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/ http://www.ebi.ac.uk/ tvorogov-2010-1 Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. in vitro In vitro solid phase assay solid phase assay western blot western blot Immuno blot Immuno blot Tvorogov D., Anisimov A., Zheng W., Leppanen VM., Tammela T., Laurinavicius S., Holnthoner W., Helotera H., Holopainen T., Jeltsch M., Kalkkinen N., Lankinen H., Ojala PM., Alitalo K. Cancer - Interactions investigated in the context of cancer Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Details of molecules provided by authors. kari.alitalo@helsinki.fi Cancer Cell (1535-6108) 2010 Only protein-protein interactions imex curation tvorogov-2010-2 Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. in vitro In vitro solid phase assay solid phase assay predetermined predetermined participant predetermined Tvorogov D., Anisimov A., Zheng W., Leppanen VM., Tammela T., Laurinavicius S., Holnthoner W., Helotera H., Holopainen T., Jeltsch M., Kalkkinen N., Lankinen H., Ojala PM., Alitalo K. Cancer - Interactions investigated in the context of cancer Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Details of molecules provided by authors. kari.alitalo@helsinki.fi Cancer Cell (1535-6108) 2010 Only protein-protein interactions imex curation tvorogov-2010-3 Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. human-endothelium Homo sapiens endothelail cells/endothelium endothelium Endothelial cells [endothelium] anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Tvorogov D., Anisimov A., Zheng W., Leppanen VM., Tammela T., Laurinavicius S., Holnthoner W., Helotera H., Holopainen T., Jeltsch M., Kalkkinen N., Lankinen H., Ojala PM., Alitalo K. Cancer - Interactions investigated in the context of cancer Antibody-mediated inhibition of VEGF-C binding to VEGFR-3. Details of molecules provided by authors. kari.alitalo@helsinki.fi Cancer Cell (1535-6108) 2010 Only protein-protein interactions imex curation vegfc_human Vascular endothelial growth factor C VEGFC Flt4 ligand Vascular endothelial growth factor-related protein protein protein human Homo sapiens Human MHLLGFFSVACSLLAAALLPGPREAPAAAAAFESGLDLSDAEPDAGEATAYASKDLEEQLRSVSSVDELMTVLYPEYWKMYKCQLRKGGWQHNREQANLNSRTEETIKFAAAHYNTEILKSIDNEWRKTQCMPREVCIDVGKEFGVATNTFFKPPCVSVYRCGGCCNSEGLQCMNTSTSYLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVYRQVHSIIRRSLPATLPQCQAANKTCPTNYMWNNHICRCLAQEDFMFSSDAGDDSTDGFHDICGPNKELDEETCQCVCRAGLRPASCGPHKELDRNSCQCVCKNKLFPSQCGANREFDENTCQCVCKRTCPRNQPLNPGKCACECTESPQKCLLKGKKFHHQTCSCYRRPCTNRQKACEPGFSYSEEVCRCVPSYWKRPQMS vgfr3_human Vascular endothelial growth factor receptor 3 Tyrosine-protein kinase receptor FLT4 FLT4 Fms-like tyrosine kinase 4 VEGFR3 protein protein human Homo sapiens Human MQRGAALCLRLWLCLGLLDGLVSGYSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPATGDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHITGNELYDIQLLPRKSLELLVGEKLVLNCTVWAEFNSGVTFDWDYPGKQAERGKWVPERRSQQTHTELSSILTIHNVSQHDLGSYVCKANNGIQRFRESTEVIVHENPFISVEWLKGPILEATAGDELVKLPVKLAAYPPPEFQWYKDGKALSGRHSPHALVLKEVTEASTGTYTLALWNSAAGLRRNISLELVVNVPPQIHEKEASSPSIYSRHSRQALTCTAYGVPLPLSIQWHWRPWTPCKMFAQRSLRRRQQQDLMPQCRDWRAVTTQDAVNPIESLDTWTEFVEGKNKTVSKLVIQNANVSAMYKCVVSNKVGQDERLIYFYVTTIPDGFTIESKPSEELLEGQPVLLSCQADSYKYEHLRWYRLNLSTLHDAHGNPLLLDCKNVHLFATPLAASLEEVAPGARHATLSLSIPRVAPEHEGHYVCEVQDRRSHDKHCHKKYLSVQALEAPRLTQNLTDLLVNVSDSLEMQCLVAGAHAPSIVWYKDERLLEEKSGVDLADSNQKLSIQRVREEDAGRYLCSVCNAKGCVNSSASVAVEGSEDKGSMEIVILVGTGVIAVFFWVLLLLIFCNMRRPAHADIKTGYLSIIMDPGEVPLEEQCEYLSYDASQWEFPRERLHLGRVLGYGAFGKVVEASAFGIHKGSSCDTVAVKMLKEGATASEHRALMSELKILIHIGNHLNVVNLLGACTKPQGPLMVIVEFCKYGNLSNFLRAKRDAFSPCAEKSPEQRGRFRAMVELARLDRRRPGSSDRVLFARFSKTEGGARRASPDQEAEDLWLSPLTMEDLVCYSFQVARGMEFLASRKCIHRDLAARNILLSESDVVKICDFGLARDIYKDPDYVRKGSARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEEFCQRLRDGTRMRAPELATPAIRRIMLNCWSGDPKARPAFSELVEILGDLLQGRGLQEEEEVCMAPRSSQSSEEGSFSQVSTMALHIAQADAEDSPPSLQRHSLAARYYNWVSFPGCLARGAETRGSSRMKTFEEFPMTPTTYKGSVDNQTDSGMVLASEEFEQIESRHRQESGFSCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHCSPSARVTFFTDNSY