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K Q Q E – – K T P Q G G A A A T A A R A A S A A Q R T R Q Q M I L I I I H W H H – – R S Q T R R H G D E E E V N V K V S V Q V R V R L T L L L L L M L I L I E Q E E E E N N N – H H P S P – – – D D S D D D P L S P L S P L S P L A P L S P L S N N K N N N Y F Y L L L F G E L F G E L F G E L F G E T F G E H F G E H 269 D S D S D S D S D S D S L L L L F F A A C T A A C T A A C T A A C T A A C V A A C V Q Q Q Q S S P L W P E E I I V I I I R R R R Q Q E E E E V V Y L C I L L F Q F K F Q F N F R F R Y G C G L L R K R E A E T T S T T T R R K R N N C N S Q N N L L L L A A A E E A T A G G G G R R A D A N A D A D A S A S G P T E N N F F F F I I Y Y Y Y Y Y F F F F A A A Q A A A R A H A R A R A L H A L H A L H A L N A L H A L H P K – P R R K T K K S S D K G Y – – Q N N A R R E G Q Q P P A R A H A C A K A T A T G R G D G R G A G T G T G R G H R C V H V Q V H V N V S V S V V V A V V E T K A R R G Q G Q G H G Q G Q G Q H A Q D N N L V L V L V L I L L L L K M L G V M TRPV4 TRPV1 TRPV2 TRPV3 TRPV5 TRPV6 A) ANK3 D S F G E P L A A C V L * * * * * 315 B) ANK4 L A V A A G F Y G A L TRPV4 TRPV1 TRPV2 TRPV3 TRPV5 TRPV6 I A I I A I I A I I A I I A V I A V * * Supplementary fig. 1. Cross-molecules conservation of amino-acids in ANK3 and ANK4 domains of human TRPV proteins. Blue frame: identical amino-acid; *: similar amino-acid. Red frame: mutated amino-acid in TRPV4; A) R269H/C, B) R315W and R316C. I A