pastoris physical association physical association 7 J/K c3b_human Complement C3b complex C3b dimer 11 unspecified role unspecified role C3 beta chain binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 10 unspecified role unspecified role C3b alpha(prime) chain binding region binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 46 48 physical association physical association human Homo sapiens Human stable complex stable complex physical interaction evidence used in manual assertion physical interaction evidence used in manual assertion IPI inferred from physical interaction 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. 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. Heterodimer 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. 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. 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. Accepted 2017-JAN-19 by ORCHARD coronavirus