PubMed:27798112 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/27798112","sourcedb":"PubMed","sourceid":"27798112","text":"Leucine-rich repeat kinase 2 exacerbates neuronal cytotoxicity through phosphorylation of histone deacetylase 3 and histone deacetylation.\nParkinson's disease (PD) is characterized by slow, progressive degeneration of dopaminergic neurons in the substantia nigra. The cause of neuronal death in PD is largely unknown, but several genetic loci, including leucine-rich repeat kinase 2 (LRRK2), have been identified. LRRK2 has guanosine triphosphatase (GTPase) and kinase activities, and mutations in LRRK2 are the major cause of autosomal-dominant familial PD. Histone deacetylases (HDACs) remove acetyl groups from lysine residues on histone tails, promoting transcriptional repression via condensation of chromatin. Here, we demonstrate that LRRK2 binds to and directly phosphorylates HDAC3 at Ser-424, thereby stimulating HDAC activity. Specifically, LRRK2 promoted the deacetylation of Lys-5 and Lys-12 on histone H4, causing repression of gene transcription. Moreover, LRRK2 stimulated nuclear translocation of HDAC3 via the phoshorylation of karyopherin subunit α2 and α6. HDAC3 phosphorylation and its nuclear translocation were increased in response to 6-hydroxydopamine (6-OHDA) treatment. LRRK2 also inhibited myocyte-specific enhancer factor 2D activity, which is required for neuronal survival. LRRK2 ultimately promoted 6-OHDA-induced cell death via positive modulation of HDAC3. These findings suggest that LRRK2 affects epigenetic histone modification and neuronal survival by facilitating HDAC3 activity and regulating its localization.","tracks":[{"project":"c_corpus","denotations":[{"id":"T2","span":{"begin":0,"end":7},"obj":"6308"},{"id":"T3","span":{"begin":0,"end":7},"obj":"SO:0001437"},{"id":"T1","span":{"begin":0,"end":7},"obj":"CHEBI:15603"},{"id":"T4","span":{"begin":0,"end":7},"obj":"D007930"},{"id":"T5","span":{"begin":0,"end":7},"obj":"CHEBI:25017"},{"id":"T6","span":{"begin":0,"end":7},"obj":"D007930"},{"id":"T7","span":{"begin":13,"end":19},"obj":"SO:0001068"},{"id":"T8","span":{"begin":71,"end":86},"obj":"GO:0016310"},{"id":"T13","span":{"begin":90,"end":111},"obj":"Q6P6W3"},{"id":"T14","span":{"begin":90,"end":111},"obj":"O88895"},{"id":"T15","span":{"begin":90,"end":111},"obj":"Q7Y0Y6"},{"id":"T16","span":{"begin":90,"end":111},"obj":"P56520"},{"id":"T17","span":{"begin":90,"end":111},"obj":"Q803C3"},{"id":"T18","span":{"begin":90,"end":111},"obj":"O15379"},{"id":"T20","span":{"begin":90,"end":111},"obj":"Q5RB76"},{"id":"T21","span":{"begin":90,"end":111},"obj":"PR:000008482"},{"id":"T22","span":{"begin":90,"end":111},"obj":"Q28DV3"},{"id":"T23","span":{"begin":90,"end":111},"obj":"Q4SFA0"},{"id":"T24","span":{"begin":90,"end":111},"obj":"Q6IRL9"},{"id":"T19","span":{"begin":90,"end":111},"obj":"C438596"},{"id":"T26","span":{"begin":116,"end":123},"obj":"PR:000041244"},{"id":"T25","span":{"begin":116,"end":123},"obj":"D006657"},{"id":"T27","span":{"begin":116,"end":123},"obj":"CHEBI:15358"},{"id":"T28","span":{"begin":116,"end":137},"obj":"GO:0016575"},{"id":"T29","span":{"begin":124,"end":137},"obj":"MOP:0001030"},{"id":"T30","span":{"begin":151,"end":158},"obj":"D004194"},{"id":"T31","span":{"begin":151,"end":158},"obj":"D004194"},{"id":"T32","span":{"begin":246,"end":262},"obj":"UBERON:0002038"},{"id":"T33","span":{"begin":309,"end":316},"obj":"32644"},{"id":"T35","span":{"begin":354,"end":361},"obj":"6308"},{"id":"T36","span":{"begin":354,"end":361},"obj":"SO:0001437"},{"id":"T34","span":{"begin":354,"end":361},"obj":"CHEBI:15603"},{"id":"T37","span":{"begin":354,"end":361},"obj":"D007930"},{"id":"T38","span":{"begin":354,"end":361},"obj":"CHEBI:25017"},{"id":"T39","span":{"begin":354,"end":361},"obj":"D007930"},{"id":"T40","span":{"begin":367,"end":373},"obj":"SO:0001068"},{"id":"T41","span":{"begin":384,"end":389},"obj":"PR:Q5S006"},{"id":"T42","span":{"begin":384,"end":389},"obj":"PR:000003033"},{"id":"T43","span":{"begin":384,"end":389},"obj":"PR:Q5S007"},{"id":"T44","span":{"begin":414,"end":419},"obj":"PR:Q5S006"},{"id":"T45","span":{"begin":414,"end":419},"obj":"PR:000003033"},{"id":"T46","span":{"begin