Datasets:

bigbio

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genia_ptm_event_corpus

like 1

[ { "id": "2419513__text", "type": "abstract", "text": [ "Vitamin B12 neuropathy is not due to failure to methylate myelin basic protein. \nIt has been proposed that the biochemical lesion in subacute combined degeneration of the cord due to vitamin B12 deficiency, is impaired methylation of residue 107 (arginine) in myelin basic protein. We have examined myelin basic protein in brains of rats in which vitamin B12 was inactivated by exposure to nitrous oxide for up to 7 days. In addition brains of fruit bats in which vitamin B12 neuropathy had been produced by feeding washed, and hence vitamin B12-free fruit, were examined. There was no difference in the methylation of arginine 107 in myelin basic protein in these animals as compared to healthy control animals. Rats given an inhibitor of transmethylation reactions (cycloleucine) showed the expected fall in methylation of myelin basic protein. " ], "offsets": [ [ 0, 847 ] ] } ]

[ { "id": "2419513_T1", "type": "Protein", "text": [ "myelin basic protein" ], "offsets": [ [ 58, 78 ] ], "normalized": [] }, { "id": "2419513_T2", "type": "Protein", "text": [ "myelin basic protein" ], "offsets": [ [ 260, 280 ] ], "normalized": [] }, { "id": "2419513_T3", "type": "Protein", "text": [ "myelin basic protein" ], "offsets": [ [ 299, 319 ] ], "normalized": [] }, { "id": "2419513_T4", "type": "Protein", "text": [ "myelin basic protein" ], "offsets": [ [ 635, 655 ] ], "normalized": [] }, { "id": "2419513_T5", "type": "Protein", "text": [ "myelin basic protein" ], "offsets": [ [ 825, 845 ] ], "normalized": [] }, { "id": "2419513_T8", "type": "Entity", "text": [ "residue 107" ], "offsets": [ [ 234, 245 ] ], "normalized": [] }, { "id": "2419513_T9", "type": "Entity", "text": [ "arginine" ], "offsets": [ [ 247, 255 ] ], "normalized": [] }, { "id": "2419513_T11", "type": "Entity", "text": [ "arginine 107" ], "offsets": [ [ 619, 631 ] ], "normalized": [] } ]

[ { "id": "2419513_E1", "type": "Protein_amino_acid_methylation", "trigger": { "text": [ "methylate" ], "offsets": [ [ 48, 57 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2419513_T1" } ] }, { "id": "2419513_E2", "type": "Protein_amino_acid_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 219, 230 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2419513_T2" }, { "role": "Site", "ref_id": "2419513_T8" } ] }, { "id": "2419513_E3", "type": "Protein_amino_acid_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 604, 615 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2419513_T4" }, { "role": "Site", "ref_id": "2419513_T11" } ] }, { "id": "2419513_E4", "type": "Protein_amino_acid_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 810, 821 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2419513_T5" } ] } ]

[ { "id": "2419513_1", "entity_ids": [ "2419513_T8", "2419513_T9" ] } ]

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[ { "id": "7309716__text", "type": "abstract", "text": [ "Human spleen histone H3. Isolation and amino acid sequence. \nThe amino acid sequence of human spleen histone H3 was investigated as a study in histone evolution, following previous investigations of human spleen histone H2B [Ohe, Y., Hayashi, H., & Iwai, K. (1979) J. Biochem. 85, 615-624] and H2A [Hayashi, T., Ohe, Y., Hayashi, H., & Iwai, K. (1980) J. Biochem. 88, 27-34]. The H3 fraction was obtained as described previously and further purified by Bio-Gel P-10 chromatography. The reduced and carboxymethylated H3 was digested with an arginine-specific protease, Clostripain, and the peptides were fractionated by repeated column chromatographies with reasonable recoveries. Most of these peptides, together with two tryptic peptides and one chymotryptic peptide obtained similarly, were sequenced by Edman degradation. Thus, the human H3 was deduced to have a sequence of 135 amino acid residues identical with that of the main component of calf thymus H3, except for one complete substitution (Ser for Cys-96) and four partial substitutions (Ser for Ala-31, Ala for Ser-87, Ile for Val-89, and gly for Met-90), which suggest the presence of at least two variants. Three methylated lysines (residues 9, 27, and 36) and two acetylated lysines (residues 14 and 23) were also found. The substitutions and modifications found in the human H3 are compared with those in the known H3 sequences of other eukaryotes, and the implications are discussed. " ], "offsets": [ [ 0, 1457 ] ] } ]

