Figure S1A. Comparison of p120 sequences. Residues involved in interaction with
E-cadherin are boxed in red. Most of them are conserved.
Figure S1B. Comparison of
β
-catenin sequences. A single
β
-catenin gene copy
was identified in every studied species except for calcareous sponges that exhibit a
duplication. All residues essential for E-cadherin interaction are boxed in pink and
are highly conserved except for the R386 and N387 residues (replaced by L and T,
respectively) in two hexactinellids and a more anecdotal change from A656 to S in
placozoans. Residues boxed in blue are involved in
α
-catenin binding and in
orange
for the DTDL PDZ binding motif.
Figure S1C. Analyses of
α
-catenins and vinculins sequences. Sequences of
α-catenins and vinculins were aligned based on the structural domains helix0 to helix5
in Mus musculus
α-catenin and vinculin. Helices are boxed and the numbers at the
end of each sequence indicate the range encompassed in the alignment. Secondary
structure prediction by JNet (Jalview option) identified six helices in all sponge
α-catenin sequences except for A. queenslandica (missing the 4 first helices) and A.
vastus (missing helix0). All species analyzed in this study have one copy of
α-catenin and one copy of vinculin well-separated in Bayesian tree with high support
(pp=1) (bottom).
Figure S2. Structure of Par3 proteins in metazoans. Par3 exhibits a conserved
N-terminal domain (CR1), three central PDZ domains, and a C-N-terminal region
containing multiple protein binding sites including the aPKC-binding motif.
Figure S5. Domain composition of PatJ (D. melanogaster), INADL and MUPP1 (M.
musculus) and Multiple PDZ containing protein (MPDZ) (O. lobularis, S. ciliatum, A.
queenslandica and O. minuta). Note that only O. lobularis exhibits an MPDZ with a
well-detected L27 domain (Evalue=8.5 10
-4
) as bilaterians. A. queenslandica and S.
ciliatum MPDZ have a low-scoring L27 domain (shaded in grey) according to the
HMM profile search. There is no recognizable similarity to the L27 domain in the N-
terminal region of O. minuta MPDZ.
Conservation
Quality
Consensus
364
366
371
374
382
385386 389 391392
401
433
434
437
438
444
477
478
M. musculus
S. coactum
D. melanogaster
O. carmela
B. floridae
M. leidy
A. digitifera-1
A. digitifera-2
T. adhaerens
O. lobularis
O. sp. SN-2011
L. complicata
S. ciliatum
A. queenslandica
P. ficiformis
O. minuta
A. vastus
486
536
574
Conservation
Quality
Consensus
M. musculus
S. coactum
D. melanogaster
O. carmela
B. floridae
M. leidy
A. digitifera-1
A. digitifera-2
T. adhaerens
O. lobularis
O. sp. SN-2011
L. complicata
S. ciliatum
A. queenslandica
P. ficiformis
O. minuta
A. vastus
86 94 112 77 161 183 124 140 1472 171 127 134 37 44 10 318 462 235 243 261 226 314 336 270 293 294 147 320 273 282 194 143 130 486 196 126 Y AM T R AQ R V R A AM F P E T L D E - - - G MQ I P S TQ - - - F D A AH P - - TN VQ R L A E P S QM L K H A V VN L I N Y QD D A E L A T R A I P E L T K L L N D - E D Q V V VN K A A VM VH Q L S K K E A S RH A I M R S P QM V S A I V R TMQN TN - D V E T A RC T AG T L H N L S H - - H R E G L L A I F K S G L S Q T R S Q R V R A AM F P E T L E E - - - G I E I P S TQ - - - F D P QQ P - - T A VQ R L S E P S QM L K H A V VN L I N Y QD D A E L A T R A I P E L I K L L N D - E D Q V V V S Q A AMM VH Q L S K K E A S RH A I MN S P QM V A A L V R A I S N S N - D L E S T K A A VG T L H N L S H - - H RQG L L A I F K S G L I Q T R S Q R V R A AM F P E T L D E - - - G TQ I P S TQ - - - F D P N Q P - - T A VQ R L A E P S QM L K H A V VN L I N Y QD D AD L A T R A I P E L T K L L N D - E D Q V V V S Q A AMM VH Q L S K K E A S RH A I MN S P QM V A A L V R AMQ T TN - D V E T T RC A AG T L H N L S H - - H RQG L L S I F K S G F V S T R S Q R I RQ AM F P E T L E E - - - G AQ I P S TQ - - - F D S T S S - - T A VQ R L A E P S L M L K Q A V VN L I N Y QD D AD L A T R A I P E L A K L L N D - D D Q V V VG Q A AMM VH Q L S R K D A S RH A I MN S P QM V A A L V R A L N N M S - D V E T T RC A AG T L H N L S H - - H RQG L L S I F K S G Q TQ S R S Q R L R A E L F P D A S E E - - - QH N P A P T P S - - - H A S P T T P V T T T L Q T L G E P T P V S H N TM E N I AH Y QD D A E L AMQ A I P E F A K L L S S - K N P E VQ V S V T TC I H A L S K K E P S MH A L L S Y P Q L I S T L L H T L S T A T - D Q E V V RC C TG T L H N L S Y - - L R E G L E S I Q K Y R RG S V R TQ R L RN Q L M P D TD Q A - - - S H - - - D N T I QN N G - - - E F S P T R P - - S T VQ R L N E P S A A L RQ V I H D L MN Y QD D N D L A T R S I P E A I N L L S H - E D P M T V VQ I A K F I N H L S K K E A S L H A I I S S TQ L L A S L I H A T R R F F E N I D L V K L T A S T L H N L S L - - QQ S G L H A I V K A S QMG S R TD R V R A AM F P D T V P E D - - - S I S M P M T - - - G Q P - - T T VQ R L A E P S QM L K N A V L N L VN Y QD D AD L A L R A I P E L T K L L Y S - E N P T A VQQ A AM V VH H L S K K E A S RH A I MN S L P MMG A L V R VMG G T S - D A E TM RC V S G T L H N L S H - - H RQG L S V I Y K S G G G G G G L S H P P H G M Y S E P I QD D P - - - M S R - M S S V S I P G T P - - - A E P - - S S MQ R L A E P S AM L RN A VM S I I N Y QD D AD L AG R V I P E A T R L L G D - G D P S V VN H A A L I VH E L S K R E A S RH A I I G N P A L I G G L VH V L G T TN - E P D AM R S I S G T L H N L S H - - H RQG L S S M Y K AG - - - A R T P S V P L Y S E P L - D D P - - - M S R - M S S V S I P G T P - - - A E P - - S S VQ R L A E P S AM L RD A VM S I I N Y QD D AD L AG R V I P E A T R L L AD - P D P S V V K Q A AM V VH E L S K R E A S RH A I I G S P A L I G G L VH V L G T TN - D P D AM R S I S G T L H N L S H - - H RQG L S S M Y K AQ - - - Y A A V A E P Y QD D P - - - M S R - M S S V S I P G T P - - - A E P A A S S MQ R L A E P S AM L RN A VM S I I N Y QD D AD L AG R V I P E A T R L L G D - G D P N V V K Q A A L V VH E L S K R E A S RH A I I G S P A L I G G L VH V L G T TN - E P D AM R S I S G T L H N L S H - - H RQG L S S M Y K AG I Q S T S G D R V R L TM F P G S S A E - - - G E E V P N TQ - - - V A P E RQ - - S N L Q RM TQ S TQ I I R