":414,"end":419},"obj":"PR:Q5S007"},{"id":"T47","span":{"begin":424,"end":433},"obj":"D006151"},{"id":"T48","span":{"begin":424,"end":433},"obj":"CHEBI:16750"},{"id":"T49","span":{"begin":424,"end":433},"obj":"D006151"},{"id":"T50","span":{"begin":434,"end":448},"obj":"Q9SIY3"},{"id":"T51","span":{"begin":450,"end":456},"obj":"D020558"},{"id":"T52","span":{"begin":498,"end":503},"obj":"PR:Q5S006"},{"id":"T53","span":{"begin":498,"end":503},"obj":"PR:000003033"},{"id":"T54","span":{"begin":498,"end":503},"obj":"PR:Q5S007"},{"id":"T55","span":{"begin":527,"end":545},"obj":"C566739"},{"id":"T57","span":{"begin":559,"end":566},"obj":"PR:000041244"},{"id":"T59","span":{"begin":559,"end":579},"obj":"D006655"},{"id":"T60","span":{"begin":595,"end":601},"obj":"CHEBI:40574"},{"id":"T61","span":{"begin":595,"end":601},"obj":"CHEBI:46887"},{"id":"T62","span":{"begin":614,"end":620},"obj":"SO:0001450"},{"id":"T63","span":{"begin":614,"end":620},"obj":"CHEBI:25094"},{"id":"T64","span":{"begin":614,"end":620},"obj":"D008239"},{"id":"T66","span":{"begin":614,"end":620},"obj":"D008239"},{"id":"T67","span":{"begin":614,"end":620},"obj":"CHEBI:18019"},{"id":"T65","span":{"begin":614,"end":620},"obj":"6536"},{"id":"T69","span":{"begin":633,"end":640},"obj":"PR:000041244"},{"id":"T68","span":{"begin":633,"end":640},"obj":"D006657"},{"id":"T70","span":{"begin":633,"end":640},"obj":"CHEBI:15358"},{"id":"T72","span":{"begin":705,"end":714},"obj":"GO:0000785"},{"id":"T71","span":{"begin":705,"end":714},"obj":"D002843"},{"id":"T73","span":{"begin":742,"end":747},"obj":"PR:Q5S006"},{"id":"T74","span":{"begin":742,"end":747},"obj":"PR:000003033"},{"id":"T75","span":{"begin":742,"end":747},"obj":"PR:Q5S007"},{"id":"T77","span":{"begin":785,"end":790},"obj":"PR:Q6P6W3"},{"id":"T78","span":{"begin":785,"end":790},"obj":"PR:O88895"},{"id":"T79","span":{"begin":785,"end":790},"obj":"PR:O15379"},{"id":"T80","span":{"begin":785,"end":790},"obj":"PR:000008482"},{"id":"T81","span":{"begin":785,"end":790},"obj":"PR:P56520"},{"id":"T82","span":{"begin":785,"end":790},"obj":"PR:Q803C3"},{"id":"T83","span":{"begin":789,"end":793},"obj":"Q9MBC1"},{"id":"T84","span":{"begin":789,"end":793},"obj":"CHEBI:40036"},{"id":"T89","span":{"begin":794,"end":797},"obj":"Q62230"},{"id":"T90","span":{"begin":794,"end":797},"obj":"PR:000001931"},{"id":"T93","span":{"begin":794,"end":797},"obj":"PR:P18168"},{"id":"T87","span":{"begin":794,"end":797},"obj":"GO:0005790"},{"id":"T91","span":{"begin":794,"end":797},"obj":"SO:0001444"},{"id":"T85","span":{"begin":794,"end":797},"obj":"CHEBI:32838"},{"id":"T86","span":{"begin":794,"end":797},"obj":"CHEBI:32839"},{"id":"T88","span":{"begin":794,"end":797},"obj":"CHEBI:29999"},{"id":"T92","span":{"begin":794,"end":797},"obj":"CHEBI:17115"},{"id":"T94","span":{"begin":823,"end":827},"obj":"PR:Q54VQ7"},{"id":"T95","span":{"begin":852,"end":857},"obj":"PR:Q5S006"},{"id":"T96","span":{"begin":852,"end":857},"obj":"PR:000003033"},{"id":"T97","span":{"begin":852,"end":857},"obj":"PR:Q5S007"},{"id":"T98","span":{"begin":871,"end":884},"obj":"MOP:0001030"},{"id":"T100","span":{"begin":888,"end":891},"obj":"CHEBI:25094"},{"id":"T101","span":{"begin":888,"end":891},"obj":"CHEBI:32563"},{"id":"T102","span":{"begin":888,"end":891},"obj":"CHEBI:133538"},{"id":"T103","span":{"begin":888,"end":891},"obj":"CHEBI:32553"},{"id":"T104","span":{"begin":888,"end":891},"obj":"CHEBI:32554"},{"id":"T105","span":{"begin":888,"end":891},"obj":"CHEBI:29967"},{"id":"T106","span":{"begin":888,"end":891},"obj":"CHEBI:18019"},{"id":"T99","span":{"begin":888,"end":891},"obj":"SO:0001450"},{"id":"T107","span":{"begin":888,"end":893},"obj":"PR:P50113"},{"id":"T108","span":{"begin":888,"end":893},"obj":"PR:Q20967"},{"id":"T110","span":{"begin":898,"end":901},"obj":"CHEBI:25094"},{"id":"T111","span":{"begin":898,"end":901},"obj":"CHEBI:32563"},{"id":"T112","span":{"begin":898,"end":901},"obj":"CHEBI:133538"},{"id":"T113","span":{"begin":898,"end":901},"obj":"CHEBI:32553"},{"id":"T114","span":{"begin":898,"end":901},"obj":"CHEBI:32554"},{"id":"T115","span":{"begin":898,"end":901},"obj":"CHEBI:29967"},{"id":"T116","span":{"begin":898,"end":901},"obj":"CHEBI:18019"},{"id":"T109","span":{"begin":898,