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/ http://www.ebi.ac.uk/ gu-2013c-1 Role of individual MARK isoforms in phosphorylation of tau at Ser²⁶² in Alzheimer's disease. mouse-3t3 Mus musculus embryo cells 3t3 Mouse embryo fibroblast cells pla proximity ligation assay pELISA pELISA PLA antibody detection identification by antibody antibody detection Gu G.J., Lund H., Wu D., Blokzijl A., Classon C., von Euler G., Landegren U., Sunnemark D., Kamali-Moghaddam M. Affinomics - Interactions curated for the Affinomics consortium. The isoform of Tau used in this publication is stated to be "4R":- this could correspond to either UniProt ID = P10636-8 (2N4R a 441 aa protein) OR to UniProt ID P10636-6 (0N4R a 410 aa protein). The 441 aa protein has been entered here, as the longer of the two isoforms, and it has a Serine residue at position 262;this publication uses an antibody to Tau phosphorylated at Ser262 - (AGG5759). [Tau isoforms differ by the inclusion of two inserts near the N-terminus (or their absence, referred to as -2N and 0N), and either three or four imperfect repeat regions (3R or 4R), corresponding to the microtubule-binding domains in the C-terminal region. masood.kamali@igp.uu.se Neuromolecular Med. (1535-1084) 2013 Only protein-protein interactions imex curation Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Alzheimers - Interactions investigated in the context of Alzheimers disease gu-2013c-2 Role of individual MARK isoforms in phosphorylation of tau at Ser²⁶² in Alzheimer's disease. human-brain-hippocampus Homo sapiens hippocampus brain_hippocampus brain hippocampus pla proximity ligation assay pELISA pELISA PLA antibody detection identification by antibody antibody detection Gu G.J., Lund H., Wu D., Blokzijl A., Classon C., von Euler G., Landegren U., Sunnemark D., Kamali-Moghaddam M. Affinomics - Interactions curated for the Affinomics consortium. Hippocampal sections from .Alzheimer’s Disease and normal (non-demented) postmortem human brain. The isoform of Tau used in this publication is stated to be "4R":- this could correspond to either UniProt ID = P10636-8 (2N4R a 441 aa protein) OR to UniProt ID P10636-6 (0N4R a 410 aa protein). The 441 aa protein has been entered here, as the longer of the two isoforms, and it has a Serine residue at position 262;this publication uses an antibody to Tau phosphorylated at Ser262 - (AGG5759). [Tau isoforms differ by the inclusion of two inserts near the N-terminus (or their absence, referred to as -2N and 0N), and either three or four imperfect repeat regions (3R or 4R), corresponding to the microtubule-binding domains in the C-terminal region. masood.kamali@igp.uu.se Neuromolecular Med. (1535-1084) 2013 Only protein-protein interactions imex curation Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Alzheimers - Interactions investigated in the context of Alzheimers disease p10636-8 Microtubule-associated protein tau Tau-4 MAPT MAPTL MTBT1 TAU Neurofibrillary tangle protein Paired helical filament-tau 2N4R protein protein human Homo sapiens Human MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL mark1_human Serine/threonine-protein kinase MARK1 MARK1 KIAA1477 MARK MAP/microtubule affinity-regulating kinase 1 PAR1 homolog