UniProt UniProt http://www.uniprot.org Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 imex curation Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation mouse-brain_hippocampal_neuron Mus musculus, brain, hippocampal neurons brain-hippocampus_neuron Hippocampal neuron anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk Accepted 2019-JUL-10 AT 16:05 BST AT 16:05 BST by MGT The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 Only protein-protein interactions imex curation imex curation OK, done this a different way. Created the interaction with the mature peptide, and added a comment about the mutation. Probably a more correct way of doing it anyway, if I'd thought about it.; EBI-21183114 - Fig. 2B and 2E-G are about sAPP695β so I have mapped the Soluble APP-beta domain from the canonical isoform onto -4 which is APP695. Its shorter, as the isoform has a chunk missing. PRO_0000000090 is PreA4 770. Numbering of Fig. 2D also refers to 695 so -4. I've used the Sortilin pro chains as a better descriptor of the mature peptide etc. ll else done.; I can't add sorl-sort as we don't have mouse evidence for that in this entry - not allowed to cross species for colocalisations any more. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 imex curation Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation mouse-brain_hippocampal_neuron Mus musculus, brain, hippocampal neurons brain-hippocampus_neuron Hippocampal neuron pla proximity ligation assay pELISA pELISA PLA antibody detection identification by antibody antibody detection Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk Accepted 2019-JUL-10 AT 16:05 BST AT 16:05 BST by MGT The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 Only protein-protein interactions imex curation imex curation OK, done this a different way. Created the interaction with the mature peptide, and added a comment about the mutation. Probably a more correct way of doing it anyway, if I'd thought about it.; EBI-21183114 - Fig. 2B and 2E-G are about sAPP695β so I have mapped the Soluble APP-beta domain from the canonical isoform onto -4 which is APP695. Its shorter, as the isoform has a chunk missing. PRO_0000000090 is PreA4 770. Numbering of Fig. 2D also refers to 695 so -4. I've used the Sortilin pro chains as a better descriptor of the mature peptide etc. ll else done.; I can't add sorl-sort as we don't have mouse evidence for that in this entry - not allowed to cross species for colocalisations any more. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 imex curation Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk 25-Jul-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. confocal microscopy confocal microscopy immunocytochemistry immunocytochemistry Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk Accepted 2019-JUL-10 AT 16:05 BST AT 16:05 BST by MGT The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 Only protein-protein interactions imex curation imex curation OK, done this a different way. Created the interaction with the mature peptide, and added a comment about the mutation. Probably a more correct way of doing it anyway, if I'd thought about it.; EBI-21183114 - Fig. 2B and 2E-G are about sAPP695β so I have mapped the Soluble APP-beta domain from the canonical isoform onto -4 which is APP695. Its shorter, as the isoform has a chunk missing. PRO_0000000090 is PreA4 770. Numbering of Fig. 2D also refers to 695 so -4. I've used the Sortilin pro chains as a better descriptor of the mature peptide etc. ll else done.; I can't add sorl-sort as we don't have mouse evidence for that in this entry - not allowed to cross species for colocalisations any more. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 imex curation Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk 25-Jul-2019: Contacted by IntAct-Help. Only protein-protein interactions imex curation mouse-brain_hippocampal_neuron Mus musculus, brain, hippocampal neurons brain-hippocampus_neuron Hippocampal neuron confocal microscopy confocal microscopy immunocytochemistry immunocytochemistry Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk Accepted 2019-JUL-10 AT 16:05 BST AT 16:05 BST by MGT The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 Only protein-protein interactions imex curation imex curation OK, done this a different way. Created the interaction with the mature peptide, and added a comment about the mutation. Probably a more correct way of doing it anyway, if I'd thought about it.; EBI-21183114 - Fig. 2B and 2E-G are about sAPP695β so I have mapped the Soluble APP-beta domain from the canonical isoform onto -4 which is APP695. Its shorter, as the isoform has a chunk missing. PRO_0000000090 is PreA4 770. Numbering of Fig. 2D also refers to 695 so -4. I've used the Sortilin pro chains as a better descriptor of the mature peptide etc. ll else done.; I can't add sorl-sort as we don't have mouse evidence for that in this entry - not allowed to cross species for colocalisations any more. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 imex curation Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk 25-Jul-2019: Contacted by IntAct-Help. 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 Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk Accepted 2019-JUL-10 AT 16:05 BST AT 16:05 BST by MGT The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 Only protein-protein interactions imex curation imex curation OK, done this a different way. Created the interaction with the mature peptide, and added a comment about the mutation. Probably a more correct way of doing it anyway, if I'd thought about it.; EBI-21183114 - Fig. 2B and 2E-G are about sAPP695β so I have mapped the Soluble APP-beta domain from the canonical isoform onto -4 which is APP695. Its shorter, as the isoform has a chunk missing. PRO_0000000090 is PreA4 770. Numbering of Fig. 2D also refers to 695 so -4. I've used the Sortilin pro chains as a better descriptor of the mature peptide etc. ll else done.; I can't add sorl-sort as we don't have mouse evidence for that in this entry - not allowed to cross species for colocalisations any more. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 imex curation Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. cg@biokemi.au.dk 25-Jul-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 bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Gustafsen C., Glerup S., Pallesen LT., Olsen D., Andersen OM., Nykjær A., Madsen P., Petersen CM. The cited reference describes 2 Sortilin mutations which block the propeptide processing site G41WRA44and R41WGG44. It is not clear which has been used cg@biokemi.au.dk Accepted 2019-JUL-10 AT 16:05 BST AT 16:05 BST by MGT The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 Only protein-protein interactions imex curation imex curation OK, done this a different