"end":901},"obj":"SO:0001450"},{"id":"T117","span":{"begin":898,"end":904},"obj":"PR:P40495"},{"id":"T118","span":{"begin":898,"end":904},"obj":"PR:O14104"},{"id":"T122","span":{"begin":908,"end":918},"obj":"Q8SQP4"},{"id":"T123","span":{"begin":908,"end":918},"obj":"P62802"},{"id":"T124","span":{"begin":908,"end":918},"obj":"P80739"},{"id":"T125","span":{"begin":908,"end":918},"obj":"Q28DR4"},{"id":"T126","span":{"begin":908,"end":918},"obj":"Q8NIG3"},{"id":"T127","span":{"begin":908,"end":918},"obj":"P82888"},{"id":"T128","span":{"begin":908,"end":918},"obj":"P62790"},{"id":"T129","span":{"begin":908,"end":918},"obj":"P84049"},{"id":"T130","span":{"begin":908,"end":918},"obj":"P62793"},{"id":"T131","span":{"begin":908,"end":918},"obj":"Q7LKT3"},{"id":"T132","span":{"begin":908,"end":918},"obj":"P62792"},{"id":"T133","span":{"begin":908,"end":918},"obj":"Q76NW2"},{"id":"T134","span":{"begin":908,"end":918},"obj":"Q76FE7"},{"id":"T135","span":{"begin":908,"end":918},"obj":"Q6WV73"},{"id":"T136","span":{"begin":908,"end":918},"obj":"P62791"},{"id":"T137","span":{"begin":908,"end":918},"obj":"Q6WZ83"},{"id":"T138","span":{"begin":908,"end":918},"obj":"P62798"},{"id":"T139","span":{"begin":908,"end":918},"obj":"P62776"},{"id":"T140","span":{"begin":908,"end":918},"obj":"P62796"},{"id":"T141","span":{"begin":908,"end":918},"obj":"P27996"},{"id":"T143","span":{"begin":908,"end":918},"obj":"P62806"},{"id":"T144","span":{"begin":908,"end":918},"obj":"P04915"},{"id":"T145","span":{"begin":908,"end":918},"obj":"Q6ZXX3"},{"id":"T146","span":{"begin":908,"end":918},"obj":"Q8I0Y4"},{"id":"T147","span":{"begin":908,"end":918},"obj":"P80738"},{"id":"T148","span":{"begin":908,"end":918},"obj":"P59259"},{"id":"T149","span":{"begin":908,"end":918},"obj":"P62800"},{"id":"T150","span":{"begin":908,"end":918},"obj":"P62803"},{"id":"T151","span":{"begin":908,"end":918},"obj":"P50566"},{"id":"T152","span":{"begin":908,"end":918},"obj":"P62805"},{"id":"T153","span":{"begin":908,"end":918},"obj":"Q76H85"},{"id":"T154","span":{"begin":908,"end":918},"obj":"P35057"},{"id":"T155","span":{"begin":908,"end":918},"obj":"P62779"},{"id":"T156","span":{"begin":908,"end":918},"obj":"P62795"},{"id":"T157","span":{"begin":908,"end":918},"obj":"P62780"},{"id":"T158","span":{"begin":908,"end":918},"obj":"Q76FF5"},{"id":"T159","span":{"begin":908,"end":918},"obj":"Q76FF1"},{"id":"T160","span":{"begin":908,"end":918},"obj":"P84050"},{"id":"T161","span":{"begin":908,"end":918},"obj":"Q6WV90"},{"id":"T162","span":{"begin":908,"end":918},"obj":"Q9U7D0"},{"id":"T163","span":{"begin":908,"end":918},"obj":"P62778"},{"id":"T164","span":{"begin":908,"end":918},"obj":"P84043"},{"id":"T165","span":{"begin":908,"end":918},"obj":"P62804"},{"id":"T166","span":{"begin":908,"end":918},"obj":"P62799"},{"id":"T167","span":{"begin":908,"end":918},"obj":"P84046"},{"id":"T168","span":{"begin":908,"end":918},"obj":"P84042"},{"id":"T169","span":{"begin":908,"end":918},"obj":"Q6PMI5"},{"id":"T170","span":{"begin":908,"end":918},"obj":"P0CG89"},{"id":"T171","span":{"begin":908,"end":918},"obj":"P84041"},{"id":"T172","span":{"begin":908,"end":918},"obj":"P62782"},{"id":"T173","span":{"begin":908,"end":918},"obj":"Q7KQD1"},{"id":"T174","span":{"begin":908,"end":918},"obj":"P62784"},{"id":"T175","span":{"begin":908,"end":918},"obj":"Q27443"},{"id":"T176","span":{"begin":908,"end":918},"obj":"Q43083"},{"id":"T177","span":{"begin":908,"end":918},"obj":"Q76MU7"},{"id":"T178","span":{"begin":908,"end":918},"obj":"P83865"},{"id":"T179","span":{"begin":908,"end":918},"obj":"P62783"},{"id":"T180","span":{"begin":908,"end":918},"obj":"P84047"},{"id":"T181","span":{"begin":908,"end":918},"obj":"P09322"},{"id":"T182","span":{"begin":908,"end":918},"obj":"Q6WV74"},{"id":"T183","span":{"begin":908,"end":918},"obj":"P69152"},{"id":"T184","span":{"begin":908,"end":918},"obj":"P62887"},{"id":"T185","span":{"begin":908,"end":918},"obj":"P90516"},{"id":"T186","span":{"begin":908,"end":918},"obj":"Q27765"},{"id":"T187","span":{"begin":908,"end":918},"obj":"P02309"},{"id":"T188","span":{"begin":908,"end":918},"obj":"P62797"},{"id":"T189","span":{"begin":908,"end":918},"obj":"P91890"},{"id":"T190","span":{"begin":908,"end":918},"obj":