UniProt UniProt http://www.uniprot.org Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Hum. Mol. Genet. (0964-6906) 2012 imex curation Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E. Rare diseases - Interactions investigated in the context of Rare genetic disease 'Syntrophin' has not been included in interaction a the used antobody is not specific elena.ambrosini@iss.it 26-Feb-2015: Contacted by IntAct-Help. Only protein-protein interactions human-u251 Homo sapiens u251 U2521 glioblastoma cell line confocal microscopy confocal microscopy immunostaining immunostaining Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E. Rare diseases - Interactions investigated in the context of Rare genetic disease 'Syntrophin' has not been included in interaction a the used antobody is not specific elena.ambrosini@iss.it Accepted 2015-FEB-16 by ORCHARD Hum. Mol. Genet. (0964-6906) 2012 imex curation Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Hum. Mol. Genet. (0964-6906) 2012 imex curation Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E. Rare diseases - Interactions investigated in the context of Rare genetic disease 'Syntrophin' has not been included in interaction a the used antobody is not specific elena.ambrosini@iss.it 26-Feb-2015: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro pull down pull down western blot western blot Immuno blot Immuno blot Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E. Rare diseases - Interactions investigated in the context of Rare genetic disease 'Syntrophin' has not been included in interaction a the used antobody is not specific elena.ambrosini@iss.it Accepted 2015-FEB-16 by ORCHARD Hum. Mol. Genet. (0964-6906) 2012 imex curation Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Hum. Mol. Genet. (0964-6906) 2012 imex curation Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E. Rare diseases - Interactions investigated in the context of Rare genetic disease 'Syntrophin' has not been included in interaction a the used antobody is not specific elena.ambrosini@iss.it 26-Feb-2015: Contacted by IntAct-Help. Only protein-protein interactions human-u251 Homo sapiens u251 U2521 glioblastoma cell line affinity chrom affinity chromatography technology Affinity purification Affinity purification affinity chrom western blot western blot Immuno blot Immuno blot Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E. Rare diseases - Interactions investigated in the context of Rare genetic disease Ouabain-affinity chromatography has been used. 'Syntrophin' has not been included in interaction a the used antobody is not specific elena.ambrosini@iss.it Accepted 2015-FEB-16 by ORCHARD Hum. Mol. Genet. (0964-6906) 2012 imex curation at1b1_human Sodium/potassium-transporting ATPase subunit beta-1 Sodium/potassium-dependent ATPase subunit beta-1 ATP1B1 ATP1B protein protein human Homo sapiens Human MARGKAKEEGSWKKFIWNSEKKEFLGRTGGSWFKILLFYVIFYGCLAGIFIGTIQVMLLTISEFKPTYQDRVAPPGLTQIPQIQKTEISFRPNDPKSYEAYVLNIVRFLEKYKDSAQRDDMIFEDCGDVPSEPKERGDFNHERGERKVCRFKLEWLGNCSGLNDETYGYKEGKPCIIIKLNRVLGFKPKPPKNESLETYPVMKYNPNVLPVQCTGKRDEDKDKVGNVEYFGLGNSPGFPLQYYPYYGKLLQPKYLQPLLAVQFTNLTMDTEIRIECKAYGENIGYSEKDRFQGRFDVKIEVKS 