[ { "id": "7309716_T1", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 13, 23 ] ], "normalized": [] }, { "id": "7309716_T2", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 101, 111 ] ], "normalized": [] }, { "id": "7309716_T3", "type": "Protein", "text": [ "histone H2B" ], "offsets": [ [ 212, 223 ] ], "normalized": [] }, { "id": "7309716_T4", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 381, 383 ] ], "normalized": [] }, { "id": "7309716_T5", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 518, 520 ] ], "normalized": [] }, { "id": "7309716_T6", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 845, 847 ] ], "normalized": [] }, { "id": "7309716_T7", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 963, 965 ] ], "normalized": [] }, { "id": "7309716_T8", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1347, 1349 ] ], "normalized": [] }, { "id": "7309716_T9", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1387, 1389 ] ], "normalized": [] }, { "id": "7309716_T11", "type": "Entity", "text": [ "residues 9" ], "offsets": [ [ 1202, 1212 ] ], "normalized": [] }, { "id": "7309716_T12", "type": "Entity", "text": [ "27" ], "offsets": [ [ 1214, 1216 ] ], "normalized": [] }, { "id": "7309716_T13", "type": "Entity", "text": [ "36" ], "offsets": [ [ 1222, 1224 ] ], "normalized": [] }, { "id": "7309716_T15", "type": "Entity", "text": [ "residues 14" ], "offsets": [ [ 1254, 1265 ] ], "normalized": [] }, { "id": "7309716_T16", "type": "Entity", "text": [ "23" ], "offsets": [ [ 1270, 1272 ] ], "normalized": [] } ]

[ { "id": "7309716_E1", "type": "Protein_amino_acid_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 1182, 1192 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7309716_T6" }, { "role": "Site", "ref_id": "7309716_T11" } ] }, { "id": "7309716_E2", "type": "Protein_amino_acid_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 1182, 1192 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7309716_T6" }, { "role": "Site", "ref_id": "7309716_T12" } ] }, { "id": "7309716_E3", "type": "Protein_amino_acid_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 1182, 1192 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7309716_T6" }, { "role": "Site", "ref_id": "7309716_T13" } ] }, { "id": "7309716_E4", "type": "Protein_amino_acid_acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 1234, 1244 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7309716_T6" }, { "role": "Site", "ref_id": "7309716_T16" } ] }, { "id": "7309716_E5", "type": "Protein_amino_acid_acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 1234, 1244 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7309716_T6" }, { "role": "Site", "ref_id": "7309716_T15" } ] } ]

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[ { "id": "3542030__text", "type": "abstract", "text": [ "Amino acid sequence of the sex steroid binding protein of human blood plasma. \nThe amino acid sequence of the sex steroid binding protein (SBP) from human plasma has been determined. The SBP subunit consists of a 373-residue polypeptide chain containing two disulfide bonds and three oligosaccharide chains. The sequence was solved primarily by analysis of peptides derived by cleavage at either lysyl or methionyl residues. In our preparations, approximately half of the protein molecules have the amino-terminal sequence Arg-Pro-Val-Leu-Pro; the other half lack Arg-Pro and begin with the valine. Preparations of Hammond et al. [Hammond, G. L., Robinson, P. A., Sugino, H., Ward, D. N., & Finne, J. (1986) J. Steroid Biochem. 24, 815] have an additional leucine at the amino terminus, making a total of 373 residues in the chain. Oligosaccharide chains are placed at Thr-7 and at Asn residues 351 and 367. The two disulfide bonds connect Cys-164 to Cys-188 and Cys-333 to Cys-361. The reported heterogeneity of preparations of the molecule may result in part from the amino-terminal microheterogeneity, in part from variations in the oligosaccharide moieties, and possibly in part from rearrangements involving cyclic imide formation in two Asn-Gly sequences. Certain hydrophobic segments are suggested as possible components of the steroid-binding sites. The protein shows no homology either with the cDNA-derived sequences of the estrogen and glucocorticoid receptors found by others to be homologous with each other or with any other protein sequence in the 1986 data base. " ], "offsets": [ [ 0, 1579 ] ] } ]

[ { "id": "3542030_T1", "type": "Protein", "text": [ "sex steroid binding protein" ], "offsets": [ [ 27, 54 ] ], "normalized": [] }, { "id": "3542030_T2", "type": "Protein", "text": [ "sex steroid binding protein" ], "offsets": [ [ 110, 137 ] ], "normalized": [] }, { "id": "3542030_T3", "type": "Protein", "text": [ "SBP" ], "offsets": [ [ 139, 142 ] ], "normalized": [] }, { "id": "3542030_T4", "type": "Protein", "text": [ "SBP" ], "offsets": [ [ 187, 190 ] ], "normalized": [] }, { "id": "3542030_T5", "type": "Protein", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 1447, 1471 ] ], "normalized": [] }, { "id": "3542030_T7", "type": "Entity", "text": [ "Thr-7" ], "offsets": [ [ 869, 874 ] ], "normalized": [] }, { "id": "3542030_T8", "type": "Entity", "text": [ "Asn residues 351" ], "offsets": [ [ 882, 898 ] ], "normalized": [] }, { "id": "3542030_T9", "type": "Entity", "text": [ "367" ], "offsets": [ [ 903, 906 ] ], "normalized": [] } ]

