M SN E Y K R I V L L KG L E P L S SH H F S L F K S L L A SD L K L E RHMQ EQ Y T K V Q I AD MM ED E F P - D D M EN E Y K R L V L L EG L E C I N KH Q F N L F K S LM V KD L N L E ED NQ E K Y T T FQ I AN MM V K K F P - AD M V K E Y K R I V L L KG L E C I N KH H F S L F K S L L A RD L S L E RD NQ E K Y S T I Q I AN MM E E K F K - PD M V N E Y K R I V L L RG L E C I N KH Y F S L F K S L L A RD L N L E RD NQ EQ Y T T I Q I AN MM E E K F P - AD M V N E Y K R I V L L RG L E C I N KH Y F S L F K S L L A RD L N L E RD NQ EQ Y T T I Q I AN MM E E K F P - AD M V N H Y K K I V L M F G L E R I ND Y N F R T L K S L L T H D L K L T Q KMQ D D Y D R I K I AD LM E E K F P - ED M V N Y Y KQ I V L L SG L E YMND Y N F RA L K S L L N H D L K L T KNMQ D D Y D R I K I AD LM E E K F P - ED M V N Y C KQ I V L L SG L E YMND Y N F RA L K S L L N H D L K L T KNMQ D D Y D R I N I AD LM E E K F P - ED M V N Y Y KQ I V L L SG L E YMND Y N F RA L K S L L N H D L K L T KNMQ D D Y D R I K I AD LM E E K F P - ED M V N E Y K E I V L I KG L EDMKD Y A F R T I K S L L R K E L N L T K KMQ D D Y D R I Q L AD L L ED K F P - QD MMA E Y KN I V L L KG L ENM ED Y Q F R T V K S L L R K E L K L T K KMQ ED Y D R I Q L AD W I ED K F P - KD - MA E Y K K I V L L KG L E SM ED Y Q F R T V K S L L R K E L K L T K K L Q ED Y D R I Q L AD WM ED K F P - K Y M V N E Y K R I V L L T G LMD I T D H E F KM V KA L L R K E L K L N - KMQ D K Y D R V K I AD LM ED K F P - KD M V N E Y K R I V L L T G LMG I ND H D F RM V K S L L S K E L K L N - RMQ DQ Y D R V K I AD LM ED K F P - KD M V N E Y K R I V L L T G LMG I ND H D F RM V K S L L S K E L K L N - KMQ D E Y D R V K I AD LM ED K F P - KD MAN N Y K K I V L L KG L E V I ND Y H F R I V K S L L S ND L K L N P KMK E E Y D K I Q I AD LM E E K F P - GD MAN N Y K K I V L L KG L E V I ND Y H F R I V K S L L S ND L K L N P KMK E E Y D K I Q I AD LM E E K F P - GD MGK K Y KN I V L L KG L E V I ND Y H F RM V K S L L S ND L K L N L KM R E E Y D K I Q I AD LM E E K F R - GD M E K K Y KN I V L L KG L E V I ND Y H F RM V K S L L S ND L K L N L KM R E E Y D K I Q I AD LM E E K F R - GD M V N E Y K K I L L L KG F E LMD D Y H F T S I K S L L A Y D L G L T T KMQ E E Y N R I K I T D LM E K K FQ - GV M V N E Y K K I L L L KG F E LMD D Y H F T T I K S L L A Y D L G L T T KMQ E E Y N R I K I T D LM E K K FQ - GV M EG E Y K K I I L L KG L E P I ND Y Q F S I V K S V L A RD L G L T ANMQ K E Y N K V K I AD LM E K K F P - GV M EG E Y K K I I L L KG L E P I ND Y Q F S I V K S V L A RD L G L T ANMQ E E Y N K V K I AD LM E K K F P - GV MG S E F K R I V L L KG FQH I KD Y Q F SM I K S L L A RD L R L T SKMQ D D Y D R I K I AD LM E V R Y P - GA MGN E F K R I V L L KG FQHMD D Y H F KM I K S L L A H D L R L T R KMQ E E Y D R I K I AD LM E E R F R - GA MGND Y K K I V L L KG FQH I ND K C F NM I K S L L A H D L K L T R KMQ D E Y D R V K I AD LM E L K F R - G P M T N K Y K K I I L L KG L E K I D E Y H F SM I K S L L A H D L E L T R EMQ D N Y D R V K I AD LM E L K F P - G I M V N E YMK