Supporting Information File 8: Authors: Saikat Chakrabarti and Anna R. Panchenko Table S3 CD_Code Family_name Rep_PDB_code No_sequences Alignment_length No-coevolved_pair No_functional_sites cd00001 PTS_IIB_man 1ble 25 352 5 4 cd00002 YbaK 1dbx 61 674 5 8 cd00003 PNPsynthase 1ho4 52 509 79 48 cd00004 Sortase 1ija 35 586 5 6 cd00006 PTS_IIA_man 1pdo 43 952 7 8 cd00008 53EXOc 1exn 56 1176 16 24 cd00009 AAA 1do2 350 5695 6 9 cd00010 AAI_LTSS 1hss 66 1049 1 22 cd00013 ADF 1cof 51 937 0 13 cd00015 ALBUMIN 1bke 59 2627 6 15 cd00016 alkPPc 1elz 29 865 45 68 cd00019 AP2Ec 1qum 40 998 9 22 cd00020 ARM 1ial 77 3340 5 11 cd00024 CHROMO 1ap0 121 5435 5 8 cd00027 BRCT 1cdz 144 3888 4 7 cd00028 B_lectin 1msa 44 4014 2 42 cd00031 CA 1ncj 168 8793 21 10 cd00032 CASc 1cp3 52 952 18 31 cd00033 CCP 1ckl 288 5659 2 2 cd00036 ChtBD3 1aiw 79 2295 2 2 cd00038 CAP_ED 1rgs 292 3499 8 11 cd00042 CY 1stf 52 1062 2 5 cd00044 CysPc 1df0 36 2630 17 3 cd00045 DED 1a1z 32 636 2 6 cd00046 DEXDc 1d9x 228 3968 13 9 cd00047 PTPc 2shp 101 3525 52 6 cd00052 EH 1qjt 57 2952 4 15 cd00056 ENDO3c 1muy 140 1569 23 17 cd00057 FA58C 1euu 26 4183 6 3 cd00063 FN3 1bqu 741 45058 6 7 cd00067 GAL4 3alc 118 2147 1 15 cd00068 GGL 1gp2 27 1252 1 15 cd00070 GLECT 1qkq 91 1317 11 29 cd00073 H15 1hst 70 771 4 27 cd00075 HATPase_c 1a4h 483 3569 6 18 cd00079 HELICc 1d2m 130 3146 128 13 cd00080 HhH2_motif 1b43 98 2158 12 1 cd00081 Hint 1dq3 77 3113 12 5 cd00084 HMG-box 1j5n 192 2925 10 6 cd00085 HNHc 1bxi 121 1262 7 11 cd00088 HPT 1qsp 87 3742 3 6 cd00089 HR1 1cxz 25 1748 2 31 cd00090 HTH_ARSR 1smt 178 1180 4 60 cd00091 NUC 1ql0 30 2364 15 10 cd00093 HTH_XRE 1lmb 557 1867 1 10 cd00108 KR 1nk1 38 1209 9 6 cd00111 Trefoil 1ps2 49 3215 1 4 cd00114 LIGANc 1dgs 44 918 22 11 cd00115 LMWPc 1d1p 72 677 5 6 cd00119 LYZ1 1lmq 50 1426 8 15 cd00120 MADS 1mnm 91 1108 3 45 cd00125 PLA2c 1bk9 59 294 8 8 cd00127 DSPc 1vhr 51 1768 7 6 cd00128 XPG 1a76 34 2611 20 66 cd00130 PAS 3pyp 183 3008 3 15 cd00134 PBPb 2lao 62 1667 15 14 cd00138 PLDc 1bys 59 3530 6 9 cd00140 beta_clamp 1unn 111 703 68 19 cd00142 PI3Kc_family 1e8x 60 5333 191 40 cd00143 PP2Cc 1a6q 137 3282 33 8 cd00145 POLBc 1clq 73 2436 116 31 cd00148 PROF 1d1j 26 323 3 19 cd00152 PTX 1b09 27 3586 11 9 cd00154 Rab 3rab 307 2963 36 33 cd00156 REC 1dcf 307 3426 23 16 cd00161 RICIN 1xyf 104 3368 14 20 cd00162 RING 1fbv 555 9747 2 8 cd00164 S1 1sro 228 3158 8 5 cd00165 S4 1dm9 266 2237 4 12 cd00168 SCP 1cfe 45 1180 7 