[ { "id": "3542030_E1", "type": "Protein_amino_acid_glycosylation", "trigger": { "text": [ "Oligosaccharide chains are placed" ], "offsets": [ [ 832, 865 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "3542030_T4" }, { "role": "Site", "ref_id": "3542030_T7" } ] }, { "id": "3542030_E2", "type": "Protein_amino_acid_glycosylation", "trigger": { "text": [ "Oligosaccharide chains are placed" ], "offsets": [ [ 832, 865 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "3542030_T4" }, { "role": "Site", "ref_id": "3542030_T8" } ] }, { "id": "3542030_E3", "type": "Protein_amino_acid_glycosylation", "trigger": { "text": [ "Oligosaccharide chains are placed" ], "offsets": [ [ 832, 865 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "3542030_T4" }, { "role": "Site", "ref_id": "3542030_T9" } ] } ]

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[ { "id": "18515076__text", "type": "abstract", "text": [ "Hsl7 is a substrate-specific type II protein arginine methyltransferase in yeast. \nThe Saccharomyces cerevisiae protein Hsl7 is a regulator of the Swe1 protein kinase in cell cycle checkpoint control. Hsl7 has been previously described as a type III protein arginine methyltransferase, catalyzing the formation of omega-monomethylarginine residues on non-physiological substrates. However, we show here that Hsl7 can also display type II activity, generating symmetric dimethylarginine residues on calf thymus histone H2A. Symmetric dimethylation is only observed when enzyme and the methyl-accepting substrate were incubated for extended times. We confirmed the Hsl7-dependent formation of symmetric dimethylarginine by amino acid analysis and thin layer chromatography with wild-type and mutant recombinant enzymes expressed from both bacteria and yeast. This result is significant because no type II activity has been previously demonstrated in S. cerevisiae. We also show that Hsl7 has little or no activity on GST-GAR, a commonly used substrate for protein arginine methyltransferases, and only minimal activity on myelin basic protein. This enzyme thus may only recognize only a small subset of potential substrate proteins in yeast, in contrast to the situation with Rmt1, the major type I methyltransferase. " ], "offsets": [ [ 0, 1316 ] ] } ]

[ { "id": "18515076_T1", "type": "Protein", "text": [ "Hsl7" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "18515076_T2", "type": "Protein", "text": [ "Hsl7" ], "offsets": [ [ 120, 124 ] ], "normalized": [] }, { "id": "18515076_T3", "type": "Protein", "text": [ "Swe1" ], "offsets": [ [ 147, 151 ] ], "normalized": [] }, { "id": "18515076_T4", "type": "Protein", "text": [ "Hsl7" ], "offsets": [ [ 201, 205 ] ], "normalized": [] }, { "id": "18515076_T5", "type": "Protein", "text": [ "Hsl7" ], "offsets": [ [ 408, 412 ] ], "normalized": [] }, { "id": "18515076_T6", "type": "Protein", "text": [ "histone H2A" ], "offsets": [ [ 510, 521 ] ], "normalized": [] }, { "id": "18515076_T7", "type": "Protein", "text": [ "Hsl7" ], "offsets": [ [ 663, 667 ] ], "normalized": [] }, { "id": "18515076_T8", "type": "Protein", "text": [ "Hsl7" ], "offsets": [ [ 981, 985 ] ], "normalized": [] }, { "id": "18515076_T9", "type": "Protein", "text": [ "myelin basic protein" ], "offsets": [ [ 1120, 1140 ] ], "normalized": [] }, { "id": "18515076_T10", "type": "Protein", "text": [ "Rmt1" ], "offsets": [ [ 1274, 1278 ] ], "normalized": [] }, { "id": "18515076_T13", "type": "Entity", "text": [ "dimethylarginine residues" ], "offsets": [ [ 469, 494 ] ], "normalized": [] } ]

[ { "id": "18515076_E1", "type": "Protein_amino_acid_methylation", "trigger": { "text": [ "generating symmetric dimethylarginine residues" ], "offsets": [ [ 448, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "18515076_T6" }, { "role": "Site", "ref_id": "18515076_T13" } ] }, { "id": "18515076_E2", "type": "Positive_regulation", "trigger": { "text": [ "generating symmetric dimethylarginine residues" ], "offsets": [ [ 448, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "18515076_E1" }, { "role": "Cause", "ref_id": "18515076_T5" } ] } ]

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[ { "id": "2833926__text", "type": "abstract", "text": [ "All three potential N-glycosylation sites of the dog kidney (Na+ + K+)-ATPase beta-subunit contain oligosaccharide. \nThe beta-subunit of dog kidney (Na+ + K+)-ATPase is a sialoglycoprotein and contains three potential N-glycosylation sites. In this study, the oligosaccharide chains of purified dog kidney beta-subunit were labeled with tritium by oxidation with sodium periodate or galactose oxidase followed by NaB3H4 reduction. The beta-subunit was extensively digested by trypsin and the radioactive peptides were purified by HPLC. The enzyme, glycopeptidase A, which catalyzes the removal of N-linked oligosaccharide chains and the conversion of the glycosylated Asn residue to Asp, was used to demonstrate that a number of purified beta-subunit tryptic peptides were glycosylated. Amino-acid analysis of these beta-subunit peptides following glycopeptidase-A treatment revealed the expected Asn to Asp conversion for Asn-157, Asn-192 and Asn-264, demonstrating that all three potential N-glycosylation sites of the dog kidney beta-subunit are glycosylated. In addition, amino-acid sequence data suggest that a disulfide bond exists between Cys-158 and Cys-174. " ], "offsets": [ [ 0, 1167 ] ] } ]

