Alternate Phosphorylation/O-GlcNAc Modification on Human Insulin IRSs: A Road towards Impaired Insulin Signaling in Alzheimer and Diabetes

Figure 2

Multiple alignments of three sequences (human, rat, and mouse). ClustalW was used to align these different sequences. The conserved sequence (highlighted red) is marked by an asterisk, semiconserved (highlighted yellow) substitution by a single dot, and conserved substitution (highlighted green) by a double dot. Ser-3, 30, 66, 78, 84, 144, 162, 164, 166, 174, 210, 222, 237, 251, 253, 262, 277, 304, 306, 308, 309, 311, 312, 318, 334, 342, 346, 358, 365, 384, 388, 391, 400, 402, 406, 414, 428, 430, 432, 438, 444, 447, 449, 450, 451, 452, 456, 458, 482, 483, 485, 487, 489, 491, 493, 499, 505, 506, 515, 518, 523, 550, 560, 577, 591, 592, 594, 606, 608, 615, 619, 620, 639, 642, 643, 644, 645, 669, 672, 679, 682, 684,, 714, 730, 731, 735, 736, 740, 749, 752, 770, 772, 785, 804, 805, 809, 827, 828, 868, 873, 894, 903, 915, 932, 941, 944, 945, 946, 947, 950, 952, 953, 956, 957, 960, 966, 967, 969, 973, 976, 984, 985, 988, 995, 1001, 1007, 1011, 1012, 1022, 1024, 1026, 1027, 1060, 1061, 1063, 1064, 1100, 1103, 1109, 1115, 1124, 1148, 1149, 1153, 1154, 1162, 1164, 1174, 1176, 1181, 1185, 1186, 1203, 1237, 1244, 1283, 1289, 1322 and 1327; Thr-117, 140, 191, 214, 225, 239, 265, 286, 314, 336, 344, 350, 363, 404, 443, 520, 527, 575, 579, 580, 599, 604, 657, 719, 776, 779, 844, 859, 891, 962, 965, 1052, 1073, 1082, 1102, 1151, 1155, 1156, 1157, 1159, 1202, 1243, 1287, 1319, and 1334 and Tyr-36, 75, 76, 111, 116, 121, 136, 184, 194, 217, 459, 503, 540, 542, 556, 576, 598, 625, 628, 632, 653, 675, 727, 742, 766, 803, 810, 823, 907, 919, 978, 1014, 1042, 1072, 1253, and 1320 are highly conserved residues. Meanwhile, Ser-357, 848, 900, and 1048 and Thr-61, 544, 777, 815, and 1302 showed conserved substitutions. Ser-14, 183, 555, 665, 667, 704, 723, 820, 852, 1234, 1282, 1295, and 1301 and Thr-713, 1066, and 1221 showed semiconserved substitutions.