MINT MINT, Dpt of Biology, University of Rome Tor Vergata MINT http://mint.bio.uniroma2.it/mint url>http://mint.bio.uniroma2.it/mint/ https://mint.bio.uniroma2.it MINT-[0-9]+ https://mint.bio.uniroma2.it/index.php/results-interactions/?id=${ac} The Molecular INTeraction database (MINT) is a relational database designed to store interactions between biological molecules. http://mint.bio.uniroma2.it The DISC1 R264Q variant increases affinity for the dopamine D2 receptor and increases GSK3 activity. The DISC1 R264Q variant increases affinity for the dopamine D2 receptor and increases GSK3 activity. Molecular brain 2020 imex curation Su P., Zhang H., Wong AHC., Liu F., Su P., Zhang H., Wong AHC., Liu F. Rare diseases - Interactions investigated in the context of Rare genetic disease Brain Disease - Neurological Diseases & Disorders Informations about construct and protein species were from 25433637, couldn't find range for Disc1-NT fang.liu@camh.ca 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 Su P., Zhang H., Wong AHC., Liu F., Su P., Zhang H., Wong AHC., Liu F. Rare diseases - Interactions investigated in the context of Rare genetic disease Informations about construct and protein species were from 25433637, couldn't find range for Disc1-NT fang.liu@camh.ca Accepted 2021-JUN-09 AT 09:22 BST AT 09:22 BST by KALPANAP Molecular brain 2020 Only protein-protein interactions imex curation imex curation The DISC1 R264Q variant increases affinity for the dopamine D2 receptor and increases GSK3 activity. The DISC1 R264Q variant increases affinity for the dopamine D2 receptor and increases GSK3 activity. Molecular brain 2020 imex curation Su P., Zhang H., Wong AHC., Liu F., Su P., Zhang H., Wong AHC., Liu F. Rare diseases - Interactions investigated in the context of Rare genetic disease Brain Disease - Neurological Diseases & Disorders Informations about construct and protein species were from 25433637, couldn't find range for Disc1-NT fang.liu@camh.ca Only protein-protein interactions imex curation in vitro In vitro pull down pull down western blot western blot Immuno blot Immuno blot Su P., Zhang H., Wong AHC., Liu F., Su P., Zhang H., Wong AHC., Liu F. Rare diseases - Interactions investigated in the context of Rare genetic disease Informations about construct and protein species were from 25433637, couldn't find range for Disc1-NT fang.liu@camh.ca Accepted 2021-JUN-09 AT 09:22 BST AT 09:22 BST by KALPANAP Molecular brain 2020 Only protein-protein interactions imex curation imex curation The DISC1 R264Q variant increases affinity for the dopamine D2 receptor and increases GSK3 activity. The DISC1 R264Q variant increases affinity for the dopamine D2 receptor and increases GSK3 activity. Molecular brain 2020 imex curation Su P., Zhang H., Wong AHC., Liu F., Su P., Zhang H., Wong AHC., Liu F. Rare diseases - Interactions investigated in the context of Rare genetic disease Brain Disease - Neurological Diseases & Disorders Informations about construct and protein species were from 25433637, couldn't find range for Disc1-NT fang.liu@camh.ca 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 Su P., Zhang H., Wong AHC., Liu F., Su P., Zhang H., Wong AHC., Liu F. Rare diseases - Interactions investigated in the context of Rare genetic disease Informations about construct and protein species were from 25433637, couldn't find range for Disc1-NT Origin species for HA-D2R is from Pmid:25433637 fang.liu@camh.ca Accepted 2021-JUN-09 AT 09:22 BST AT 09:22 BST by KALPANAP Molecular brain 2020 Only protein-protein interactions imex curation