[ { "id": "2833926_T1", "type": "Protein", "text": [ "(Na+ + K+)-ATPase beta-subunit" ], "offsets": [ [ 60, 90 ] ], "normalized": [] }, { "id": "2833926_T2", "type": "Entity", "text": [ "Asn-157" ], "offsets": [ [ 923, 930 ] ], "normalized": [] }, { "id": "2833926_T3", "type": "Entity", "text": [ "Asn-192" ], "offsets": [ [ 932, 939 ] ], "normalized": [] }, { "id": "2833926_T4", "type": "Entity", "text": [ "Asn-264" ], "offsets": [ [ 944, 951 ] ], "normalized": [] } ]

[ { "id": "2833926_E1", "type": "Protein_amino_acid_glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 1049, 1061 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2833926_T1" }, { "role": "Site", "ref_id": "2833926_T2" } ] }, { "id": "2833926_E2", "type": "Protein_amino_acid_glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 1049, 1061 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2833926_T1" }, { "role": "Site", "ref_id": "2833926_T3" } ] }, { "id": "2833926_E3", "type": "Protein_amino_acid_glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 1049, 1061 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "2833926_T1" }, { "role": "Site", "ref_id": "2833926_T4" } ] } ]

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[ { "id": "1859361__text", "type": "abstract", "text": [ "The amino acid sequence of the aspartate aminotransferase from baker's yeast (Saccharomyces cerevisiae). \n1. The single (cytosolic) aspartate aminotransferase was purified in high yield from baker's yeast (Saccharomyces cerevisiae). 2. Amino-acid-sequence analysis was carried out by digestion of the protein with trypsin and with CNBr; some of the peptides produced were further subdigested with Staphylococcus aureus V8 proteinase or with pepsin. Peptides were sequenced by the dansyl-Edman method and/or by automated gas-phase methods. The amino acid sequence obtained was complete except for a probable gap of two residues as indicated by comparison with the structures of counterpart proteins in other species. 3. The N-terminus of the enzyme is blocked. Fast-atom-bombardment m.s. was used to identify the blocking group as an acetyl one. 4. Alignment of the sequence of the enzyme with those of vertebrate cytosolic and mitochondrial aspartate aminotransferases and with the enzyme from Escherichia coli showed that about 25% of residues are conserved between these distantly related forms. 5. Experimental details and confirmatory data for the results presented here are given in a Supplementary Publication (SUP 50164, 25 pages) that has been deposited at the British Library Document Supply Centre, Boston Spa. Wetherby, West Yorkshire LS23 7 BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1991) 273, 5. " ], "offsets": [ [ 0, 1449 ] ] } ]

[ { "id": "1859361_T1", "type": "Protein", "text": [ "aspartate aminotransferase" ], "offsets": [ [ 31, 57 ] ], "normalized": [] }, { "id": "1859361_T2", "type": "Protein", "text": [ "aspartate aminotransferase" ], "offsets": [ [ 132, 158 ] ], "normalized": [] }, { "id": "1859361_T3", "type": "Protein", "text": [ "V8 proteinase" ], "offsets": [ [ 419, 432 ] ], "normalized": [] }, { "id": "1859361_T4", "type": "Protein", "text": [ "aspartate aminotransferases" ], "offsets": [ [ 941, 968 ] ], "normalized": [] }, { "id": "1859361_T5", "type": "Entity", "text": [ "N-terminus" ], "offsets": [ [ 723, 733 ] ], "normalized": [] } ]

[ { "id": "1859361_E1", "type": "Protein_amino_acid_acetylation", "trigger": { "text": [ "blocking group as an acetyl one" ], "offsets": [ [ 812, 843 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "1859361_T2" }, { "role": "Site", "ref_id": "1859361_T5" } ] } ]

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[ { "id": "7439154__text", "type": "abstract", "text": [ "Pancreatic ribonucleases of mammals with ruminant-like digestion. Amino-acid sequences of hippopotamus and sloth ribonucleases. \nHigh levels of pancreatic ribonucleases are found in ruminants, species that have a ruminant-like digestion and several species with coecal digestion. Pancreatic ribonucleases from several independently evolved species with ruminant-like digestion were investigated to test a hypothesis that glycosylation of ribonucleases may have some function in species with coecal digestion and that glycosylation of the enzyme may not be advantageous for ruminants. Ribonucleases from the hippopotamus, two-toed sloth and three-toed sloth were isolated by extraction with sulfuric acid and affinity chromatography. Complete amino acid sequences were determined for the ribonucleases from the hippopotamus and two-toed sloth and a partial sequence for the enzyme from the three-toed sloth. The amino acids 75-78 of hippopotamus ribonuclease were positioned by homology with other artiodactyl ribonucleases. In hippopotamus ribonuclease a heterogeneity was found at position 37, half of the molecules containing glutamine acid the other half lysine. Hippopotamus ribonuclease differs less from pig and bovine ribonuclease than these differ from each other, because more ancestral characteristics have been retained. Although hippopotamus ribonuclease contains all four Asn-X-Ser/Thr sequences previously found to be glycosylation sites in one or more pancreatic ribonucleases, only the sequence Asn-Met-Thr (34-36) is glycosylated in the variant with glutamine at position 37, while the variant with lysine at this position is carbohydrate-free. Both sloth ribonucleases are completely glycosylated at the sequence Ans-Met-Thr (34-36) with a simple type of carbohydrate chain. The amino acid sequence of two-toed sloth ribonuclease shows some interesting coupled replacements. " ], "offsets": [ [ 0, 1902 ] ] } ]