way. Created the interaction with the mature peptide, and added a comment about the mutation. Probably a more correct way of doing it anyway, if I'd thought about it.; EBI-21183114 - Fig. 2B and 2E-G are about sAPP695β so I have mapped the Soluble APP-beta domain from the canonical isoform onto -4 which is APP695. Its shorter, as the isoform has a chunk missing. PRO_0000000090 is PreA4 770. Numbering of Fig. 2D also refers to 695 so -4. I've used the Sortilin pro chains as a better descriptor of the mature peptide etc. ll else done.; I can't add sorl-sort as we don't have mouse evidence for that in this entry - not allowed to cross species for colocalisations any more. p05067-8 Amyloid-beta precursor protein APP A4 AD1 ABPP Alzheimer disease amyloid protein Cerebral vascular amyloid peptide PreA4 Protease nexin-II APPI PreA4 751 Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAIPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN A major isoform. C987C557C5A3714E a4_mouse Amyloid-beta precursor protein App Alzheimer disease amyloid A4 protein homolog ABPP Amyloidogenic glycoprotein Amyloid precursor protein A4 AD1 Alzheimer disease amyloid protein Amyloid-beta (A4) precursor protein Amyloid-beta A4 protein protein protein mouse Mus musculus Mouse MLPSLALLLLAAWTVRALEVPTDGNAGLLAEPQIAMFCGKLNMHMNVQNGKWESDPSGTKTCIGTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHTHIVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDSVDSADAEEDDSDVWWGGADTDYADGGEDKVVEVAEEEEVADVEEEEADDDEDVEDGDEVEEEAEEPYEEATERTTSTATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCVPFFYGGCGGNRNNFDTEEYCMAVCGSVSTQSLLKTTSEPLPQDPDKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPHHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHPFGVDSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFGHDSGFEVRHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN 988D89E089092A3E sorl_mouse Sortilin-related receptor Sorl1 Sorting protein-related receptor containing LDLR class A repeats SorLA-1 Low-density lipoprotein receptor relative with 11 ligand-binding repeats Gp250 protein protein mouse Mus musculus Mouse MATRSSRRESRLPFLFALVALLPRGALGGGWTQRLHGGPAPLPQDRGFFVVQGDPRDLRLGTHGDAPGASPAARKPLRTRRSAALQPQPIQVYGQVSLNDSHNQMVVHWAGEKSNVIVALARDSLALARPKSSDVYVSYDYGKSFSKISEKLNFGVGNNSEAVISQFYHSPADNKRYIFVDAYAQYLWITFDFCSTIHGFSIPFRAADLLLHSKASNLLLGFDRSHPNKQLWKSDDFGQTWIMIQEHVKSFSWGIDPYDQPNAIYIERHEPFGFSTVLRSTDFFQSRENQEVILEEVRDFQLRDKYMFATKVVHLPGSQQQSSVQLWVSFGRKPMRAAQFVTKHPINEYYIADAAEDQVFVCVSHSNNSTNLYISEAEGLKFSLSLENVLYYSPGGAGSDTLVRYFANEPFADFHRVEGLQGVYIATLINGSMNEENMRSVITFDKGGTWEFLQAPAFTGYGEKINCELSQGCSLHLAQRLSQLLNLQLRRMPILSKESAPGLIIATGSVGKNLASKTNVYISSSAGARWREALPGPHYYTWGDHGGIIMAIAQGMETNELKYSTNEGETWKTFVFSEKPVFVYGLLTEPGEKSTVFTIFGSNKESVHSWLILQVNATDALGVPCTENDYKLWSPSDERGNECLLGHKTVFKRRTPHATCFNGEDFDRPVVVSNCSCTREDYECDFGFKMSEDLSLEVCVPDPEFSGKPYSPPVPCPVGSSYRRTRGYRKISGDTCSGGDVEARLEGELVPCPLAEENEFILYAMRKSIYRYDLASGATEQLPLSGLRAAVALDFDYERNCLYWSDLALDTIQRLCLNGSTGQEVIINSGLETVEALAFEPLSQLLYWVDAGFKKIEVANPDGDFRLTIVNSSVLDRPRALVLVPQEGVMFWTDWGDLKPGIYRSYMDGSAAYRLVSEDVKWPNGISVDSQWIYWTDAYLDCIERITFSGQQRSVILDSLPHPYAIAVFKNEIYWDDWSQLSIFRASKHSRSQVEILASQLTGLMDMKVFYKGKNAGSNACVPQPCSLLCLPKANNSKSCRCPEGVASSVLPSGDLMCDCPQGYQRKNNTCVKEENTCLRNQYRCSNGNCINSIWWCDFDNDCGDMSDERNCPTTVCDADTQFRCQESGTCIPLSYKCDLEDDCGDNSDESHCEMHQCRSDEFNCSSGMCIRSSWVCDGDNDCRDWSDEANCTAIYHTCEASNFQCHNGHCIPQRWACDGDADCQDGSDEDPVSCEKKCNGFHCPNGTCIPSSKHCDGLRDCPDGSDEQHCEPFCTRFMDFVCKNRQQCLFHSMVCDGIVQCRDGSDEDAAFAGCSQDPEFHKECDEFGFQCQNGVCISLIWKCDGMDDCGDYSDEANCENPTEAPNCSRYFQFHCENGHCIPNRWKCDRENDCGDWSDEKDCGDSHVLPSPTPGPSTCLPNYFHCSSGACVMGTWVCDGYRDCADGSDEEACPSLANSTAASTPTQFGQCDRFEFECHQPKKCIPNWKRCDGHQDCQDGQDEANCPTHSTLTCTSREFKCEDGEACIVLSERCDGFLDCSDESDEKACSDELTVYKVQNLQWTADFSGDVTLTWMRPKKMPSASCVYNVYYRVVGESIWKTLETHSNKTSTVLKVLKPDTTYQVKVQVHCLNKVHNTNDFVTLRTPEGLPDAPRNLQLSLNSEEEGVILGHWAPPVHTHGLIREYIVEYSRSGSKMWASQRAASNSTEIKNLLLNALYTVRVAAVTSRGIGNWSDSKSITTIKGKVIQAPNIHIDSYDENSLSFTLTMDGDIKVNGYVVNLFWSFDAHKQEKKTLSFRGGSALSHRVSNLTAHTSYEISAWAKTDLGDSPLAFEHILTRGSSPPAPSLKAKAINQTAVECIWTGPKNVVYGIFYATSFLDLYRNPKSVTTSLHNKTVIVSKDEQYLFLVRVLIPYQGPSSDYVVVKMIPDSRLPPRHLHAVHIGKTSALIKWESPYDSPDQDLFYAIAVKDLIRKTDRSYKVRSRNSTVEYSLSKLEPGGKYHIIVQLGNMSKDSSIKITTVSLSAPDALKIITENDHVLLFWKSLALKEKQFNETRGYEIHMSDSAVNLTAYLGNTTDNFFKVSNLKMGHNYTFTVQARCLFGSQICGEPAVLLYDELSSGADAAVIQAARSTDVAAVVVPILFLILLSLGVGFAILYTKHRRLQSSFSAFANSHYSSRLGSAIFSSGDDLGEDDEDAPMITGFSDDVPMVIA DIP protein O88307 original sequence version: 73 mint Likely to be a multifunctional endocytic receptor, that may be implicated in the uptake of lipoproteins and of proteases. Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. Binds the receptor-associated protein (RAP). Could play a role in cell-cell interaction. May play a role in neural organization, as well as the establishment of embryonic organ systems 5D7F53806EFE2CB0 sort_mouse Sortilin Sort1 Neurotensin receptor 3 protein protein mouse Mus musculus Mouse MERPRGAADGLLRWPLGLLLLLQLLPPAAVGQDRLDAPPPPAPPLLRWAGPVGVSWGLRAAAPGGPVPRAGRWRRGAPAEDQDCGRLPDFIAKLTNNTHQHVFDDLSGSVSLSWVGDSTGVILVLTTFQVPLVIVSFGQSKLYRSEDYGKNFKDITNLINNTFIRTEFGMAIGPENSGKVILTAEVSGGSRGGRVFRSSDFAKNFVQTDLPFHPLTQMMYSPQNSDYLLALSTENGLWVSKNFGEKWEEIHKAVCLAKWGPNNIIFFTTHVNGSCKADLGALELWRTSDLGKTFKTIGVKIYSFGLGGRFLFASVMADKDTTRRIHVSTDQGDTWSMAQLPSVGQEQFYSILAANEDMVFMHVDEPGDTGFGTIFTSDDRGIVYSKSLDRHLYTTTGGETDFTNVTSLRGVYITSTLSEDNSIQSMITFDQGGRWEHLRKPENSKCDATAKNKNECSLHIHASYSISQKLNVPMAPLSEPNAVGIVIAHGSVGDAISVMVPDVYISDDGGYSWAKMLEGPHYYTILDSGGIIVAIEHSNRPINVIKFSTDEGQCWQSYVFTQEPIYFTGLASEPGARSMNISIWGFTESFITRQWVSYTVDFKDILERNCEEDDYTTWLAHSTDPGDYKDGCILGYKEQFLRLRKSSVCQNGRDYVVAKQPSVCPCSLEDFLCDFGYFRPENASECVEQPELKGHELEFCLYGKEEHLTTNGYRKIPGDKCQGGMNPAREVKDLKKKCTSNFLNPTKQNSKSNSVPIILAIVGLMLVTVVAGVLIVKKYVCGGRFLVHRYSVLQQHAEADGVEALDSTSHAKSGYHDDSDEDLLE DIP protein Q6PHU5 original sequence version: 45 DIP protein Q6PHU5 original sequence version: 62 Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi mint 9A7A73C6FE1C8201 a4_human Amyloid-beta precursor protein APP A4 AD1 Alzheimer disease amyloid protein ABPP PreA4 Cerebral vascular amyloid peptide Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN DIP protein P05067 original sequence version: 160 DIP protein P05067 original sequence version: 207 DIP protein P05067 original sequence version: 185 DIP protein P05067 original sequence version: 188 A12EE761403740F5 sorl_human Sortilin-related receptor Sorting protein-related receptor containing LDLR class A repeats SorLA-1 Low-density lipoprotein receptor relative with 11 ligand-binding repeats SORL1 C11orf32 protein protein human Homo sapiens Human