107D3C04394F2D11 mlc1_human Membrane protein MLC1 MLC1 KIAA0027 WKL1 protein protein human Homo sapiens Human MTQEPFREELAYDRMPTLERGRQDPASYAPDAKPSDLQLSKRLPPCFSHKTWVFSVLMGSCLLVTSGFSLYLGNVFPAEMDYLRCAAGSCIPSAIVSFTVSRRNANVIPNFQILFVSTFAVTTTCLIWFGCKLVLNPSAININFNLILLLLLELLMAATVIIAARSSEEDCKKKKGSMSDSANILDEVPFPARVLKSYSVVEVIAGISAVLGGIIALNVDDSVSGPHLSVTFFWILVACFPSAIASHVAAECPSKCLVEVLIAISSLTSPLLFTASGYLSFSIMRIVEMFKDYPPAIKPSYDVLLLLLLLVLLLQAGLNTGTAIQCVRFKVSARLQGASWDTQNGPQERLAGEVARSPLKEFDKEKAWRAVVVQMAQ mint homomint 9AF70B87D979F459 trpv4_human Transient receptor potential cation channel subfamily V member 4 TRPV4 Osm-9-like TRP channel 4 Vanilloid receptor-like channel 2 Vanilloid receptor-like protein 2 Vanilloid receptor-related osmotically-activated channel Transient receptor potential protein 12 VRL2 VROAC protein protein human Homo sapiens Human MADSSEGPRAGPGEVAELPGDESGTPGGEAFPLSSLANLFEGEDGSLSPSPADASRPAGPGDGRPNLRMKFQGAFRKGVPNPIDLLESTLYESSVVPGPKKAPMDSLFDYGTYRHHSSDNKRWRKKIIEKQPQSPKAPAPQPPPILKVFNRPILFDIVSRGSTADLDGLLPFLLTHKKRLTDEEFREPSTGKTCLPKALLNLSNGRNDTIPVLLDIAERTGNMREFINSPFRDIYYRGQTALHIAIERRCKHYVELLVAQGADVHAQARGRFFQPKDEGGYFYFGELPLSLAACTNQPHIVNYLTENPHKKADMRRQDSRGNTVLHALVAIADNTRENTKFVTKMYDLLLLKCARLFPDSNLEAVLNNDGLSPLMMAAKTGKIGIFQHIIRREVTDEDTRHLSRKFKDWAYGPVYSSLYDLSSLDTCGEEASVLEILVYNSKIENRHEMLAVEPINELLRDKWRKFGAVSFYINVVSYLCAMVIFTLTAYYQPLEGTPPYPYRTTVDYLRLAGEVITLFTGVLFFFTNIKDLFMKKCPGVNSLFIDGSFQLLYFIYSVLVIVSAALYLAGIEAYLAVMVFALVLGWMNALYFTRGLKLTGTYSIMIQKILFKDLFRFLLVYLLFMIGYASALVSLLNPCANMKVCNEDQTNCTVPTYPSCRDSETFSTFLLDLFKLTIGMGDLEMLSSTKYPVVFIILLVTYIILTFVLLLNMLIALMGETVGQVSKESKHIWKLQWATTILDIERSFPVFLRKAFRSGEMVTVGKSSDGTPDRRWCFRVDEVNWSHWNQNLGIINEDPGKNETYQYYGFSHTVGRLRRDRWSSVVPRVVELNKNSNPDEVVVPLDSMGNPRCDGHQQGYPRKWRTDDAPL DIP protein Q9HBA0 original sequence version: 98 DIP protein Q9HBA0 original sequence version: 131 C62056B86C5A6FB6 hecam_human Hepatocyte cell adhesion molecule HEPACAM protein protein human Homo sapiens Human MKRERGALSRASRALRLAPFVYLLLIQTDPLEGVNITSPVRLIHGTVGKSALLSVQYSSTSSDRPVVKWQLKRDKPVTVVQSIGTEVIGTLRPDYRDRIRLFENGSLLLSDLQLADEGTYEVEISITDDTFTGEKTINLTVDVPISRPQVLVASTTVLELSEAFTLNCSHENGTKPSYTWLKDGKPLLNDSRMLLSPDQKVLTITRVLMEDDDLYSCMVENPISQGRSLPVKITVYRRSSLYIILSTGGIFLLVTLVTVCACWKPSKRKQKKLEKQNSLEYMDQNDDRLKPEADTLPRSGEQERKNPMALYILKDKDSPETEENPAPEPRSATEPGPPGYSVSPAVPGRSPGLPIRSARRYPRSPARSPATGRTHSSPPRAPSSPGRSRSASRTLRTAGVHIIREQDEAGPVEISA 3CB5111207135F3C ouabain ouabain 3-(alpha-L-rhamnopyranosyloxy)-1beta,5beta,11alpha,14,19-pentahydroxy-5beta-card-20(22)-enolide G-Strophanthin Ouabagenin L-Rhamnoside Ouabagenin-L-rhamnosid Ouabain Ouabain anhydrous Ouabaine Oubain Strodival 3-(6-deoxy-alpha-L-mannopyranosyloxy)-1beta,5beta,11alpha,14,19-pentahydroxy-5beta-card-20(22)-enolide small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) LPMXVESGRSUGHW-HBYQJFLCSA-N LPMXVESGRSUGHW-HBYQJFLCSA-N at1b1_rat Sodium/potassium-transporting ATPase subunit beta-1 Atp1b1 Sodium/potassium-dependent ATPase subunit beta-1 protein protein rat Rattus norvegicus (Rat) Rat MARGKAKEEGSWKKFIWNSEKKEFLGRTGGSWFKILLFYVIFYGCLAGIFIGTIQVMLLTISELKPTYQDRVAPPGLTQIPQIQKTEISFRPNDPKSYEAYVLNIIRFLEKYKDSAQKDDMIFEDCGSMPSEPKERGEFNHERGERKVCRFKLDWLGNCSGLNDESYGYKEGKPCIIIKLNRVLGFKPKPPKNESLETYPLTMKYNPNVLPVQCTGKRDEDKDKVGNIEYFGMGGFYGFPLQYYPYYGKLLQPKYLQPLLAVQFTNLTLDTEIRIECKAYGENIGYSEKDRFQGRFDVKIEVKS 