I V L L KG L EH I ND Y Y F N V V K S L L A H D L G L T T KMQ D E Y N R I K I AH L I E E K FQ - GA M V N E YMK I F L L KG L Q P I N E Y R F NM I K S L L A H D L Q L N K KAQ Y GY N R I Q I AD L T ED K F R - GA M V N E Y K K I L L L KG L Q P I S E Y Q F NM V K S V L A H D L Q L N K KAQ Y GY N K I Q I AD LM ED K F P - GA M V N E Y K K I V L L KG L QA I N E Y Q F NM I K S L L A ND L Q L N K K T Q Y E Y D R I Q I AD LM E E K F R - GA M V N E Y K K I L L L KG L EA I ND Y H F H I I K S L L A D D L Q L N K K T Q D GY N R I Q I AD LM E E K FQ - GA M V N E Y K K I V L L KG L E L I SD Y Q F N T I K S L L E ND L Q L T K KM R D E Y N R I Q I AD KM E E T F P - GA M T A E Y K K I V L L KG L E S I ND Y Q F N T I K S L L A RD L Q L T K KMQ D E Y D R I K I AD LM E E K F R - GA MAN E Y K K I V L L KG L EA I D D Y H F N I I K S L L K SD L K L T R KMQ E E Y N R I Q I AD L I E E K F P - G S M V N E Y K K I V L L KG F EA I SD Y H F N T I K S L L A SD L K L T K KMQ D D Y D R I K I AD LM E K K F P - G P M EA E Y K K I I L L KG L EA I KD Y H F D I I K S L L A SD L K L T K KMQ D E Y D R I K I AD L I E V K F P - G P M V N E YQ K I V L L KG L E P I SA Y H F SM V K S L L A H G L Q L T A K PQ D E Y SK I E I A K LMA E K Y R - GA MQ S E F K K I I L L KG L E P I N E Y Q F SM V K F L L A SD L K L T R KAQ N E Y N R I Q I AD LM T EN F P - RA M E S E Y K R I V L L KG L E P I S E Y H F S I V K S L L A H D L K L S R KAQ N E Y N R I Q I AD LM E V K F R - GA MK R E F K K I L L L KG L E P I S E Y H F S I V K S L F A KD L K L T E KAQ N E Y N R I Q I AD LM E E S F P - EG M E S E Y R EM L L L T G L D H I T E E E L K R F K Y F A L T E FQ I A R S T L D V AD R T E L AD H L I Q SA G - A A M E SD F R EM L L L T G L D H I T E E E L K R F K Y L A L T E F N I P R K T L N I AD R T E L AD Q L I Q SA G - A A M E I E Y K E I L L L KG L D D I T D E E L Q K F K F F L R D V L K S S T GK L E KAN R T E V AD LM I QN A GGV I M E SK Y K E I L L L T G L D N I T D E E L D R F K F F L P D E L K V S T A K L EN AN R T E V AN LM I QN V G - A V M E SK Y K E I L L L T G L D G I T D E E L D R F K F F L P D E F D I P KGK L K T A P R T E L AN LM I QN A G - V V M E SK Y K E I L L L T G L D N I T D E E L D R F K F F L S D E F N I A T GK L H T AN R I Q V A T LM I QN A G - A V M E SK Y K E I L L L T G L D N I T D E E L D R F K F F L S D E F N I A T GK L H T AN R I Q V AN LM I QN A G - A V MN K K F G E I - L L SG L E E L QN E D F K K F K F F L S ND C LM - M R V H N - L D R I D L A T CMK KQ L P - C P MM SK L G E I - L L E S L T E L D E E E F K I C K Y H L K N RG L I - I RM E GKGD R T D I A E SMKA K F G - A V MKN A Y GVM - L L RA L D E L G S E E F K K Y K F F L N N EG LM - T R KQ DQAD K T D L SK Y L I E K F G - A L
