Bestrophin – VMD2Last update: 07.01.13

The sequence is given according to Genebank: NC_000011, NM_004183, AF139813

Exons are taken from (1), Primers are given according to (1), Nucleotide numbering, Aminoacid numbering

Sequence variations:

Polymorphism,

rare variant,

VMD2,

AVMD,

AMD,

Drusen

Bull’s Eye Maculopathy

VMD2 + AVMD

VMD2 + AMD

Bull’s Eye Maculopathy + AVMD

Drusen + AMD

Drusen+VMD

ARB

VCRP

Multifocal vitelliform Dystrophy

LCA

Retinal Dystrophy

RP like

R: RFP-TM domain [16]

r: invariant RFP motif

T: predicted transmembrane domain [16]

K: KVAE-x-L-[IL]-NP-[FLM]-GEDDDDFE-[TFLVC]-N-x(2)-[IVL]-DRN sequence

S: src-motif binding Cav-subunit

P: Phosphorylation site

C: important rundown of current

Ca: Predicted Ca-binding loop

A: acidic domain

Cg: Channel gating

|------> TU15-Ex0_F

-370 -360 -350 -340 -330 -320 -310 -300

agcc caaca ccctc caaga agaaa ttaga ggggc catgg ccagg ctgtg ctagc cgttg cttct gagca gatta

tcgg gttgt gggag gttct tcttt aatct ccccg gtacc ggtcc gacac gatcg gcaacg aaga ctcgt ctaat

t (1,2) c (0) (1,2,13) t

-290 | -280 | -260 -250 -240 -230 |

caaga aggga ctaag acaag gactc ctttg tggag gtcct ggctt aggga gtcaa gtgac ggcgg ctcag cactc

gttct tccct gattc tgttc ctgag gaaac acctc cagga ccgaa tccct cagtt cactg ccgcc gagtc gtgag

t (33)

-220 -210 -200 -190 | -180 -170 -160 -150

acgtg ggcag tgcca gcctc taaga gtggg caggg gcact ggcca cagag tccca gggag tccca ccagC CTAGT

tgcac ccgtc acggt cggag attct caccc gtccc cgtga ccggt gtctc agggt ccctc agggt ggtcG GATCA

t(13)

-140 -130 | -110 -100 -90 -80 |-

CGCCA GACCT TCTGT GGGAT CATCG GACCC ACCTG GAACC CCACC Tgtga gtaca aggtg cccca ggtgg actcc

GCGGT CTGGA AGACA CCCTA GTAGC CTGGG TGGAC CTTGG GGTGG Acact catgt tccac ggggt ccacc tgagg

TU15-Ex0_R <------|

------> TU15-Ex1_F

-70 -60 -50 -40 -30 -20 -10

ctaca aaccc ccaat cggtg tccct ctcta ccagG ACCCA AGCCC ACCTG CTGCA GCCCA CTGCC TGGCC

gatgt ttggg ggtta gccac aggga gagat ggtcC TGGGT TCGGG TGGAC GACGT CGGGT GACGG ACCGG

G=Ala (47)

|T=Ile (47)

|A=Asn (37)

|| C=Thr (35)

|| | G=Ala (39)

|| | |T=Ile (47)

|| | || C=His (47)

|| | || | A=ter (45)

|| | || ||G=Ala (19)

|| | || ||C=Pro(2,4,12,41,42)

|| | || | | |G=Arg (3,47)

|| | || | | |A=Lys (47)

|| | || |||| A=Met (1,2,47)

|| | || | | || C=Leu (47)

|| | || |||| |A=Glu (21)

|| | || |||| |C=Ala (4,5,12,39,47)

|| | || |||| || A=Thr (1,2,47)

|| | || |||| || |T=Val (12,47)

|| | || |||| || || T=Ile (14)

|| | || | | || || || | T=Cys (47)

|| | || | | || || || | |C=Pro (47)

|| | || |||| || || | |A=His (7)

|| | || |||| || || | || A=Asp (39)

|| | || |||| || || | || | A=Tyr (18,42)

|| | || | ||| || || | || | T=Phe (6,47)

|| | || | | || || || | || | | C=Ser (47)

|| | || || || || || | || | | G=Cys (3,6,47)

|| | || | | || || || | || | | | T=Leu (47)

|| | || | | || || || | || | | | | G=Val (56)

|| | || | | || || || | || | | | | | G=Val(2)

