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/ SMPDL3b modulates insulin receptor signaling in diabetic kidney disease. SMPDL3b modulates insulin receptor signaling in diabetic kidney disease. Nature communications 2019 imex curation Mitrofanova A., Mallela SK., Ducasa GM., Yoo TH., Rosenfeld-Gur E., Zelnik ID., Molina J., Varona Santos J., Ge M., Sloan A., Kim JJ., Pedigo C., Bryn J., Volosenco I., Faul C., Zeidan YH., Garcia Hernandez C., Mendez AJ., Leibiger I., Burke GW., Futerman AH., Barisoni L., Ishimoto Y., Inagi R., Merscher S., Fornoni A. afornoni@med.miami.edu 21-Nov-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation mouse-kidney-glomerulus mouse kidney-glomerulus kidney-glomerulus kidney glomerulus anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Mitrofanova A., Mallela SK., Ducasa GM., Yoo TH., Rosenfeld-Gur E., Zelnik ID., Molina J., Varona Santos J., Ge M., Sloan A., Kim JJ., Pedigo C., Bryn J., Volosenco I., Faul C., Zeidan YH., Garcia Hernandez C., Mendez AJ., Leibiger I., Burke GW., Futerman AH., Barisoni L., Ishimoto Y., Inagi R., Merscher S., Fornoni A. afornoni@med.miami.edu Accepted 2019-OCT-02 AT 14:00 BST AT 14:00 BST by MARTA Nature communications 2019 Only protein-protein interactions imex curation imex curation SMPDL3b modulates insulin receptor signaling in diabetic kidney disease. SMPDL3b modulates insulin receptor signaling in diabetic kidney disease. Nature communications 2019 imex curation Mitrofanova A., Mallela SK., Ducasa GM., Yoo TH., Rosenfeld-Gur E., Zelnik ID., Molina J., Varona Santos J., Ge M., Sloan A., Kim JJ., Pedigo C., Bryn J., Volosenco I., Faul C., Zeidan YH., Garcia Hernandez C., Mendez AJ., Leibiger I., Burke GW., Futerman AH., Barisoni L., Ishimoto Y., Inagi R., Merscher S., Fornoni A. afornoni@med.miami.edu 21-Nov-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. anti tag coip anti tag coimmunoprecipitation anti tag coip anti tag western anti tag western blot anti tag western Mitrofanova A., Mallela SK., Ducasa GM., Yoo TH., Rosenfeld-Gur E., Zelnik ID., Molina J., Varona Santos J., Ge M., Sloan A., Kim JJ., Pedigo C., Bryn J., Volosenco I., Faul C., Zeidan YH., Garcia Hernandez C., Mendez AJ., Leibiger I., Burke GW., Futerman AH., Barisoni L., Ishimoto Y., Inagi R., Merscher S., Fornoni A. Please can you check;I have added an "inhibitory_region" for the longer isoform - but the aa numbering I find does NOT match What Uniprot states for Isoform 2: "745-756: Missing." but when aligning the two sequences I make it 744-755. Please let me know what you find, and if I am correct I will inform Uniprot. afornoni@med.miami.edu Accepted 2019-OCT-02 AT 14:00 BST AT 14:00 BST by MARTA Nature communications 2019 Only protein-protein interactions imex curation imex curation asm3b_mouse Acid sphingomyelinase-like phosphodiesterase 3b Smpdl3b Asml3b protein protein mouse Mus musculus Mouse MTLLGWLIFLAPWGVAGAQLGRFWHISDLHLDPNYTVSKDPLQVCPSAGSQPVLNAGPWGDYLCDSPWALINSSLYAMKEIEPKPDFILWTGDDTPHVPNESLGEAAVLAIVERLTNLIKEVFPDTKVYAALGNHDFHPKNQFPAQSNRIYNQVAELWRPWLSNESYALFKRGAFYSEKLPGPSRAGRVVVLNTNLYYSNNEQTAGMADPGEQFRWLGDVLSNASRDGEMVYVIGHVPPGFFEKTQNKAWFRESFNEEYLKVIQKHHRVIAGQFFGHHHTDSFRMFYDNTGAPINVMFLTPGVTPWKTTLPGVVDGANNPGIRIFEYDRATLNLKDLVTYFLNLRQANVQETPRWEQEYRLTEAYQVPDASVSSMHTALTRIASEPHILQRYYVYNSVSYNHLTCEDSCRIEHVCAIQHVAFNTYATCLHGLGAKLVPGFLLILTLLPSLHVLEVL 11BD6AF4806FD990 q03135-1 Caveolin-1 CAV1 CAV protein protein human Homo sapiens Human MSGGKYVDSEGHLYTVPIREQGNIYKPNNKAMADELSEKQVYDAHTKEIDLVNRDPKHLNDDVVKIDFEDVIAEPEGTHSFDGIWKASFTTFTVTKYWFYRLLSALFGIPMALIWGIYFAILSFLHIWAVVPCIKSFLIEIQCISRVYSIYVHTVCDPLFEAVGKIFSNVRINLQKEI 2424DE9B5E6521D5 cav1_mouse Caveolin-1 Cav1 Cav protein protein mouse Mus musculus Mouse MSGGKYVDSEGHLYTVPIREQGNIYKPNNKAMADEVTEKQVYDAHTKEIDLVNRDPKHLNDDVVKIDFEDVIAEPEGTHSFDGIWKASFTTFTVTKYWFYRLLSTIFGIPMALIWGIYFAILSFLHIWAVVPCIKSFLIEIQCISRVYSIYVHTFCDPLFEAIGKIFSNIRISTQKEI DIP protein P49817 original sequence version: 94 DIP protein P49817 original sequence version: 143 DIP protein P49817 original sequence version: 168 CF88FE9B1D3D67AE q92485-2 Acid sphingomyelinase-like phosphodiesterase 3b SMPDL3B ASML3B ASMLPD protein protein human Homo sapiens Human