A G L GK F I K F C AG LD R L I N F C AG L GE L I E F C SG L GK L I A F C SG L GK L I E F C A G L SK L I E VW A G L SK L I E V C A G L SK L I E V C A G L SK L I E V C A G L SK L I E V C AG LD K L I KV C AG LD K L I KV C A G L DQ L I K L Y A GV DQ L I K L Y A GV V Q L I K L Y A G L GK L I E F F A G L GK L I E F F A G L GK L I K I F A G L GK L I Q I F AC LD K L I E LA AC LD K L I E LA ACVNK L I D L F ACVNK L I D L F ACV EK L I D L I ACVDK L I E L V DCVDK L I E L V T CVN I L E E L L ACVNK L I E L L AC LD V RT GL F T C LD I L I E L F AC LD T L I E L F T C LD I L I E L F ACVDK L I E L F A SVD K L I E L F A SVD K L I E L L T CVDK L I E L L A GV N K L I E L L T CVDK L I D L Y T CVDK L I E L Y ACVDA L I K L Y ACVDA L I D L Y SA V T KA I N I F SA V A KA I S I F SA L D K T I A I F SA V T K T I H V F SA V T K T I H I F SA VMK T I R I F SA VMK T I R I F S FMN K F I E I L SA L KH I T N V F PA L KT T I K L F
ED L P A L R K RA E R V P T L K K RA E K V P A L R K RA E E V P A L R K RA E E V P A L R K RA EG I P E F ED H A ED I P E L AD H V ED I P E L A A R V ED I P E L A A R V ES I EELKELT EH I KD L KD L A EH I KD L KD L A K E I PG L RN I A KQ I PG L GD I A KQ I PG L GD I A K E I P T L GD L A K E I P T L GD L A ED I P T L ED L A KD I P T L ED L A KDM P S L KN L V KDM P S L KN L V K EMQD C ED I V K EM P S L T D I V KD I E E L KD L A KG I D D I KH L V K E I D E I KD L A SDM I K Y KD T V KD I P E F KG L F KD I ED L KD L A ED I EG L KD L A ED I EN L KD L A KD I ED L KD L A KDM PQ L KD T V KDM PQ L KD L A KD I P K L E C L V KD I P S L KD I V KD I P S L K E I V KD I P E L K S L V KD I A E L KQ L A KD I A E L K E L A KD I A E L KD L A Q K L - N YMH I A Q K L - N YMD I A Q K L - N YMHQA Q K L - N YMH V A Q R L - K YMH V A Q K L - N YM L L A Q K L - N YM L L A K KM - N L N E T A K KM - N L N E I V KDM - N L N E T A
E I LKRER I Q E I L KK ER S E E I L KK ER S E E I L KK ER S E E I L KK ER S E D T L R K EM E K D I L RKKK EK D I L R K EM E K D I L R K EM E K D N L K R E KA K K K L K T E KA K K K L K T E KA K D T L K KA KA K N K L KN E KA K N K L KN E KA K ET L KR EK L K ET L KR EK L K ET L KK EK L K ET L KK EK L K N N L R K E K SK N N L R K E K SK I N L RN GK R K KQ L RN E K V K KT L RK ER L K K P LQK EK L K KV L RK EK L K K E F RK EK L K K K P R K E KQ K K T F T Y EN T K K T L RH E K I K E T L KQ E K L K K T L KQ E K I K K K L K C E KA K K S L R S E K SK GT L KN E K I K E T L R KQ K SK E I L R R E K SK KN L R S E K L K K T L KN E K L K K T L KN E K L K K T L KH E K L K NA L E EKKK E KA L E E K K K E K I L K E EK EK K S LQ E EK EK KR LQ E EK EK KR LQ E EK EK KR LQ E EK EK K K Y K EQ K E E EN L QA K KAQ Q R I QN E I SK
Supplementary Figure 4. Alignment of pyrin domains from PYHIN proteins. Alignment was performed with ClustalW2, with minor adjustment to position the gaps in accordance with evident gaps in a nucleotide sequence alignment. The pyrin domain is encoded by a single exon in all PYHIN proteins. Sequences were derived from three sources – (i) reference sequences for established genes, (ii) predicted genes in NCBI or Ensembl databases, (iii) de novo exon prediction following identification of sequences homologous to human IFI16 or AIM2 using TBLASTN searches. See Table 1 and Online Resource Table 2 for accession numbers for sequences used.