c protein protein human Homo sapiens Human MSARTPLPTVNERDTENHTSVDGYTEPHIQPTKSSSRQNIPRCRNSITSATDEQPHIGNYRLQKTIGKGNFAKVKLARHVLTGREVAVKIIDKTQLNPTSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKYIVHRDLKAENLLLDGDMNIKIADFGFSNEFTVGNKLDTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKKLLVLNPIKRGSLEQIMKDRWMNVGHEEEELKPYTEPDPDFNDTKRIDIMVTMGFARDEINDALINQKYDEVMATYILLGRKPPEFEGGESLSSGNLCQRSRPSSDLNNSTLQSPAHLKVQRSISANQKQRRFSDHAGPSIPPAVSYTKRPQANSVESEQKEEWDKDVARKLGSTTVGSKSEMTASPLVGPERKKSSTIPSNNVYSGGSMARRNTYVCERTTDRYVALQNGKDSSLTEMSVSSISSAGSSVASAVPSARPRHQKSMSTSGHPIKVTLPTIKDGSEAYRPGTTQRVPAASPSAHSISTATPDRTRFPRGSSSRSTFHGEQLRERRSVAYNGPPASPSHETGAFAHARRGTSTGIISKITSKFVRRDPSEGEASGRTDTSRSTSGEPKERDKEEGKDSKPRSLRFTWSMKTTSSMDPNDMMREIRKVLDANNCDYEQKERFLLFCVHGDARQDSLVQWEMEVCKLPRLSLNGVRFKRISGTSIAFKNIASKIANELKL mark2_human Serine/threonine-protein kinase MARK2 MAP/microtubule affinity-regulating kinase 2 ELKL motif kinase 1 PAR1 homolog MARK2 EMK1 PAR1 homolog b protein protein human Homo sapiens Human MSSARTPLPTLNERDTEQPTLGHLDSKPSSKSNMIRGRNSATSADEQPHIGNYRLLKTIGKGNFAKVKLARHILTGKEVAVKIIDKTQLNSSSLQKLFREVRIMKVLNHPNIVKLFEVIETEKTLYLVMEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKFIVHRDLKAENLLLDADMNIKIADFGFSNEFTFGNKLDTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKKFLILNPSKRGTLEQIMKDRWMNVGHEDDELKPYVEPLPDYKDPRRTELMVSMGYTREEIQDSLVGQRYNEVMATYLLLGYKSSELEGDTITLKPRPSADLTNSSAPSPSHKVQRSVSANPKQRRFSDQAAGPAIPTSNSYSKKTQSNNAENKRPEEDRESGRKASSTAKVPASPLPGLERKKTTPTPSTNSVLSTSTNRSRNSPLLERASLGQASIQNGKDSLTMPGSRASTASASAAVSAARPRQHQKSMSASVHPNKASGLPPTESNCEVPRPSTAPQRVPVASPSAHNISSSGGAPDRTNFPRGVSSRSTFHAGQLRQVRDQQNLPYGVTPASPSGHSQGRRGASGSIFSKFTSKFVRRNLSFRFARRNLNEPESKDRVETLRPHVVGSGGNDKEKEEFREAKPRSLRFTWSMKTTSSMEPNEMMREIRKVLDANSCQSELHEKYMLLCMHGTPGHEDFVQWEMEVCKLPRLSLNGVRFKRISGTSMAFKNIASKIANELKL mark3_human MAP/microtubule affinity-regulating kinase 3 Cdc25C-associated protein kinase 1 C-TAK1 Serine/threonine-protein kinase p78 Ser/Thr protein kinase PAR-1 Protein kinase STK10 MARK3 CTAK1 EMK2 ELKL motif kinase 2 protein protein human Homo sapiens Human MSTRTPLPTVNERDTENHTSHGDGRQEVTSRTSRSGARCRNSIASCADEQPHIGNYRLLKTIGKGNFAKVKLARHILTGREVAIKIIDKTQLNPTSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLIMEYASGGEVFDYLVAHGRMKEKEARSKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVGGKLDTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVLNPIKRGTLEQIMKDRWINAGHEEDELKPFVEPELDISDQKRIDIMVGMGYSQEEIQESLSKMKYDEITATYLLLGRKSSELDASDSSSSSNLSLAKVRPSSDLNNSTGQSPHHKVQRSVSSSQKQRRYSDHAGPAIPSVVAYPKRSQTSTADSDLKEDGISSRKSSGSAVGGKGIAPASPMLGNASNPNKADIPERKKSSTVPSSNTASGGMTRRNTYVCSERTTADRHSVIQNGKENSTIPDQRTPVASTHSISSAATPDRIRFPRGTASRSTFHGQPRERRTATYNGPPASPSLSHEATPLSQTRSRGSTNLFSKLTSKLTRRNMSFRFIKRLPTEYERNGRYEGSSRNVSAEQKDENKEAKPRSLRFTWSMKTTSSMDPGDMMREIRKVLDANNCDYEQRERFLLFCVHGDGHAENLVQWEMEVCKLPRLSLNGVRFKRISGTSIAFKNIASKIANELKL mark4_human MAP/microtubule affinity-regulating kinase 4 MARK4 KIAA1860 MARKL1 MAP/microtubule affinity-regulating kinase-like 1 protein protein human Homo sapiens Human