86C3120F463B7B2B trpv4_rat Transient receptor potential cation channel subfamily V member 4 Trpv4 Vroac Osm-9-like TRP channel 4 Vanilloid receptor-related osmotically-activated channel protein protein rat Rattus norvegicus (Rat) Rat MADPGDGPRAAPGDVAEPPGDESGTSGGEAFPLSSLANLFEGEEGSSSLSPVDASRPAGPGDGRPNLRMKFQGAFRKGVPNPIDLLESTLYESSVVPGPKKAPMDSLFDYGTYRHHPSDNKRWRRKVVEKQPQSPKAPAPQPPPILKVFNRPILFDIVSRGSTADLDGLLSYLLTHKKRLTDEEFREPSTGKTCLPKALLNLSNGRNDTIPVLLDIAERTGNMREFINSPFRDIYYRGQTALHIAIERRCKHYVELLVAQGADVHAQARGRFFQPKDEGGYFYFGELPLSLAACTNQPHIVNYLTENPHKKADMRRQDSRGNTVLHALVAIADNTRENTKFVTKMYDLLLLKCSRLFPDSNLETVLNNDGLSPLMMAAKTGKIGVFQHIIRREVTDEDTRHLSRKFKDWAYGPVYSSLYDLSSLDTCGEEVSVLEILVYNSKIENRHEMLAVEPINELLRDKWRKFGAVSFYINVVSYLCAMVIFTLTAYYQPLEGTPPYPYRTTVDYLRLAGEVITLLTGVLFFFTSIKDLFMKKCPGVNSLFVDGSFQLLYFIYSVLVVVSAALYLAGIEAYLAVMVFALVLGWMNALYFTRGLKLTGTYSIMIQKILFKDLFRFLLVYLLFMIGYASALVTLLNPCTNMKVCNEDQSNCTVPSYPACRDSETFSAFLLDLFKLTIGMGDLEMLSSAKYPVVFILLLVTYIILTFVLLLNMLIALMGETVGQVSKESKHIWKLQWATTILDIERSFPVFLRKAFRSGEMVTVGKSSDGTPDRRWCFRVDEVNWSHWNQNLGIINEDPGKSEIYQYYGFSHTMGRLRRDRWSSVVPRVVELNKNSGTDEVVVPLDNLGNPNCDGHQQGYAPKWRAEDAPL DIP protein Q9ERZ8 original sequence version: 74 5D50684DA08C354B aqp4_human Aquaporin-4 AQP4 Mercurial-insensitive water channel WCH4 protein protein human Homo sapiens Human MSDRPTARRWGKCGPLCTRENIMVAFKGVWTQAFWKAVTAEFLAMLIFVLLSLGSTINWGGTEKPLPVDMVLISLCFGLSIATMVQCFGHISGGHINPAVTVAMVCTRKISIAKSVFYIAAQCLGAIIGAGILYLVTPPSVVGGLGVTMVHGNLTAGHGLLVELIITFQLVFTIFASCDSKRTDVTGSIALAIGFSVAIGHLFAINYTGASMNPARSFGPAVIMGNWENHWIYWVGPIIGAVLAGGLYEYVFCPDVEFKRRFKEAFSKAAQQTKGSYMEVEDNRSQVETDDLILKPGVVHVIDVDRGEEKKGKDQSGEVLSSV 1A1600CF0DC11052 kcj10_human ATP-sensitive inward rectifier potassium channel 10 KCNJ10 ATP-dependent inwardly rectifying potassium channel Kir4.1 Inward rectifier K(+) channel Kir1.2 Potassium channel, inwardly rectifying subfamily J member 10 protein protein human Homo sapiens Human MTSVAKVYYSQTTQTESRPLMGPGIRRRRVLTKDGRSNVRMEHIADKRFLYLKDLWTTFIDMQWRYKLLLFSATFAGTWFLFGVVWYLVAVAHGDLLELDPPANHTPCVVQVHTLTGAFLFSLESQTTIGYGFRYISEECPLAIVLLIAQLVLTTILEIFITGTFLAKIARPKKRAETIRFSQHAVVASHNGKPCLMIRVANMRKSLLIGCQVTGKLLQTHQTKEGENIRLNQVNVTFQVDTASDSPFLILPLTFYHVVDETSPLKDLPLRSGEGDFELVLILSGTVESTSATCQVRTSYLPEEILWGYEFTPAISLSASGKYIADFSLFDQVVKVASPSGLRDSTVRYGDPEKLKLEESLREQAEKEGSALSVRISNV D9DA013FF4003533 atp1b1-mlc1 1 5 unspecified role unspecified role neutral component neutral component nucl transfection nucleic acid transfection nucl transfection n-terminus 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 Q15049:p.Cys125Arg mutation disrupting mutation disrupting interaction mutation disrupting certain certain sequence position certain certain certain sequence position certain C R Variant in in Leukoencephalopathy, megalencephalic, with subcortical cysts, 1 (MLC1) [MIM:60400]; UniProt FTId: VAR_067765 Wed May 02 14:42:08 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'cys125arg' Tue Jun 30 19:06:42 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Cys125Arg' Q15049:p.Ser280Leu mutation disrupting