MATRSSRRESRLPFLFTLVALLPPGALCEVWTQRLHGGSAPLPQDRGFLVVQGDPRELRLWARGDARGASRADEKPLRRKRSAALQPEPIKVYGQVSLNDSHNQMVVHWAGEKSNVIVALARDSLALARPKSSDVYVSYDYGKSFKKISDKLNFGLGNRSEAVIAQFYHSPADNKRYIFADAYAQYLWITFDFCNTLQGFSIPFRAADLLLHSKASNLLLGFDRSHPNKQLWKSDDFGQTWIMIQEHVKSFSWGIDPYDKPNTIYIERHEPSGYSTVFRSTDFFQSRENQEVILEEVRDFQLRDKYMFATKVVHLLGSEQQSSVQLWVSFGRKPMRAAQFVTRHPINEYYIADASEDQVFVCVSHSNNRTNLYISEAEGLKFSLSLENVLYYSPGGAGSDTLVRYFANEPFADFHRVEGLQGVYIATLINGSMNEENMRSVITFDKGGTWEFLQAPAFTGYGEKINCELSQGCSLHLAQRLSQLLNLQLRRMPILSKESAPGLIIATGSVGKNLASKTNVYISSSAGARWREALPGPHYYTWGDHGGIITAIAQGMETNELKYSTNEGETWKTFIFSEKPVFVYGLLTEPGEKSTVFTIFGSNKENVHSWLILQVNATDALGVPCTENDYKLWSPSDERGNECLLGHKTVFKRRTPHATCFNGEDFDRPVVVSNCSCTREDYECDFGFKMSEDLSLEVCVPDPEFSGKSYSPPVPCPVGSTYRRTRGYRKISGDTCSGGDVEARLEGELVPCPLAEENEFILYAVRKSIYRYDLASGATEQLPLTGLRAAVALDFDYEHNCLYWSDLALDVIQRLCLNGSTGQEVIINSGLETVEALAFEPLSQLLYWVDAGFKKIEVANPDGDFRLTIVNSSVLDRPRALVLVPQEGVMFWTDWGDLKPGIYRSNMDGSAAYHLVSEDVKWPNGISVDDQWIYWTDAYLECIERITFSGQQRSVILDNLPHPYAIAVFKNEIYWDDWSQLSIFRASKYSGSQMEILANQLTGLMDMKIFYKGKNTGSNACVPRPCSLLCLPKANNSRSCRCPEDVSSSVLPSGDLMCDCPQGYQLKNNTCVKQENTCLRNQYRCSNGNCINSIWWCDFDNDCGDMSDERNCPTTICDLDTQFRCQESGTCIPLSYKCDLEDDCGDNSDESHCEMHQCRSDEYNCSSGMCIRSSWVCDGDNDCRDWSDEANCTAIYHTCEASNFQCRNGHCIPQRWACDGDTDCQDGSDEDPVNCEKKCNGFRCPNGTCIPSSKHCDGLRDCSDGSDEQHCEPLCTHFMDFVCKNRQQCLFHSMVCDGIIQCRDGSDEDAAFAGCSQDPEFHKVCDEFGFQCQNGVCISLIWKCDGMDDCGDYSDEANCENPTEAPNCSRYFQFRCENGHCIPNRWKCDRENDCGDWSDEKDCGDSHILPFSTPGPSTCLPNYYRCSSGTCVMDTWVCDGYRDCADGSDEEACPLLANVTAASTPTQLGRCDRFEFECHQPKTCIPNWKRCDGHQDCQDGRDEANCPTHSTLTCMSREFQCEDGEACIVLSERCDGFLDCSDESDEKACSDELTVYKVQNLQWTADFSGDVTLTWMRPKKMPSASCVYNVYYRVVGESIWKTLETHSNKTNTVLKVLKPDTTYQVKVQVQCLSKAHNTNDFVTLRTPEGLPDAPRNLQLSLPREAEGVIVGHWAPPIHTHGLIREYIVEYSRSGSKMWASQRAASNFTEIKNLLVNTLYTVRVAAVTSRGIGNWSDSKSITTIKGKVIPPPDIHIDSYGENYLSFTLTMESDIKVNGYVVNLFWAFDTHKQERRTLNFRGSILSHKVGNLTAHTSYEISAWAKTDLGDSPLAFEHVMTRGVRPPAPSLKAKAINQTAVECTWTGPRNVVYGIFYATSFLDLYRNPKSLTTSLHNKTVIVSKDEQYLFLVRVVVPYQGPSSDYVVVKMIPDSRLPPRHLHVVHTGKTSVVIKWESPYDSPDQDLLYAVAVKDLIRKTDRSYKVKSRNSTVEYTLNKLEPGGKYHIIVQLGNMSKDSSIKITTVSLSAPDALKIITENDHVLLFWKSLALKEKHFNESRGYEIHMFDSAMNITAYLGNTTDNFFKISNLKMGHNYTFTVQARCLFGNQICGEPAILLYDELGSGADASATQAARSTDVAAVVVPILFLILLSLGVGFAILYTKHRRLQSSFTAFANSHYSSRLGSAIFSSGDDLGEDDEDAPMITGFSDDVPMVIA DIP protein Q92673 original sequence version: 154 4C215BB33E65C0B2 q99523-pro_0000033163 Sortilin 100 kDa NT receptor Glycoprotein 95 Neurotensin receptor 3 SORT1 protein protein human Homo sapiens Human SAPGEDEECGRVRDFVAKLANNTHQHVFDDLRGSVSLSWVGDSTGVILVLTTFHVPLVIMTFGQSKLYRSEDYGKNFKDITDLINNTFIRTEFGMAIGPENSGKVVLTAEVSGGSRGGRIFRSSDFAKNFVQTDLPFHPLTQMMYSPQNSDYLLALSTENGLWVSKNFGGKWEEIHKAVCLAKWGSDNTIFFTTYANGSCKADLGALELWRTSDLGKSFKTIGVKIYSFGLGGRFLFASVMADKDTTRRIHVSTDQGDTWSMAQLPSVGQEQFYSILAANDDMVFMHVDEPGDTGFGTIFTSDDRGIVYSKSLDRHLYTTTGGETDFTNVTSLRGVYITSVLSEDNSIQTMITFDQGGRWTHLRKPENSECDATAKNKNECSLHIHASYSISQKLNVPMAPLSEPNAVGIVIAHGSVGDAISVMVPDVYISDDGGYSWTKMLEGPHYYTILDSGGIIVAIEHSSRPINVIKFSTDEGQCWQTYTFTRDPIYFTGLASEPGARSMNISIWGFTESFLTSQWVSYTIDFKDILERNCEEKDYTIWLAHSTDPEDYEDGCILGYKEQFLRLRKSSVCQNGRDYVVTKQPSICLCSLEDFLCDFGYYRPENDSKCVEQPELKGHDLEFCLYGREEHLTTNGYRKIPGDKCQGGVNPVREVKDLKKKCTSNFLSPEKQNSKSNSVPIILAIVGLMLVTVVAGVLIVKKYVCGGRFLVHRYSVLQQHAEANGVDGVDALDTASHTNKSGYHDDSDEDLLE 78 831 D84A44B881C93DFE sort_human Sortilin SORT1 Neurotensin receptor 3 Glycoprotein 95 100 kDa NT receptor protein protein human Homo sapiens Human MERPWGAADGLSRWPHGLGLLLLLQLLPPSTLSQDRLDAPPPPAAPLPRWSGPIGVSWGLRAAAAGGAFPRGGRWRRSAPGEDEECGRVRDFVAKLANNTHQHVFDDLRGSVSLSWVGDSTGVILVLTTFHVPLVIMTFGQSKLYRSEDYGKNFKDITDLINNTFIRTEFGMAIGPENSGKVVLTAEVSGGSRGGRIFRSSDFAKNFVQTDLPFHPLTQMMYSPQNSDYLLALSTENGLWVSKNFGGKWEEIHKAVCLAKWGSDNTIFFTTYANGSCKADLGALELWRTSDLGKSFKTIGVKIYSFGLGGRFLFASVMADKDTTRRIHVSTDQGDTWSMAQLPSVGQEQFYSILAANDDMVFMHVDEPGDTGFGTIFTSDDRGIVYSKSLDRHLYTTTGGETDFTNVTSLRGVYITSVLSEDNSIQTMITFDQGGRWTHLRKPENSECDATAKNKNECSLHIHASYSISQKLNVPMAPLSEPNAVGIVIAHGSVGDAISVMVPDVYISDDGGYSWTKMLEGPHYYTILDSGGIIVAIEHSSRPINVIKFSTDEGQCWQTYTFTRDPIYFTGLASEPGARSMNISIWGFTESFLTSQWVSYTIDFKDILERNCEEKDYTIWLAHSTDPEDYEDGCILGYKEQFLRLRKSSVCQNGRDYVVTKQPSICLCSLEDFLCDFGYYRPENDSKCVEQPELKGHDLEFCLYGREEHLTTNGYRKIPGDKCQGGVNPVREVKDLKKKCTSNFLSPEKQNSKSNSVPIILAIVGLMLVTVVAGVLIVKKYVCGGRFLVHRYSVLQQHAEANGVDGVDALDTASHTNKSGYHDDSDEDLLE