A A VQN L VN Y Q S N T E L T A K A L P E I I S L L S H - QD Q T V I T E A S K L I H D L S K K E A S L T A I N AN P A A V K G I I Q T L A S VN - N A E VQ K P L S G A VH N I S S - - N S QG L L V I Y N C S R TN G QG E R L K S A L F T E S H S D - - - RN C A S T P - - - TD - - H Q - - TN VQ R L T R S S Q A I K K S I TN L L L Y K TD T E I T TQ V I P E L L K V L K D - TN R E I I E K A S L V I A T L A K K E A S RN A L L S T P L V L T A L I Q A I G H N V - N D E A A K Y S S S A I S S L S V - - N P L G V K M I H TC D M S G G Q AD R L K A T L F P E T L E S - - - N S VQ S TQ - - - VD T T K S - - TN VQ R L T V P S QD I K Q S L C N L L K H Q S D T E V T S R V I P E L L R V L Q L - S D RD I I E K A AWV VD S L A K K D A S RQ A I L S S P K L I V A L I N A VG TN V - N D E T A K L A AN T L S T L S S - - K P QG K R L I H S C D - - - - T A E Q V R S RQQ P S T AH T - - - A T V A P S S S S TN T F A F A A A A T S G A E S - - S S A L R I AQG V E I L Q S A L G D L AN F QN D S D L A V RM V P E L TQ L I A S - G N T V T V TQ A L D M AQQ L S R TD A S R P I MC D S P Q L V AN L M K L AG K S D V E AD V V S K AM A V V Y D I S K - - E D QG L VH I RQC H - - - WD A TD QQN D TD L A V RM V P E L TQ L L T S - G N I T T L TQ A L D M AH Q L S R TD A S R P I MC D S P A L V AN L M K L A S K T E L D V E V I S K AM S V V Y N I S K - - E D QG L VH I RQC H - - - N H S - - S G V E RN R S N K S AG R P QD L S A S AQQD D S D V A L RM V P E L TQ L L S P G S S K A T V S Q A L TM AH Q L S R TD A S R P I MC D S A E L V AN L V K L A S N A E L D VD V I S Q AM A V V Y N I S K - - E D QG L VH I RQC H S H V S P Q AG G S G G I A S A S S S P G L Q L G Q A I A A L S R S A A S T P S Q E T T - - - L VD R L A - - A V E Q R L S V T A K G L Q S S S V K Q L S S AD A TD L I T K S MD D I V F A L S K P E N N A V L L P A AN I V F H L S K AD G A R S VMG Q S K T L M S A I I G A L A L TQ - T T E V V L K L S G A AH F L TQ K Y K A A T T A Y I H E C G A A AG P S P R A S P G M L S M T S S G - - - S S V S P A T P - - - V A V E V S - - T P E R R L Q TM L R S L Q AG AM K Q V A P G E A S D I A L K V I D D L T S VM T S - E D QQ S L L I C S N I I F Q F S K L D G S RQ V I S Q S K M L M P R L L K A L A S TQ - V T E V V L K L AG A L H N L C H - Y G K Q A V A S L H QC G - - - G VG T P H G E S - - - T P E L R L R V T L K A F Q - G N M K Q I S A S E A S D V AQ K C TD D L L A L L C S - E E N Q S L L L A S N I I F Q L S K L E G S R S V I S Q S R A L I S P L L K A L A S TQ - S T E V V L K L G G A L H N M TQ - R RG G A L S V I H QC G - - - 0 0 0 0 0 0 0 0 01010 0 0 - - - 0 0 0 0 0 020 - - - 0 0 0 - -1 10 010 0 0 0 0 0 0 010 0 0145 51246579 95 5756 696537930 -263 356207527 72 28 8939785279536217823+835 54242-3295 5315 576743972- -123741293452 +++ T R S Q R V R A AM F P E T L E E D P Q L G Q A I A AM S R S M S + T S I P S T+ S TN T F A F A A A+ F D P A E P ++ T+ VQ R L A E P S QM L K N A V+N L I N Y QD D AD L A T R A I P E L T K L L S D + E D + V V V+Q A AMM VH Q L S K K E A S RH A I M+ S P Q L V A A L V+ A L G T TN L D V E V V R+ A S G T L H N L S H K Y H RQG L + S I + K C G 236 244 262 227 315 337 271 294 295 148 321 274 283 195 144 131 487 197 127 411 419 438 402 493 512 402 469 470 323 496 452 461 370 319 306 662 372 302 G I P A L V K M L G S P VD S V L F Y A I T T L H N L L L H Q E G A - - - K M A V R L AG G L Q K M V A L L N K TN - V K F L A I T TD C L Q I L A Y G N Q E S K L I I L A S G G P Q A L VN I M R T Y T Y E K L L WT T S R V L K V L S VC S S N K P A I V E AG G MQ A L G L H L TD P S Q R L VQN C L WT L RN L S D A A T - - K - Q E G M E G L L G T L VQ L L G S G I P A L V K L L S S P V E S V L F Y A I T T L H N L L L H QD G S - - - K M A V R L AG G L Q K M V T L L Q RN N - V K F L A I V TD C L Q I L A Y G N Q E S K L I I L A S G G P N E L V R I M R S Y D Y E K L L WT T S R V L K V L S VC S S N K P A I VD AG G MQ A L AMH L G N M S P R L VQN C L WT L RN L S D A A T - - K - V E G L E A L L Q S L VQ V L G S G I P A L V K L L G S Q V E S V L F Y A I T T L H N L L L H Q E G S - - - K M A V R L AG G L Q K M V A L L Q RN N - V K F L A I V TD C L Q I L A Y G N Q E S K L I I L A S G G P G E L V R I M R T Y T Y E K L L WT T S R V L K V L S VC S S N K P A I V E AG G MQ A L G QH L S H Q S P R L VQN C L WT L RN L S D A A T - - K QQ E A L E G L L Q T L VH M L AH G I P A L V K L L G S Q V E A V V F Y A I T T L H N L L L H Q E G A - - - K M A V R L AG G L Q K M V A L L G RG N - V K F L A I V TD C L H V L A Y G N Q E S K L I I L A S G G P A E L V R I M K T Y T Y E K L L F T T S R V L K V L S VD TD N K M A I V E AG G MQ A L AMH L G H Q S N R L VQN C L WT L RN L S D A A T - - K - E D G L D N L L QM L VQ L L S S G I P I L C E L L S N S S E N V L Y Y T I T T L H N M I Q RH K S S - - - Q L D I C L S G G L E K M V S V L K Y S D K P Q F V AM V A E C I H M L C H R N P D K K Q A V A AC S G P L H L V K L L Q T S S V E Y V TWA V A R A L K T L S VC N K N K K C I L E AG G MQ A L A RH L D TG S Q R V T E E V L Y TM RN L S N A V K G G S - VD N VD P I L T K L MD V L A R S V T I L L E M V R Y L S Q P VM F Y A I T T L H N L L L N Y A E S - - - RMD I F L S RG L E VM I Q L L P F N N - V K F Q A I V AD C M Y I L AH S H P D C K S V I Y N S E G H I I L I D I I S N C D Y E K L L WT A I R V L K L L S I T A S T K VN L I K AG AMQ A L A RH L N S D S N R I V I H T L WTM RN L S D A A T - - K - V E N I N N A L G S L VH L L N S G I P A L V R L L G - - - L L - - - K F L A I T VD C L H V L A Y G N Q E S K L N I L G S G G P A E L I R I M K V Y T Y E K L L WT T S R L L K V L S VC P MN K Q A I V E C G G I Q A L AH H L G S R S G R L VQN C MWC L RN L S D A A T - - H - L E N L G G L L Q L L I Q F L G V G I P A L V R L L G S P V E N V L F Y A I T T L H N L L L H QD G S - - - K M S L R I AG G L Q K M V S L L S RG N - P K F L A I T VD C L H I L A Y G S Q E S K L S I L G C G G P A E L V R I M K T F T Y E K L L WT T S R L L K V L S VC P MN K Q A I VD AG G L A A L T AH L TG R S S R L VQN C L WC L RN L S D A A S - - H - L QN QQQ L L Q I L I QM L S I G I P A L V R L L G S Q V E N V L F Y A I T T L H N L L L H Q E G S - - - K M S L R I AG G L Q K L V