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

Figure 1

Multiple alignments of eight sequences (human, green monkey, pig, chicken, Chinese hamster, mouse, rat, and western clawed frog). 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. Multiple alignment showed that Ser-11, 24, 36, 57, 63, 68, 193, 199, 217, 228, 243, 261, 270, 272, 273, 274, 277, 281, 295, 307, 312, 323, 329, 330, 337, 345, 348, 350, 362, 372, 374, 383, 385, 388, 391, 393, 394, 395, 396, 398, 402, 404, 412, 413, 415, 417, 419, 421, 427, 428, 433, 434, 440, 441, 444, 449, 527, 531, 541, 543, 547, 574, 581, 616, 636, 639, 641, 666, 668, 672, 720, 741, 744, 763, 766, 795, 807, 808, 809, 810, 812, 813, 862, 869, 892, 1038, 1041, 1070, 1078, 1084, 1100, 1101, 1105, 1142, 1143, 1145, 1223, 1227, and 1231; Thr-88, 188, 191, 231, 252, 305, 309, 311, 335, 387, 397, 403, 446, 453, 525, 530, 533, 539, 552, 579, 608, 700, 743, 811, 847, 859, 870, 1073, and 1103; and Tyr-18, 46, 47, 87, 107, 183, 431, 465, 483, 551, 582, 612, 632, 662, 695, 732, 750, 764, 800, 896, 941, 989, 1001, 1179, and 1229 are highly conserved residues. Meanwhile, Ser-137, 268, 303, 380, 770, 792, 815, 910, 974, 1011, 1037, and 1106; Thr-351, 354, 535, 693, 729, 793, 991, 1017, and 1111; and Tyr-765 showed conserved substitutions. Ser-58, 78, 99, 105, 135, 139, 189, 315, 341, 463, 486, 629, 691, 694, 747, 794, 918, 925, 985, 995, 1000, 1005, 1025, 1035, 1131, 1132, 1217, 1218, and 1222; and Thr-300, 979, 1004, 1030, and 1107 showed semiconserved substitutions.