"P62781"},{"id":"T191","span":{"begin":908,"end":918},"obj":"Q6V9I2"},{"id":"T192","span":{"begin":908,"end":918},"obj":"P62777"},{"id":"T193","span":{"begin":908,"end":918},"obj":"P84048"},{"id":"T194","span":{"begin":908,"end":918},"obj":"Q4R362"},{"id":"T195","span":{"begin":908,"end":918},"obj":"Q6LAF1"},{"id":"T196","span":{"begin":908,"end":918},"obj":"P04914"},{"id":"T197","span":{"begin":908,"end":918},"obj":"Q7M3Z5"},{"id":"T198","span":{"begin":908,"end":918},"obj":"P62787"},{"id":"T199","span":{"begin":908,"end":918},"obj":"P35059"},{"id":"T200","span":{"begin":908,"end":918},"obj":"P62801"},{"id":"T201","span":{"begin":908,"end":918},"obj":"P62789"},{"id":"T202","span":{"begin":908,"end":918},"obj":"Q6LAF3"},{"id":"T203","span":{"begin":908,"end":918},"obj":"PR:000008603"},{"id":"T204","span":{"begin":908,"end":918},"obj":"Q8MTV8"},{"id":"T205","span":{"begin":908,"end":918},"obj":"Q6WV72"},{"id":"T206","span":{"begin":908,"end":918},"obj":"P84045"},{"id":"T207","span":{"begin":908,"end":918},"obj":"Q5RCS7"},{"id":"T208","span":{"begin":908,"end":918},"obj":"P91882"},{"id":"T209","span":{"begin":908,"end":918},"obj":"P85945"},{"id":"T210","span":{"begin":908,"end":918},"obj":"P84044"},{"id":"T211","span":{"begin":908,"end":918},"obj":"P91849"},{"id":"T212","span":{"begin":908,"end":918},"obj":"P84040"},{"id":"T213","span":{"begin":908,"end":918},"obj":"Q9HDF5"},{"id":"T214","span":{"begin":908,"end":918},"obj":"Q71V09"},{"id":"T215","span":{"begin":908,"end":918},"obj":"Q76FD9"},{"id":"T216","span":{"begin":908,"end":918},"obj":"P62788"},{"id":"T217","span":{"begin":908,"end":918},"obj":"Q8J1L3"},{"id":"T218","span":{"begin":908,"end":918},"obj":"P62794"},{"id":"T219","span":{"begin":908,"end":918},"obj":"Q8T7J8"},{"id":"T220","span":{"begin":908,"end":918},"obj":"P40287"},{"id":"T221","span":{"begin":908,"end":918},"obj":"Q7K8C0"},{"id":"T222","span":{"begin":908,"end":918},"obj":"P08436"},{"id":"T142","span":{"begin":908,"end":918},"obj":"D006657"},{"id":"T223","span":{"begin":942,"end":946},"obj":"SO:0000704"},{"id":"T224","span":{"begin":947,"end":960},"obj":"GO:0006351"},{"id":"T225","span":{"begin":972,"end":977},"obj":"PR:Q5S006"},{"id":"T226","span":{"begin":972,"end":977},"obj":"PR:000003033"},{"id":"T227","span":{"begin":972,"end":977},"obj":"PR:Q5S007"},{"id":"T228","span":{"begin":997,"end":1010},"obj":"SO:0000199"},{"id":"T230","span":{"begin":1014,"end":1019},"obj":"PR:Q6P6W3"},{"id":"T231","span":{"begin":1014,"end":1019},"obj":"PR:O88895"},{"id":"T232","span":{"begin":1014,"end":1019},"obj":"PR:O15379"},{"id":"T233","span":{"begin":1014,"end":1019},"obj":"PR:000008482"},{"id":"T234","span":{"begin":1014,"end":1019},"obj":"PR:P56520"},{"id":"T235","span":{"begin":1014,"end":1019},"obj":"PR:Q803C3"},{"id":"T236","span":{"begin":1046,"end":1057},"obj":"GO:0005646"},{"id":"T245","span":{"begin":1077,"end":1082},"obj":"PR:Q6P6W3"},{"id":"T246","span":{"begin":1077,"end":1082},"obj":"PR:O88895"},{"id":"T247","span":{"begin":1077,"end":1082},"obj":"PR:O15379"},{"id":"T248","span":{"begin":1077,"end":1082},"obj":"PR:000008482"},{"id":"T249","span":{"begin":1077,"end":1082},"obj":"PR:P56520"},{"id":"T250","span":{"begin":1077,"end":1082},"obj":"PR:Q803C3"},{"id":"T251","span":{"begin":1083,"end":1098},"obj":"GO:0016310"},{"id":"T252","span":{"begin":1115,"end":1128},"obj":"SO:0000199"},{"id":"T253","span":{"begin":1159,"end":1176},"obj":"D016627"},{"id":"T254","span":{"begin":1159,"end":1176},"obj":"D016627"},{"id":"T255","span":{"begin":1159,"end":1176},"obj":"CHEBI:78741"},{"id":"T259","span":{"begin":1178,"end":1184},"obj":"D016627"},{"id":"T260","span":{"begin":1178,"end":1184},"obj":"D016627"},{"id":"T261","span":{"begin":1178,"end":1184},"obj":"CHEBI:78741"},{"id":"T262","span":{"begin":1197,"end":1202},"obj":"PR:Q5S006"},{"id":"T263","span":{"begin":1197,"end":1202},"obj":"PR:000003033"},{"id":"T264","span":{"begin":1197,"end":1202},"obj":"PR:Q5S007"},{"id":"T265","span":{"begin":1218,"end":1225},"obj":"CL:0000187"},{"id":"T268","span":{"begin":1218,"end":1253},"obj":"O89038"},{"id":"T269","span":{"begin":1218,"end":1253},"obj":"Q63943"},{"id":"T271","span":{"begin":1218,"end":1253},"obj":"PR:000010312"},{"id":"T272","span