1 || | || | | || || || | || | | | | |60 |

ATG ACC ATC ACT TAC ACA AGC CAA GTG GCT AAT GCC CGC TTA GGC TCC TTC TCC CGC CTG CTG CTG

TAC TGG TAG TGA ATG TGT TCG GTT CAC CGA TTA CGG GCG AAT CCG AGG AAG AGG GCG GAC GAC GAC

Met Thr Ile Thr Tyr Thr Ser Gln Val Ala Asn Ala Arg Leu Gly Ser Phe Ser Arg Leu Leu Leu

M T I T Y T S Q V A N A R L G S F S R L L L

1 5 10 15 20

TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

T=Cys (1,3,44,47)

| T=Trp (3,47)

| |A=Gln (1)

| || C=Arg (14)

| || | G=Arg (2)

| || | | C=His (14)

| || | | |G=Cys (23)

| || | | ||G=ter (24,42)

| || | | ||T=Tyr (7) A=Lys (21)

| || | | ||| G=Arg (3,47) |

| || | | ||| |C=Asn (47) | C=Leu (1,4,10) C=Pro (14,18)

| || | | ||| || | | 120 |

TGC TGG CGG GGC AGC ATC TAC AAG CTG CTA TAT GGC GAG TTC TTA ATC TTC CTG CTC TGC TAC TAC

ACG ACC GCC CCG TCG TAG ATG TTC GAC GAT ATA CCG CTC AAG AAT TAG AAG GAC GAG ACG ATG ATG

Cys Trp Arg Gly Ser Ile Tyr Lys Leu Leu Tyr Gly Glu Phe Leu Ile Phe Leu Leu Cys Tyr Tyr

C W R G S I Y K L L Y G E F L I F L L C Y Y

25 30 35 40

TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

T=Cys (47,50

|A=His (2,42)

135 || 152

ATC ATC CGC TTT ATT TAT AG gtaaa gctgg caggg ctggg ccggg gggcc tggga aggat gtggc tgg

TAG TAG GCG AAA TAA ATA TC cattt cgacc gtccc gaccc ggccc cccgg accct tccta caccg acc

Ile Ile Arg Phe Ile Tyr Arg TU15-Ex1_R <------|

I I R F I Y R

45 50 51

TTTTTTT

IVS 2 (3043 bp)

(3) Thr=A

|------> TU-Ex2_F 153 |

ag tctca gccat ctcct cgctg cgtcc acaca attcc acccc caccc ccacc cccag G CTG GCC CTC ACG

tc agagt cggta gagga gcgac gcagg tgtgt taagg tgggg gtggg ggtgg gggtc C GAC CGG GAG TGC

Arg Leu Ala Leu Thr

R L A L T

51 55

C=Leu (13)

| G=Trp (0)

| | T=Ser (0)

| | | G=Asp (47)

| | || G=Val (4)

| | || |A=Asn (6,42)

| | || ||A=Ile (3,6,7,13)

| | || ||| A=Gln (13)

| | || ||| | T=Phe (37)

| | || ||| | | G=Val(47)

T=Leu (2) | | || ||| | | |A=Asn(47)

| 180 195 | | 210 || ||| || ||

GAA GAA CAA CAG CTG ATG TTT GAG AAA CTG ACT CTG TAT TGC GAC AGC TAC ATC CAG CTC ATC CCC

CTT CTT GTT GTC GAC TAC AAA CTC TTT GAC TGA GAC ATA ACG CTG TCG ATG TAG GTC GAG TAG GGG

Glu Glu Gln Gln Leu Met Phe Glu Lys Leu Thr Leu Tyr Cys Asp Ser Tyr Ile Gln Leu Ile Pro

