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/ Monomeric C-reactive protein inhibits renal cell-directed complement activation mediated by properdin. Monomeric C-reactive protein inhibits renal cell-directed complement activation mediated by properdin. American journal of physiology. Renal physiology 2016 imex curation O'Flynn J., van der Pol P., Dixon KO., Prohászka Z., Daha MR., van Kooten C. J.O_flynn@lumc.nl 21-Nov-2019: 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 O'Flynn J., van der Pol P., Dixon KO., Prohászka Z., Daha MR., van Kooten C. CRP is composed of five identical subunits that are stabilized by calcium ions. This 125-kDa pentameric form (pCRP) is modified on calcium depletion, heat or urea treatment and dissociates into monomeric units of 23 kDa, termed monomeric CRP (mCRP). J.O_flynn@lumc.nl Accepted 2019-OCT-03 AT 09:31 BST AT 09:31 BST by LIVIAP American journal of physiology. Renal physiology 2016 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 p02741-pro_0000023526 C-reactive protein CRP PTX1 protein protein human Homo sapiens Human QTDMSRKAFVFPKESDTSYVSLKAPLTKPLKAFTVCLHFYTELSSTRGYSIFSYATKRQDNEILIFWSKDIGYSFTVGGSEILFEVPEVTVAPVHICTSWESASGIVEFWVDGKPRVRKSLKKGYTVGAEASIILGQEQDSFGGNFEGSQSLVGDIGNVNMWDFVLSPDEINTIYLGGPFSPNVLNWRALKYEVQGEVFTKPQLWP 19 224 A92702FEF9CEDFBF 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 prop_human Properdin CFP PFC Complement factor P protein protein human Homo sapiens Human MITEGAQAPRLLLPPLLLLLTLPATGSDPVLCFTQYEESSGKCKGLLGGGVSVEDCCLNTAFAYQKRSGGLCQPCRSPRWSLWSTWAPCSVTCSEGSQLRYRRCVGWNGQCSGKVAPGTLEWQLQACEDQQCCPEMGGWSGWGPWEPCSVTCSKGTRTRRRACNHPAPKCGGHCPGQAQESEACDTQQVCPTHGAWATWGPWTPCSASCHGGPHEPKETRSRKCSAPEPSQKPPGKPCPGLAYEQRRCTGLPPCPVAGGWGPWGPVSPCPVTCGLGQTMEQRTCNHPVPQHGGPFCAGDATRTHICNTAVPCPVDGEWDSWGEWSPCIRRNMKSISCQEIPGQQSRGRTCRGRKFDGHRCAGQQQDIRHCYSIQHCPLKGSWSEWSTWGLCMPPCGPNPTRARQRLCTPLLPKYPPTVSMVEGQGEKNVTFWGRPLPRCEELQGQKLVVEEKRPCLHVPACKDPEEEEL 5EB42B63F0283917 crp-cfp-1 1 6 unspecified role unspecified role prey prey purified purified human-blood human blood blood BLOOD 3 unspecified role unspecified role bait bait purified purified n-formylmet modres protein modification ModRes certain certain sequence position certain certain certain sequence position certain P02741-PRO_0000023526:p.[Cys36Ala;Cys97Ala] mutation mutation certain certain sequence position certain certain certain sequence position certain C A certain certain sequence position certain certain certain sequence position certain C A Wed Sep 25 15:19:13 BST 2019 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Cyc36Ala;Cys97Ala' Tue Jun 30 19:29:22 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Cys36Ala;Cys97Ala]' ecoli Escherichia coli (strain K12) direct interaction direct interaction 3A The mod =MOD:00482 -n-formly-met is not in the Database, even as "hidden". crp-cfp-2 1 14 unspecified role unspecified role prey prey purified purified 6 unspecified role unspecified role ancillary ancillary purified purified human-blood human blood blood BLOOD 3 unspecified role unspecified role bait bait purified purified n-formylmet modres protein modification ModRes certain certain sequence position certain certain certain sequence position certain P02741-PRO_0000023526:p.[Cys36Ala;Cys97Ala] mutation mutation certain certain sequence position certain certain certain sequence position certain C A certain certain sequence position certain certain certain sequence position certain C A Wed Sep 25 14:39:24 BST 2019 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Cyc36Ala;Cys97Ala' Tue Jun 30 17:03:32 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Cys36Ala;Cys97Ala]' ecoli Escherichia coli (strain K12) physical association physical association 3B The mod =MOD:00482 -n-formly-met is not in the Database, even as "hidden". c3b_human Complement C3b complex C3b dimer 5 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 4 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 22 20 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