MRLLAWLIFLANWGGARAEPGKFWHIADLHLDPDYKVSKDPFQVCPSAGSQPVPDAGPWGDYLCDSPWALINSSIYAMKEIEPEPDFILWTGDDTPHVPDEKLGEAAVLEIVERLTKLIREVFPDTKVYAALGNHDFHPKNQFPAGSNNIYNQIAELWKPWLSNESIALFKKGAFYCEKLPGPSGAGRIVVLNTNLYYTSNALTADMADPGQQFQWLEDVLTDASKAGDMVYIVGHVPPGFFEKTQNKAWFREGFNEKYLKVVRKHHRVIAGQFFGHHHTDSFRMLYDDAGVPISAMFITPGVTPWKTTLPGVVNGANNPAIRVFEYDRATLSLKVRSPAEARGGGWEGLKCITTFPHSQLIHLPLTTEPQEG No experimental confirmation available. p06213-2 Insulin receptor HIR-A INSR protein protein human Homo sapiens Human MATGGRRGAAAAPLLVAVAALLLGAAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDICPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHSECLGNCSQPDDPTKCVACRNFYLDGRCVETCPPPYYHFQDWRCVNFSFCQDLHHKCKNSRRQGCHQYVIHNNKCIPECPSGYTMNSSNLLCTPCLGPCPKVCHLLEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGYLKIRRSYALVSLSFFRKLRLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSYIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPLRSNDPKSQNHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVFWERQAEDSELFELDYCLKGLKLPSRTWSPPFESEDSQKHNQSEYEDSAGECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRPSRKRRSLGDVGNVTVAVPTVAAFPNTSSTSVPTSPEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDTPEERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRIRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPLGPLYASSNPEYLSASDVFPCSVYVPDEWEVSREKITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFHSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGRDGGSSLGFKRSYEEHIPYTHMNGGKKNGRILTLPRSNPS DIP protein P06213-2 original sequence version: 186 A396F39279C2764D p06213-1 Insulin receptor INSR HIR-B protein protein human Homo sapiens Human MATGGRRGAAAAPLLVAVAALLLGAAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDICPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHSECLGNCSQPDDPTKCVACRNFYLDGRCVETCPPPYYHFQDWRCVNFSFCQDLHHKCKNSRRQGCHQYVIHNNKCIPECPSGYTMNSSNLLCTPCLGPCPKVCHLLEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGYLKIRRSYALVSLSFFRKLRLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSYIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPLRSNDPKSQNHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVFWERQAEDSELFELDYCLKGLKLPSRTWSPPFESEDSQKHNQSEYEDSAGECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRKTSSGTGAEDPRPSRKRRSLGDVGNVTVAVPTVAAFPNTSSTSVPTSPEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDTPEERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRIRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPLGPLYASSNPEYLSASDVFPCSVYVPDEWEVSREKITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFHSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGRDGGSSLGFKRSYEEHIPYTHMNGGKKNGRILTLPRSNPS DIP protein P06213-1 original sequence version: 159 DIP protein P06213-1 original sequence version: 135 insr_mouse Insulin receptor Insr protein protein mouse Mus musculus Mouse MGFGRGCETTAVPLLVAVAALLVGTAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDVCPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHKECLGNCSEPDDPTKCVACRNFYLDGQCVETCPPPYYHFQDWRCVNFSFCQDLHFKCRNSRKPGCHQYVIHNNKCIPECPSGYTMNSSNLMCTPCLGPCPKVCQILEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGFLKIRRSYALVSLSFFRKLHLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSFIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPQRSNDPKSQTPSHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVYWERQAEDSELFELDYCLKGLKLPSRTWSPPFESDDSQKHNQSEYDDSASECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRPSRKRRSLEEVGNVTATTLTLPDFPNVSSTIVPTSQEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDSPDERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRVRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPMGPLYASSNPEYLSASDVFPSSVYVPDEWEVPREKITLLRELGQGSFGMVYEGNAKDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSHLRSLRPDAENNPGRPPPTLQEMIQMTAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFYSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGREGGSSLSIKRTYDEHIPYTHMNGGKKNGRVLTLPRSNPS DIP protein P15208 original sequence version: 104 DIP protein P15208 original sequence version: 144 DIP protein P15208 original sequence version: 148 mint This receptor binds insulin and has a tyrosine-protein kinase activity B0FA7DBD2AD4646A insr-smpdl3b-1 2 6 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed C-terminus gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 