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/ Association of insulin receptor substrate 1 (IRS-1) y895 with Grb-2 mediates the insulin signaling involved in IRS-1-deficient brown adipocyte mitogenesis. Association of insulin receptor substrate 1 (IRS-1) y895 with Grb-2 mediates the insulin signaling involved in IRS-1-deficient brown adipocyte mitogenesis. Molecular and cellular biology 2001 imex curation Valverde AM., Mur C., Pons S., Alvarez AM., White MF., Kahn CR., Benito M. benito@eucmax.sim.ucm.es 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation mouse-brown_adipose Mouse Brown Adipose Tissue brown_adipose Brown Adipose Tissue anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Valverde AM., Mur C., Pons S., Alvarez AM., White MF., Kahn CR., Benito M. IRS-1 Y895F construct is of rat origin; tracked from the given back reference 8196603 benito@eucmax.sim.ucm.es Accepted 2019-MAY-30 AT 10:10 BST AT 10:10 BST by PPORRAS Molecular and cellular biology 2001 Only protein-protein interactions imex curation imex curation Grb2-mIRS interaction captured 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 irs1_mouse Insulin receptor substrate 1 Irs1 Irs-1 protein protein mouse Mus musculus Mouse MASPPDTDGFSDVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAPKRSIPLESCFNINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHNRAKAHHDGAGGGCGGSCSGSSGVGEAGEDLSYDTGPGPAFKEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQVDDSVVAQNMHETILEAMRAMSDEFRPRSKSQSSSSCSNPISVPLRRHHLNNPPPSQVGLTRRSRTESITATSPASMVGGKPGSFRVRASSDGEGTMSRPASVDGSPVSPSTNRTHAHRHRGSSRLHPPLNHSRSIPMPSSRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSPSDGGFISSDEYGSSPCDFRSSFRSVTPDSLGHTPPARGEEELSNYICMGGKGASTLAAPNGHYILSRGGNGHRYIPGANLGTSPALPGDEAAGAADLDNRFRKRTHSAGTSPTISHQKTPSQSSVASIEEYTEMMPAAYPPGGGSGGRLPGYRHSAFVPTHSYPEEGLEMHHLERRGGHHRPDTSNLHTDDGYMPMSPGVAPVPSNRKGNGDYMPMSPKSVSAPQQIINPIRRHPQRVDPNGYMMMSPSGSCSPDIGGGSSSSSSISAAPSGSSYGKPWTNGVGGHHTHALPHAKPPVESGGGKLLPCTGDYMNMSPVGDSNTSSPSECYYGPEDPQHKPVLSYYSLPRSFKHTQRPGEPEEGARHQHLRLSSSSGRLRYTATAEDSSSSTSSDSLGGGYCGARPESSLTHPHHHVLQPHLPRKVDTAAQTNSRLARPTRLSLGDPKASTLPRVREQQQQQQSSLHPPEPKSPGEYVNIEFGSGQPGYLAGPATSRSSPSVRCPPQLHPAPREETGSEEYMNMDLGPGRRATWQESGGVELGRIGPAPPGSATVCRPTRSVPNSRGDYMTMQIGCPRQSYVDTSPVAPVSYADMRTGIAAEKASLPRPTGAAPPPSSTASSSASVTPQGATAEQATHSSLLGGPQGPGGMSAFTRVNLSPNHNQSAKVIRADTQGCRRRHSSETFSAPTRAGNTVPFGAGAAVGGSGGGGGGGSEDVKRHSSASFENVWLRPGDLGGVSKESAPVCGAAGGLEKSLNYIDLDLAKEHSQDCPSQQQSLPPPPPHQPLGSNEGNSPRRSSEDLSNYASISFQKQPEDRQ DIP protein P35569 original sequence version: 136 DIP protein P35569 original sequence version: 120 C0E9B2D890DADD87 irs1_rat Insulin receptor substrate 1 pp185 Irs1 Irs-1 protein protein rat Rattus norvegicus (Rat) Rat MASPPDTDGFSDVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAPKRSIPLESCFNINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHNRAKAHHDGAGGGCGGSCSGSSGVGEAGEDLSYDTGPGPAFKEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQVDDSVVAQNMHETILEAMRAMSDEFRPRTKSQSSSSCSNPISVPLRRHHLNNPPPSQVGLTRRSRTESITATSPASMVGGKPGSFRVRASSDGEGTMSRPASVDGSPVSPSTNRTHAHRHRGSSRLHPPLNHSRSIPMPSSRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSPSDGGFISSDEYGSSPCDFRSSFRSVTPDSLGHTPPARGEEELSNYICMGGKGASTLTAPNGHYILSRGGNGHRYIPGATMGTSPALTGDEAAGAADLDNRFRKRTHSAGTSPTISHQKTPSQSSVVSIEEYTEMMPAAYPPGGGSGGRLPGYRHSAFVPTHSYPEEGLEMHHLERRGGHHRPDSSNLHTDDGYMPMSPGVAPVPSNRKGNGDYMPMSPKSVSAPQQIINPIRRHPQRVDPNGYMMMSPSGSCSPDIGGGSCSSSSISAAPSGSSYGKPWTNGVGGHHTHALPHAKPPVESGGGKLLPCTGDYMNMSPVGDSNTSSPSECYYGPEDPQHKPVLSYYSLPRSFKHTQRPGEPEEGARHQHLRLSSSSGRLRYTATAEDSSSSTSSDSLGGGYCGARPESSVTHPHHHALQPHLPRKVDTAAQTNSRLARPTRLSLGDPKASTLPRVREQQQQQQQQQQSSLHPPEPKSPGEYVNIEFGSGQPGYLAGPATSRSSPSVRCLPQLHPAPREETGSEEYMNMDLGPGRRATWQESGGVELGRVGPAPPGAASICRPTRSVPNSRGDYMTMQIGCPRQSYVDTSPVAPVSYADMRTGIAAEKVSLPRTTGAAPPPSSTASASASVTPQGAAEQAAHSSLLGGPQGPGGMSAFTRVNLSPNHNQSAKVIRADTQGCRRRHSSETFSAPTRAANTVSFGAGAAGGGSGGGSEDVKRHSSASFENVWLRPGDLGGASKESAPGCGAAGGLEKSLNYIDLDLVKDVKQHPQDCPSQQQSLPPPPPHQPLGSNEGSSPRRSSEDLSTYASINFQKQPEDRQ A274BC7540CA85C5 grb2_mouse Growth factor receptor-bound protein 2 Grb2 Adapter protein GRB2 SH2/SH3 adapter GRB2 protein protein mouse Mus musculus Mouse MEAIAKYDFKATADDELSFKRGDILKVLNEECDQNWYKAELNGKDGFIPKNYIEMKPHPWFFGKIPRAKAEEMLSKQRHDGAFLIRESESAPGDFSLSVKFGNDVQHFKVLRDGAGKYFLWVVKFNSLNELVDYHRSTSVSRNQQIFLRDIEQMPQQPTYVQALFDFDPQEDGELGFRRGDFIHVMDNSDPNWWKGACHGQTGMFPRNYVTPVNRNV 97F4A4FE4B248DDF p98083-1 SHC-transforming protein 1 Shc1 SHC-transforming protein A Shc ShcA Src homology 2 domain-containing-transforming protein C1 p66 protein protein mouse Mus musculus Mouse MDLLPPKPKYNPLRNESLSSLEEGASGSTPPEELPSPSASSLGPILPPLPGDDSPTTLCSFFPRMSNLKLANPAGGRLGPKGEPGKAAEDGEGSAGAALRDSGLLPLLQDMNKLSGGGGRRTRVEGGQLGGEEWTRHGSFVNKPTRGWLHPNDKVMGPGVSYLVRYMGCVEVLQSMRALDFNTRTQVTREAISLVCEAVPGAKGATRRRKPCSRPLSSILGRSNLKFAGMPITLTVSTSSLNLMAADCKQIIANHHMQSISFASGGDPDTAEYVAYVAKDPVNQRACHILECPEGLAQDVISTIGQAFELRFKQYLRNPPKLVTPHDRMAGFDGSAWDEEEEEPPDHQYYNDFPGKEPPLGGVVDMRLREGAARPTLPSAQMSSHLGATLPIGQHAAGDHEVRKQMLPPPPCPGRELFDDPSYVNIQNLDKARQAGGGAGPPNPSLNGSAPRDLFDMKPFEDALRVPPPPQSMSMAEQLQGEPWFHGKLSRREAEALLQLNGDFLVRESTTTPGQYVLTGLQSGQPKHLLLVDPEGVVRTKDHRFESVSHLISYHMDNHLPIISAGSELCLQQPVDRKV DIP protein P98083-1 original sequence version: 84 mint 99C22E64412B6236 shc1_mouse SHC-transforming protein 1 ShcA Shc1 Shc Src homology 2 domain-containing-transforming protein C1 SHC-transforming protein A protein protein mouse Mus musculus Mouse MDLLPPKPKYNPLRNESLSSLEEGASGSTPPEELPSPSASSLGPILPPLPGDDSPTTLCSFFPRMSNLKLANPAGGRLGPKGEPGKAAEDGEGSAGAALRDSGLLPLLQDMNKLSGGGGRRTRVEGGQLGGEEWTRHGSFVNKPTRGWLHPNDKVMGPGVSYLVRYMGCVEVLQSMRALDFNTRTQVTREAISLVCEAVPGAKGATRRRKPCSRPLSSILGRSNLKFAGMPITLTVSTSSLNLMAADCKQIIANHHMQSISFASGGDPDTAEYVAYVAKDPVNQRACHILECPEGLAQDVISTIGQAFELRFKQYLRNPPKLVTPHDRMAGFDGSAWDEEEEEPPDHQYYNDFPGKEPPLGGVVDMRLREGAARPTLPSAQMSSHLGATLPIGQHAAGDHEVRKQMLPPPPCPGRELFDDPSYVNIQNLDKARQAGGGAGPPNPSLNGSAPRDLFDMKPFEDALRVPPPPQSMSMAEQLQGEPWFHGKLSRREAEALLQLNGDFLVRESTTTPGQYVLTGLQSGQPKHLLLVDPEGVVRTKDHRFESVSHLISYHMDNHLPIISAGSELCLQQPVDRKV 