MSSRTVLAPGNDRNSDTHGTLGSGRSSDKGPSWSSRSLGARCRNSIASCPEEQPHVGNYRLLRTIGKGNFAKVKLARHILTGREVAIKIIDKTQLNPSSLQKLFREVRIMKGLNHPNIVKLFEVIETEKTLYLVMEYASAGEVFDYLVSHGRMKEKEARAKFRQIVSAVHYCHQKNIVHRDLKAENLLLDAEANIKIADFGFSNEFTLGSKLDTFCGSPPYAAPELFQGKKYDGPEVDIWSLGVILYTLVSGSLPFDGHNLKELRERVLRGKYRVPFYMSTDCESILRRFLVLNPAKRCTLEQIMKDKWINIGYEGEELKPYTEPEEDFGDTKRIEVMVGMGYTREEIKESLTSQKYNEVTATYLLLGRKTEEGGDRGAPGLALARVRAPSDTTNGTSSSKGTSHSKGQRSSSSTYHRQRRHSDFCGPSPAPLHPKRSPTSTGEAELKEERLPGRKASCSTAGSGSRGLPPSSPMVSSAHNPNKAEIPERRKDSTSTPNNLPPSMMTRRNTYVCTERPGAERPSLLPNGKENSSGTPRVPPASPSSHSLAPPSGERSRLARGSTIRSTFHGGQVRDRRAGGGGGGGVQNGPPASPTLAHEAAPLPAGRPRPTTNLFTKLTSKLTRRVADEPERIGGPEVTSCHLPWDQTETAPRLLRFPWSVKLTSSRPPEALMAALRQATAAARCRCRQPQPFLLACLHGGAGGPEPLSHFEVEVCQLPRPGLRGVLFRRVAGTALAFRTLVTRISNDLEL tau_human Microtubule-associated protein tau MAPT MTBT1 TAU Neurofibrillary tangle protein Paired helical filament-tau MAPTL protein protein human Homo sapiens Human MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQEPESGKVVQEGFLREPGPPGLSHQLMSGMPGAPLLPEGPREATRQPSGTGPEDTEGGRHAPELLKHQLLGDLHQEGPPLKGAGGKERPGSKEEVDEDRDVDESSPQDSPPSKASPAQDGRPPQTAAREATSIPGFPAEGAIPLPVDFLSKVSTEIPASEPDGPSVGRAKGQDAPLEFTFHVEITPNVQKEQAHSEEHLGRAAFPGAPGEGPEARGPSLGEDTKEADLPEPSEKQPAAAPRGKPVSRVPQLKARMVSKSKDGTGSDDKKAKTSTRSSAKTLKNRPCLSPKHPTPGSSDPLIQPSSPAVCPEPPSSPKYVSSVTSRTGSSGAKEMKLKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL mapt-mark1 1567132 n/a 1567134 unspecified role unspecified role neutral component neutral component possible_phospho_ser262 opser O-phospho-L-serine (2S)-2-amino-3-(phosphonooxy)propanoic acid 2-amino-3-hydroxypropanoic acid 3-phosphate 2-azanyl-3-(phosphonooxy)propanoic acid ACT_SITE Phosphoserine intermediate MOD_RES Phosphoserine O-phospho-L-serine O-phosphonoserine O-phosphorylated L-serine O3-phosphoserine serine phosphate ester OPSer Phospho Phospho Seryl Phosphorylation phosphorylations certain certain sequence position certain certain certain sequence position certain false n/a 1567135 unspecified role unspecified role neutral component neutral component proximity proximity close-contact colocalization neighbourhood interaction false false false Figure 1,2-1 Staurosporine, a non-selective kinase inhibitor. mapt-mark1-1 1567132 n/a 1567134 unspecified role unspecified role neutral component neutral component possible_phospho_ser262 opser O-phospho-L-serine (2S)-2-amino-3-(phosphonooxy)propanoic acid 2-amino-3-hydroxypropanoic acid 3-phosphate 2-azanyl-3-(phosphonooxy)propanoic acid ACT_SITE Phosphoserine intermediate MOD_RES Phosphoserine O-phospho-L-serine O-phosphonoserine O-phosphorylated L-serine O3-phosphoserine serine phosphate ester OPSer Phospho Phospho Seryl Phosphorylation phosphorylations certain certain sequence position certain certain certain sequence position certain false n/a 1567136 unspecified role unspecified role neutral component neutral component proximity proximity close-contact colocalization neighbourhood interaction false false false Figure 1,2-2 Staurosporine, a non-selective kinase inhibitor. mapt-mark2-2 1567132 n/a 1567134 unspecified role unspecified role neutral component neutral component possible_phospho_ser262 opser O-phospho-L-serine (2S)-2-amino-3-(phosphonooxy)propanoic acid 2-amino-3-hydroxypropanoic acid 3-phosphate 2-azanyl-3-(phosphonooxy)propanoic acid ACT_SITE Phosphoserine intermediate MOD_RES Phosphoserine O-phospho-L-serine O-phosphonoserine O-phosphorylated L-serine O3-phosphoserine serine phosphate ester OPSer Phospho Phospho Seryl Phosphorylation phosphorylations certain certain sequence