":{"begin":1218,"end":1253},"obj":"Q14814"},{"id":"T270","span":{"begin":1218,"end":1253},"obj":"D064326"},{"id":"T273","span":{"begin":1235,"end":1243},"obj":"SO:0000165"},{"id":"T274","span":{"begin":1305,"end":1310},"obj":"PR:Q5S006"},{"id":"T275","span":{"begin":1305,"end":1310},"obj":"PR:000003033"},{"id":"T276","span":{"begin":1305,"end":1310},"obj":"PR:Q5S007"},{"id":"T277","span":{"begin":1331,"end":1337},"obj":"D016627"},{"id":"T278","span":{"begin":1331,"end":1337},"obj":"D016627"},{"id":"T279","span":{"begin":1331,"end":1337},"obj":"CHEBI:78741"},{"id":"T280","span":{"begin":1346,"end":1356},"obj":"GO:0008219"},{"id":"T282","span":{"begin":1384,"end":1389},"obj":"PR:Q6P6W3"},{"id":"T283","span":{"begin":1384,"end":1389},"obj":"PR:O88895"},{"id":"T284","span":{"begin":1384,"end":1389},"obj":"PR:O15379"},{"id":"T285","span":{"begin":1384,"end":1389},"obj":"PR:000008482"},{"id":"T286","span":{"begin":1384,"end":1389},"obj":"PR:P56520"},{"id":"T287","span":{"begin":1384,"end":1389},"obj":"PR:Q803C3"},{"id":"T288","span":{"begin":1419,"end":1424},"obj":"PR:Q5S006"},{"id":"T289","span":{"begin":1419,"end":1424},"obj":"PR:000003033"},{"id":"T290","span":{"begin":1419,"end":1424},"obj":"PR:Q5S007"},{"id":"T292","span":{"begin":1444,"end":1451},"obj":"PR:000041244"},{"id":"T291","span":{"begin":1444,"end":1451},"obj":"D006657"},{"id":"T293","span":{"begin":1444,"end":1451},"obj":"CHEBI:15358"},{"id":"T294","span":{"begin":1444,"end":1464},"obj":"SO:0001700"},{"id":"T295","span":{"begin":1444,"end":1464},"obj":"GO:0016570"},{"id":"T297","span":{"begin":1503,"end":1508},"obj":"PR:Q6P6W3"},{"id":"T298","span":{"begin":1503,"end":1508},"obj":"PR:O88895"},{"id":"T299","span":{"begin":1503,"end":1508},"obj":"PR:O15379"},{"id":"T300","span":{"begin":1503,"end":1508},"obj":"PR:000008482"},{"id":"T301","span":{"begin":1503,"end":1508},"obj":"PR:P56520"},{"id":"T302","span":{"begin":1503,"end":1508},"obj":"PR:Q803C3"},{"id":"T303","span":{"begin":1537,"end":1549},"obj":"GO:0051179"}],"attributes":[{"subj":"T2","pred":"source","obj":"c_corpus"},{"subj":"T3","pred":"source","obj":"c_corpus"},{"subj":"T1","pred":"source","obj":"c_corpus"},{"subj":"T4","pred":"source","obj":"c_corpus"},{"subj":"T5","pred":"source","obj":"c_corpus"},{"subj":"T6","pred":"source","obj":"c_corpus"},{"subj":"T7","pred":"source","obj":"c_corpus"},{"subj":"T8","pred":"source","obj":"c_corpus"},{"subj":"T13","pred":"source","obj":"c_corpus"},{"subj":"T14","pred":"source","obj":"c_corpus"},{"subj":"T15","pred":"source","obj":"c_corpus"},{"subj":"T16","pred":"source","obj":"c_corpus"},{"subj":"T17","pred":"source","obj":"c_corpus"},{"subj":"T18","pred":"source","obj":"c_corpus"},{"subj":"T20","pred":"source","obj":"c_corpus"},{"subj":"T21","pred":"source","obj":"c_corpus"},{"subj":"T22","pred":"source","obj":"c_corpus"},{"subj":"T23","pred":"source","obj":"c_corpus"},{"subj":"T24","pred":"source","obj":"c_corpus"},{"subj":"T19","pred":"source","obj":"c_corpus"},{"subj":"T26","pred":"source","obj":"c_corpus"},{"subj":"T25","pred":"source","obj":"c_corpus"},{"subj":"T27","pred":"source","obj":"c_corpus"},{"subj":"T28","pred":"source","obj":"c_corpus"},{"subj":"T29","pred":"source","obj":"c_corpus"},{"subj":"T30","pred":"source","obj":"c_corpus"},{"subj":"T31","pred":"source","obj":"c_corpus"},{"subj":"T32","pred":"source","obj":"c_corpus"},{"subj":"T33","pred":"source","obj":"c_corpus"},{"subj":"T35","pred":"source","obj":"c_corpus"},{"subj":"T36","pred":"source","obj":"c_corpus"},{"subj":"T34","pred":"source","obj":"c_corpus"},{"subj":"T37","pred":"source","obj":"c_corpus"},{"subj":"T38","pred":"source","obj":"c_corpus"},{"subj":"T39","pred":"source","obj":"c_corpus"},{"subj":"T40","pred":"source","obj":"c_corpus"},{"subj":"T41","pred":"source","obj":"c_corpus"},{"subj":"T42","pred":"source","obj":"c_corpus"},{"subj":"T43","pred":"source","obj":"c_corpus"},{"subj":"T44","pred":"source","obj":"c_corpus"},{"subj":"T45","pred":"source","obj":"c_corpus"},{"subj":"T46","pred":"source","obj":"c_corpus"},{"subj":"T47","pred":"source","obj":"c_corpus"},{"subj":"T48","pred":"source","obj":"c_corpus"},{"subj":"T49","pred":"source","obj":"c_corpus"},{"subj":"T50","pred":"source","obj":"c_corpus"