imex curation disc1_human Disrupted in schizophrenia 1 protein DISC1 KIAA0457 protein protein human Homo sapiens Human MPGGGPQGAPAAAGGGGVSHRAGSRDCLPPAACFRRRRLARRPGYMRSSTGPGIGFLSPAVGTLFRFPGGVSGEESHHSESRARQCGLDSRGLLVRSPVSKSAAAPTVTSVRGTSAHFGIQLRGGTRLPDRLSWPCGPGSAGWQQEFAAMDSSETLDASWEAACSDGARRVRAAGSLPSAELSSNSCSPGCGPEVPPTPPGSHSAFTSSFSFIRLSLGSAGERGEAEGCPPSREAESHCQSPQEMGAKAASLDGPHEDPRCLSRPFSLLATRVSADLAQAARNSSRPERDMHSLPDMDPGSSSSLDPSLAGCGGDGSSGSGDAHSWDTLLRKWEPVLRDCLLRNRRQMEVISLRLKLQKLQEDAVENDDYDKAETLQQRLEDLEQEKISLHFQLPSRQPALSSFLGHLAAQVQAALRRGATQQASGDDTHTPLRMEPRLLEPTAQDSLHVSITRRDWLLQEKQQLQKEIEALQARMFVLEAKDQQLRREIEEQEQQLQWQGCDLTPLVGQLSLGQLQEVSKALQDTLASAGQIPFHAEPPETIRSLQERIKSLNLSLKEITTKVCMSEKFCSTLRKKVNDIETQLPALLEAKMHAISGNHFWTAKDLTEEIRSLTSEREGLEGLLSKLLVLSSRNVKKLGSVKEDYNRLRREVEHQETAYETSVKENTMKYMETLKNKLCSCKCPLLGKVWEADLEACRLLIQSLQLQEARGSLSVEDERQMDDLEGAAPPIPPRLHSEDKRKTPLKVLEEWKTHLIPSLHCAGGEQKEESYILSAELGEKCEDIGKKLLYLEDQLHTAIHSHDEDLIQSLRRELQMVKETLQAMILQLQPAKEAGEREAAASCMTAGVHEAQA 63C3FDF2F59830C6 disc1_mouse Disrupted in schizophrenia 1 homolog Disc1 protein protein mouse Mus musculus Mouse MQGGGPRGAPIHSPSHGADSGHGLPPAVAPQRRRLTRRPGYMRSTAGSGIGFLSPAVGMPHPSSAGLTGQQSQHSQSKAGQCGLDPGSHCQASLVGKPFLKSSLVPAVASEGHLHPAQRSMRKRPVHFAVHSKNDSRQSERLTGSFKPGDSGFWQELLSSDSFKSLAPSLDAPWNKGSRGLKTVKPLASPALNGPADIASLPGFQDTFTSSFSFIQLSLGAAGERGEAEGCLPSREAEPLHQRPQEMAAEASSSDRPHGDPRHLWTFSLHAAPGLADLAQVTRSSSRQSECGTVSSSSSDTGFSSQDASSAGGRGDQGGGWADAHGWHTLLREWEPMLQDYLLSNRRQLEVTSLILKLQKCQEKVVEDGDYDTAETLRQRLEELEQEKGRLSWALPSQQPALRSFLGYLAAQIQVALHGATQRAGSDDPEAPLEGQLRTTAQDSLPASITRRDWLIREKQRLQKEIEALQARMSALEAKEKRLSQELEEQEVLLRWPGCDLMALVAQMSPGQLQEVSKALGETLTSANQAPFQVEPPETLRSLRERTKSLNLAVRELTAQVCSGEKLCSSLRRRLSDLDTRLPALLEAKMLALSGSCFSTAKELTEEIWALSSEREGLEMFLGRLLALSSRNSRRLGIVKEDHLRCRQDLALQDAAHKTRMKANTVKCMEVLEGQLSSCRCPLLGRVWKADLETCQLLMQSLQLQEAGSSPHAEDEEQVHSTGEAAQTAALAVPRTPHPEEEKSPLQVLQEWDTHSALSPHCAAGPWKEDSHIVSAEVGEKCEAIGVKLLHLEDQLLGAMYSHDEALFQSLQGELQTVKETLQAMILQLQPTKEAGEASASYPTAGAQETEA B55A850B15028E6F drd2_human D(2) dopamine receptor DRD2 Dopamine D2 receptor protein protein human Homo sapiens Human MDPLNLSWYDDDLERQNWSRPFNGSDGKADRPHYNYYATLLTLLIAVIVFGNVLVCMAVSREKALQTTTNYLIVSLAVADLLVATLVMPWVVYLEVVGEWKFSRIHCDIFVTLDVMMCTASILNLCAISIDRYTAVAMPMLYNTRYSSKRRVTVMISIVWVLSFTISCPLLFGLNNADQNECIIANPAFVVYSSIVSFYVPFIVTLLVYIKIYIVLRRRRKRVNTKRSSRAFRAHLRAPLKGNCTHPEDMKLCTVIMKSNGSFPVNRRRVEAARRAQELEMEMLSSTSPPERTRYSPIPPSHHQLTLPDPSHHGLHSTPDSPAKPEKNGHAKDHPKIAKIFEIQTMPNGKTRTSLKTMSRRKLSQQKEKKATQMLAIVLGVFIICWLPFFITHILNIHCDCNIPPVLYSAFTWLGYVNSAVNPIIYTTFNIEFRKAFLKILHC 9BF8EA36C988A2E2 drd2_mouse D(2) dopamine receptor Dopamine D2 receptor Drd2 protein protein mouse Mus musculus Mouse MDPLNLSWYDDDLERQNWSRPFNGSEGKPDRPHYNYYAMLLTLLIFIIVFGNVLVCMAVSREKALQTTTNYLIVSLAVADLLVATLVMPWVVYLEVVGEWKFSRIHCDIFVTLDVMMCTASILNLCAISIDRYTAVAMPMLYNTRYSSKRRVTVMIAIVWVLSFTISCPLLFGLNNTDQNECIIANPAFVVYSSIVSFYVPFIVTLLVYIKIYIVLRKRRKRVNTKRSSRAFRANLKTPLKGNCTHPEDMKLCTVIMKSNGSFPVNRRRMDAARRAQELEMEMLSSTSPPERTRYSPIPPSHHQLTLPDPSHHGLHSNPDSPAKPEKNGHAKIVNPRIAKFFEIQTMPNGKTRTSLKTMSRRKLSQQKEKKATQMLAIVLGVFIICWLPFFITHILNIHCDCNIPPVLYSAFTWLGYVNSAVNPIIYTTFNIEFRKAFMKILHC mint This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase 2EC8460CA11FC7F0 drd2-disc1-2 3 4 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed flag tag 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 Q9NRI5:p.Arg264Gln mutation increasing mutation increasing interaction mutation increasing certain certain sequence position certain certain certain sequence position certain R Q Mon Jun 28 16:58:05 BST 2021 This feature has been corrected as a result of our quality control procedures. The original label