vgfr2_human Vascular endothelial growth factor receptor 2 Kinase insert domain receptor Protein-tyrosine kinase receptor flk-1 KDR FLK1 Fetal liver kinase 1 VEGFR2 protein protein human Homo sapiens Human MQSKVLLAVALWLCVETRAASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLDWLWPNNQSGSEQRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQDYRSPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDGNRISWDSKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKPFVAFGSGMESLVEATVGERVRIPAKYLGYPPPEIKWYKNGIPLESNHTIKAGHVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVPPQIGEKSLISPVDSYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPYPCEEWRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVNKVGRGERVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYKLGPQPLPIHVGELPTPVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQDQGDYVCLAQDRKTKKRHCVVRQLTVLERVAPTITGNLENQTTSIGESIEVSCTASGNPPPQIMWFKDNETLVEDSGIVLKDGNRNLTIRRVRKEDEGLYTCQACSVLGCAKVEAFFIIEGAQEKTNLEIIILVGTAVIAMFFWLLLVIILRTVKRANGGELKTGYLSIVMDPDELPLDEHCERLPYDASKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFRQGKDYVGAIPVDLKRRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHGEPSQRPTFSELVEHLGNLLQANAQQDGKDYIVLPISETLSMEEDSGLSLPTSPVSCMEEEEVCDPKFHYDNTAGISQYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDNQTDSGMVLASEELKTLEDRTKLSPSFGGMVPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYSSEEAELLKLIEIGVQTGSTAQILQPDSGTTLSSPPV vegfc-vegfr3 1012108 n/a 1012111 unspecified role unspecified role bait bait c_terminal 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 false vegfc_mature sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false drome-schneider_2 Drosophila melanogaster late embryo cells Fruit fly schneider_2 Established from the late embryo of Drosophila melanogaster Mixture of diploid and tetraploid. Originally had some XY cells now predominantly XX. n/a 1012112 unspecified role unspecified role prey prey region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false drome-schneider_2 Drosophila melanogaster late embryo cells Fruit fly schneider_2 Established from the late embryo of Drosophila melanogaster Mixture of diploid and tetraploid. Originally had some XY cells now predominantly XX. physical association physical association false false false Fig 1C Unlike the 3C5 antibody, the 2E11 antibody did not block the binding of VEGFR-3 extracellular domain to immobilized VEGF-C. 3C5 antibody vegfc-flt4 1012109 n/a 1012111 unspecified role unspecified role bait bait vegfc_mature sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false c_terminal 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 false drome-schneider_2 Drosophila melanogaster late embryo cells Fruit fly schneider_2 Established from the late embryo of Drosophila melanogaster Mixture of diploid and tetraploid. Originally had some XY cells now predominantly XX. n/a 1012112 unspecified role unspecified role prey prey region alk phosphatase tag alkaline phosphatase tag alk phosphatase tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false mouse-3t3 Mus musculus embryo cells 3t3 Mouse embryo fibroblast cells physical association physical association false false false Fig 1D Unlike the 3C5 antibody, the 2E11 antibody did not block the binding of VEGFR-3 extracellular domain to immobilized VEGF-C. flt4-kdr-2 1012110 n/a 1012112 unspecified role unspecified role bait bait n/a 1012113 unspecified role unspecified role prey prey physical association physical association false false false Fig 4A. VEGF-C Antibodies 2E11 and 3C5 inhibit the formation of VEGFR-2/VEGFR-3 heterodimers.