},{"subj":"T51","pred":"source","obj":"c_corpus"},{"subj":"T52","pred":"source","obj":"c_corpus"},{"subj":"T53","pred":"source","obj":"c_corpus"},{"subj":"T54","pred":"source","obj":"c_corpus"},{"subj":"T55","pred":"source","obj":"c_corpus"},{"subj":"T57","pred":"source","obj":"c_corpus"},{"subj":"T59","pred":"source","obj":"c_corpus"},{"subj":"T60","pred":"source","obj":"c_corpus"},{"subj":"T61","pred":"source","obj":"c_corpus"},{"subj":"T62","pred":"source","obj":"c_corpus"},{"subj":"T63","pred":"source","obj":"c_corpus"},{"subj":"T64","pred":"source","obj":"c_corpus"},{"subj":"T66","pred":"source","obj":"c_corpus"},{"subj":"T67","pred":"source","obj":"c_corpus"},{"subj":"T65","pred":"source","obj":"c_corpus"},{"subj":"T69","pred":"source","obj":"c_corpus"},{"subj":"T68","pred":"source","obj":"c_corpus"},{"subj":"T70","pred":"source","obj":"c_corpus"},{"subj":"T72","pred":"source","obj":"c_corpus"},{"subj":"T71","pred":"source","obj":"c_corpus"},{"subj":"T73","pred":"source","obj":"c_corpus"},{"subj":"T74","pred":"source","obj":"c_corpus"},{"subj":"T75","pred":"source","obj":"c_corpus"},{"subj":"T77","pred":"source","obj":"c_corpus"},{"subj":"T78","pred":"source","obj":"c_corpus"},{"subj":"T79","pred":"source","obj":"c_corpus"},{"subj":"T80","pred":"source","obj":"c_corpus"},{"subj":"T81","pred":"source","obj":"c_corpus"},{"subj":"T82","pred":"source","obj":"c_corpus"},{"subj":"T83","pred":"source","obj":"c_corpus"},{"subj":"T84","pred":"source","obj":"c_corpus"},{"subj":"T89","pred":"source","obj":"c_corpus"},{"subj":"T90","pred":"source","obj":"c_corpus"},{"subj":"T93","pred":"source","obj":"c_corpus"},{"subj":"T87","pred":"source","obj":"c_corpus"},{"subj":"T91","pred":"source","obj":"c_corpus"},{"subj":"T85","pred":"source","obj":"c_corpus"},{"subj":"T86","pred":"source","obj":"c_corpus"},{"subj":"T88","pred":"source","obj":"c_corpus"},{"subj":"T92","pred":"source","obj":"c_corpus"},{"subj":"T94","pred":"source","obj":"c_corpus"},{"subj":"T95","pred":"source","obj":"c_corpus"},{"subj":"T96","pred":"source","obj":"c_corpus"},{"subj":"T97","pred":"source","obj":"c_corpus"},{"subj":"T98","pred":"source","obj":"c_corpus"},{"subj":"T100","pred":"source","obj":"c_corpus"},{"subj":"T101","pred":"source","obj":"c_corpus"},{"subj":"T102","pred":"source","obj":"c_corpus"},{"subj":"T103","pred":"source","obj":"c_corpus"},{"subj":"T104","pred":"source","obj":"c_corpus"},{"subj":"T105","pred":"source","obj":"c_corpus"},{"subj":"T106","pred":"source","obj":"c_corpus"},{"subj":"T99","pred":"source","obj":"c_corpus"},{"subj":"T107","pred":"source","obj":"c_corpus"},{"subj":"T108","pred":"source","obj":"c_corpus"},{"subj":"T110","pred":"source","obj":"c_corpus"},{"subj":"T111","pred":"source","obj":"c_corpus"},{"subj":"T112","pred":"source","obj":"c_corpus"},{"subj":"T113","pred":"source","obj":"c_corpus"},{"subj":"T114","pred":"source","obj":"c_corpus"},{"subj":"T115","pred":"source","obj":"c_corpus"},{"subj":"T116","pred":"source","obj":"c_corpus"},{"subj":"T109","pred":"source","obj":"c_corpus"},{"subj":"T117","pred":"source","obj":"c_corpus"},{"subj":"T118","pred":"source","obj":"c_corpus"},{"subj":"T122","pred":"source","obj":"c_corpus"},{"subj":"T123","pred":"source","obj":"c_corpus"},{"subj":"T124","pred":"source","obj":"c_corpus"},{"subj":"T125","pred":"source","obj":"c_corpus"},{"subj":"T126","pred":"source","obj":"c_corpus"},{"subj":"T127","pred":"source","obj":"c_corpus"},{"subj":"T128","pred":"source","obj":"c_corpus"},{"subj":"T129","pred":"source","obj":"c_corpus"},{"subj":"T130","pred":"source","obj":"c_corpus"},{"subj":"T131","pred":"source","obj":"c_corpus"},{"subj":"T132","pred":"source","obj":"c_corpus"},{"subj":"T133","pred":"source","obj":"c_corpus"},{"subj":"T134","pred":"source","obj":"c_corpus"},{"subj":"T135","pred":"source","obj":"c_corpus"},{"subj":"T136","pred":"source","obj":"c_corpus"},{"subj":"T137","pred":"source","obj":"c_corpus"},{"subj":"T138","pred":"source","obj":"c_corpus"},{"subj":"T139","pred":"source","obj":"c_corpus"},{"subj":"T140","pred":"source","obj":"c_corpus"},{"subj":"T141","pred":"source","obj":"c_corpus"},{"subj":"T143","pred":"source","obj":"c_corpus"},{"subj":"T144","pred":"source","obj":"c_corpus"},{"subj":