S L L S RG N - P K F L A I T VD C L H I L T Y G N Q E S K L S I L G C G G S A E L V R I M RM F T Y E K L L WT T S R L L K V L S VC P MN K Q A I V E AN G V A I L T AQ L S G R S S R L VQN C L WC L RN L S D A S S - - H - L QN QQQ L L Q I L I H L L S G G I A A L V R L L G S P V E N V L F Y A I T T L H N L L L H Q E G S - - - K M S L R I AG G L Q K M V S L L S RG N - P K F L A I T VD C L H I L A Y AN Q E S K L S I L G C G G P A E L V R I M K T Y N Y E K L L WT T S R L L K V L S VC L MN K Q A I VD AG G VG V L T VH L TG R S S R L VQN C L WC L RN L S D A S S - - H - L P N QQH L L Q I L I Q F L S L G I P F L V R L L T S P VD A V L F Y A V T T I H N M L L H F E P A - - - K MD V R L AG G L E K M V A L L V K D N - V K F L A I T VD C L H I L A Y G H QD S K L I V L A S G G P S L L V R I M R I Y T Y E K L L WT V S R L L K A L S VC S S N K P E I VQ AG G MQ V L S L H L G H R S N R L VQN I L F T L RN L S D A A T - - K - QD N L D E L L QQ L I G F L S S G L A F I M L L L T S D V E H V I V F A I TC L H N M L G C RH N A S V Y M E E F RN RG G VQH L V R L L N G H R - E R V L A I I AD C L H L L A I N N E E T K Q I I Y N Y N G S V L L V K I L AD S N F E K L I W I VG R L I K V L T TC P N H K Q A I VQ AG G I P I L S K H L T S N S P R I VQ L Y L R P L L T L S D V V R - - P - E D N L E S L I AM L L N L L RM G I G F L L S L L K S E G E Y I VM F A I TC L H N I F MC QN D S A T Y K E T F R S K G G VQH L V R L L N G N R - V K L L A I I TD C L H L L AC N N A E T K L T I Y E Y N G P V L L V K M L T E N T Y E K L L WT I G R L L R I L V L C P S N K H A I VQ AG G L P A L S K H L N N S S P R I AQ T Y L R S L L T L S D I A R - - P - E D N L E P M T L M L L N L L QG G I A T L V RH L S S N T E M L M F L A I S T L H N M L QN L E Y S - - - K G D I R L AG G I Q R F V S L L H H S N - V K V I C M A I D C L Y L I C Y S H P E S K L L V L S AN G P I E I V R I L R TH S Y E K L L WA T S R L G K V L S VC P S N K P AM VD AG AMQ A F S I H L E H K S Q R F VQN V L WAM RN L S D Q A T - - T - L P G MG D L L H S L I D L L A S G I A A L V RH L S S N V E L L M F N A I S T L H N L L QN L E Y S - - - K AD I R L AG G I Q R F V S L L H H AN - A K L VC M A I D C L Y L I C F S H P E S K L L V L S AN G P I E V V R I L R TQ S Y E K L L WA T S R L A K V L S VC P S N K P AM VD AG AMQ A F S I H L E H K S Q R F I QN L L WAM RN L S D Q A T - - N - L P G L G D L L H S L I E L L S S G I T A L I RH L S S N T E T L M F H S I S T L H N L L QN L E P S - - - K AD I R L AG G VQ R F V S L L H H P N - V K L VC M A VD C L Y L I S Y S H P E S K L L V L S AN G A V E I V R I L RN H T Y E K L L WA S S R L A K V L S VC P S N K P A L VD AG AMQ V F C MH L E H K S P R V VQN I L WAM RN L S D Q A T - - N - Q P G L G D L L H S L I Q L L S S G T R V I C S M L K F A I E G A I V Y A VQ I L Y I L L T E V P A S - - - K K V V R E C E A I QG L V Y L L G R I R RD R L L A L I L D C L Y H I C MG D P D S K L M TM AC N G P Q E I V R V L Q TN D Y Q K L V T TG M R V L K V L S I C QH V K E S I V K C G G MQ VM A K H I H G E G - K I K RN V L L T I RN L S D T AG - - K - E P N M E P I I G S C L E L L G D G T R V I C QM L K F T I D G A T V Y A VQ I L Y S L L N K E P E S - - - K V E A R E H D G L QN L V A L L G R T V RD R L L A L I L D C L Y H L C I G D P S S K L V I L G C S G P Q E I I R V L RN N T Y P K L I M T AM R V L K V L S I S K E T K D A I V E N G G L Q AM A AH I TG E P - R I K RN V L L T I RN L S D I AG - - S - Q RD L E P M L A TC L D L L G D G T P V I C QM L K F T I D G A T V Y A VQ I L Y N L L Q S Q P D A - - - K I V A R RN D G L QN L V A L L G R T V RD R L L A L I MD C L Y H L S I G D Q E S K L I I L N C QG P Q E I I R V L N TN T Y A K L I M T AM R V L K V L S I C A K A K Q V I VQ K G G I Q AM A K H M TG E S - R L K RN V L L T I RN L S D A T S - - S - QQD L K D V L V TC VQM L S D 8634+825940 0 01010101210230980 0 0 0 02- - - 0 0 010 0 0 032101202 20 0 0 0 - 07 769 95 59*964+74 43 364*5 565454*2519 958943 3763796 65 5 5*7 795*6 652 2 2*139 9547+857872692 2 26097342594695+* *8564- -2-4 4563176238 827*41 G I P A L V R L L G S P V E N V L F Y A I T T L H N L L L H Q E G S ++ Y K MD V R L AG G L Q K M V S L L G R+N R V K F L A I T VD C L H I L A Y G N Q E S K L I I L A+G G P A E L V R I + R T Y T Y E K L L WT T S R L L K V L S VC P S N K P A I V E AG G MQ A L A K H L T+ R S P R L VQN C L WT L RN L S D A A TG G K Q++N L E + L L Q S L I Q L L S S 412 420 439 403 494 513 403 470 471 324 497 453 462 371 320 307 663 373 303 575 588 604 562 651 674 570 620 635 488 660 625 634 532 481 468 818 528 457 D - D I N V V TC A AG I L S N L TC N N Y K N K MM VC Q VG G I E A L V R T V L R - - AG D R - - - E D I T E P A I C A L RH L T S RH Q E A E M AQN A V R L H Y G L P V V V K L L H P P S H WP L I K A T VG L I RN L A L C P AN H A P L R E QG A - I P R L VQ L L V R AH QD TQ R - R T S MG G TQQQ - - - - F V E G V RM E E I V E G C TG T - D VN V V TC A AG I L S N L TC N N Q RN K A T VC Q VG G VD A L V R T I I N - - AG D R - - - E E I T E P A VC A L RH L T S RH VD S E L AQN A V R L N Y G L S V I V K L L H P P S RWP L I K A V I G L I RN L A L C P AN H A P L R E H G A - I H H L V R L L M R A F QD T E RQ R S S I A T TG S QQ P S A Y AD G V RM E E I V E G T VG N - D I N I V TC A AG I L S N L TC N N G RN K M I VC Q VG G I E A L V R T I L Q - - AG D R - - - E D I T E P A VC A L RH L T S RH P E A E M AQN A V R L H Y G L P V L V K L L H P P S RWP L I K A V I G L M RN L A L C P AN H A P L R E QG A - L P R L I Q L L M R AH QD TQ R - R A S MG S T S S Q - - G G Y VD G V RM E E I V E G T VG N - D I Q V V TC A AG I L S N L TC N N P RN K Q L VC R F G G I E A L V R TC L Q - - AG D R - - - E E I T E P A VC A L RH L T S RH AD A E A AQN A V R I H Y G L P V L V K L L H P P A RWP L I K A V I G L M RN L A L C P AN H A P I R E H G G - L P R L VQ L L M R AN QD MQ R - R P G H N V - - - V I D G V RMD D I V E G T VG T - N I N L I AC S VG C L S N L TC N N P N N K K T V F R AG G L D T L L RC L L Q - - N Q A I - - - P S V A E P L L C T L RH I N Y K H S E Y E Q TQH A F R T S G G I S L I T K V L S T AQH WA V I K A AC G L I RN L A L N A AN I P F F K E TG L - L L