4 cd00170 SEC14 1aua 109 4756 13 18 cd00171 Sec7 1pbv 34 2459 9 22 cd00172 SERPIN 1ova 91 1245 32 10 cd00173 SH2 1aya 197 2853 2 6 cd00175 SNc 2sns 30 1471 11 7 cd00176 SPEC 1quu 168 8538 3 6 cd00179 SynN 1dn1 69 354 13 63 cd00180 S_TKc 1jnk 254 5791 93 54 cd00182 TBOX 1xbr 32 3352 6 30 cd00184 TNF 1a8m 33 471 2 13 cd00185 TNFR 1d0g 49 740 9 38 cd00186 TOP1Ac 1cy7 62 2530 222 29 cd00189 TPR 1a17 137 2617 4 25 cd00195 UBCc 2ucz 70 5185 5 27 cd00200 WD40 1tbg 90 3677 24 40 cd00201 WW 1f8a 134 4625 1 2 cd00202 ZnF_GATA 2gat 43 2002 2 28 cd00205 rhv 1vbb 55 2970 7 9 cd00206 snake_toxin 1nea 46 106 1 8 cd00209 DHFR 2cd2 127 1018 22 5 cd00211 PTS_IIA_fru 1a6j 109 1685 21 3 cd00212 PTS_IIB_glc 1iba 88 1332 9 8 cd00213 S-100 1mr8 134 3222 3 55 cd00214 Calpain_III 1kfu 25 2482 88 4 cd00215 PTS_IIA_lac 1e2a 27 130 9 13 cd00223 TOPRIM_TopoIIB_SPO 1d3y 51 1059 17 14 cd00229 SGNH_hydrolase 1esc 187 4491 7 11 cd00232 HemeO 1j77 42 1360 17 8 cd00237 p23 1ejf 35 1414 5 9 cd00254 LT_GEWL 154l 226 3671 12 5 cd00260 Sialidase 1eus 55 2769 37 13 cd00261 AAI_SS 1hss 58 901 2 15 cd00264 BPI 1bp1 31 831 8 32 cd00265 MADS_MEF2_like 1egw 41 736 2 38 cd00266 MADS_SRF_like 1mnm 46 1036 1 47 cd00268 DEADc 1qde 61 1188 18 12 cd00269 DEXHc 1d9z 135 3951 43 12 cd00272 Chemokine_CC 1cm9 41 300 2 36 cd00287 ribokinase_pfkB_like 1bx4 36 1259 14 9 cd00291 SirA_YedF_YeeD 1dcj 192 953 3 8 cd00298 alpha-crystallin-Hsps 1gme 30 369 8 25 cd00299 GST_C_family 1eem 227 1863 40 18 cd00300 LDH 1a5z 148 625 131 30 cd00304 RT_like 1qaj 25 1724 17 12 cd00305 Cu-Zn_Superoxide_Dismutase 1yaz 67 630 17 25 cd00309 chaperonin_type_I_II 1aon 308 964 155 43 cd00311 TIM 1tre 229 831 38 26 cd00314 plant_peroxidase 1fhf 97 838 29 14 cd00315 Cyt_C5_DNA_methylase 1dct 36 781 21 38 cd00317 cyclophilin 1rmh 91 2033 17 12 cd00318 Phosphoglycerate_kinase 1qpg 26 599 51 24 cd00320 cpn10 1aon 97 456 6 29 cd00321 SO_family_Moco 1sox 104 1455 34 12 cd00325 chitinase_glyco_hydro_19 2baa 57 878 23 10 cd00326 alpha_CA 1znc 176 3904 26 10 cd00329 TopoII_MutL_Trans 1ei1 294 2198 47 1 cd00331 IGPS 1pii 133 1170 48 35 cd00332 PAL-HAL 1gk2 86 1047 203 50 cd00333 MIP 1fx8 27 1118 9 12 cd00336 Ribosomal_L22 1jj2 132 938 7 47 cd00338 Ser_Recombinase 1gdt 179 858 16 6 cd00342 gram_neg_porins 1osm 191 760 74 44 cd00351 TS_Pyrimidine_HMase 1nje 69 1406 14 31 cd00353 Ribosomal_S15p_S13e 1a32 114 726 2 24 cd00354 FBPase 1fta 61 545 55 24 cd00355 Ribosomal_L30_L7 1jj2 70 322 3 