"T145","pred":"source","obj":"c_corpus"},{"subj":"T146","pred":"source","obj":"c_corpus"},{"subj":"T147","pred":"source","obj":"c_corpus"},{"subj":"T148","pred":"source","obj":"c_corpus"},{"subj":"T149","pred":"source","obj":"c_corpus"},{"subj":"T150","pred":"source","obj":"c_corpus"},{"subj":"T151","pred":"source","obj":"c_corpus"},{"subj":"T152","pred":"source","obj":"c_corpus"},{"subj":"T153","pred":"source","obj":"c_corpus"},{"subj":"T154","pred":"source","obj":"c_corpus"},{"subj":"T155","pred":"source","obj":"c_corpus"},{"subj":"T156","pred":"source","obj":"c_corpus"},{"subj":"T157","pred":"source","obj":"c_corpus"},{"subj":"T158","pred":"source","obj":"c_corpus"},{"subj":"T159","pred":"source","obj":"c_corpus"},{"subj":"T160","pred":"source","obj":"c_corpus"},{"subj":"T161","pred":"source","obj":"c_corpus"},{"subj":"T162","pred":"source","obj":"c_corpus"},{"subj":"T163","pred":"source","obj":"c_corpus"},{"subj":"T164","pred":"source","obj":"c_corpus"},{"subj":"T165","pred":"source","obj":"c_corpus"},{"subj":"T166","pred":"source","obj":"c_corpus"},{"subj":"T167","pred":"source","obj":"c_corpus"},{"subj":"T168","pred":"source","obj":"c_corpus"},{"subj":"T169","pred":"source","obj":"c_corpus"},{"subj":"T170","pred":"source","obj":"c_corpus"},{"subj":"T171","pred":"source","obj":"c_corpus"},{"subj":"T172","pred":"source","obj":"c_corpus"},{"subj":"T173","pred":"source","obj":"c_corpus"},{"subj":"T174","pred":"source","obj":"c_corpus"},{"subj":"T175","pred":"source","obj":"c_corpus"},{"subj":"T176","pred":"source","obj":"c_corpus"},{"subj":"T177","pred":"source","obj":"c_corpus"},{"subj":"T178","pred":"source","obj":"c_corpus"},{"subj":"T179","pred":"source","obj":"c_corpus"},{"subj":"T180","pred":"source","obj":"c_corpus"},{"subj":"T181","pred":"source","obj":"c_corpus"},{"subj":"T182","pred":"source","obj":"c_corpus"},{"subj":"T183","pred":"source","obj":"c_corpus"},{"subj":"T184","pred":"source","obj":"c_corpus"},{"subj":"T185","pred":"source","obj":"c_corpus"},{"subj":"T186","pred":"source","obj":"c_corpus"},{"subj":"T187","pred":"source","obj":"c_corpus"},{"subj":"T188","pred":"source","obj":"c_corpus"},{"subj":"T189","pred":"source","obj":"c_corpus"},{"subj":"T190","pred":"source","obj":"c_corpus"},{"subj":"T191","pred":"source","obj":"c_corpus"},{"subj":"T192","pred":"source","obj":"c_corpus"},{"subj":"T193","pred":"source","obj":"c_corpus"},{"subj":"T194","pred":"source","obj":"c_corpus"},{"subj":"T195","pred":"source","obj":"c_corpus"},{"subj":"T196","pred":"source","obj":"c_corpus"},{"subj":"T197","pred":"source","obj":"c_corpus"},{"subj":"T198","pred":"source","obj":"c_corpus"},{"subj":"T199","pred":"source","obj":"c_corpus"},{"subj":"T200","pred":"source","obj":"c_corpus"},{"subj":"T201","pred":"source","obj":"c_corpus"},{"subj":"T202","pred":"source","obj":"c_corpus"},{"subj":"T203","pred":"source","obj":"c_corpus"},{"subj":"T204","pred":"source","obj":"c_corpus"},{"subj":"T205","pred":"source","obj":"c_corpus"},{"subj":"T206","pred":"source","obj":"c_corpus"},{"subj":"T207","pred":"source","obj":"c_corpus"},{"subj":"T208","pred":"source","obj":"c_corpus"},{"subj":"T209","pred":"source","obj":"c_corpus"},{"subj":"T210","pred":"source","obj":"c_corpus"},{"subj":"T211","pred":"source","obj":"c_corpus"},{"subj":"T212","pred":"source","obj":"c_corpus"},{"subj":"T213","pred":"source","obj":"c_corpus"},{"subj":"T214","pred":"source","obj":"c_corpus"},{"subj":"T215","pred":"source","obj":"c_corpus"},{"subj":"T216","pred":"source","obj":"c_corpus"},{"subj":"T217","pred":"source","obj":"c_corpus"},{"subj":"T218","pred":"source","obj":"c_corpus"},{"subj":"T219","pred":"source","obj":"c_corpus"},{"subj":"T220","pred":"source","obj":"c_corpus"},{"subj":"T221","pred":"source","obj":"c_corpus"},{"subj":"T222","pred":"source","obj":"c_corpus"},{"subj":"T142","pred":"source","obj":"c_corpus"},{"subj":"T223","pred":"source","obj":"c_corpus"},{"subj":"T224","pred":"source","obj":"c_corpus"},{"subj":"T225","pred":"source","obj":"c_corpus"},{"subj":"T226","pred":"source","obj":"c_corpus"},{"subj":"T227","pred":"source","obj":"c_corpus"},{"subj":"T228","pred":"source","obj":"c_corpus"},{"subj":"T230","pred":"source","obj":"c_corpus"},{"subj":"T231","pred