H L I Q AC L R I TD H Y K G - - - G I N - - - E N RD G I K L E D I MWE S L K N - E P S I I MC I G G I I S N L TC N N S QN K T Y L C K I G G VQ A L L D V L S A - - Y S D R - - - E D I I E P A I C A L RH L TN K H P Y S E I AQN S V RD H K G I P I V I N I L K N C N S F A V R K A I VG L I RN I A L C Q Y N I P I L Y E F H G - I N K L TD I L L E TC Q VMN Q - R L S K H S T - - - T E I D G I R L E D I I E S T VG A - D F N Y V TC A AG I L S N L TC N N P QN K V L VC Q L G G V E A L L R TC V N - - AG D R - - - E D I T E P A VC A L RH L T S RH S E A E M AQN T I R V S Y G I P S I I R L L H H P S RWP L I K A V I G L L RN L A L Y G E N H I A I R E N A A - L P K L VQ L L M K AQQ VMQ R - R L S L G P N G L P Y AD G I QD G V RM E E I V E G C VG N D V A S V TC A VG I L S N L TC N N L QN K V V VC QC G G I E A L L R I C S Q AG D H D E I A E P A VC A L RH L T S RH P E A E M AQN T I R L Q Y G I P I I V K I L D P P S K WP L L K A V I G L I RN L A L S P H N H T P I R E N G G I H R L C Q L L S N AH Q I VQ R Q L S L G P D T K P A R V -N - D V T S V E C A AG I L S -N L TC -N -N QQ-N K V I VC QC G G I E A L L R TC AQ - - AG S R - - - D E V A E P A VC A L RH L T S RH P E A E M AQ-N T I R L Q Y G I P L I V K I L D P P S K WP L L K A A I G L I R-N L A L S P Q-N H G A I R E -N G G - I H R L C Q L L T K S QQ T I Q R - R L A L G P D AG P - - - A R V E G V Y M E E V V E G C VG D - D P N S V TC A VG I L S N L TC N N I QN K V V VC QC G G I E A L L R I C AQ - - TG N R - - - D E I A E P A VC A L RH L T S RH P E A E M AQN T I R L Q Y G I P I I V K I L D P P S K WP L L K A V VG L I RN L A L S P H N Y Q P I RQN G G - I H R L C Q L L S K AH E M VQ R - R L A L A P D AG P - - - A R V E G VQM E E I V E G C V G N - D VH Y L TC A AG V L S N L TC N N A K N K TM VC Q L RG I E A L L R T I G N - - N TD K - - - G E V I E RC VC T L RH I T S RH L A A E M AQN A I R E L N G I P M L MN L L Q P Q T R Y P L I K A L I G L F RN L S L C S D N H T V L R E QG C - I P K L WQ L L N R S F Q E L Q R - R S G Q P G M - - - - A L G I VD G V S MN E V V E C S T A K E D T T S MM Y I VG I L S N I TC N N P I N K T A I C N H N G I H I L L Y I V L E - - F S Q K RD I N I N S P Q I N E L L E A V I C T L RH V T S K H E R E D F AQN E V R E Q K G L D V I L Q L F L N T TH WT L I K AC L G L L RN L S I S TH N R I E L R K L S V - I P Q L V E L L R R A I E I L F K - T T E H G N T - - - T TQ E G VN M E D V L V L I L S K C D VN MM T S A AG I L S N I TC N N P QN K D A I C E H N G I Q V L I N I V I C - - Y TQ K TD V S I N T P QH N E L L E G I I C T L RH V T S RH Q K A E F AQN E V R L Q K G L D L V L Q L F L T T TH WT L I K AC L G L L RN L S L S S TN R S E L R R L S V - I P Q L I E L L R R S L D I L K K - T AD E I N Y - - - E P QD G VN M E D V L V L V L S E - D A T T V TC A AG I L S N L TC N N E QN K V T VC R E G G I E A L I R TC AQ - - AG D H - - - D D I T E P A VC A L RH L TN RH L E A E V AQN A V RH H H G V R V L V R L L D P P S K WP L I K A V L G L L RN L A L C P AN H T A V R E C G G - VH R L V E L L I A A R K D I D A - C N A RG T S - - - S F VD G VH M E E I V E G T TG E - D T T T V TC A AG I L S N L TC N N E QN K V I VC R E G G I E A L I R TC AQ - - AG D H - - - D D I T E P A VC A L RH L TN RH L E A E V AQN A V RH H H G V R V L V R L L D P P S K WP L I K A V L G L L RN L A L C P G N H T A V R E C G G - VH R L V E L L I A A R K D I D A - C N A RG A S - - - A F I D G VH M E E I V E G T TG E - D P T I V TC A AG I L S N L TC N N E QN K V T VC R E G G I E A L I R TC I Q - - AG D H - - - D D I T E P A VC A L RH L TN RH L E A E V AQN A V R Y H N G I R T L V R L L D P P S K WP L I K A V L G L L RN L A L C P AN H T T V R E AG G - VH R L V E L L I A A R K D I D A - C I A RG T S - - - A F VD G VH M E E I V E G T TG S - D V T T V TC S VG I L S N L TC N N P P N K N F L F M K S G I Q S L L Q L C S Y C S P D N Q - - - K D I I E RC L C T L RH M TN G F E R A E H A TQ A F L VN D G H K L I S R Y M A - P S S WY F T K H A AG L L D N I A A Y H TN H A I L C E D P D L L P R L A A V I N M V K S S H D V - - - K QD N I S L R E VH D MC MQ N - D I T T V TC A VG I L S N L TC N N P H N K Q Y L C V K S G I E A L MQ L C H K C S P VH Q - - - QD I V E R S L C T L RH M TN G H E R AD V A TQ TMC I H QG H M L V AN Y MQ - P S S WF F T K H A AG I L QN L T AN Q AN H P A I C E H E S L L P S V VH V L E F I K Q T P H E - - - Y L D D V K L Y D V S E MC Q R T - D V T T V TC C VG I L S N L TC N N P S N K S I V Y Q E N G V E A L VH L C QQC F QG QH - - - Y E I I E RC L C T L RH I TN G H E K VD V A TQ R VC I H G G L E L I AN L L R - T E K WV L I K P A AG L L QN I A A VC P N H P A I C D S E A - L G A A VQ VMN F I Q P RMD Q - - - V L E E I K I S E V F E TC L R 3-73 34845 58*8+* *+* * * *1 1* *2497314*945*84682 2- -4324- - - -1695*359*7* * *8+6472 2 2927953742 2 2*425956 681054 49374*257*+86*+7 7421*4 417451 13-913742782 25321232- 0 0 0 0 0 0 0 - - - -13 3021 1 1320 0 0 0 0 0 N +D V T T V TC A AG I L S N L TC N N P QN K V+ VC Q E G G I E A L L R TC L QC S AG D R+D ++ I N + P Q+++ I T E P A VC A L RH L T S RH P E A E M AQN A V R L H Y G I P V I V K L L D P P S K WP L I K A V I G L L RN L A L C P AN H ++ L R E N G G L I P R L VQ L L M R AH QD +Q RQ R L S L G P T++ P + A+ A F VD G V RM E E I V E G + VG 576 589 605 563 652 675 571 621 636 489 661 626 635 533 482 469 819 529 458 717 724 741 702 787 802 639 733 763 625 819 769 780 665 559 601 931 643 551 A L H I L A RD VH N R I V I RG L N T I P L F VQ L L Y S P I E N I Q R V A AG V L C E L AQD K E A A E A I E A E G A T - - - A P L T E L - L H - S RN E G V A T Y A A A V L F RM S E D K P QD - - - Y K K R - - - L S V E L - - - - T S S L F R T E P M - - - AWN - E T AD L G L D I G AQG E A L G Y RQD D P S Y R A L H I L A R E S H N R A L I RQQ S V I P I F V R L L F N E I E N I Q R V A AG V L C E L A AD K E G A E I I E Q E G A T G P L TD L L H S RN E G V A T Y A A A V L F RM S E D K P QD Y K K R L S I E L TN S L L R E D N N I WA N AD L G MG P D L QD M L G P E E A Y -A L H I L -A RD -AH N R -A V I R S L N C I P L F VQ L L Y S N I E N I Q R V -A -AG V L C E L -AQD K E S -A E I I E -A E G -A T - - - -A P L