E E Q Q L M F E K L T L Y C D S Y I Q L I P

60 65 70 75

TTTTTTTTTTTTTTTTTTTTTTTT

G=Leu (21,47)

A=Leu (3)

| A=Met (47)

| | G=Val (12,41,56)

| | | 247

ATT TCC TTC GTG CTG G gtgag ttccc ccttc tggct gttcc gggtc cctgt ggccg cccag gctcc agaca

TAA AGG AAG CAC GAC C cactc aaggg ggaag accga caagg cccag ggaca ccggc gggtc cgagg tctgt

Ile Ser Phe Val Leu Gly TU15-Ex3_F <------

I S F V L G

80 83

TTTTTTTTTTTTTTTTTTTTTTT

ggcca gggga ggatc acgag gagct g

ccggt cccct cctag tgctc ctcga c

----|

IVS 3 (337 bp)

t (14) t

|------> TU15-Ex3_F | |

ag aaagc tggag gagcc gaggc atcgc cgggc gctgg gccct gggct ctggc cgcag cctgg cccct cgccc

tc tttcg acctc ctcgg ctccg tagcg gcccg cgacc cggga cccga gaccg gcgtc ggacc gggga gcggg

G=Val (47)

| C=His (4,5,12,47,55,56)

| | A=Met (25,42,46,47)

| | | T=Ile (3,47)

| | | | G=Gly (39)

| | | | T=Cys (12,42,47)

| | | | A=Ser (2,42)

| | | | |A=His (6,56)

| | | | || CC=Pro (50)

| | | | || C=Arg (47)

| | | | || | C=Cys(4,7,12,42,47)

| | | | || | | (12) His=C

| | | | || | | (56, |

| | | | || | | 47) Arg=G|

t(14) t (14) | | | C=Ala(9)| || | |(47) Glu=G||

| | | | | |----del-(17,42,47)--| |||

| | 248 | | | | | 270 | || | | 285|||

ctcgc ccccc gcccc tcctg cccag GC TTC TAC GTG ACG CTG GTC GTG ACC CGC TGG TGG AAC CAG TAC

gagcg ggggg cgggg aggac gggtc CG AAG ATG CAC TGC GAC CAG CAC TGG GCG ACC ACC TTG GTC ATG

Gly Phe Tyr Val Thr Leu Val Val Thr Arg Trp Trp Asn Gln Tyr

G F Y V T L V V T R W W N Q Y

83 85 90 95

TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

C=His (56)

T=Tyr (47)

| A=Lys (2,22,42,47)

|| G=Arg (2)

| | | A=Thr (3,47,51)

| | | |T=Leu (47)

| | | || C=Arg (14)

| | | || | C=His (14)

| | | || | | A=Glu (4,5,12,42) G=Leu (26)

| | | || | | | T=Cys (3,42) | (42,3,8,13) Gln=C

| | | || | | || 330 | 345 |

GAG AAC CTG CCG TGG CCC GAC CGC CTC ATG AGC CTG GTG TCG GGC TTC GTC GAA GGC AAG GAC GAG

CTC TTG GAC GGC ACC GGG CTG GCG GAG TAC TCG GAC CAC AGC CCG AAG CAG CTT CCG TTC CTG CTC

Glu Asn Leu Pro Trp Pro Asp Arg Leu Met Ser Leu Val Ser Gly Phe Val Glu Gly Lys Asp Glu

E N L P W P D R L M S L V S G F V E G K D E

100 105 110 115

A=Ser (48)

| G=Lys (3,47)

| | G=Val (27)

| | | A=Ser(3,12,47)

| | | | (52,51,47,42,18,3) His=A

| | | | 53 (52,47,2) Ser=A|

| | | | (47,3) Arg=G ||

| || | (36) Val=G| ||

360 375 | || | || ||

CAA GGC CGG CTG CTG CGG CGC ACG CTC ATC CGC TAC GCC AAC CTG GGC AAC GTG CTC ATC CTG CGC

GTT CCG GCC GAC GAC GCC GCG TGC GAG TAG GCG ATG CGG TTG GAC CCG TTG CAC GAG TAG GAC GCG

Gln Gly Arg Leu Leu Arg Arg Thr Leu Ile Arg Tyr Ala Asn Leu Gly Asn Val Leu Ile Leu Arg