31 cd00374 RNase_T2 1ioo 96 781 25 11 cd00381 IMPDH 1zfj 71 700 45 9 cd00385 Isoprenoid_Biosyn_C1 5eat 324 1529 64 27 cd00386 Heme_Cu_Oxidase_III_like 2occ 169 1167 34 9 cd00389 microbial_RNases 1rtu 25 286 1 4 cd00392 Ribosomal_L13 1s72 132 802 14 25 cd00395 Tyr_Trp_RS_core 4ts1 89 1011 37 57 cd00397 DNA_BRE_C 2crx 25 993 4 18 cd00400 Voltage_gated_ClC 1kpl 112 1125 83 33 cd00405 PRAI 1pii 218 1308 58 9 cd00407 Urease_beta 4ubp 47 1552 15 29 cd00408 DHDPS-like 1dhp 251 574 94 26 cd00412 pyrophosphatase 1i6t 90 543 12 14 cd00413 Glyco_hydrolase_16 1gbg 142 2252 26 3 cd00418 GlxRS_core 1euq 73 1680 133 33 cd00419 Ferrochelatase_C 1hrk 136 663 90 16 cd00421 intradiol_dioxygenase 1dmh 146 525 27 7 cd00423 Pterin_binding 1aj0 36 1394 18 20 cd00430 Ala_racemase 1l6g 112 988 87 50 cd00431 cysteine_hydrolases 1yac 203 1548 30 5 cd00446 GrpE 1dkg 217 1001 39 26 cd00447 NusB_Sun 1eyv 29 611 2 3 cd00448 YjgF_like 1jd1 296 870 22 37 cd00452 KDPG_aldolase 1eua 78 837 37 26 cd00457 PEBP_RKIP 1fux 37 382 7 4 cd00462 PTH 2pth 153 401 28 7 cd00464 SK 1kag 109 3829 14 19 cd00466 DHQase_II 1h0s 89 231 33 42 cd00476 SAICAR_synt 1obg 63 707 41 25 cd00477 FTHFS 1fpm 47 1129 273 7 cd00480 malate_synt 1d8c 41 2031 5 5 cd00481 Ribosomal_L19e 1jj2 34 402 6 103 cd00483 HPPK 1eqm 103 985 19 33 cd00484 PEPCK_ATP 1k3c 28 717 132 45 cd00487 Pep_deformylase 1g27 155 485 35 13 cd00488 PCD_DCoH 1dcp 112 458 14 35 cd00493 FabA_FabZ 1mka 161 3523 18 25 cd00496 PheRS_alpha_core 1eiy 43 859 29 89 cd00497 PseudoU_synth_TruA_like 1dj0 32 949 6 15 cd00498 Hsp33 1i7f 41 613 16 15 cd00501 Peptidase_C15 1a2z 56 445 12 40 cd00516 PRTase_typeII 1qpo 185 1132 51 12 cd00528 MoaC 1ekr 53 1265 25 70 cd00537 MTHFR 1b5t 78 1077 19 18 cd00567 ACAD 1ege 69 1337 36 10 cd00571 UreE 1ear 33 509 6 10 cd00575 NOS_oxygenase 1nsi 48 1534 50 32 cd00592 HTH_MerR-like 1jbg 124 633 6 72 cd00593 RIBOc 1jfz 197 3304 8 23 cd00618 PLA2_like 1bk9 101 1263 5 8 cd00635 YBL036c_PLPDEIII 1b54 82 991 43 9 cd00636 TroA-like 1toa 367 1351 62 4 cd00651 TFold 1is8 69 1205 1 4 cd00657 Ferritin_like 1lko 487 1581 19 6 cd00680 Ring_hydroxylating_alpha 1eg9 68 625 32 37 cd00985 Maf_Ham1 1exc 180 1051 22 5 cd01037 Restriction_endonuclease_like 1cw0 99 2174 1 4 cd01066 APP_MetAP 1jaw 102 1493 22 4 cd01292 metallo-dependent_hydrolases 1k6w 50 2644 18 2 cd01483 E1_enzyme_family 1jw9 46 1709 12 13 cd01949 GGDEF 1w25 511 2399 73 13 cd02000 TPP_E1_PDC_ADC_BCADC 1dtw 150 1352 105 68