T E L - L H - S RN E G V -A T Y -A -A -A V L F RM S E D K P QD - - - Y K K R - - - L S V E L - - - - T S S L C R -AD -AM - - - P W-A - E P H E L - - - H D P G MMMM P P D E P -A Y R A L H I L A R E AH N R A V I R S L H C I S L F VQ L L Y S P N E N I Q R V A AG V L C E L AQD K E G A E A I E A E N A T Q P L TD L L H S RN E G I A A Y A A A V L F RM S E D K S QD Y K K R L S V E L T S S L F R E D A P WQ E M E G D L MD T Y QM P G A Y T Y P Q E S MD Y -T L E S V S C H P E I R AQ L D N P I S AH L L M K C I N S N N E N L VQ V A L S S V VQ F E S H E N F M V L I K N D P R F - - - E L I G K L - C H - F RN P K I AQM A A V L S N R L N E VQ VD V K P - - P - - - -T AM E Q P P H Q -T P G I F VN G G V - - - QWG - - - E S V P H V R -T E N G S A A S H L A L H V V S RH P Q Y R A L L TD S K C I R I F TQ L L R S N S N S I VC V A TG V L S E L AQD K E G A R AMH Y L G T P - - - Q I L QN L - A S - H RD E A I A T F A T S A L Y RM S E D RG S I - - - N R RQ - - G P S I D L N G S F TG S L S R S E R F E L - - - N N S MN S R S A L H I L A RD P H N R V V I RG L QC I P I F VQ L L Y S N H E T I V R L T TG A L C E M AQD K E S AD I I E A E N A S S A L T E L L -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- L L Y S S H E N V V R V A S G A L C E M A F E K E Y A E A I E A E N A A -- -- -- -- -- -- -- -- -- A P L T E L -- L Q -- S RN E G I A T Y A A A A L F RM S E D K S QD -- -- -- -- -- -- -- -- -- -- -- -- -- Y R T R -- -- -- L S V E L -- -- -- -- T S T L A R TD S A -- -- -- -- -- -- -- G G QWS -- E TD T F -- -- -- -- -- S R P L RQQ L QQQ L I A R P A L H I L A RD I S N R A L I RG L N S I P L F VQ L L Y S S H E N V V R V A AG A L C E M AQD K E N AD T I E A E N A T A P L T E L L Q S RN E G I A T Y A A A T L F RM S E D K S QD Y R T R L S V E L T S S L A R TD S G G QWS QQ AD V F G RQ L P -A L H V L -A RD P G S R -AD I R -A L N C I P L F VQ L L Y S S H E N I V R V -A -AG -A L C E M -AQD K E Y -AD -A I E -A E N -A -A - - - -A P L T E L - L Q - S RN E G I -A T Y -A -A -A -A L F RM S E D K S QD - - - Y R T R - - - L S V E L - - - - T S S L -A R TD S -AG - - - G G QWS - E S D M F - - - -AQ S L R - - - H RQG L G R -A A L H L L A RD P Y N R L I M RQ L N V I P M F VQ L L Y M RN E G I Q R A A VG G L S E L A L D P E G A E Q I E R E G A P - - - T P L G E L - L H - S P N E G I A A Y A A A V L F C L S D D RN G E L P H L P AD I G G G V P Y RQD Y MG L D TN P - - - - P Q S Y Y S T S T P P L H QQQ L RG H Y S N P G S V P - - - G S Q P F - - - - T P N M S E P T V E V L A K D H VN RN L I G K H D S I P V I I R L L F S D R K R V L E H A V AC L C E L S G D Q F N MQ E M E R AN C S D M L V K L L Q RC QD E N I E A Y V TM T L H K F N E F RN Y D G N K I I S G G L MD T I P AN I P T A P RN V T P I G D L D Y Y N M S D D P G L A F Y N P G N N T V E I L S RD A I N RH M I G K QD I I P L L V A L L Y S E RN R L I E H C AG C L C E L AQD V Y N I Q VM E R E N C A E AMN K L MH Q TQD E T I V A Y A AM T L H R L N E H R T L D AH K M MN E E M L S G L M P M I P P G P G N V T P VG D L D Y F P M A E D P N F Y F Y N P D QN A Y -A L H I L -A RD VQN R T I L QN L QC V P L F VQ L L Y F D V E N I Q R V -A S G V L Y E L -AQ S K D S -A I VM E K -AG -A T - - - S P L T E L - L H - S RN E -A I -A T Y S -A -A I L L K L S E D K TG D - - - Y K K R - - - L S V E L - - - - S N S L F R -A E -A - - - H WS -A P S D V -A - - - N F -AD L - - - - G D G M S S V A L H I L A RD VQN R T I L QN L QC V P L F VQ L L Y F D V E N I Q R V A A G V L Y E L AQ S K E S S M VM E K AG A T A P L T E L L H S RN E A I A T -A L H I L -A RD VQN R T I L QN L QC V P L F VQ L L Y F D V E N I Q R V -A S G V L Y E L -AQ S K E -A -AQ VM E K -AG -A T - - - -A P L T E L - L H - S RN E -A V -A T Y S -A -A V L F K L S E D K S S D - - - Y K K R - - - L S V E L - - - - S N S L F R S E -A - - - H WS -A P S D V -A - - - N F -AD L - - - - N D G L S S V C L K A L VQN E N N H Q K L L S L D C M A L L E E A S H MD P H I N AM E N L T I G AD P A P E P A TQ E L N E L F N L D G G AD D Y G D A A S A V E P F G K K L TD E V G L A L L S G N P AM A E D Y L N L G G E D F D A L H S L Q Y L L Q V E AN H S C L I R L N C V P L L Q E A A A A E P L L AM E N M S L S N D P Q P P I P N P MN D F L Q S I N L E N VG D I S E L D L L A T A P S D V S T A V L E V E R A L L D D P S L N AD D L L N L D F Q E L E A L R M I QH L AG N L AN H T A L F S L N C G P F L A A A A AN E E H I I AMQG L S L T P S D T P S V P S N P A S I L G L D P TD L P D MG D F D A V L L QQQ L H D E D L AG L D I N E L L -021020 0 0 0 0 030 010 0 0 0 0101 10 0120 0 0 01020 01 1021204642013253 3953 3634- - - -427538-50 - 0 0 0 0 010 01 10 0 0 0 0 0 010 01 10 0 - - - 0 010 - - - 0 0 0 0 0 - - - - 0 01 10 0 0 0 0 0 0 0 0 0 0 0 0 0 0 -A L H I L -A RD P H N R -A+ I R+ L N C I P L F VQ L L Y S +H E N I Q R V -A -A G V L C E L -AQD K E + -A E -A I E -A E G -A T+D P + P ++ P + -A P L T E L + L H + S RN E G I -A T Y -A -A -A V L F RM S E D K S QD + P H L P +D I G G G V P Y K K R Y MG L S V E L ++++ T S S L F R TD + -AG L H QQQ L G G QWS + E +D L L + L D M E D + P + L ++ Y N +D G + S Y + 718 725 742 703 788 803 734 764 626 820 770 781 666 560 602 932 644 552 757 816 837 722 882 931 819 856 717 955 841 859 736 611 670 946 687 596 S F H S G G Y G QD A L G MD P MM E H E MG G H H P G AD Y P VD G L P D L G E G L Y G Q G P P S VH S S H G G R A F H QQG Y D T L P I D S MQG L E I S S P VG G G G AG G A P G N G G A VG G A S G G G G N I G A I P P S G A P T S P Y S MD M D VG E I D AG G E G M F S H H S S V S S VH S G QH S TMG RQ P H Q VQ P R TG L Y S TG S Y H D Q P P H T P I D H G MD H MD MG P G P G G P H H MQG A AG G H P S H S D Y P QD L D L G I P T AD L G MQG P VD Y G H H Y D F H G D P N M S N D V VD L D A T T AQ Y RN D S F I K S P G S M P V V P P G AG G P L Q P S P H QQ Y S P R Y H A P S P H VQ H S T Y N G V A F P T T Y S T S P H Y T TQ S T Y H P F P G F H H T P Y Q P P P S Y R E D A Y S H H S G I MN I N E MMN MQ P A L S N G G QQD I N I N V P V S D AG G I S S P H I N G M Y E Q I QN L S L D AG S N Y D G I P A E QQ S MH S Y Y S N P S H RG P VN P S I H S N N S VQH N P P E S Y T P T K F A T G TN N S N S V A S S G G Y QG