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/ Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. The Journal of biological chemistry 2015 imex curation Fisher OS., Liu W., Zhang R., Stiegler AL., Ghedia S., Weber JL., Boggon TJ. Rare diseases - Interactions investigated in the context of Rare genetic disease titus.boggon@yale.edu 21-Nov-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. anti tag coip anti tag coimmunoprecipitation anti tag coip anti tag western anti tag western blot anti tag western Fisher OS., Liu W., Zhang R., Stiegler AL., Ghedia S., Weber JL., Boggon TJ. Rare diseases - Interactions investigated in the context of Rare genetic disease titus.boggon@yale.edu Accepted 2019-NOV-04 AT 11:33 GMT AT 11:33 GMT by PPORRAS The Journal of biological chemistry 2015 Only protein-protein interactions imex curation imex curation Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. The Journal of biological chemistry 2015 imex curation Fisher OS., Liu W., Zhang R., Stiegler AL., Ghedia S., Weber JL., Boggon TJ. Rare diseases - Interactions investigated in the context of Rare genetic disease titus.boggon@yale.edu 21-Nov-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro bio-layer interferometry bio-layer interferometry bli bli predetermined predetermined participant predetermined Fisher OS., Liu W., Zhang R., Stiegler AL., Ghedia S., Weber JL., Boggon TJ. Rare diseases - Interactions investigated in the context of Rare genetic disease titus.boggon@yale.edu Accepted 2019-NOV-04 AT 11:33 GMT AT 11:33 GMT by PPORRAS The Journal of biological chemistry 2015 Only protein-protein interactions imex curation imex curation Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. The Journal of biological chemistry 2015 imex curation Fisher OS., Liu W., Zhang R., Stiegler AL., Ghedia S., Weber JL., Boggon TJ. Rare diseases - Interactions investigated in the context of Rare genetic disease titus.boggon@yale.edu 21-Nov-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro x-ray diffraction x-ray crystallography X-ray X-ray x-ray diffraction predetermined predetermined participant predetermined Fisher OS., Liu W., Zhang R., Stiegler AL., Ghedia S., Weber JL., Boggon TJ. Rare diseases - Interactions investigated in the context of Rare genetic disease titus.boggon@yale.edu Accepted 2019-NOV-04 AT 11:33 GMT AT 11:33 GMT by PPORRAS The Journal of biological chemistry 2015 Only protein-protein interactions imex curation imex curation Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. The Journal of biological chemistry 2015 imex curation Fisher OS., Liu W., Zhang R., Stiegler AL., Ghedia S., Weber JL., Boggon TJ. Rare diseases - Interactions investigated in the context of Rare genetic disease titus.boggon@yale.edu 21-Nov-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro pull down pull down weight by comassie molecular weight estimation by coomasie staining weight by comassie Fisher OS., Liu W., Zhang R., Stiegler AL., Ghedia S., Weber JL., Boggon TJ. Rare diseases - Interactions investigated in the context of Rare genetic disease titus.boggon@yale.edu Accepted 2019-NOV-04 AT 11:33 GMT AT 11:33 GMT by PPORRAS The Journal of biological chemistry 2015 Only protein-protein interactions imex curation imex curation Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. The Journal of biological chemistry 2015 imex curation Fisher OS., Liu W., Zhang R., Stiegler AL., Ghedia S., Weber JL., Boggon TJ. Rare diseases - Interactions investigated in the context of Rare genetic disease titus.boggon@yale.edu 21-Nov-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation in vitro In vitro molecular sieving molecular sieving Gel Filtration Size Exclusion Chromatography Size Exclusion Chromatography Gel Filtration Sizing column weight identificat confirmation by molecular weight weight identificat Fisher OS., Liu W., Zhang R., Stiegler AL., Ghedia S., Weber JL., Boggon TJ. Rare diseases - Interactions investigated in the context of Rare genetic disease titus.boggon@yale.edu Accepted 2019-NOV-04 AT 11:33 GMT AT 11:33 GMT by PPORRAS The Journal of biological chemistry 2015 Only protein-protein interactions imex curation imex curation ccm2_human Cerebral cavernous malformations 2 protein CCM2 C7orf22 Malcavernin PP10187 protein protein human Homo sapiens Human MEEEGKKGKKPGIVSPFKRVFLKGEKSRDKKAHEKVTERRPLHTVVLSLPERVEPDRLLSDYIEKEVKYLGQLTSIPGYLNPSSRTEILHFIDNAKRAHQLPGHLTQEHDAVLSLSAYNVKLAWRDGEDIILRVPIHDIAAVSYVRDDAAHLVVLKTAQDPGISPSQSLCAESSRGLSAGSLSESAVGPVEACCLVILAAESKVAAEELCCLLGQVFQVVYTESTIDFLDRAIFDGASTPTHHLSLHSDDSSTKVDIKETYEVEASTFCFPESVDVGGASPHSKTISESELSASATELLQDYMLTLRTKLSSQEIQQFAALLHEYRNGASIHEFCINLRQLYGDSRKFLLLGLRPFIPEKDSQHFENFLETIGVKDGRGIITDSFGRHRRALSTTSSSTTNGNRATGSSDDRSAPSEGDEWDRMISDISSDIEALGCSMDQDSA 43F9C153B4DE460E krit1_human Krev interaction trapped protein 1 KRIT1 CCM1 Cerebral cavernous malformations 1 protein protein protein human Homo sapiens Human MGNPENIEDAYVAVIRPKNTASLNSREYRAKSYEILLHEVPIEGQKKKRKKVLLETKLQGNSEITQGILDYVVETTKPISPANQGIRGKRVVLMKKFPLDGEKMGREASLFIVPSVVKDNTKYTYTPGCPIFYCLQDIMRVCSESSTHFATLTARMLIALDKWLDERHAQSHFIPALFRPSPLERIKTNVINPAYATESGQTENSLHMGYSALEIKSKMLALEKADTCIYNPLFGSDLQYTNRVDKVVINPYFGLGAPDYSKIQIPKQEKWQRSMSSVTEDKERQWVDDFPLHRSACEGDSELLSRLLSERFSVNQLDSDHWAPIHYACWYGKVEATRILLEKGKCNPNLLNGQLSSPLHFAAGGGHAEIVQILLNHPETDRHITDQQGRSPLNICEENKQNNWEEAAKLLKEAINKPYEKVRIYRMDGSYRSVELKHGNNTTVQQIMEGMRLSQETQQYFTIWICSENLSLQLKPYHKPLQHVRDWPEILAELTNLDPQRETPQLFLRRDVRLPLEVEKQIEDPLAILILFDEARYNLLKGFYTAPDAKLITLASLLLQIVYGNYESKKHKQGFLNEENLKSIVPVTKLKSKAPHWTNRILHEYKNLSTSEGVSKEMHHLQRMFLQNCWEIPTYGAAFFTGQIFTKASPSNHKVIPVYVGVNIKGLHLLNMETKALLISLKYGCFMWQLGDTDTCFQIHSMENKMSFIVHTKQAGLVVKLLMKLNGQLMPTERNS DIP protein O00522 original sequence version: 156 D11F75ED629E85AC krit1-ccm2-3 1 6 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed living cell living cell Q9BSQ5:p.Cys210Asp mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain C D Tue Jun 30 19:23:03 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Cys210Asp' Q9BSQ5:p.