Q G R L L R R T L I R Y A N L G N V L I L R

120 125 130 135 140

TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

T=Phe (47)

| G=Gly (45)

| |A=Asn (37)

| || AA=Lys(8,13,20,42,47)

| || || T=ter (3,42)G=Ala (28,42,47)

| || 435|| | 450 | 465 481

AGC GTC AGC ACC GCA GTC TAC AAG CGC TTC CCC AGC GCC CAG CAC CTG GTG CAA GCA G gtggg cggac

TCG CAG TCG TGG CGT CAG ATG TTC GCG AAG GGG TCG CGG GTC GTG GAC CAC GTT CGT C caccc gcctg

Ser Val Ser Thr Ala Val Tyr Lys Arg Phe Pro Ser Ala Gln His Leu Val Gln Ala Gly

S V S T A V Y K R F P S A Q H L V Q A G

145 150 155 161

TTTTTTTTTTTTTTTTTTTTTTTTTTT

rrrrrrrrrrr

cggga gcaac gggga ggcac cgggc agagc caggg gccga gatgg gcgcg gcagg aatgg aagat gggtg ga

gccct cgttg cccct ccgtg gcccg tctcg gtccc cggct ctacc cgcgc cgtcc ttacc ttcta cccac ct

TU15-Ex3_R <------|

IVS 4 (755 bp)

t (2,4,13)

|------> TU15-Ex_F | 482 495

gcca tccct tctgc aggtt ctccc accca ccgcc ttctt cactc cactc tgcag GC TTT ATG ACT CCG GCA

cggt aggga agacg tccaa gaggg tgggt ggcgg aagaa gtgag gtgag acgtc CG AAA TAC TGA GGC CGT

Gly Phe Met Thr Pro Ala

G F M T P A

161 165

del (47,51)

510 525 |-| 540 555

GAA CAC AAG CAG TTG GAG AAA CTG AGC CTA CCA CAC AAC ATG TTC TGG GTG CCC TGG GTG TGG TTT

CTT GTG TTC GTC AAC CTC TTT GAC TCG GAT GGT GTG TTG TAC AAG ACC CAC GGG ACC CAC ACC AAA

Glu His Lys Gln Leu Glu Lys Leu Ser Leu Pro His Asn Met Phe Trp Val Pro Trp Val Trp Phe

E H K Q L E K L S L P H N M F W V P W V W F

170 175 180 185

|- del (47)-|

C=Thr (36) |

| A=Leu (3,0)

T=Val (3,17,42,47,50) | | A=Ile(3)

insTGG (18,41,42) T=ter (2) | | | |A=Gln (14)

C=Pro (23,50) | | C=Thr (3,47) | | | || A=Asn

570 | | | | | || || |(2,22)

GCC AAC CTG TCA ATG AAG GCG TGG CTT GGA GGT CGA ATC CGG GAC CCT ATC CTG CTC CAG AGC CTG

CGG TTG GAC AGT TAC TTC CGC ACC GAA CCT CCA GCT TAG GCC CTG GGA TAG GAC GAG GTC TCG GAC

Ala Asn Leu Ser Met Lys Ala Trp Leu Gly Gly Arg Ile Arg Asp Pro Ile Leu Leu Gln Ser Leu

A N L S M K A W L G G R I R D P I L L Q S L

190 195 200 205 210

c(2)

636|

CTG AAC gtgag cccac tgtac agaca gggct gccgc

GAC TTG cactc gggtg acatg tctgt cccga cggcg

Leu Asn TU15-Ex4_R <------|

L N

212

IVS 5 (311 bp)