MQH MQQQQQQQ QQ P P Q A A A A A A A AH H A A V A RQM S G G G VG P Q V P G G F N P S Y Q QQQ P M I P Q A S Y QQQQ P Q P D L S Y D G M V G Q S G G H S Y Q P A P P S A L H Q L P P QG G S F S H H G P P P VQ RQ T S G G M S Q V P G G F N P S F H G G A P H QQH L P P VM S S Q P P H H H M A P A H Y P QQ Q P D M S Y D G F G S F G G P A T F AQQ A P P P P Q A P F QQ S P VH S H H H I G G G G G G G AG I MQ RQ T S G G Q I P G G F N P S F Q AQQ P P S G AG P G A P H A F QH QQ E L S F D G F TG S A A AG G P S G L M T P H S E F E L P L D F D E Y AH G AG S Y H H S G V H T P G S H P H S G H H T P S H P H H S G I H T P G G G S H P H S A H H S G I H T P AG G S H S G VH T P N H Y L P S S Y P QN P A P P I P H H P I A P Q A P P TH P Y H Q P P QQ S MG P N Y Y R V Q TQG G Y G H I Q E QQ MD Y Y G N C V P MQQN QH I S H TH G F P D S R M T P S L F Y P D K Q S Y Y E MN S Q P MQ I P Y Y H P E QD L T Y Q Y N T VQ T TQD H Q MD N G H C I Q I H P N S H AM T P S M P P N H S F P D P R L H P P P Y Y AD K P D Y Y D I AN L Q V P TH QQ E A Y Y P Q E L G Y G Y N S M G G S V I S S R AG A S S M A S S N Y G Y G G Q R RG V R RG P G H G N QQ A A I A E S A L E E I P P D M L E L L D D P A L I E A AM AN AG G Y G Y G G Q R K P M R RG P G H QQ AM I A E S A L E E I S P D M L D L L D D P A L I E A AM AN AG -G -G - - - S V I S S R - - - A-G - -G S V A S S -G F - - - -G Y -G AQ R K P A R RM - - - P -G -G - - -G Q A A - - - I A E S A - - - L E E I S P D M L E L L D D P A L V E A AM AH A S -G S G M AN F TQ S G G E Q E K S QMG E Y G Q P G G P S D L D D P A V S N V L K D L L QMQ S F P S P G C D S S S S A E D F G K Y T T A S G E F L N T E P AD A S V M E D L L A S L P G A S P G S AG QG QG G 0 0 0 0 0 0 0 0 0 0 0 0 0 -G -G Y +++ S +M-G T Y S Q++N D S F I +++-G +MD ++ E ++ A-G A+ S S +H S -G QH + T P ++ A P H QQ A P + T-G L T P S + S H H H +-G I H T P I -G -G -G S D ++-G +-G P + P -G Y +-G + R R P A S -G -G + S -G +Q+ P -G -G F N P S A + S Y Y + VQQH L +D L I AQQ P ++ P + P H +H H + P Q A P P TH Q+QQ P +Q++ Y S P D M L E L L D D P -G L + E A AM A+ A-G -G 758 817 838 723 883 932 820 857 718 956 842 860 737 612 671 947 688 597 781 843 858 742 895 949 838 879 737 977 860 885 755 630 697 951 698 607 - - - H AQD L M - D G L P P - - - G D S N Q - - - L AWF D TD L - - - A L N F D L - D AM P T P P - - - N D N N N - - L A AWY D TD C - - - L - E G L P P QG - - - G D N N Q - - - L AWF D TD L - - - H Q - - - P P - - - G G H Y QN P G G P L Y D TD L - - - Q P P Q - S N RN WY A A - I AH Q T P I WD E S N S F RM VQ E -- -- -- -- -- -- -- -- G -- -- F P L -- -- AMQ TD -- -- -- -- -- -- -- -- -- -- G P QQ Y F D TD L - - - G QD F P MQ E S MQ T E - - - G S QH F F D TD L - - - G G G F A V - E S MQ TD - - - Q K Y F D TD L - - - N Y N P P S P A L MD T - - - AN TG W I D TD L D F P I P Q T R E F Y Q QD I P Q Y F L D Y P P Q TM R E F Y P TH H D V S Q P I F RH F -- -- -- -- -- -- -- -- QH G D D S -- E G MG S -- -- -- -- -- -- -- -- -- -- -- -- -- S AWQD TD L - - - H L G D D S - E G MG S - - - S TWQD TD L QH H H QQQQH G G D D M - D N MG S - - - S AWQD TD L S S N R E T S M T S S S G F S S P G A Y P G P S AM T -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- 0 0 0 0 0 -- -- -- -- -- -- -- -- -- -- -- -- -- -- --10 -QH H H QQQ-QH +G F P + P E +M P + F Y P T+G D +N QN +N S AWF D TD L Conservat i on Qual i t y Consensus M. musculus D. melanogaster B. floridae N. vectensis M. leidyi T. adhaerens C. candelabrum O. lobularis O. carmela Oscarella-sp A. queenslandica A. vastus O. minuta S. ciliatum-1 S. coactum-1 L. complicata-1 S. ciliatum_2 S. coactum-2 L. complicata-2 Conservat i on Qual i t y Consensus M. musculus D. melanogaster B. floridae N. vectensis M. leidyi T. adhaerens C. candelabrum O. lobularis O. carmela Oscarella-sp A. queenslandica A. vastus O. minuta S. ciliatum-1 S. coactum-1 L. complicata-1 S. ciliatum_2 S. coactum-2 L. complicata-2 Conservat i on Qual i t y Consensus M. musculus D. melanogaster B. floridae N. vectensis M. leidyi T. adhaerens C. candelabrum O. lobularis O. carmela Oscarella-sp A. queenslandica A. vastus O. minuta S. ciliatum-1 S. coactum-1 L. complicata-1 S. ciliatum_2 S. coactum-2 L. complicata-2 Conservat i on Qual i t y Consensus M. musculus D. melanogaster B. floridae N. vectensis M. leidyi T. adhaerens C. candelabrum O. lobularis O. carmela Oscarella-sp A. queenslandica A. vastus O. minuta S. ciliatum-1 S. coactum-1 L. complicata-1 S. ciliatum_2 S. coactum-2 L. complicata-2 Conservat i on Qual i t y Consensus M. musculus D. melanogaster B. floridae N. vectensis M. leidyi T. adhaerens C. candelabrum O. lobularis O. carmela Oscarella-sp A. queenslandica A. vastus O. minuta S. ciliatum-1 S. coactum-1 L. complicata-1 S. ciliatum_2 S. coactum-2 L. complicata-2 Conservat i on Qual i t y Consensus M. musculus D. melanogaster B. floridae N. vectensis M. leidyi T. adhaerens C. candelabrum O. lobularis O. carmela Oscarella-sp A. queenslandica A. vastus O. minuta S. ciliatum-1 S. coactum-1 L. complicata-1 S. ciliatum_2 S. coactum-2 L. complicata-2 K335 W338 R342 R386N387 D390
R90 R93 R95 T112 T120 R124L125E127 L132
L139I140
Y142D145 E147D146R469H470 K508
R582 R612 A656
L261
Y333K K A HV L A A S V E Q A T E N F L E K GD K I A K E S Q F L K E E L V V A V E D V R K QGD L MK S A AG E F ADD P C S S V K RG N MV R A A R A L L S A V T R L L I L ADMAD V Y K L L VQ L K V V E DG I L K L R NA K K A HV L S A L V K K A T E T F I D K G E I I A K D Y P D I QDDMMA A I DD C K K T GD T MY A A S Q E F ADD P C S S MK RG A MV R A A R A L L S A V T R L L I I ADMAD V HM L L K H L R I V E E S L E R V RQ A K R A S A L V A A V E K A T E N F I Q K G E Q I A Y E N P D I T Q E M L T A VD E V K K T GD AMS I A A R E F S E D P C S S L K RG N MV R A A R N L L S A V T R L L I L ADMVD V H L L L K S L H I V E DD L NK L K NA K NA HK L AQD I E D A T V R L I K T G E S I S K D F P E I R E E M I A A C K D C RG AGD T MH I S S K E F ADD P C T S T K RMT MV R A A R A L L S S V T R L L C V ADMAD V C R L L A S L K L V E R R L K D L E G A R K L L Q HA K H I NE I C Y E L I K F A R E V A K E HP D V E Y E L NQ A C