99C22E64412B6236 p98083-3 SHC-transforming protein 1 Shc1 Shc ShcA SHC-transforming protein A Src homology 2 domain-containing-transforming protein C1 p47 protein protein mouse Mus musculus Mouse MGPGVSYLVRYMGCVEVLQSMRALDFNTRTQVTREAISLVCEAVPGAKGATRRRKPCSRPLSSILGRSNLKFAGMPITLTVSTSSLNLMAADCKQIIANHHMQSISFASGGDPDTAEYVAYVAKDPVNQRACHILECPEGLAQDVISTIGQAFELRFKQYLRNPPKLVTPHDRMAGFDGSAWDEEEEEPPDHQYYNDFPGKEPPLGGVVDMRLREGAARPTLPSAQMSSHLGATLPIGQHAAGDHEVRKQMLPPPPCPGRELFDDPSYVNIQNLDKARQAGGGAGPPNPSLNGSAPRDLFDMKPFEDALRVPPPPQSMSMAEQLQGEPWFHGKLSRREAEALLQLNGDFLVRESTTTPGQYVLTGLQSGQPKHLLLVDPEGVVRTKDHRFESVSHLISYHMDNHLPIISAGSELCLQQPVDRKV Produced by alternative initiation at Met-46 of isoform p52. 5064FFF6CE5BD930 p98083-2 SHC-transforming protein 1 p52 Shc1 Shc ShcA SHC-transforming protein A Src homology 2 domain-containing-transforming protein C1 protein protein mouse Mus musculus Mouse MNKLSGGGGRRTRVEGGQLGGEEWTRHGSFVNKPTRGWLHPNDKVMGPGVSYLVRYMGCVEVLQSMRALDFNTRTQVTREAISLVCEAVPGAKGATRRRKPCSRPLSSILGRSNLKFAGMPITLTVSTSSLNLMAADCKQIIANHHMQSISFASGGDPDTAEYVAYVAKDPVNQRACHILECPEGLAQDVISTIGQAFELRFKQYLRNPPKLVTPHDRMAGFDGSAWDEEEEEPPDHQYYNDFPGKEPPLGGVVDMRLREGAARPTLPSAQMSSHLGATLPIGQHAAGDHEVRKQMLPPPPCPGRELFDDPSYVNIQNLDKARQAGGGAGPPNPSLNGSAPRDLFDMKPFEDALRVPPPPQSMSMAEQLQGEPWFHGKLSRREAEALLQLNGDFLVRESTTTPGQYVLTGLQSGQPKHLLLVDPEGVVRTKDHRFESVSHLISYHMDNHLPIISAGSELCLQQPVDRKV DIP protein P98083-2 original sequence version: 155 Produced by alternative splicing. DF33594E80107A3E irs2_mouse Insulin receptor substrate 2 Irs2 4PS protein protein mouse Mus musculus Mouse MASAPLPGPPASAGGDGPNLNNNNNNNNHSVRKCGYLRKQKHGHKRFFVLRGPGTGGDEASAAGGSPPQPPRLEYYESEKKWRSKAGAPKRVIALDCCLNINKRADAKHKYLIALYTKDEYFAVAAENEQEQEGWYRALTDLVSEGRSGEGGSGTTGGSCSASLPGVLGGSAGAAGCDDNYGLVTPATAVYREVWQVNLKPKGLGQSKNLTGVYRLCLSARTIGFVKLNCEQPSVTLQLMNIRRCGHSDSFFFIEVGRSAVTGPGELWMQADDSVVAQNIHETILEAMKALKELFEFRPRSKSQSSGSSATHPISVPGARRHHHLVNLPPSQTGLVRRSRTDSLAATPPAAKCTSCRVRTASEGDGGAAGGAGTAGGRPMSVAGSPLSPGPVRAPLSRSHTLSAGCGGRPSKVTLAPAGGALQHSRSMSMPVAHSPPAATSPGSLSSSSGHGSGSYPLPPGSHPHLPHPLHHPQGQRPSSGSASASGSPSDPGFMSLDEYGSSPGDLRAFSSHRSNTPESIAETPPARDGSGGELYGYMSMDRPLSHCGRPYRRVSGDGAQDLDRGLRKRTYSLTTPARQRQVPQPSSASLDEYTLMRATFSGSSGRLCPSFPASSPKVAYNPYPEDYGDIEIGSHKSSSSNLGADDGYMPMTPGAALRSGGPNSCKSDDYMPMSPTSVSAPKQILQPRLAAALPPSGAAVPAPPSGVGRTFPVNGGGYKASSPAESSPEDSGYMRMWCGSKLSMENPDPKLLPNGDYLNMSPSEAGTAGTPPDFSAALRGGSEGLKGIPGHCYSSLPRSYKAPCSCSGDNDQYVLMSSPVGRILEEERLEPQATPGAGTFGAAGGSHTQPHHSAVPSSMRPSAIGGRPEGFLGQRCRAVRPTRLSLEGLQTLPSMQEYPLPTEPKSPGEYINIDFGEAGTRLSPPAPPLLASAASSSSLLSASSPASSLGSGTPGTSSDSRQRSPLSDYMNLDFSSPKSPKPSTRSGDTVGSMDGLLSPEASSPYPPLPPRPSTSPSSLQQPLPPAPGDLYRLPPASAATSQGPTAGSSMSSEPGDNGDYTEMAFGVAATPPQPIVAPPKPEGARVASPTSGLKRLSLMDQVSGVEAFLQVSQPPDPHRGAKVIRADPQGGRRRHSSETFSSTTTVTPVSPSFAHNSKRHNSASVENVSLRKSSEGSSTLGGGDEPPTSPGQAQPLVAVPPVPQARPWNPGQPGALIGCPGGSSSPMRRETSVGFQNGLNYIAIDVRGEQGSLAQSQPQPGDKNSWSRTRSLGGLLGTVGGSGASGVCGGPGTGALPSASTYASIDFLSHHLKEATVVKE