[Ile136Ala;Ile139Ala] mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain I A certain certain sequence position certain certain certain sequence position certain I A Tue Jun 30 19:52:59 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Ile136Ala;Ile139Ala]' region flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 7 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed living cell living cell region gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association Figure 5f ccm2-krit1-9 4 6 unspecified role unspecified role prey prey purified purified Q9BSQ5:p.Cys210Asp mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain C D Tue Jun 30 17:54:07 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Cys210Asp' Q9BSQ5:p.[Ile136Ala;Ile139Ala] mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain I A certain certain sequence position certain certain certain sequence position certain I A Tue Jun 30 20:11:02 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Ile136Ala;Ile139Ala]' Q9BSQ5:p.Phe217Ala mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain F A Tue Jun 30 16:06:21 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe217Ala' region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range ecoli Escherichia coli (strain K12) 7 unspecified role unspecified role bait bait purified purified O00522:p.Val248Asp mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain V D Tue Jun 30 19:39:10 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Val248Asp' O00522:p.[Tyr252Ala;Phe253Ala] mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain Y A certain certain sequence position certain certain certain sequence position certain F A Tue Jun 30 18:26:17 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Tyr252Ala;Phe253Ala]' O00522:p.Val244Leu mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain V L Tue Jun 30 18:24:00 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Val244Leu' region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) direct interaction direct interaction Figure 2c, 5b, 5c, 5d, 6c, 6d krit1-ccm2-4 3 6 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range ecoli Escherichia coli (strain K12) 7 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined direct interaction direct interaction Table 2, Figure 3a 2.75Å Rwork: 0.22 Rfree: 0.25 ccm2-krit1-10 5 6 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range ecoli Escherichia coli (strain K12) 7 unspecified role unspecified role neutral component neutral component purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined direct interaction direct interaction Figure 2e ccm2-krit1-11 2 6 unspecified role unspecified role unspecified role unspecified role purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range ecoli Escherichia coli (strain K12) 7 unspecified role unspecified role unspecified role unspecified role purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ecoli Escherichia coli (strain K12) direct interaction direct interaction Figure 5a, Table 4 ccm2-krit1-12 2 6 unspecified role unspecified role unspecified role unspecified role purified purified region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range ecoli Escherichia coli (strain K12) 7 unspecified role unspecified role unspecified role unspecified role purified purified region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain region biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range region binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction Figure 5a, Table 4 krit1-ccm2-5 1 6 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed living cell living cell region flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 7 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed living cell living cell O00522:p.Tyr195Ala mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain Y A Tue Jun 30 18:10:21 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Tyr195Ala' region gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined O00522:p.Phe234Ala mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain F A Tue Jun 30 17:01:34 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe234Ala' O00522:p.[Tyr252Ala;Phe253Ala] mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain Y A certain certain sequence position certain certain certain sequence position certain F A Tue Jun 30 19:28:22 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Tyr252Ala;Phe253Ala]' O00522:p.[Phe234Ala;Tyr252Ala;Phe253Ala] mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain F A certain certain sequence position certain certain certain sequence position certain Y A certain certain sequence position certain certain certain sequence position certain F A Wed Sep 18 13:35:55 BST 2019 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Phe254Ala;Thr252Ala;Phe253Ala]' Tue Jun 30 18:12:10 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.[Phe234Ala;Tyr252Ala;Phe253Ala]' physical association physical association Figure 2b