mutation disrupting interaction mutation disrupting certain certain sequence position certain certain certain sequence position certain S L Variant in in Leukoencephalopathy, megalencephalic, with subcortical cysts, 1 (MLC1) [MIM:60400]; dbSNP:rs121908341; UniProt FTId: VAR_011702 Wed May 02 17:58:37 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ser280leu' Tue Jun 30 18:58:00 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ser280Leu' MLC1 mutant ser246 (variant in MLC1) does colocalize at plasma membrane 4 unspecified role unspecified role neutral component neutral component colocalization colocalization 3 ouabain-atp1b1 3 5 unspecified role unspecified role prey prey nucl transfection nucleic acid transfection nucl transfection n-terminus 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 8 unspecified role unspecified role bait bait 4 unspecified role unspecified role prey prey cell lysate cell lysate 12 unspecified role unspecified role prey prey cell lysate cell lysate association association 4; 1st left and S2 syntrophin was shown to be copurifying but cannot be mapped to UniProt as the used antibody is not specific MLC1 and ATP1B1 copurified in isoosmotic and hypoosmotic conditions mlc1-atp1b1 2 5 unspecified role unspecified role bait bait region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ecoli Escherichia coli (strain K12) 9 unspecified role unspecified role prey prey rat-astrocyte Rattus norvegicus astrocyte astrocyte Astrocytes [Brain astrocytes; Astroglia] 10 unspecified role unspecified role prey prey rat-astrocyte Rattus norvegicus astrocyte astrocyte Astrocytes [Brain astrocytes; Astroglia] association association 8 mlc1-atp1b1-2 2 5 unspecified role unspecified role bait bait Q15049:p.Ser280Leu mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing certain certain sequence position certain certain certain sequence position certain S L Wed May 02 20:20:21 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ser280leu' Tue Jun 30 20:14:54 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ser280Leu' Q15049:p.Ser246Arg mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing certain certain sequence position certain certain certain sequence position certain S R Wed May 02 16:12:48 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ser246arg' Tue Jun 30 20:05:34 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ser246Arg' Q15049:p.Cys125Arg mutation disrupting mutation disrupting interaction mutation disrupting certain certain sequence position certain certain certain sequence position certain C R Wed May 02 19:49:21 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'cys125arg' Tue Jun 30 18:31:34 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Cys125Arg' region his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined true ecoli Escherichia coli (strain K12) 4 unspecified role unspecified role prey prey human-u251 Homo sapiens u251 U2521 glioblastoma cell line physical association physical association S1 ouabain-atp1b1-1 3 5 unspecified role unspecified role prey prey nucl transfection nucleic acid transfection nucl transfection n-terminus 