[ { "id": "7439154_T1", "type": "Protein", "text": [ "ribonucleases" ], "offsets": [ [ 11, 24 ] ], "normalized": [] }, { "id": "7439154_T2", "type": "Protein", "text": [ "ribonucleases" ], "offsets": [ [ 113, 126 ] ], "normalized": [] }, { "id": "7439154_T3", "type": "Protein", "text": [ "ribonucleases" ], "offsets": [ [ 155, 168 ] ], "normalized": [] }, { "id": "7439154_T4", "type": "Protein", "text": [ "ribonucleases" ], "offsets": [ [ 292, 305 ] ], "normalized": [] }, { "id": "7439154_T5", "type": "Protein", "text": [ "ribonucleases" ], "offsets": [ [ 439, 452 ] ], "normalized": [] }, { "id": "7439154_T6", "type": "Protein", "text": [ "Ribonucleases" ], "offsets": [ [ 586, 599 ] ], "normalized": [] }, { "id": "7439154_T7", "type": "Protein", "text": [ "ribonucleases" ], "offsets": [ [ 790, 803 ] ], "normalized": [] }, { "id": "7439154_T8", "type": "Protein", "text": [ "ribonuclease" ], "offsets": [ [ 949, 961 ] ], "normalized": [] }, { "id": "7439154_T9", "type": "Protein", "text": [ "ribonucleases" ], "offsets": [ [ 1013, 1026 ] ], "normalized": [] }, { "id": "7439154_T10", "type": "Protein", "text": [ "ribonuclease" ], "offsets": [ [ 1045, 1057 ] ], "normalized": [] }, { "id": "7439154_T11", "type": "Protein", "text": [ "ribonuclease" ], "offsets": [ [ 1185, 1197 ] ], "normalized": [] }, { "id": "7439154_T12", "type": "Protein", "text": [ "ribonuclease" ], "offsets": [ [ 1231, 1243 ] ], "normalized": [] }, { "id": "7439154_T13", "type": "Protein", "text": [ "ribonuclease" ], "offsets": [ [ 1361, 1373 ] ], "normalized": [] }, { "id": "7439154_T14", "type": "Protein", "text": [ "ribonucleases" ], "offsets": [ [ 1485, 1498 ] ], "normalized": [] }, { "id": "7439154_T15", "type": "Protein", "text": [ "ribonucleases" ], "offsets": [ [ 1681, 1694 ] ], "normalized": [] }, { "id": "7439154_T16", "type": "Protein", "text": [ "ribonuclease" ], "offsets": [ [ 1844, 1856 ] ], "normalized": [] }, { "id": "7439154_T17", "type": "Entity", "text": [ "Asn-Met-Thr (34-36)" ], "offsets": [ [ 1518, 1537 ] ], "normalized": [] } ]

[ { "id": "7439154_E1", "type": "Protein_amino_acid_glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 1541, 1553 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "7439154_T14" }, { "role": "Site", "ref_id": "7439154_T17" } ] } ]

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[ { "id": "19304754__text", "type": "abstract", "text": [ "The transcriptional coactivator MAML1 regulates p300 autoacetylation and HAT activity. \nMAML1 is a transcriptional coregulator originally identified as a Notch coactivator. MAML1 is also reported to interact with other coregulator proteins, such as CDK8 and p300, to modulate the activity of Notch. We, and others, previously showed that MAML1 recruits p300 to Notch-regulated genes through direct interactions with the DNA-CSL-Notch complex and p300. MAML1 interacts with the C/H3 domain of p300, and the p300-MAML1 complex specifically acetylates lysines of histone H3 and H4 tails in chromatin in vitro. In this report, we show that MAML1 potentiates p300 autoacetylation and p300 transcriptional activation. MAML1 directly enhances p300 HAT activity, and this coincides with the translocation of MAML1, p300 and acetylated histones to nuclear bodies. " ], "offsets": [ [ 0, 855 ] ] } ]