NR T CD V Y NVMK MK I E GDD K HD S AG T I I D I A K Q L I NNV A R I L I V T D S AD L I L I NK T I E D V K Q C L K A V E Q C K E ADD L I K L V H L A I NE L I E HGQ I V A ND NP K I AD R V Y Q A Y E E L HD AG S C L L A A T E S F V HE P S S Q I K R S A L L K A V F N L Y P I L NK L L S I ADMVD I S N L V K M L HE L E D H L Q L V L D S A L A R F V A E G R K I G R E NR E I E I DMR S A CD R V E S T G K E MHA T A RD F L D N P C S S A R R NE L V E S A R E L L T A V T D L L I I AD A AD V I R L K S A A RQ VD NWL QQME R A R S A T L VD S L D K A R K C F V A E G R K I AQ L N R E V E R E M L I A C E G V E S AG L A T RD A A E H F M L D P C S S E K R S E L V E V A K E L L T S V A R L L L I AD T AD V NH L K S A A R S V NT WL Y K L E R A R N I Y K L I Q I VD K A T E N F NA V A E N I A T E NP E F Q E E L WL S I E E V HT AG N L L HE A A F D Y T S D V L A P R K R E G ME Q A A AG L L K A V T R L L V L I D L I D I N E L F K A S NR VD V K L RQ I RD V -Q S L V AD A-Q H I L S V L S K L -Q R A V P -Q I P VD ND VG L T AG V R HR I G I NY D S AME HA E E L V T - C L R-Q P G P G T AG NS I A VD P - - - A A R A S -Q A L L T S V T C A L Y E Y D-Q T I V NR I E MS G-Q-Q I A R L G E E L S S L L MT Q S M I T DGQ R I Q T V L AD L Q R K A A L I E R NDD L G I T A A V R HR I I MD Y D S A V E HADD I V A - Q L T Q S T T G - A AD I L A VD K - - - I G R S AQG I L S S V T S A L F A F DQ T V I I R I E A I A A K I S E NG T S L T R I L E A I S V S L L L Q S L DQ A V S S L V HT A E I I A Y E N D K K V R R K M L N A V NR L K T S A K Q L S Q L MS D N I P P S P T HC I D T E K S P S L RD V A R V L L Y D V A C V L S V AD K VD E R K L Q E A T Q S I E S C L D S L RD V M L S A V HR L K G S A RQ L R E R V VG S S L L N S C E NE NP GQD V T V R E V S R A L L Y D V A S V L S V AD K L DG K R L V E T S L S V E NC L E K L K HA P D L T A P V A A VQ A A V S N L V R VG K E T VQ T T E DQ I L K RDMP P A F I K V E NA C T K L VQ A AQM L Q S D P Y S V P A RD Y L I DG S RG I L S G T S D L L L T F D E A E V R K I I R V C K G I L E Y L T V A E V V P D L A R P VQ A V C A A VQ N L V K V A K E T A E T S Q D V I L K Q E MP I A Y T R V E E A S H L L VD A S DM L R AD P Y S R P A R E K L I DG A RG I L S G T S Q L L L T F D E A E V R K I I R V C K S V L E Y L A I A E V V P D L A R P VQ A V C A A VQ N L V K V A K E T A E T S Q D V I L K Q E MP I A Y T R V E E A S H L L VD A S DM L R AD P Y S R P A R E K L I DG A RG I L S G T S Q L L L T F D E A E V R K I I R V C K S V L E Y L A I A E V V P D L S R P VQ V V S A A V A N L V K VG RD T I NS S D D K I L RQDMP S A L HR V E G A S Q L L E E A S DM L R S D P Y S G P A R K K L I E G S RG I L QG T S S L L L C F D E S E V R K I I Q E C K R V L D Y L A V A E V I P D L S NP I MA VG A A V A N L V K VG K E T A T Q S K D K I L K Q E MP L A F T R V E E S S M L L VQ A S K L L K RD P Y S S E A RQ K L I DG A RG I L S G T S A L L L T F D E A E V R K I V T F C R S L L E Y L P VG E MV P D L VD N I K L V L T C V S N L A T V A E S T AQQ S N D A T F I RD F P S AMD A V NS S S A A L N E A V L E L R T D P Y S S QG R R K L I T G A K G I L T G T CD L L L MY D E S E V R K I V K NC E A V K S Y F P V C L E V P D I T MP VQ A A C A A V A N L VQ VGQD T A NA S S D E K F K Q E MNV A L E V V K NS S V N L NQ A A H L L K DG S S S L E A R N I L I DG T K G I L S G T S D L L F S Y D E S E V K K I V R V C NNV K D Y MP NA S V I QD L T P L V K G VG L A V S N L V E V A T GMV S T T N D E E F K V E L P P S V E MV K Q A S T D L DD A A R L L K AD QG S R E G K R K L L DG A RG V I NGMS D L L V C AD R S E V R K M I K T C R N VQ E Y L D V A K V I E D L T P L VQG VG I A V T N L VQ V A A S MV E T S N D E D F K A E L P P S MQ E VQQ A A V F L S D A A R L L K AD QG S P E G K R K L L DG A RG V I NGMS D L L MC A D R S E V R K MV K V C R S VQ E Y L D V A K V I S D L VQ P V T A V K A A VD N L V E VG RQ T L K S A K D E K V HT DMP P T F E A I E S A C T L L L Q A A K G L S Q E E Q T P T D K K K L L DG S RG I L QG V S H L L L V Y DQ Y E V R K I I K T C E G V I D Y I K V A E I V MV K MC E G I I E Y I K V S E MV P D L S E P V S A V S A A VG K L V T VG K E T A E S S E D K Q L QQD L P R AWE A A E V S S T Q L A E A A A T L RD N P R S G P G R R L L I S G A RG I L E A V S D L L L T F D E S E V R R I I S V C E S VQ E Y V K V AD V I P D L S E P V S A V S A A VG T L V K VG K E T A E S S N D E Q L QQD L P R AWE S A E L A S QQ L T E A AQ T L RD N P R S A P G R R L L I S G A RG I L E A V S D L L L T F D E A E V R R I I MV C E S V K E Y L S V AD V I P D L T P Q VD V V A A A V T T L V T VG E Q T ADD S E D P I L K K E L P R P L K S VQ K S ADQ L V E A AQ T L K E N P V S L P G R R L L I VG A RG I L QG I S D L L I T ND E S E V R T MV A A C RG S Q T V L RD A H I V P D L T P Q VD V V A A A VMT L V K VG E Q T ADD S D DQ I L K K E L P R S L K S V E K A S S Q L V E A S Q T L K E N G K S MP G R R L L I VG A RG I L QG I S D L L I T ND E S E V R T MV V A C RD S Q V V L RD A AG V Q N I G L H L K E V T A A V E N L L Q VGQ N L S A T S K D E I L K K E L P S AGD K I E Q S C T L V NQ A A R A F E P G S QG N I E D K H L M L DG A RG I L S G V S T L L L VWD E S E I R K V L G I C A R I I E Y L S V V E Q V HN I G L H L K E V T A A V E N L L Q VGQ N L S E T S K D E L L K K E L P V AG E K I E Q S C L L V NK A A K A F E P G AQG E V E D K H L M L DG A RG I L S G V S M L L L VWD E S E I R K V L D I CD R I V E Y L S V V E Q V -010 0 0 0 0 0 010 010 0 010 0 020 0 0 0 0 0 - - - 0 0 010 0210 01 10 0 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 0 0 0 - 0 0 0 0 0 0 0 0 0 - - -10 0 010 0210 0 010120 0 040 0 0 0 0 010 0 0 0 0 0 0 0 0 010 0 0 0 0 0 -P D L +-P L VQ A V+A A V E N L V K VG E E T A E T S ++G+D+ I L K Q E M-P S A+E R V E +A S D L L V E +A A R E L K DD S -P C S S +A R R K +++ L I DG A RG I L S G V S D L L L T AD E A E V R K I V K V C R S V E E Y L K V A E V V L ++
helix 0
helix 1
helix 2
