Sequence-Structure-Function-Analysis

Naturally occurring single substitutions at GPHRs

Receptor
hTSHR
hLHCGR
hFSHR

Cys-box1LRR0LRR1LRR2LRR3LRR4LRR5LRR6LRR7LRR8LRR9Cys-box2Cys-box3TMH1ICL1TMH2ECL1TMH3ICL2TMH4ECL2TMH5ICL3TMH6ECL3TMH7Helix8
M R P A D L L Q L V L L L D L ------P R D L G G M G ----C S S P P C E C H Q E E D F R V T C K D I Q --R I P S -L P P S T Q T L K L I E T H L R T I P S H A F S N L P N I S R I Y V S I D V T L Q Q L E S H S F Y N L S K V T H I E I R N T R N L T Y I D P D A L K E L P L L K F L G I F N T G L K M F P D L T K V Y S T D I F F I L E I T D N P Y M T S I P V N A F Q G L C N E T L T L K L Y N N G F T S V Q G Y A F N G T K L D A V Y L N K N K Y L T V I D K D A F G G V Y S G P S L L D V S Q T S V T A L P S K G L E H L K E L I A R N T W T L K K L P L S L S F L H L T R A D L S Y P S H C C A F K N Q K K I R G I L E -S L M ------C N E S S M Q S L R Q R K S V N A L N S P L H Q E Y E E N L G D S I V G Y K E K S K F Q D T H N N A H Y Y V F F E E Q E D E I I G F G Q E L K N P Q E E T L Q A F D S H Y D Y T I C G D S E D M V C T P K S D E F N P C EDIMGYKFLRIVVWFVSLLALLGNVFVLLILLTSH Y K LNVPRFLMCNLAFADFCMGMYLLLIASVDLYTHSEYY N H A I D W Q T GPGCNTAGFFTVFASELSVYTLTVITLERWYAITF A M R L D R K IRLRHACAIMVGGWVCCFLLALLPLVG I S S Y A K V S I C L P M D T E TPLALAYIVFVLTLNIVAFVIVCCCYVKIYITVRN P Q Y N P GDKDTKIAKRMAVLIFTDFICMAPISFYALSAILN K P L I T VSNSKILLVLFYPLNSCANPFLYAIFTKAFQRDVFILLSK F G I C K R Q A Q A Y R G Q R V P P K N S T D I Q V Q K V T H D M R Q G L H N M E D V Y E L I E N S H L T P K K Q G Q I S E E Y M Q T V L
M K Q R F S A L Q L L K L L L L L Q P P L P R A L R E A L ----C P -E P C N C V P --D G A L R C P G P T ---------A G L T R L S L A Y L P V K V I P S Q A F R G L N E V I K I E I S Q I D S L E R I E A N A F D N L L N L S E I L I Q N T K N L R Y I E P G A F I N L P R L K Y L S I C N T G I R K F P D V T K V F S S E S N F I L E I C D N L H I T T I P G N A F Q G M N N E S V T L K L Y G N G F E E V Q S H A F N G T T L T S L E L K E N V H L E K M H N G A F R G A -T G P K T L D I S S T K L Q A L P S Y G L E S I Q R L I A T S S Y S L K K L P S R E T F V N L L E A T L T Y P S H C C A F R N L P T K E Q N F S H S I S E N F S K Q C -E S T V R K V N N K T L Y S S M ------------------------------------------------------L A E S E L S G W D --Y E Y G F C L P -K T P R C A P E P D A F N P C EDIMGYDFLRVLIWLINILAIMGNMTVLFVLLTSR Y K LTVPRFLMCNLSFADFCMGLYLLLIASVDSQTKGQYY N H A I D W Q T GSGCSTAGFFTVFASELSVYTLTVITLERWHTITY A I H L D Q K LRLRHAILIMLGGWLFSSLIAMLPLVG V S N Y M K V S I C F P M D V E TTLSQVYILTILILNVVAFFIICACYIKIYFAVRN P E L M A TNKDTKIAKKMAILIFTDFTCMAPISFFAISAAFK V P L I T VTNSKVLLVLFYPINSCANPFLYAIFTKTFQRDFFLLLSK F G C C K R R A E L Y R R K D F S A Y T S N C K N G F T G S N K P S Q S T L K L S T L H C Q G T A L L D K T R Y T E C ----------
M A L L L V S L L A F L S L G S G ----------------C H H R I C H C S ---N R V F L C Q E S K V T E I P S D L P R N A I E L R F V L T K L R V I Q K G A F S G F G D L E K I E I S Q N D V L E V I E A D V F S N L P K L H E I R I E K A N N L L Y I N P E A F Q N L P N L Q Y L L I S N T G I K H L P D V H K I H S L Q -K V L L D I Q D N I N I H T I E R N S F V G L S F E S V I L W L N K N G I Q E I H N C A F N G T Q L D E L N L S D N N N L E E L P N D V F H G A -S G P V I L D I S R T R I H S L P S Y G L E N L K K L R A R S T Y N L K K L P T L E K L V A L M E A S L T Y P S H C C A F A N W R R Q I S E L -H P I -------C N K S I L R Q -E V D Y M T Q T R G ---------------------------------------Q R S S L A E D N -E S S Y S R G F D M T Y T E --F D Y D L C N E V V D V T C S P K P D A F N P C EDIMGYNILRVLIWFISILAITGNIIVLVILTTSQ Y K LTVPRFLMCNLAFADLCIGIYLLLIASVDIHTKSQYH N Y A I D W Q T GAGCDAAGFFTVFASELSVYTLTAITLERWHTITH A M Q L D C K VQLRHAASVMVMGWIFAFAAALFPIFG I S S Y M K V S I C L P M D I D SPLSQLYVMSLLVLNVLAFVVICGCYIHIYLTVRN P N I V S SSSDTRIAKRMAMLIFTDFLCMAPISFFAISASLK V P L I T VSKAKILLVLFHPINSCANPFLYAIFTKNFRRDFFILLSK C G C Y E M Q A Q I Y R T E T S S T V H N T H P R N G H C S S A P R V T N G S T Y I L V P L S H L A Q N -----------------

Annotation

Conserved Residue in TMH

Transmembrane Helix

		- activating mutations
		- inactivating mutations
		- activating and inactivating mutations are known

Extracellular Cysteine boxes

Receptor	Cys-box1	Cys-box2	Cys-box3
hTSHR	24-41	283-301	390-408
hLHCGR	30-44	279-304	336-353
hFSHR	18-32	275-292	338-356