[ { "id": "19304754_T1", "type": "Protein", "text": [ "MAML1" ], "offsets": [ [ 32, 37 ] ], "normalized": [] }, { "id": "19304754_T2", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 48, 52 ] ], "normalized": [] }, { "id": "19304754_T3", "type": "Protein", "text": [ "MAML1" ], "offsets": [ [ 88, 93 ] ], "normalized": [] }, { "id": "19304754_T4", "type": "Protein", "text": [ "MAML1" ], "offsets": [ [ 173, 178 ] ], "normalized": [] }, { "id": "19304754_T5", "type": "Protein", "text": [ "CDK8" ], "offsets": [ [ 249, 253 ] ], "normalized": [] }, { "id": "19304754_T6", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 258, 262 ] ], "normalized": [] }, { "id": "19304754_T7", "type": "Protein", "text": [ "MAML1" ], "offsets": [ [ 338, 343 ] ], "normalized": [] }, { "id": "19304754_T8", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 353, 357 ] ], "normalized": [] }, { "id": "19304754_T9", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 446, 450 ] ], "normalized": [] }, { "id": "19304754_T10", "type": "Protein", "text": [ "MAML1" ], "offsets": [ [ 452, 457 ] ], "normalized": [] }, { "id": "19304754_T11", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 492, 496 ] ], "normalized": [] }, { "id": "19304754_T12", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 506, 510 ] ], "normalized": [] }, { "id": "19304754_T13", "type": "Protein", "text": [ "MAML1" ], "offsets": [ [ 511, 516 ] ], "normalized": [] }, { "id": "19304754_T14", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 560, 570 ] ], "normalized": [] }, { "id": "19304754_T15", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 575, 577 ] ], "normalized": [] }, { "id": "19304754_T16", "type": "Protein", "text": [ "MAML1" ], "offsets": [ [ 636, 641 ] ], "normalized": [] }, { "id": "19304754_T17", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 654, 658 ] ], "normalized": [] }, { "id": "19304754_T18", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 679, 683 ] ], "normalized": [] }, { "id": "19304754_T19", "type": "Protein", "text": [ "MAML1" ], "offsets": [ [ 712, 717 ] ], "normalized": [] }, { "id": "19304754_T20", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 736, 740 ] ], "normalized": [] }, { "id": "19304754_T21", "type": "Protein", "text": [ "MAML1" ], "offsets": [ [ 800, 805 ] ], "normalized": [] }, { "id": "19304754_T22", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 807, 811 ] ], "normalized": [] }, { "id": "19304754_T24", "type": "Entity", "text": [ "lysines" ], "offsets": [ [ 549, 556 ] ], "normalized": [] } ]

[ { "id": "19304754_E1", "type": "Protein_amino_acid_acetylation", "trigger": { "text": [ "acetylates" ], "offsets": [ [ 538, 548 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "19304754_T14" }, { "role": "Site", "ref_id": "19304754_T24" } ] }, { "id": "19304754_E2", "type": "Protein_amino_acid_acetylation", "trigger": { "text": [ "acetylates" ], "offsets": [ [ 538, 548 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "19304754_T15" }, { "role": "Site", "ref_id": "19304754_T24" } ] }, { "id": "19304754_E3", "type": "Protein_amino_acid_acetylation", "trigger": { "text": [ "autoacetylation" ], "offsets": [ [ 659, 674 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "19304754_T17" } ] } ]

[]

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[ { "id": "18611394__text", "type": "abstract", "text": [ "Characterisation of the in vitro activity of the depsipeptide histone deacetylase inhibitor spiruchostatin A. \nWe recently completed the total synthesis of spiruchostatin A, a depsipeptide natural product with close structural similarities to FK228, a histone deacetylase (HDAC) inhibitor (HDI) currently being evaluated in clinical trials for cancer. Here we report a detailed characterisation of the in vitro activity of spiruchostatin A. Spiruchostatin A was a potent (sub-nM) inhibitor of class I HDAC activity in vitro and acted as a prodrug, requiring reduction for activity. Spiruchostatin A was a potent (low nM) inhibitor of the growth of various cancer cell lines. Spiruchostatin A-induced acetylation of specific lysine residues within histones H3 and H4, and increased the expression of p21(cip1/waf1), but did not induce acetylation of alpha-tubulin. Spiruchostatin A also induced cell cycle arrest, differentiation and cell death in MCF7 breast cancer cells. Like FK228, spiruchostatin A was both an inducer and substrate of the ABCB1 drug efflux pump. Whereas spiruchostatin A and FK228-induced protracted histone acetylation, hydroxamate HDI-induced short-lived histone acetylation. Using a subset of HDI-target genes identified by microarray analysis, we demonstrated that these differences in kinetics of histone acetylation between HDI correlated with differences in the kinetics of induction or repression of specific target genes. Our results demonstrate that spiruchostatin A is a potent inhibitor of class I HDACs and anti-cancer agent. Differences in the kinetics of action of HDI may be important for the clinical application of these compounds. " ], "offsets": [ [ 0, 1671 ] ] } ]

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[ { "id": "18611394_E1", "type": "Protein_amino_acid_acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 700, 711 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "18611394_T1" }, { "role": "Site", "ref_id": "18611394_T8" } ] }, { "id": "18611394_E2", "type": "Protein_amino_acid_acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 700, 711 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "18611394_T2" }, { "role": "Site", "ref_id": "18611394_T8" } ] }, { "id": "18611394_E3", "type": "Protein_amino_acid_acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 834, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "18611394_T6" } ] } ]