(47) Pro=C

(4) Arg=C |

(56,47,3,6) His=A| |

(47,1,6,7,42) Cys=T|| |

(29) Gly=G|| |

(2,12,42) Ser=A|| |

(23) Phe=T||| |

(8,13,20,42) Ile=T | ||| |

A=Lys (47) | | ||| |

t (3) |G=Gly(21,51)| |||| |

|------> TU15-Ex5_F | 637| 645 | |||| |

g gggca ggtgg tgttc agaac cccat ccccc tcttc tgccc cccag GAG ATG AAC ACC TTG CGT ACT CAG

c cccgt ccacc acaag tcttg gggta ggggg agaag acggg gggtc CTC TAC TTG TGG AAC GCA TGA GTC

Glu Met Asn Thr Leu Arg Thr Gln

E M N T L R T Q

213 215 220

T=Phe (47)

| G=Trp (11)

|| A=Glu (27,42)

|| T=Val(3)

|| | A=Met (2)

|| | | T=Pro (3,47)

|| | || A=Asn (4,12,41,42,47)

|| | || |T=Phe (30)

|| | || |G=Cys (1,3,47)

|| | || || A=Asn (36)

|| | || || | A=Asn (47)

|| | || || | C=Thr (39)

|| | || || | | C=Thr (27)

|| | || || | | |G=Arg (2,22)

|| | || || | | || A=Asn (30)

|| | || || | | || |A=Ile (3,13)

|| | || || | | || || T=Leu (47)

|| | || || | | || || A=Gln (27)

|| | || || | | || || G=Ala (53)

|| | || || | | || || | G=Val (21)

|| | || || | | || || | | A=Met (1)

|| | || || | | || || | | C=Leu(6)

| | || || | | || || | | |C=Ala (35,42)

|| || || | | || || | | ||

|| | || || | | || || | | || G=Cys (25,42)

|| | || || | | || || | | || | T=Ser (30)

|| | || || | | || || | | || | |G=Arg (2,22)

|| | || || | | || || | | || | || a (47)

|| | || 675 || | | || || | | || | || 714|

TGT GGA CAC CTG TAT GCC TAC GAC TGG ATT AGT ATC CCA CTG GTG TAT ACA CAG gtgag gacta ggctg

ACA CCT GTG GAC ATA CGG ATG CTG ACC TAA TCA TAG GGT GAC CAC ATA TGT GTC cactc ctgat ccgac

Cys Gly His Leu Tyr Ala Tyr Asp Trp Ile Ser Ile Pro Leu Val Tyr Thr Gln <------

C G H L Y A Y D W I S I P L V Y T Q

225 230 235 238

TTTTTTTTTTTTTTTTTTT

gtgag gctgc c

cactc cgacg g

------| TU15Ex5_R

IVS 6 (599 bp)

(46,14) Asn=A

(14) Val=C |

(55,25) Met=A

ins tcc (13) | | |

| del (13) |-----| | | |

|------> TU15-Ex6_F | del (1) |------| 715 | |

tgat ttcag ggttc ccacc tagcc ctttg ctacc acatc ctcct cctcc tcctc ctcct cccag GTG GTG ACT

acta aagtc ccaag ggtgg atcgg gaaac gatgg tgtag gagga ggagg aggag gagga gggtc CAC CAC TGA

Val Val Thr

V V T

239 240

RRRRRRRRRRR

TTTTTTTTTTT

A=Met (31)

| A=Thr (3,42,47)

| |T=Val (2,22,41,42,47,56) T=Trp (37) del (14,57)

| || 735 750 | |

GTG GCG GTG TAC AGC TTC TTC CTG ACT TGT CTA GTT GGG CGG CAG TTT CTG AAC CCA GCC AAG GCC

CAC CGC CAC ATG TCG AAG AAG GAC TGA ACA GAT CAA CCC GCC GTC AAA GAC TTG GGT CGG TTC CGG

Val Ala Val Tyr Ser Phe Phe Leu Thr Cys Leu Val Gly Arg Gln Phe Leu Asn Pro Ala Lys Ala