":"source","obj":"c_corpus"},{"subj":"T232","pred":"source","obj":"c_corpus"},{"subj":"T233","pred":"source","obj":"c_corpus"},{"subj":"T234","pred":"source","obj":"c_corpus"},{"subj":"T235","pred":"source","obj":"c_corpus"},{"subj":"T236","pred":"source","obj":"c_corpus"},{"subj":"T245","pred":"source","obj":"c_corpus"},{"subj":"T246","pred":"source","obj":"c_corpus"},{"subj":"T247","pred":"source","obj":"c_corpus"},{"subj":"T248","pred":"source","obj":"c_corpus"},{"subj":"T249","pred":"source","obj":"c_corpus"},{"subj":"T250","pred":"source","obj":"c_corpus"},{"subj":"T251","pred":"source","obj":"c_corpus"},{"subj":"T252","pred":"source","obj":"c_corpus"},{"subj":"T253","pred":"source","obj":"c_corpus"},{"subj":"T254","pred":"source","obj":"c_corpus"},{"subj":"T255","pred":"source","obj":"c_corpus"},{"subj":"T259","pred":"source","obj":"c_corpus"},{"subj":"T260","pred":"source","obj":"c_corpus"},{"subj":"T261","pred":"source","obj":"c_corpus"},{"subj":"T262","pred":"source","obj":"c_corpus"},{"subj":"T263","pred":"source","obj":"c_corpus"},{"subj":"T264","pred":"source","obj":"c_corpus"},{"subj":"T265","pred":"source","obj":"c_corpus"},{"subj":"T268","pred":"source","obj":"c_corpus"},{"subj":"T269","pred":"source","obj":"c_corpus"},{"subj":"T271","pred":"source","obj":"c_corpus"},{"subj":"T272","pred":"source","obj":"c_corpus"},{"subj":"T270","pred":"source","obj":"c_corpus"},{"subj":"T273","pred":"source","obj":"c_corpus"},{"subj":"T274","pred":"source","obj":"c_corpus"},{"subj":"T275","pred":"source","obj":"c_corpus"},{"subj":"T276","pred":"source","obj":"c_corpus"},{"subj":"T277","pred":"source","obj":"c_corpus"},{"subj":"T278","pred":"source","obj":"c_corpus"},{"subj":"T279","pred":"source","obj":"c_corpus"},{"subj":"T280","pred":"source","obj":"c_corpus"},{"subj":"T282","pred":"source","obj":"c_corpus"},{"subj":"T283","pred":"source","obj":"c_corpus"},{"subj":"T284","pred":"source","obj":"c_corpus"},{"subj":"T285","pred":"source","obj":"c_corpus"},{"subj":"T286","pred":"source","obj":"c_corpus"},{"subj":"T287","pred":"source","obj":"c_corpus"},{"subj":"T288","pred":"source","obj":"c_corpus"},{"subj":"T289","pred":"source","obj":"c_corpus"},{"subj":"T290","pred":"source","obj":"c_corpus"},{"subj":"T292","pred":"source","obj":"c_corpus"},{"subj":"T291","pred":"source","obj":"c_corpus"},{"subj":"T293","pred":"source","obj":"c_corpus"},{"subj":"T294","pred":"source","obj":"c_corpus"},{"subj":"T295","pred":"source","obj":"c_corpus"},{"subj":"T297","pred":"source","obj":"c_corpus"},{"subj":"T298","pred":"source","obj":"c_corpus"},{"subj":"T299","pred":"source","obj":"c_corpus"},{"subj":"T300","pred":"source","obj":"c_corpus"},{"subj":"T301","pred":"source","obj":"c_corpus"},{"subj":"T302","pred":"source","obj":"c_corpus"},{"subj":"T303","pred":"source","obj":"c_corpus"}]},{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":139,"end":263},"obj":"DRI_Background"},{"id":"T2","span":{"begin":264,"end":413},"obj":"DRI_Background"},{"id":"T3","span":{"begin":414,"end":558},"obj":"DRI_Background"},{"id":"T4","span":{"begin":559,"end":715},"obj":"DRI_Background"},{"id":"T5","span":{"begin":716,"end":837},"obj":"DRI_Outcome"},{"id":"T6","span":{"begin":838,"end":961},"obj":"DRI_Background"},{"id":"T7","span":{"begin":962,"end":1076},"obj":"DRI_Background"},{"id":"T8","span":{"begin":1077,"end":1196},"obj":"DRI_Background"},{"id":"T9","span":{"begin":1197,"end":1304},"obj":"DRI_Outcome"},{"id":"T10","span":{"begin":1391,"end":1550},"obj":"DRI_Background"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T2","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T3","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T4","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T5","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T6","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T7","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T8","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T9","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T10","pred":"source","obj":"PubMed_ArguminSci"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"c_corpus","color":"#ec93ce","default":true},{"id":"PubMed_ArguminSci","color":"#93e8ec"}]}]}}