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 true Q15049:p.Ser246Arg mutation mutation certain certain sequence position certain certain certain sequence position certain true S R decreasing amount of copurifying MLC1 with ATP1B1, no KCNJ10/Kir4.1 Wed May 02 18:06:56 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ser246arg' Tue Jun 30 18:03:43 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ser246Arg' 8 unspecified role unspecified role bait bait 4 unspecified role unspecified role prey prey cell lysate cell lysate association association 4; 2nd and S2 syntrophin was shown to be copurifying but cannot be mapped to UniProt as the used antibody is not specific copurification in isoosomotic and hypoosmotic conditions ouabain-atp1b1-2 3 4 unspecified role unspecified role prey prey cell lysate cell lysate 8 unspecified role unspecified role bait bait association association 4; 3rd and S2 Transfected and overexpressed MLC1 with ser280leu (variant in MLC1 (Leukoencephalopathy, megalencephalic, with subcortical cysts, 1; MIM:60400; UniProt FTId VAR_011702) was not copurified (isoosmotic and hypoosmotic conditions) ouabain-atp1b1-3 3 5 unspecified role unspecified role prey prey nucl transfection nucleic acid transfection nucl transfection Q15049:p.Cys125Arg mutation mutation certain certain sequence position certain certain certain sequence position certain true C R Variant in MLC1 (Leukoencephalopathy, megalencephalic, with subcortical cysts, 1 ; [MIM:60400; dbSNP:rs281875314; UniProt FTId VAR_067765 Wed May 02 16:47:02 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'cys125arg' Tue Jun 30 16:12:59 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Cys125Arg' n-terminus 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 true 8 unspecified role unspecified role bait bait 4 unspecified role unspecified role prey prey cell lysate cell lysate association association 4; 4th right and S2 syntrophin was shown to be copurifying but cannot be mapped to UniProt as the used antibody is not specific MLC1 copurified in isoosmotic but not in hypoosmoti conditions ouabain-aqp4-1 3 6 unspecified role unspecified role prey prey 11 unspecified role unspecified role prey prey 8 unspecified role unspecified role bait bait 7 unspecified role unspecified role prey prey association association fig. 9 Copurification under hypoosmotic conditions with MLC1 wildtype overexpressed. Overexpression of MLC1 ser246arg resulred in loss of aquaporin-4 and less Hepacam copurified. Overexpression of MLC1 ser280leu disrupted the copurification at all. Overexpression of MLC1 cys125arg resulted in less TRP4 and Hepacam and no aquaporin-4 copurified. ouabain-aqp4-2 3 6 unspecified role unspecified role prey prey 8 unspecified role unspecified role bait bait 7 unspecified role unspecified role prey prey association association Fig. 9 Copurification under isoosmotic conditions with wildtype MLC1 overexpressed (not shown on blot). Overexpression of MLC1 ser246arg resulted in copurification of aquaporin-4. Overexpressing MLC1 ser280leu disrupted the copurifiction. Overexpressing MLC1 cys125arg resulted in less Aquaporin-4 copurified.