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[ { "id": "18974389__text", "type": "abstract", "text": [ "Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer. \nPURPOSE: Epigenetic modifications of histone have crucial roles in the control of gene activity, nuclear architecture, and genomic stability. In this respect, they may contribute to the development and progression of cancer. We investigated whether epigenetic changes of histone H4 are involved in lung carcinogenesis. EXPERIMENTAL DESIGN: Epigenetic modifications of histone H4 were studied by immunohistochemistry in normal lung and 157 lung carcinoma using antibodies specifically recognizing the acetylated (Ac) lysines 5 (K5), K8, K12, K16, and trimethylated (me3) K20 residues of histone H4. Western blotting was used to validate the immunohistochemistry results. H4K20me3 was also studied in 17 preneoplastic lesions. Expression of the Suv4-20h1/2 trimethyltransferases was analyzed by quantitative reverse transcription-PCR in a subset of tumor samples. RESULTS: As compared with normal lung, cancer cells displayed an aberrant pattern of histone H4 modifications with hyperacetylation of H4K5/H4K8, hypoacetylation of H4K12/H4K16, and loss of H4K20 trimethylation. Alteration of H4K20 trimethylation was frequent in squamous cell carcinoma (67%) and was observed in early precursors lesions in which the level of H4K20me3 staining strongly decreased with disease progression. In adenocarcinoma, the down-regulation of H4K20me3 was less frequent (28%) but allowed the identification of a subgroup of stage I adenocarcinoma patients with reduced survival (P = 0.007). Loss of H4K20 trimethylation was associated with decreased expression of Suv4-20h2, a specific H4K20 trimethyltransferase involved in telomere length maintenance. CONCLUSIONS: Our findings indicate an important role of histone H4 modifications in bronchial carcinogenesis and highlight H4K20me3 as a candidate biomarker for early detection of and therapeutic approaches to lung cancer. " ], "offsets": [ [ 0, 1978 ] ] } ]

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[ { "id": "18974389_1", "entity_ids": [ "18974389_T5", "18974389_T6", "18974389_T7", "18974389_T8", "18974389_T9", "18974389_T10" ] } ]

[]

[ { "id": "16352673__text", "type": "abstract", "text": [ "Ascorbic acid-independent synthesis of collagen in mice. \nThe mouse has become the most important model organism for the study of human physiology and disease. However, until the recent generation of mice lacking the enzyme gulanolactone oxidase (Gulo), the final enzyme in the ascorbic acid biosynthesis pathway, examination of the role of ascorbic acid in various biochemical processes using this model organism has not been possible. In the mouse, similar to most mammals but unlike humans who carry a mutant copy of this gene, Gulo produces ascorbic acid from glucose. We report here that, although ascorbic acid is essential for survival, its absence does not lead to measurable changes in proline hydroxylation. Vitamin C deficiency had no significant effect on the hydroxylation of proline and collagen production during tumor growth or in angiogenesis associated with tumor or mammary gland growth. This suggests that factors other than ascorbic acid can support proline hydroxylation and collagen synthesis in vivo. Furthermore, the failure of Gulo-/- mice to thrive on a vitamin C-deficient diet therefore suggests that ascorbic acid plays a critical role in survival other than the maintenance of the vasculature. " ], "offsets": [ [ 0, 1225 ] ] } ]

[ { "id": "16352673_T1", "type": "Protein", "text": [ "collagen" ], "offsets": [ [ 39, 47 ] ], "normalized": [] }, { "id": "16352673_T2", "type": "Protein", "text": [ "gulanolactone oxidase" ], "offsets": [ [ 224, 245 ] ], "normalized": [] }, { "id": "16352673_T3", "type": "Protein", "text": [ "Gulo" ], "offsets": [ [ 247, 251 ] ], "normalized": [] }, { "id": "16352673_T4", "type": "Protein", "text": [ "Gulo" ], "offsets": [ [ 531, 535 ] ], "normalized": [] }, { "id": "16352673_T5", "type": "Protein", "text": [ "collagen" ], "offsets": [ [ 801, 809 ] ], "normalized": [] }, { "id": "16352673_T6", "type": "Protein", "text": [ "collagen" ], "offsets": [ [ 997, 1005 ] ], "normalized": [] }, { "id": "16352673_T7", "type": "Entity", "text": [ "proline" ], "offsets": [ [ 695, 702 ] ], "normalized": [] }, { "id": "16352673_T10", "type": "Entity", "text": [ "proline" ], "offsets": [ [ 789, 796 ] ], "normalized": [] }, { "id": "16352673_T11", "type": "Entity", "text": [ "proline" ], "offsets": [ [ 971, 978 ] ], "normalized": [] } ]

[ { "id": "16352673_E1", "type": "Protein_amino_acid_hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 703, 716 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "16352673_T4" }, { "role": "Site", "ref_id": "16352673_T7" } ] }, { "id": "16352673_E2", "type": "Protein_amino_acid_hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 772, 785 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "16352673_T5" }, { "role": "Site", "ref_id": "16352673_T10" } ] }, { "id": "16352673_E3", "type": "Protein_amino_acid_hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 979, 992 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "16352673_T6" }, { "role": "Site", "ref_id": "16352673_T11" } ] } ]