DIP protein P81122 original sequence version: 60 823A5458DA21C9C7 grb2-shc1-18 1 5 unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level 7 unspecified role unspecified role bait bait living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level physical association physical association Figure 3, Figure 7 Insulin IRS-1 deficient cells lacked tyrosine phosphorylation of SHC and showed no SHC-Grb-2 association in response to insulin insr-shc1-2 1 2 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level purified purified 6 unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level 9 unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level 8 unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level association association Figure 3 Insulin irs1-shc1-1 1 3 unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level 7 unspecified role unspecified role bait bait living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level physical association physical association Figure 4, Figure 7 Insulin grb2-irs2-1 1 10 unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level 5 unspecified role unspecified role bait bait living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level physical association physical association Figure 5a Wortmannin (CHEBI:52289) or LY294002 (CHEBI:65329) treatment increased IRS-2-Grb-2 association twofold grb2-irs1-4 1 5 unspecified role unspecified role bait bait living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level 4 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed living cell living cell P35570:p.Tyr895Phe mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain Y F Tue Jun 30 16:35:33 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Tyr895Phe' 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 physical association physical association Figure 6b irs1-shc1-2 1 4 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed living cell living cell P35570:p.Tyr895Phe 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 F Tue Jun 30 19:49:10 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Tyr895Phe' 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 7 unspecified role unspecified role bait bait living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level physical association physical association Figure 7 insr-shc1-3 1 2 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level purified purified 9 unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level 8 unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level association association Figure 3 Insulin grb2-irs1-5 1 3 unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level 5 unspecified role unspecified role bait bait living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level physical association physical association Figure 6b