7 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed C-terminus flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range physical association physical association Figure 3A-1 SMPDL3b interacts with both IR isoforms but preferentially with IRA. SMPDL3b interacts with both IR isoforms but preferentially with IRA. insr-smpdl3b-2 2 6 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed C-terminus gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 8 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed C-terminus flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range inhibitory_region biological feature biological feature certain certain sequence position certain certain certain sequence position certain physical association physical association Figure 3A-2 SMPDL3b interacts with both IR isoforms but preferentially with IRA. SMPDL3b interacts with both IR isoforms but preferentially with IRA. insr-smpdl3b-3 2 6 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed n-terminus ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range Q92485-2:p.His135Ala 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 H A Tue Jun 30 18:31:42 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.His135Ala' 7 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed C-terminus flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range physical association physical association Figure 3B-1 SMPDL3b interacts with both IR isoforms but preferentially with IRA. SMPDL3b interacts with both IR isoforms but preferentially with IRA. insr-smpdl3b-4 2 6 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed n-terminus ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range Q92485-2:p.His135Ala 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 H A Tue Jun 30 16:39:17 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.His135Ala' 8 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed C-terminus flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range physical association physical association Figure 3B-2 SMPDL3b interacts with both IR isoforms but preferentially with IRA. SMPDL3b interacts with both IR isoforms but preferentially with IRA. insr-smpdl3b-5 2 6 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed n-terminus ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range Q92485-2:p.His135Ala 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 H A Tue Jun 30 18:46:29 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.His135Ala' 4 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed C-terminus flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range C-terminus myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range physical association physical association Figure 3B-3 insr-smpdl3b-6 2 4 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed c-terminus gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 7 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed C-terminus flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range physical association physical association Figure 3C-1, 3F-lane 1 Overexpression of SMPDL3b facilitates the interaction of caveolin-1 and IRA while interfering with the ability of IRB to bind caveolin-1. methyl-beta-cyclodextrin:CHEBI:133151- caveolin-1 inhibitor insr-cav1-1 2 4 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed c-terminus gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range 8 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed C-terminus flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range physical association physical association Figure 3C-2, 3F Overexpression of SMPDL3b facilitates the interaction of caveolin-1 and IRA while interfering with the ability of IRB to bind caveolin-1. methyl-beta-cyclodextrin:CHEBI:133151- caveolin-1 inhibitor 345ertdfg-1 1 9 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level 3 unspecified role unspecified role prey prey physiological level physiological level endogenous level endogenous endogenous endogenous level 5 unspecified role unspecified role prey prey physiological level physiological level endogenous level endogenous endogenous endogenous level association association Figure 3D