V A V Y S F F L T C L V G R Q F L N P A K A

245 250 255 260

TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

G=Arg (47)

| A=Ile (3,42,47) (47) Cys=G

| | G=Leu (3,47) (3,42,47) del |

795 810 | | | 840 |-| | 855

TAC CCT GGC CAT GAG CTG GAC CTC GTT GTG CCC GTC TTC ACG TTC CTG CAG TTC TTC TTC TAT GTT

ATG GGA CCG GTA CTC GAC CTG GAG CAA CAC GGG CAG AAG TGC AAG GAC GTC AAG AAG AAG ATA CAA

Tyr Pro Gly His Glu Leu Asp Leu Val Val Pro Val Phe Thr Phe Leu Gln Phe Phe Phe Tyr Val

Y P G H E L D L V V P V F T F L Q F F F Y V

265 270 275 280 285

TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

A=ter (23,50)g (47)

| 867 |

GGC TGG CTG AAG gtggg cctct ccagg gccct gctgg gctgg aggca tggcc agagg ggtca tggcc agcag

CCG ACC GAC TTC caccc ggaga ggtcc cggga cgacc cgacc tccgt accgg tctcc ccagt accgg tcgtc

Gly Trp Leu Lys TU15-Ex6_R <-

G W L K

289

TTTTTTTTTTT KKK

ctgcc tgaga cgagg atg

gacgg actct gctcc tac

------<

IVS 7 (1046 bp)

(47) g

TU15-Ex7_F |------> |

gctg aggtt taaag gggga agctg gcttt gagga gttct gcctg agggt ttaca gagcc tcacc tgtcc ccaag

cgac tccaa atttc cccct tcgac cgaaa ctcct caaga cggac tccca aatgt ctcgg agtgg acagg ggttc

A=Lys (32,47)

| A=Lys (12,42,44)

| | C=His (27,42)

| | | T=Phe (57)

| | | G=Val (14)

| | | | G=Val (47)

| | | | |C=Thr (15)

| | | | || G=Asp (23)

| | | | || C=His (3,47)

| | | | ||--|del(1,2,42,47)

| | | | || |G=Ser (6,47,56)

| | | | || ||A=Lys (18,42)

| | | | || ||| G=Ala (1,3,47)

| | | | || ||| T=Ser (13,34,47)

| | | | || ||| | C=Ser (14,42)

| | | | || ||| | | A=Arg (41,43)

| | | | || ||| | | |A=Glu (4,12,42)

| | | | || ||| | | |C=Ala (41)

| | | | || ||| | | || A=Lys (3,47)

| | | | || ||| | | || | C=Asp (3,7,13,34,42,47)

| | | | || ||| | | || | | |-| del (3,47)

| | | | || ||| | | || | | A=Asn (2,47)

| | | | || ||| | | || | | |G=Gly (37)

| | | | || ||| | | || | | ||G=Glu (7,38,42,47)

| | | | || ||| | | || | | ||| T=Asn (56)

| | | | || ||| | | || | | ||| C=His (10)

| | | | || ||| | | || | | ||| |T=Val (3,47)

| | | | || ||| | | || | | ||| |C=Ala (47,56)

| | | | || ||| | | || | | ||| |G=Gly (3,47)