- - G NE QD L G I Q Y K A L K P E VD K L N I MA A K RQQ E L K - - - - D VG NRDQMA A A RG I L Q K NV P I L Y T A S Q A C L Q - - - HP D V A A Y K A NRD L I Y K Q L QQ A V T G I S NA AQ A - - QDQQ A L NNA F RQ Y G K D V VG L ND I AMK RQ ND L I - - - - D P A R RD E MA A A R NT L K K NS MM L Y T A S K A F L R - - - HP D V A A A K A NRD Y V Y K Q V CD A V NS L S NT AQ A - - S S QD E L MD NMRQ F G R NAG E L I K Q A A K RQQ E L K - - - - D P Q L RDD L A A A R AM L K K HS T M L L T A S K V Y V R - - - HP E L D L A K V NRD F I L K Q V CD A V NT I S D V AQG - - S NT AD L L NS F K N L G ND L MN L AQ L S G R RQ AD L K - - - - D P L R RD E MA A A R A I L K D A S K M L L S S S K A Y V R - - - HP E V A S A K A NRD F I I S QMNE A V NS I S GG T AQ - - I E F C A L D E I F Q K L R S VMD T L MK Q I A S RQMD L L - - - - D T Q K K D E L G L V R S MWMR C K E R L Y T S S R V A I V - - - HP E L E S G V T NR N L V L Q E I NE S I K K L Q A I I K G - - RD E NS L DQ N L D N F A Y H L DQ VDD A V K R RQ F D L K - - - - D E D K K DQ L S A A R A N L L T A S Q L L NV V S K T H F K - - - Y E N L P P A K A NC A A I T S E I R E F V NR I V T I I Q S - - A S P D E V T Y L Y RG Y G ND L E K L L K L T A R RQ T D V K - - - - S P S I S E K L A L A R L K L K R I NNV L L NS MT L HV K - - - Y P D V A S A K V NRD F A L S Q A S E A V R S I V E S L D E - - I S P E E V VQ L Y QG Y A I D L E N L L K L T T R RQMD V K - - - - S RWV S E K L A F A K V K L R RMGD I L S R S V K L HVQ - - - Y P D I A S A K V NRD F T L S E A T Q A V R S I T E C L D E - - - MK - - - - G NA AQQ L L V A A HT E L K Q C NK I L I T S T K I F L E - - - HP E D P HAQ E NRD Y V I Q RMQ E A V K T I S M L ADG - - NNWDD F V HS MK V V A K E I Q HV S E MA I A RQ K E L K - - - - NS T A K Q L L V A A Y VD L T Q Y NRM L I T S T K A F L Q - - - HP E D E S A I E NR D Y I I T RMS E V L K T I AQ L ADG S T V P S D R L QD V L K S L S E T V V V F AQ L T E A R C K D L K - - - - D P CQ K S DME A S R I T ME HC F R T L MS S I K VM L Q - - - HT S L S I C RMNC L A V ND N F MD T A A L MK L A AG V S P V HVD S L QD S L K Q L S D HMV K L S E I T RG R I QD L K - - - - DG CQ R NE MD C C R VM L E HC F R S F L S A V K V R L Q - - - HS V L S I G RMNCMA VMD N F L E V VG T I T R A A A L - - V S L T E L Y QQ I T Q F T P VMA R L A K L A K Q RQ NE L D C C E D NS C L V E S L S WHR R V L T I G C AM L I S S C K C Y V R - - - HP D I E T A R I NRD F S F D V I L E S S N I I A R I MGD - - L S L Q E L Y Q H I RQ F T P VMAG L T K L A RQ RQ E E L A C C E E NS C L V E S L S WY R R E L AMG C A L L I P S C K C Y V K - - - HP D L Q T S R S T RD F A L E V I L D A A NY I S R I A K E - - E T ME D L V T Y T K N L G P GMT K MA K M I D E RQQ E L T - - - - HQ E HR VM L V N S MNT V K E L L P V L I S AMK I F V T T K NS K - NQG I E E A L K NR N F T V E K MS A E I NE I I R V L Q L - - E T ME D L V T F V K N L T P GMT GMS K MVD A R S K E L T - - - - HQQ HR E S L A H S L Q V V K D L T P V L I S G I K I F V T T R R P Q - G L G I P E A I E NR NY V V NK MS A E I S E I I R V L Q L - - E T ME D L V T F V K N L T P GMT GMS K MVD A R S K E L T - - - - HQQ HR E S L A H S L Q V V K D L T P V L I S G I K I F V T T R R P QDG K G I P E A I E NR NY V V NK MS A E I S E I I R V L Q L - - NT ME Q L VQ F L K D L S P C L S K V HR E VG A R E K E L T - - - - HQ V HS E I L V R C L E Q V K T L A P I L I C S MK V Y I H I V E QQ - G RG A E E A A E NR NY L A A RMS D E L Q E I I R V L Q L - - E E MQD L L T F V A N L S P A I Q NV A K A V E S R A A E L T - - - - HT V HR DM L K S S L S K L S GMV P L L I S S MK A F V K T P P - - - G AG R P E AQ E S R N F I I NK MS A E I T E I I R V L Q L - - G T L E D L S F Y I K N L T P G L T Q V C K A VQ NR AQ E L L - - - - HK P Y AD I L R R E T E Q L K K F A P M L I G A S K S L I NAQ N - - - E E L T NA A HQ N L D NT I E K MNA S MK E I I R V L L M - - T HE AD Y Q T Y T K S V K S A VD N L L I R I R A R ADD L L - - - - I E L NRQ L L K R S C I N I E D A V T S I E S V L K A I I DD - - - NQ E A E P L Q NS RD S F VG I V C E E L E E I I R V L M L - - D V E AD L A T F L Q N L T P GMT S MMK V V E S R HP E L T - - - - N L R HA L M L K D E L R T V R E Q I P I L I S S I K V Y C L V F A K K G A T G L K E AG F G RD HV I T K L Y V S I E E I I R V L Q L - - D V E AD L A T F L Q N L T P GMT S MMK V V E Q R HP E L T - - - - N L A HAQM L K S E L G T V R E Q I P I L I S S I R V C C L V I V K DG S S GMK D A A F G RD Y V I Q K L F I A I E E I I R V L Q L - - Q S ME E L L Q F T K N L S P A I T NMT K Q VDG R R E D L T - - - - NA S HA A I L E D E S E Q V K K G L P L L L S AMK A F V T I K RDG - R K G A E D AQ E NR NY I VG A I T D S I R E I I R V L Q L - - E S I E D V I T F T E N L A P N L T S MV K L VD T R R E E L T - - - - NA S HS A I L E D E L NQ V R K G L P L L L S A L K T L VG L K K T K - S E G I L D AQ E NRD F I VG S L T E S I I E I I R V L Q L - - E I MS D L V I F I K N L T P G L T G L NK L I D NR A K E L T - - - - NP V HA A K L V E HC S NV K K A V P M L I A S V K L V C S L R A S Q - S GD A T D A A S S R S WL MS T I NE D L NE I I R I L Q I - - E I MDD L V T F I K N L T P G A T G L NK L I D NR A K E L T - - - - NP V HA A K L V E HCD HV K K S I P M L I S S I K L V C S L K A S R - S GD V S E A A S S R NWL VG T MNE D L D E I I R I L K I - - RG I P N L I E F I K G L T P S L T E T S K HVD R RQ K E L T - - - - NA T HA A E L VD HCD H L R K F V P M L I S S I K L V S H L E A RG - G A R S R E A ND NRD F V V K S MNE H I E E I I R I L Q L - - RGMP N L V E F V K R L T P S L T E T S K HVD R RQ K E L T - - - - NA S HA A E L V E HCD H L R K F V P M L I S S I K L V S H L E HRG - A A S T K D A V E NRD Y V T R AMNE H I E E I I R I L Q L - - E T Y E E V A T V S S N L Q P GMNS L V NHV R A R ADD L I - - - - E K N L E DM L NS E V R NT E K Y HS V L I S S MQMY V S V R S S P K L E G L L D AQ RG R NC T QGM L VG S I Q E I K R I I L L - - E T HE E V A T V S S N L Q P GMNS L V NHV R A R ADD L I - - - - D K T L QGM L NE E VQ NT E R Y Q S V L MS CMQMY V S V RG S QG P QG L L D AQ RG R NA AQ R T L VD S I NE L K R I L Q L - - 0 0 0 0 010 0 0 0 0 010 0 010 0 0 0 0 0 0 0 030 0382- - - -1 102 232921 12 2 25212 2 2382 26565241- - - 012 21042174324 43262315219325 523
S +E +ME D L V T F +K N L T P GMT G L S K L VD A RQ K E L T C C E +NP +HRD+ L +A A R R+ L K K +V P M L I S S I K ++VQ L R A S QG HP G L E E A+E NRD F V V+K M+E A I NE I I R V L Q L