position certain certain certain sequence position certain false n/a 1567137 unspecified role unspecified role neutral component neutral component proximity proximity close-contact colocalization neighbourhood interaction false false false Figure 1,2-3 Staurosporine, a non-selective kinase inhibitor. mapt-mark3 1567132 n/a 1567138 unspecified role unspecified role neutral component neutral component n/a 1567134 unspecified role unspecified role neutral component neutral component possible_phospho_ser262 opser O-phospho-L-serine (2S)-2-amino-3-(phosphonooxy)propanoic acid 2-amino-3-hydroxypropanoic acid 3-phosphate 2-azanyl-3-(phosphonooxy)propanoic acid ACT_SITE Phosphoserine intermediate MOD_RES Phosphoserine O-phospho-L-serine O-phosphonoserine O-phosphorylated L-serine O3-phosphoserine serine phosphate ester OPSer Phospho Phospho Seryl Phosphorylation phosphorylations certain certain sequence position certain certain certain sequence position certain false proximity proximity close-contact colocalization neighbourhood interaction false false false Figure 1,2, Supp fig 5,6 Staurosporine, a non-selective kinase inhibitor, CagA peptide (GFPLKRHDGVDDLSKVG) - a MARK protein substrate mimic/inhibitor of tau phosphorylation. mapt-mark2-3 1567133 n/a 1567139 unspecified role unspecified role neutral component neutral component n/a 1567137 unspecified role unspecified role neutral component neutral component proximity proximity close-contact colocalization neighbourhood interaction false false false Figure 4-6 Interactions were found in the cytoplasm and neuropil of CA-field neurons mapt-mark1-2 1567133 n/a 1567135 unspecified role unspecified role neutral component neutral component n/a 1567139 unspecified role unspecified role neutral component neutral component proximity proximity close-contact colocalization neighbourhood interaction false false false Figure 4-6 Interactions were found in the cytoplasm and neuropil of CA-field neurons mapt-mark3-1 1567133 n/a 1567138 unspecified role unspecified role neutral component neutral component n/a 1567139 unspecified role unspecified role neutral component neutral component proximity proximity close-contact colocalization neighbourhood interaction false false false Figure 4-6, Supp Fig 9. Interactions were found in the cytoplasm and neuropil of CA-field neurons. Clusters of MARK4–tau interactions were also detected in the soma of CA-neurons to a larger extent in AD cases than non-AD cases. (see fig 4H) The number of MARK4–tau interactions was significantly elevated in all CA fields of AD brains as compared to non-AD brains. Numbers of MARK4–tau interactions strongly correlated with Braak stages and importantly were observed already at Braak stage 1. mapt-mark1-2 1567133 n/a 1567136 unspecified role unspecified role neutral component neutral component n/a 1567139 unspecified role unspecified role neutral component neutral component proximity proximity close-contact colocalization neighbourhood interaction false false false Figure 4-6 Interactions were found in the cytoplasm and neuropil of CA-field neurons. MARK2–tau interactions were elevated in AD cases the CA2–CA1 field, and the number of detected MARK2–tau interactions correlated with the Braak stages.