| | | | || ||| | | || | | ||| |------| del (18,41) (2) Val=T

| | | | || ||| | | || | | ||| || G=Gly (47) (22,2) Gly=G|

| | | | || ||| | | || | | ||| || |A=Glu (10) (47,22,2) Gly=G ||

| | | | || ||| | | || | | ||| || ||A=Asn (47) (47) Thr=C ||

| | | | || ||| | | || | | ||||| |||T=Val (21) | ||

| | | | || ||| | | || | | ||| || || ||| A=Tyr (47) | ||

| | | | || ||| | | || | | ||| || || ||| C=Ser (1,47,54) | ||

| | | | || ||| | | || | | ||| || || ||| | G=Gly (3,47) | ||

| | | | || ||| | | || | | ||| || || ||| | |C=Asp (3,47) | ||

| | | | || ||| | | || | | ||| || || ||| | || G=Ala (3,47) | ||

| | | | || ||| | | || | | ||| || || ||| | || |T=Ile (3,7,42,47)|

| | | | || ||| | | || | | ||| || || ||| | || || G=Ser (10) ||

| | | | || ||| | | || | | ||| || || ||| | || || | C=Arg(47)||

| | | | || ||| | | || | | ||| || || ||| | || || | | | ||

| | | | || ||| | | || | | ||| || || ||| | || || | | | ||

| | | | || ||| | | || | | ||| || || ||| | || || | | | ||

| | | | || ||| | | || | | ||| || || ||| | || || | | | ||

868 | | | | ||--||| | | || | | |-| || ||||| | || || | | | ||

GTG GCA GAG CAG CTC ATC AAC CCC TTT GGA GAG GAT GAT GAT GAT TTT GAG ACC AAC TGG ATT GTC

CAC CGT CTC GTC GAG TAG TTG GGG AAA CCT CTC CTA CTA CTA CTA AAA CTC TGG TTG ACC TAA CAG

Val Ala Glu Gln Leu Ile Asn Pro Phe Gly Glu Asp Asp Asp Asp Phe Glu Thr Asn Trp Ile Val

V A E Q L I N P F G E D D D D F E T N W I V

290 295 300 305 310

TTTTTTTTTTTTTTTTTTTTTTT

KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK

AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

A=Asn (2,18,42,47,51)

|C=Glu (48,56)

|| C=Pro (47)

|| |T=His (47)

|| 948

GAC AGG AAT TTG CAG gtatg gggag aggga gagaa accat accat ggacc ttccc caaag tggac ccaaa

CTG TCC TTA AAC GTC catac ccctc tccct ctctt tggta tggta cctgg aaggg gtttc acctg ggttt

Asp Arg Asn Leu Gln <------| TU15-Ex7_R

D R N L Q

315 316

KKKKKKKKKKK

CaCaCaCaCaCaCaCaCaCa

IVS 8 (179 bp)

del (3)

|------> TU15-Ex8_F |

cct ccaag tcatc aggca catac aaggt cctgc ctggg atgat ctttc tgtgg gactt cttct gtccc tggtg

gga ggttc agtag tccgt gtatg ttcca ggacg gaccc tacta gaaag acacc ctgaa gaaga caggg accac

A=Met (18,42) C=Thr (18,42)

949 960 | 990 1005

accag GTG TCC CTG TTG GCT GTG GAT GAG ATG CAC CAG GAC CTG CCT CGG ATG GAG CCG GAC ATG TAC

tggtc CAC AGG GAC AAC CGA CAC CTA CTC TAC GTG GTC CTG GAC GGA GCC TAC CTC GGC CTG TAC ATG

Val Ser Leu Leu Ala Val Asp Glu Met His Gln Asp Leu Pro Arg Met Glu Pro Asp Met Tyr

V S L L A V D E M H Q D L P R M E P D M Y

317 320 325 330 335

CaCaCaCaCaCaCaCaCaCaCaCaCaCaCa SSSSSSSSSSSSSSSSS

T=Pro (2,4)

| A=Glu (13) T=Val (0)

1020 | | 1035 1050 1065 |

TGG AAT AAG CCC GAG CCA CAG CCC CCC TAC ACA GCT GCT TCC GCC CAG TTC CGT CGA GCC TCC TTT

ACC TTA TTC GGG CTC GGT GTC GGG GGG ATG TGT CGA CGA AGG CGG GTC AAG GCA GCT CGG AGG AAA

Trp Asn Lys Pro Glu Pro Gln Pro Pro Tyr Thr Ala Ala Ser Ala Gln Phe Arg Arg Ala Ser Phe