DIP protein Q99523 original sequence version: 97 DIP protein Q99523-1 original sequence version: 127 91F96A3035A4B43A p05067-4 Amyloid-beta precursor protein APP A4 AD1 ABPP Alzheimer disease amyloid protein Cerebral vascular amyloid peptide PreA4 Protease nexin-II APPI PreA4 695 Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVRVPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN DIP protein P05067-4 original sequence version: 183 DIP protein P05067-4 original sequence version: 198 DIP protein P05067-4 original sequence version: 224 A major isoform. 4F6EA0139F969D56 q99523-pro_0000033162 Removed in mature form SORT1 100 kDa NT receptor Glycoprotein 95 Neurotensin receptor 3 protein protein human Homo sapiens Human QDRLDAPPPPAAPLPRWSGPIGVSWGLRAAAAGGAFPRGGRWRR 34 77 8B4FBA7D1F064300 app-sort1-1 1 10 unspecified role unspecified role prey prey physiological level physiological level endogenous level endogenous endogenous endogenous level 8 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level physical association physical association Fig. 1C sort1-app-1 5 15 unspecified role unspecified role prey prey purified purified beta region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain 13 unspecified role unspecified role bait bait purified purified c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range crigr-cho_k1 Cricetulus griseus ovary K1 cho_k1 Chinese Hamster Ovary K1 direct interaction direct interaction Fig 2B app-sort1-2 2 10 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level 8 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level proximity proximity close-contact colocalization neighbourhood interaction Fig. 1E app-sorl1-11 2 9 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level 8 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level proximity proximity close-contact colocalization neighbourhood interaction Fig. 1E sort1-app-2 5 7 unspecified role unspecified role prey prey purified purified c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range ectodomain region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain range range crigr-cho_k1 Cricetulus griseus ovary K1 cho_k1 Chinese Hamster Ovary K1 13 unspecified role unspecified role bait bait purified purified c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range crigr-cho_k1 Cricetulus griseus ovary K1 cho_k1 Chinese Hamster Ovary K1 direct interaction direct interaction Fig 2C sort1-app-3 5 15 unspecified role unspecified role prey prey purified purified c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range beta region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain crigr-cho_k1 Cricetulus griseus ovary K1 cho_k1 Chinese Hamster Ovary K1 13 unspecified role unspecified role bait bait purified purified c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range crigr-cho_k1 Cricetulus griseus ovary K1 cho_k1 Chinese Hamster Ovary K1 direct interaction direct interaction Fig 2C, 2E, 2F, 2G Acidic pH app-sort1-3 6 11 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level 14 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed physical association physical association Fig 2H This inhibition was confirmed in a coimmunoprecipitation experiment in which sortilin, but not a sortilin variant with mutated propeptide processing site (prosortilin), was pulled down together with membrane-spanning APP (Fig. 2H), showing that the interaction with APP requires propeptide cleavage of sortilin. Mutation of the propeptide cleavage site inhibited this interaction showing that the interaction with APP requires propeptide cleavage of sortilin. app-sort1-4 3 7 tag fluorescence tag visualisation by fluorescence tag fluorescence immunocytochemistry immunocytochemistry unspecified role unspecified role neutral component neutral component protein delivery protein delivery region alexa 488 label alexa 488 label undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ectodomain region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain range range 14 unspecified role unspecified role neutral component neutral component over-expressed over expressed level over-expressed colocalization colocalization Fig 4A sort1-app-4 5 15 unspecified role unspecified role prey prey purified purified d6a region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 13 unspecified role unspecified role bait bait purified purified c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range crigr-cho_k1 Cricetulus griseus ovary K1 cho_k1 Chinese Hamster Ovary K1 direct interaction direct interaction Fig 2D sort1-app-5 5 16 inhibitor inhibitor unspecified role unspecified role purified purified n-terminal gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range ecoli Escherichia coli (strain K12) 15 unspecified role unspecified role prey prey purified purified c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range beta region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain crigr-cho_k1 Cricetulus griseus ovary K1 cho_k1 Chinese Hamster Ovary K1 13 unspecified role unspecified role bait bait purified purified c-terminal his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range crigr-cho_k1 Cricetulus griseus ovary K1 cho_k1 Chinese Hamster Ovary K1 physical association physical association Fig 2G Acidic pH The interaction was completely inhibited by saturation of sortilin with a GST-fusion protein containing the sortilin propeptide suggesting that interaction with APP requires propeptide cleavage of sortilin app-sort1-5 4 10 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level 8 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level colocalization colocalization Fig. 1D app-sorl1-14 3 7 tag fluorescence tag visualisation by fluorescence tag fluorescence immunocytochemistry immunocytochemistry unspecified role unspecified role neutral component neutral component protein delivery protein delivery region alexa 488 label alexa 488 label undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined ectodomain region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain range range 12 unspecified role unspecified role neutral component neutral component over-expressed over expressed level over-expressed colocalization colocalization Fig 4A app-sorl1-15 4 9 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level 8 unspecified role unspecified role neutral component neutral component physiological level physiological level endogenous level endogenous endogenous endogenous level physical association physical association Fig. 1D