was 'Q9NRI5:p.arg264gln' 6 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed ha tag ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association fig. 1 a-c As shown in Fig. 1a, we found that the human R264Q DISC1 variant, but not the control A83V variant located outside the binding domain, is associated with significantly lower DISC1 protein levels compared to wildtype (WT) DISC1, when transfected into HEK-293 T cells. However, DISC1- D2R complex levels are significantly increased in DISC1R264Q (Fig. 1a-c), but not DISC1A83V (Fig. 1d-f) drd2-disc1-1 3 4 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed flag tag 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 Q9NRI5:p.Ala83Val mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing certain certain sequence position certain certain certain sequence position certain A V 6 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed ha tag ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association fig. 1 d-f As shown in Fig. 1a, we found that the human R264Q DISC1 variant, but not the control A83V variant located outside the binding domain, is associated with significantly lower DISC1 protein levels compared to wildtype (WT) DISC1, when transfected into HEK-293 T cells. However, DISC1- D2R complex levels are significantly increased in DISC1R264Q (Fig. 1a-c), but not DISC1A83V (Fig. 1d-f) disc1-drd2-1 1 4 unspecified role unspecified role prey prey purified purified n-term domain binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q9NRI5:p.Arg264Gln mutation increasing mutation increasing interaction mutation increasing certain certain sequence position certain certain certain sequence position certain R Q gst tag 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 ecolx Escherichia coli 6 unspecified role unspecified role bait bait purified purified tat tag tat tag transactivating tag Tat tag tat tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined binding 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 fig. 2 drd2-disc1-3 1 5 unspecified role unspecified role prey prey purified purified n-term domain binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q811T9:p.Leu100Pro mutation increasing mutation increasing interaction mutation increasing certain certain sequence position certain certain certain sequence position certain L P Mon Jun 28 17:19:50 BST 2021 This feature has been corrected as a result of our quality control procedures. The original label was 'Q811T9 :leu100pro' gst tag 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 ecolx Escherichia coli 6 unspecified role unspecified role bait bait purified purified tat tag tat tag transactivating tag Tat tag tat tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined binding 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 fig. 4 c-d disc1-drd2-2 2 7 unspecified role unspecified role prey prey cell lysate cell lysate physiological level physiological level endogenous level endogenous endogenous endogenous level mouse-striatum Mus musculus, striatum striatum striatum 5 unspecified role unspecified role bait bait purified purified gst tag 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 n-term domain binding region binding-associated region binding region undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined Q811T9:p.Leu100Pro mutation increasing mutation increasing interaction mutation increasing certain certain sequence position certain certain certain sequence position certain L P ecolx Escherichia coli physical association physical association fig. 4a-b