W N K P E P Q P P Y T A A S A Q F R R A S F

340 345 350 355

PPPPPPPPPPPPP

CgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCg

|-del (47)--|

1080 1095 1100 |

ATG GGC TCC ACC TTC AAC ATC AG gtgtg gccag agcca ggggg ctggg tggga agccc ctcct agtgc

TAC CCG AGG TGG AAG TTG TAG TC cacac cggtc tcggt ccccc gaccc accct tcggg gagga tcacg

Met Gly Ser Thr Phe Asn Ile Ser TU15-Ex8_R <------

M G S T F N I S

360 365 367

CgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCg

agggg tctgc ctag

tcccc agacg gatc

------|

IVS 9 (2116 bp)

insG (47)

|------> TU15-Ex9_F1 1101 1110 | 1125

actgg ctcag ccctg catct cctgt ttctt tccag C CTG AAC AAA GAG GAG ATG GAG TTC CAG CCC AAT

tgacc gagtc gggac gtaga ggaca aagaa aggtc G GAC TTG TTT CTC CTC TAC CTC AAG GTC GGG TTA

Ser Leu Asn Lys Glu Glu Met Glu Phe Gln Pro Asn

S L N K E E M E F Q P N

367 370 375

CCCCCCCCCCCCCCCCC

CgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCgCg

1140 1155 1170 1185 1200

CAG GAG GAC GAG GAG GAT GCT CAC GCT GGC ATC ATT GGC CGC TTC CTA GGC CTG CAG TCC CAT GAT

GTC CTC CTG CTC CTC CTA CGA GTG CGA CCG TAG TAA CCG GCG AAG GAT CCG GAC GTC AGG GTA CTA

Gln Glu Asp Glu Glu Asp Ala His Ala Gly Ile Ile Gly Arg Phe Leu Gly Leu Gln Ser His Asp

Q E D E E D A H A G I I G R F L G L Q S H D

380 385 390 395 400

CgCgCg

1215 1230 1245 1260

CAC CAT CCT CCC AGG GCA AAC TCA AGG ACC AAA CTA CTG TGG CCC AAG AGG GAA TCC CTT CTC CAC

GTG GTA GGA GGG TCC CGT TTG AGT TCC TGG TTT GAT GAC ACC GGG TTC TCC CTT AGG GAA GAG GTG

His His Pro Pro Arg Ala Asn Ser Arg Thr Lys Leu Leu Trp Pro Lys Arg Glu Ser Leu Leu His

H H P P R A N S R T K L L W P K R E S L L H

405 410 415 420

1275 1290 1305 1320

GAG GGC CTG CCC AAA AAC CAC AAG GCA GCC AAA CAG AAC GTT AGG GGC CAG GAA GAC AAC AAG GCC

CTC CCG GAC GGG TTT TTG GTG TTC CGT CGG TTT GTC TTG CAA TCC CCG GTC CTT CTG TTG TTC CGG

Glu Gly Leu Pro Lys Asn His Lys Ala Ala Lys Gln Asn Val Arg Gly Gln Glu Asp Asn Lys Ala

E G L P K N H K A A K Q N V R G Q E D N K A

425 430 435 440

|------> TU15-Ex9_F2

1335 1350 1365 1380 1395

TGG AAG CTT AAG GCT GTG GAC GCC TTC AAG TCT GCC CCA CTG TAT CAG AGG CCA GGC TAC TAC AGT

ACC TTC GAA TTC CGA CAC CTG CGG AAG TTC AGA CGG GGT GAC ATA GTC TCC GGT CCG ATG ATG TCA

Trp Lys Leu Lys Ala Val Asp Ala Phe Lys Ser Ala Pro Leu Tyr Gln Arg Pro Gly Tyr Tyr Ser

W K L K A V D A F K S A P L Y Q R P G Y Y S

445 450 455 460 465

Tu15-Ex9_R1 <------

G=Thr (1,2,4,6,7)

| del (48)