[]

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[ { "id": "3667614__text", "type": "abstract", "text": [ "Effect of propeptide mutations on post-translational processing of factor IX. Evidence that beta-hydroxylation and gamma-carboxylation are independent events. \nPost-translational processing of Factor IX includes glycosylation, cleavage of the signal peptide and propeptide, vitamin K-dependent carboxylation of specific glutamic acid residues to form gamma-carboxyglutamic acid, and beta-hydroxylation of aspartic acid at residue 64 to form beta-hydroxyaspartic acid. The human Factor IX cDNA coding sequence was modified in the propeptide region (residue -18 to -1) using oligonucleotide-directed site-specific mutagenesis, and the altered Factor IX cDNA was expressed in Chinese hamster ovary cells. The effects of the mutations on proteolytic processing, gamma-carboxylation, and beta-hydroxylation were assessed by direct structural analysis. After purification, the molecular weight of each of the recombinant Factor IX species and its NH2-terminal amino acid sequence were shown to be identical to those of plasma Factor IX. gamma-Carboxyglutamic acid and beta-hydroxyaspartic acid analyses revealed that recombinant wild-type Factor IX contained 9.2 gamma-carboxyglutamic acid and 0.3 beta-hydroxyaspartic acid residues/molecule compared with 11.4 gamma-carboxyglutamic acid and 0.39 beta-hydroxyaspartic acid residues in plasma Factor IX. When the 18-residue propeptide was deleted or when the cells were grown in the presence of sodium warfarin, secreted Factor IX contained no detectable gamma-carboxyglutamic acid but 0.36 and 0.40 residues of beta-hydroxyaspartic acid, respectively. Point mutations leading to substitution of alanine for phenylalanine at residue -16 or glutamic acid for alanine at residue -10 contained 0.2 and 1.7 gamma-carboxyglutamic acid residues, respectively, and 0.2 residues of beta-hydroxyaspartic acid. These data confirm that the propeptide mutations made do not interfere with proteolytic processing and that the Factor IX propeptide contains a recognition site that designates the adjacent glutamic acid-rich domain for gamma-carboxylation. In contrast, beta-hydroxylation of aspartic acid 64 is an independent process which does not require vitamin K and is mediated through a hydroxylation recognition site in the mature Factor IX, not in the propeptide. " ], "offsets": [ [ 0, 2301 ] ] } ]

[ { "id": "3667614_T1", "type": "Protein", "text": [ "factor IX" ], "offsets": [ [ 67, 76 ] ], "normalized": [] }, { "id": "3667614_T2", "type": "Protein", "text": [ "Factor IX" ], "offsets": [ [ 193, 202 ] ], "normalized": [] }, { "id": "3667614_T3", "type": "Protein", "text": [ "Factor IX" ], "offsets": [ [ 478, 487 ] ], "normalized": [] }, { "id": "3667614_T4", "type": "Protein", "text": [ "Factor IX" ], "offsets": [ [ 641, 650 ] ], "normalized": [] }, { "id": "3667614_T5", "type": "Protein", "text": [ "Factor IX" ], "offsets": [ [ 915, 924 ] ], "normalized": [] }, { "id": "3667614_T6", "type": "Protein", "text": [ "Factor IX" ], "offsets": [ [ 1020, 1029 ] ], "normalized": [] }, { "id": "3667614_T7", "type": "Protein", "text": [ "Factor IX" ], "offsets": [ [ 1133, 1142 ] ], "normalized": [] }, { "id": "3667614_T8", "type": "Protein", "text": [ "Factor IX" ], "offsets": [ [ 1336, 1345 ] ], "normalized": [] }, { "id": "3667614_T9", "type": "Protein", "text": [ "Factor IX" ], "offsets": [ [ 1464, 1473 ] ], "normalized": [] }, { "id": "3667614_T10", "type": "Protein", "text": [ "Factor IX" ], "offsets": [ [ 1956, 1965 ] ], "normalized": [] }, { "id": "3667614_T11", "type": "Protein", "text": [ "Factor IX" ], "offsets": [ [ 2267, 2276 ] ], "normalized": [] }, { "id": "3667614_T13", "type": "Entity", "text": [ "aspartic acid at residue 64" ], "offsets": [ [ 405, 432 ] ], "normalized": [] }, { "id": "3667614_T15", "type": "Entity", "text": [ "aspartic acid 64" ], "offsets": [ [ 2120, 2136 ] ], "normalized": [] } ]

[ { "id": "3667614_E1", "type": "Protein_amino_acid_hydroxylation", "trigger": { "text": [ "beta-hydroxylation" ], "offsets": [ [ 383, 401 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "3667614_T2" }, { "role": "Site", "ref_id": "3667614_T13" } ] }, { "id": "3667614_E2", "type": "Protein_amino_acid_hydroxylation", "trigger": { "text": [ "beta-hydroxylation" ], "offsets": [ [ 2098, 2116 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "3667614_T11" }, { "role": "Site", "ref_id": "3667614_T15" } ] } ]

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